Author: "Cauda, Roberto (ORCID:0000-0002-1498-4229)" - Searchworks@Jio Institute Digital Library Search Results

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258 results on '"Cauda, Roberto (ORCID:0000-0002-1498-4229)"'

1. Genome-based comparison between the recombinant SARS-CoV-2 XBB and its parental lineages

Author: Scarpa, Fabio, Sanna, Daria, Azzena, Ilenia, Casu, Marco, Cossu, Piero, Fiori, Pier Luigi, Benvenuto, Domenico, Imperia, Elena, Giovanetti, Marta, Ceccarelli, Giancarlo, Cauda, Roberto, Cassone, Antonio, Pascarella, Stefano, Ciccozzi, Massimo, Cauda, Roberto (ORCID:0000-0002-1498-4229), Scarpa, Fabio, Sanna, Daria, Azzena, Ilenia, Casu, Marco, Cossu, Piero, Fiori, Pier Luigi, Benvenuto, Domenico, Imperia, Elena, Giovanetti, Marta, Ceccarelli, Giancarlo, Cauda, Roberto, Cassone, Antonio, Pascarella, Stefano, Ciccozzi, Massimo, and Cauda, Roberto (ORCID:0000-0002-1498-4229)
Abstract: Recombination is the main contributor to RNA virus evolution, and SARS-CoV-2 during the pandemic produced several recombinants. The most recent SARS-CoV-2 recombinant is the lineage labeled XBB, also known as Gryphon, which arose from BJ.1 and BM.1.1.1. Here we performed a genome-based survey aimed to compare the new recombinant with its parental lineages that never became dominant. Genetic analyses indicated that the recombinant XBB and its first descendant XBB.1 show an evolutionary condition typical of an evolutionary blind background with no further epidemiologically relevant descendant. Genetic variability and expansion capabilities are slightly higher than parental lineages. Bayesian Skyline Plot indicates that XBB reached its plateau around October 6, 2022 and after an initial rapid growth the viral population size did not further expand, and around November 10, 2022 its levels of genetic variability decreased. Simultaneously with the reduction of the XBB population size, an increase of the genetic variability of its first sub-lineage XBB.1 occurred, that in turn reached the plateau around November 9, 2022 showing a kind of vicariance with its direct progenitors. Structure analysis indicates that the affinity for ACE2 surface in XBB/XBB.1 RBDs is weaker than for BA.2 RBD. In conclusion, at present XBB and XBB.1 do not show evidence about a particular danger or high expansion capability. Genome-based monitoring must continue uninterrupted in order to individuate if further mutations can make XBB more dangerous or generate new subvariants with different expansion capability. This article is protected by copyright. All rights reserved.
Published: 2023

2. Genome-based comparison between the recombinant SARS-CoV-2 XBB and its parental lineages

Author: Scarpa, Fabio, Sanna, Daria, Azzena, Ilenia, Casu, Marco, Cossu, Piero, Fiori, Pier Luigi, Benvenuto, Domenico, Imperia, Elena, Giovanetti, Marta, Ceccarelli, Giancarlo, Cauda, Roberto, Cassone, Antonio, Pascarella, Stefano, Ciccozzi, Massimo, Cauda, Roberto (ORCID:0000-0002-1498-4229), Scarpa, Fabio, Sanna, Daria, Azzena, Ilenia, Casu, Marco, Cossu, Piero, Fiori, Pier Luigi, Benvenuto, Domenico, Imperia, Elena, Giovanetti, Marta, Ceccarelli, Giancarlo, Cauda, Roberto, Cassone, Antonio, Pascarella, Stefano, Ciccozzi, Massimo, and Cauda, Roberto (ORCID:0000-0002-1498-4229)
Abstract: Recombination is the main contributor to RNA virus evolution, and SARS-CoV-2 during the pandemic produced several recombinants. The most recent SARS-CoV-2 recombinant is the lineage labeled XBB, also known as Gryphon, which arose from BJ.1 and BM.1.1.1. Here we performed a genome-based survey aimed to compare the new recombinant with its parental lineages that never became dominant. Genetic analyses indicated that the recombinant XBB and its first descendant XBB.1 show an evolutionary condition typical of an evolutionary blind background with no further epidemiologically relevant descendant. Genetic variability and expansion capabilities are slightly higher than parental lineages. Bayesian Skyline Plot indicates that XBB reached its plateau around October 6, 2022 and after an initial rapid growth the viral population size did not further expand, and around November 10, 2022 its levels of genetic variability decreased. Simultaneously with the reduction of the XBB population size, an increase of the genetic variability of its first sub-lineage XBB.1 occurred, that in turn reached the plateau around November 9, 2022 showing a kind of vicariance with its direct progenitors. Structure analysis indicates that the affinity for ACE2 surface in XBB/XBB.1 RBDs is weaker than for BA.2 RBD. In conclusion, at present XBB and XBB.1 do not show evidence about a particular danger or high expansion capability. Genome-based monitoring must continue uninterrupted in order to individuate if further mutations can make XBB more dangerous or generate new subvariants with different expansion capability. This article is protected by copyright. All rights reserved.
Published: 2023

3. Genetic and structural genome-based survey reveals the low potential for epidemiological expansion of the SARS-CoV-2 XBB.1.5 sublineage

Author: Scarpa, Fabio, Imperia, Elena, Azzena, Ilenia, Giovanetti, Marta, Benvenuto, Domenico, Locci, Chiara, Casu, Marco, Fiori, Pier Luigi, Maruotti, Antonello, Ceccarelli, Giancarlo, Borsetti, Alessandra, Caruso, Arnaldo, Cauda, Roberto, Cassone, Antonio, Via, Allegra, Pascarella, Stefano, Sanna, Daria, Ciccozzi, Massimo, Cauda, Roberto (ORCID:0000-0002-1498-4229), Scarpa, Fabio, Imperia, Elena, Azzena, Ilenia, Giovanetti, Marta, Benvenuto, Domenico, Locci, Chiara, Casu, Marco, Fiori, Pier Luigi, Maruotti, Antonello, Ceccarelli, Giancarlo, Borsetti, Alessandra, Caruso, Arnaldo, Cauda, Roberto, Cassone, Antonio, Via, Allegra, Pascarella, Stefano, Sanna, Daria, Ciccozzi, Massimo, and Cauda, Roberto (ORCID:0000-0002-1498-4229)
Abstract: not available
Published: 2023

4. Genetic and Structural Data on the SARS-CoV-2 Omicron BQ.1 Variant Reveal Its Low Potential for Epidemiological Expansion

Author: Scarpa, Fabio, Sanna, Daria, Benvenuto, Domenico, Borsetti, Alessandra, Azzena, Ilenia, Casu, Marco, Fiori, Pier Luigi, Giovanetti, Marta, Maruotti, Antonello, Ceccarelli, Giancarlo, Caruso, Arnaldo, Caccuri, Francesca, Cauda, Roberto, Cassone, Antonio, Pascarella, Stefano, Ciccozzi, Massimo, Cauda, Roberto (ORCID:0000-0002-1498-4229), Scarpa, Fabio, Sanna, Daria, Benvenuto, Domenico, Borsetti, Alessandra, Azzena, Ilenia, Casu, Marco, Fiori, Pier Luigi, Giovanetti, Marta, Maruotti, Antonello, Ceccarelli, Giancarlo, Caruso, Arnaldo, Caccuri, Francesca, Cauda, Roberto, Cassone, Antonio, Pascarella, Stefano, Ciccozzi, Massimo, and Cauda, Roberto (ORCID:0000-0002-1498-4229)
Abstract: The BQ.1 SARS-CoV-2 variant, also known as Cerberus, is one of the most recent Omicron descendant lineages. Compared to its direct progenitor BA.5, BQ.1 has some additional spike mutations in some key antigenic sites, which confer further immune escape ability over other circulating lineages. In such a context, here, we perform a genome-based survey aimed at obtaining a complete-as-possible nuance of this rapidly evolving Omicron subvariant. Genetic data suggest that BQ.1 represents an evolutionary blind background, lacking the rapid diversification that is typical of a dangerous lineage. Indeed, the evolutionary rate of BQ.1 is very similar to that of BA.5 (7.6 x 10(-4) and 7 x 10(-4) subs/site/year, respectively), which has been circulating for several months. The Bayesian Skyline Plot reconstruction indicates a low level of genetic variability, suggesting that the peak was reached around 3 September 2022. Concerning the affinity for ACE2, structure analyses (also performed by comparing the properties of BQ.1 and BA.5 RBD) indicate that the impact of the BQ.1 mutations may be modest. Likewise, immunoinformatic analyses showed moderate differences between the BQ.1 and BA5 potential B-cell epitopes. In conclusion, genetic and structural analyses on SARS-CoV-2 BQ.1 suggest no evidence of a particularly dangerous or high expansion capability. Genome-based monitoring must continue uninterrupted for a better understanding of its descendants and all other lineages.
Published: 2022

5. The value of electrostatic potentials of the spike receptor binding and N-terminal domains in addressing transmissibility and infectivity of SARS-CoV-2 variants of concern

Author: Pascarella, Stefano, Ciccozzi, Massimo, Bianchi, Martina, Benvenuto, Domenico, Cauda, Roberto, Cassone, Antonio, Cauda, Roberto (ORCID:0000-0002-1498-4229), Pascarella, Stefano, Ciccozzi, Massimo, Bianchi, Martina, Benvenuto, Domenico, Cauda, Roberto, Cassone, Antonio, and Cauda, Roberto (ORCID:0000-0002-1498-4229)
Abstract: Comparison of the surface electrostatic potential of the N-terminal (NTD) and the Receptor Binding Domains (RBD) of the Wuhan and Omicron Spikes. The entire Spikes are represented with transparent ribbon models. Only the NTD and RBD surfaces of the chain A are represented. Domain net charges are reported within parenthesis beside the domain labels. Surface color ranges from -5.0 (red) to + 5.0 (blue) kT/e. Image, graphical abstract
Published: 2022

6. COVID-19 atypical Parsonage-Turner syndrome: a case report

Author: Zazzara, Maria Beatrice, Modoni, Anna, Bizzarro, Alessandra, Lauria, Alessandra, Ciciarello, Francesca, Pais, Cristina, Galluzzo, Vincenzo, Landi, Francesco, Tostato, Matteo, Gremese, Elisa, Bernabei, Roberto, Fantoni, Massimo, Gasbarrini, Antonio, Settanni, Carlo Romano, Porcari, Serena, Benvenuto, Francesca, Bramato, Giulia, Brandi, Vincenzo, Carfì, Angelo, Lo Monaco, Maria Rita, Martone, Anna Maria, Marzetti, Emanuele, Napolitano, Carmen, Pagano, Francesco Cosimo, Rocchi, Sara, Rota, Elisabetta, Salerno, Andrea Maria, Tosato, Matteo, Tritto, Marcello, Calvani, Riccardo, Catalano, Lucio, Picca, Anna, Savera, Giulia, Cauda, Roberto, Murri, Rita, Cingolani, Antonella, Ventura, Giulio, Taddei, Eleonora, Moschese, Davide, Ciccullo, Arturo, Stella, Leonardo, Addolorato, Giovanni, Franceschi, Francesco, Mingrone, Gertrude, Zocco, Maria Assunta, Sanguinetti, Maurizio, Cattani Franchi, Paola, Marchetti, Simona, Posteraro, Brunella, Sali, Michela, Rizzo, Stanislao, Savastano, Maria Cristina, Gambini, Gloria, Cozzupoli, Maria Grazia, Culiersi, Carola, Passali, Giulio Cesare, Paludetti, Gaetano, Galli, Jacopo, Crudo, Fabrizio, Di Cintio, Giovanni, Longobardi, Ylenia, Tricarico, Laura, Santantonio, Mariaconsiglia, Di Cesare, Tiziana, Guarino, Mariateresa, Corbò, Marco, Settimi, Stefano, Mele, Dario Antonio, Brigato, Francesca, Buonsenso, Danilo, Valentini, Piero, Sinatti, Dario, De Rose, Gabriella, Richeldi, Luca, Lombardi, Francesco, Calabrese, Angelo, Varone, Francesco, Leone, Paolo Maria, Siciliano, Matteo, Corbo, Giuseppe Maria, Montemurro, Giuliano, Calvello, Mariarosaria, Intini, Enrica, Simonetti, Jacopo, Pasciuto, Giuliana, Adiletta, Veronica, Sofia, Carmelo, Licata, Maria Angela Vittoria Anna Chiara, Sani, Gabriele, Janiri, Delfina, Simonetti, Alessio, Modica, Marco, Montanari, Silvia, Catinari, Antonello, Terenzi, Beatrice, Natale, Luigi, Larici, Anna Rita, Marano, Riccardo, Pirronti, Tommaso, Infante, Amato, Paglionico, Annamaria, Petricca, Luca, Tolusso, Barbara, Alivernini, Stefano, Di Mario, Clara, Santoliquido, Angelo, Santoro, Luca, Nesci, Antonio, Di Giorgio, Angela, Null, Null, Landi, Francesco (ORCID:0000-0002-3472-1389), Gremese, Elisa (ORCID:0000-0002-2248-1058), Bernabei, Roberto (ORCID:0000-0002-9197-004X), Fantoni, Massimo (ORCID:0000-0001-6913-8460), Gasbarrini, Antonio (ORCID:0000-0002-7278-4823), Lo Monaco, Maria Rita (ORCID:0000-0002-1457-7981), Marzetti, Emanuele (ORCID:0000-0001-9567-6983), Pagano, Francesco, Salerno, Andrea, Calvani, Riccardo (ORCID:0000-0001-5472-2365), Cauda, Roberto (ORCID:0000-0002-1498-4229), Murri, Rita (ORCID:0000-0003-4263-7854), Cingolani, Antonella (ORCID:0000-0002-3793-2755), Ventura, Giulio (ORCID:0000-0002-0304-7264), Addolorato, Giovanni (ORCID:0000-0002-1522-9946), Zocco, Maria Assunta (ORCID:0000-0002-0814-9542), Sanguinetti, Maurizio (ORCID:0000-0002-9780-7059), Cattani, Paola (ORCID:0000-0003-4678-4763), Posteraro, Brunella (ORCID:0000-0002-1663-7546), Sali, Michela (ORCID:0000-0003-3609-2990), Rizzo, Stanislao (ORCID:0000-0001-6302-063X), Savastano, Maria Cristina (ORCID:0000-0003-1397-4333), Passali, Giulio Cesare (ORCID:0000-0002-8176-0962), Paludetti, Gaetano (ORCID:0000-0003-2480-1243), Galli, Jacopo (ORCID:0000-0001-6353-6249), Settimi, Stefano (ORCID:0000-0003-0104-1501), Mele, Dario, Valentini, Piero (ORCID:0000-0001-6095-9510), Richeldi, Luca (ORCID:0000-0001-8594-1448), Corbo, Giuseppe Maria (ORCID:0000-0002-8104-4659), Licata, Maria Angela, Sani, Gabriele (ORCID:0000-0002-9767-8752), Natale, Luigi (ORCID:0000-0002-7949-5119), Larici, Anna Rita (ORCID:0000-0002-1882-6244), Marano, Riccardo (ORCID:0000-0003-2710-2093), Pirronti, Tommaso (ORCID:0000-0003-3138-4097), Tolusso, Barbara (ORCID:0000-0002-9108-6609), Alivernini, Stefano (ORCID:0000-0002-7383-4212), Santoliquido, Angelo (ORCID:0000-0003-1539-4017), Zazzara, Maria Beatrice, Modoni, Anna, Bizzarro, Alessandra, Lauria, Alessandra, Ciciarello, Francesca, Pais, Cristina, Galluzzo, Vincenzo, Landi, Francesco, Tostato, Matteo, Gremese, Elisa, Bernabei, Roberto, Fantoni, Massimo, Gasbarrini, Antonio, Settanni, Carlo Romano, Porcari, Serena, Benvenuto, Francesca, Bramato, Giulia, Brandi, Vincenzo, Carfì, Angelo, Lo Monaco, Maria Rita, Martone, Anna Maria, Marzetti, Emanuele, Napolitano, Carmen, Pagano, Francesco Cosimo, Rocchi, Sara, Rota, Elisabetta, Salerno, Andrea Maria, Tosato, Matteo, Tritto, Marcello, Calvani, Riccardo, Catalano, Lucio, Picca, Anna, Savera, Giulia, Cauda, Roberto, Murri, Rita, Cingolani, Antonella, Ventura, Giulio, Taddei, Eleonora, Moschese, Davide, Ciccullo, Arturo, Stella, Leonardo, Addolorato, Giovanni, Franceschi, Francesco, Mingrone, Gertrude, Zocco, Maria Assunta, Sanguinetti, Maurizio, Cattani Franchi, Paola, Marchetti, Simona, Posteraro, Brunella, Sali, Michela, Rizzo, Stanislao, Savastano, Maria Cristina, Gambini, Gloria, Cozzupoli, Maria Grazia, Culiersi, Carola, Passali, Giulio Cesare, Paludetti, Gaetano, Galli, Jacopo, Crudo, Fabrizio, Di Cintio, Giovanni, Longobardi, Ylenia, Tricarico, Laura, Santantonio, Mariaconsiglia, Di Cesare, Tiziana, Guarino, Mariateresa, Corbò, Marco, Settimi, Stefano, Mele, Dario Antonio, Brigato, Francesca, Buonsenso, Danilo, Valentini, Piero, Sinatti, Dario, De Rose, Gabriella, Richeldi, Luca, Lombardi, Francesco, Calabrese, Angelo, Varone, Francesco, Leone, Paolo Maria, Siciliano, Matteo, Corbo, Giuseppe Maria, Montemurro, Giuliano, Calvello, Mariarosaria, Intini, Enrica, Simonetti, Jacopo, Pasciuto, Giuliana, Adiletta, Veronica, Sofia, Carmelo, Licata, Maria Angela Vittoria Anna Chiara, Sani, Gabriele, Janiri, Delfina, Simonetti, Alessio, Modica, Marco, Montanari, Silvia, Catinari, Antonello, Terenzi, Beatrice, Natale, Luigi, Larici, Anna Rita, Marano, Riccardo, Pirronti, Tommaso, Infante, Amato, Paglionico, Annamaria, Petricca, Luca, Tolusso, Barbara, Alivernini, Stefano, Di Mario, Clara, Santoliquido, Angelo, Santoro, Luca, Nesci, Antonio, Di Giorgio, Angela, Null, Null, Landi, Francesco (ORCID:0000-0002-3472-1389), Gremese, Elisa (ORCID:0000-0002-2248-1058), Bernabei, Roberto (ORCID:0000-0002-9197-004X), Fantoni, Massimo (ORCID:0000-0001-6913-8460), Gasbarrini, Antonio (ORCID:0000-0002-7278-4823), Lo Monaco, Maria Rita (ORCID:0000-0002-1457-7981), Marzetti, Emanuele (ORCID:0000-0001-9567-6983), Pagano, Francesco, Salerno, Andrea, Calvani, Riccardo (ORCID:0000-0001-5472-2365), Cauda, Roberto (ORCID:0000-0002-1498-4229), Murri, Rita (ORCID:0000-0003-4263-7854), Cingolani, Antonella (ORCID:0000-0002-3793-2755), Ventura, Giulio (ORCID:0000-0002-0304-7264), Addolorato, Giovanni (ORCID:0000-0002-1522-9946), Zocco, Maria Assunta (ORCID:0000-0002-0814-9542), Sanguinetti, Maurizio (ORCID:0000-0002-9780-7059), Cattani, Paola (ORCID:0000-0003-4678-4763), Posteraro, Brunella (ORCID:0000-0002-1663-7546), Sali, Michela (ORCID:0000-0003-3609-2990), Rizzo, Stanislao (ORCID:0000-0001-6302-063X), Savastano, Maria Cristina (ORCID:0000-0003-1397-4333), Passali, Giulio Cesare (ORCID:0000-0002-8176-0962), Paludetti, Gaetano (ORCID:0000-0003-2480-1243), Galli, Jacopo (ORCID:0000-0001-6353-6249), Settimi, Stefano (ORCID:0000-0003-0104-1501), Mele, Dario, Valentini, Piero (ORCID:0000-0001-6095-9510), Richeldi, Luca (ORCID:0000-0001-8594-1448), Corbo, Giuseppe Maria (ORCID:0000-0002-8104-4659), Licata, Maria Angela, Sani, Gabriele (ORCID:0000-0002-9767-8752), Natale, Luigi (ORCID:0000-0002-7949-5119), Larici, Anna Rita (ORCID:0000-0002-1882-6244), Marano, Riccardo (ORCID:0000-0003-2710-2093), Pirronti, Tommaso (ORCID:0000-0003-3138-4097), Tolusso, Barbara (ORCID:0000-0002-9108-6609), Alivernini, Stefano (ORCID:0000-0002-7383-4212), and Santoliquido, Angelo (ORCID:0000-0003-1539-4017)
Abstract: Background Neurological manifestations of Sars-CoV-2 infection have been described since March 2020 and include both central and peripheral nervous system manifestations. Neurological symptoms, such as headache or persistent loss of smell and taste, have also been documented in COVID-19 long-haulers. Moreover, long lasting fatigue, mild cognitive impairment and sleep disorders appear to be frequent long term neurological manifestations after hospitalization due to COVID-19. Less is known in relation to peripheral nerve injury related to Sars-CoV-2 infection. Case presentation We report the case of a 47-year-old female presenting with a unilateral chest pain radiating to the left arm lasting for more than two months after recovery from Sars-CoV-2 infection. After referral to our post-acute outpatient service for COVID-19 long haulers, she was diagnosed with a unilateral, atypical, pure sensory brachial plexus neuritis potentially related to COVID-19, which occurred during the acute phase of a mild Sars-CoV-2 infection and persisted for months after resolution of the infection. Conclusions We presented a case of atypical Parsonage-Turner syndrome potentially triggered by Sars-CoV-2 infection, with symptoms and repercussion lasting after viral clearance. A direct involvement of the virus remains uncertain, and the physiopathology is unclear. The treatment of COVID-19 and its long-term consequences represents a relatively new challenge for clinicians and health care providers. A multidisciplinary approach to following-up COVID-19 survivors is strongly advised.
Published: 2022

7. SARS-CoV-2 shifting transmission dynamics and hidden reservoirs potentially limit efficacy of public health interventions in Italy

Author: Giovanetti, Marta, Cella, Eleonora, Benedetti, Francesca, Rife Magalis, Brittany, Fonseca, Vagner, Fabris, Silvia, Campisi, Giovanni, Ciccozzi, Alessandra, Angeletti, Silvia, Borsetti, Alessandra, Tambone, Vittoradolfo, Sagnelli, Caterina, Pascarella, Stefano, Riva, Alberto, Ceccarelli, Giancarlo, Marcello, Alessandro, Azarian, Taj, Wilkinson, Eduan, de Oliveira, Tulio, Alcantara, Luiz Carlos Junior, Cauda, Roberto, Caruso, Arnaldo, Dean, Natalie E, Browne, Cameron, Lourenco, Jose, Salemi, Marco, Zella, Davide, Ciccozzi, Massimo, Cauda, Roberto (ORCID:0000-0002-1498-4229), Giovanetti, Marta, Cella, Eleonora, Benedetti, Francesca, Rife Magalis, Brittany, Fonseca, Vagner, Fabris, Silvia, Campisi, Giovanni, Ciccozzi, Alessandra, Angeletti, Silvia, Borsetti, Alessandra, Tambone, Vittoradolfo, Sagnelli, Caterina, Pascarella, Stefano, Riva, Alberto, Ceccarelli, Giancarlo, Marcello, Alessandro, Azarian, Taj, Wilkinson, Eduan, de Oliveira, Tulio, Alcantara, Luiz Carlos Junior, Cauda, Roberto, Caruso, Arnaldo, Dean, Natalie E, Browne, Cameron, Lourenco, Jose, Salemi, Marco, Zella, Davide, Ciccozzi, Massimo, and Cauda, Roberto (ORCID:0000-0002-1498-4229)
Abstract: We investigated SARS-CoV-2 transmission dynamics in Italy, one of the countries hit hardest by the pandemic, using phylodynamic analysis of viral genetic and epidemiological data. We observed the co-circulation of multiple SARS-CoV-2 lineages over time, which were linked to multiple importations and characterized by large transmission clusters concomitant with a high number of infections. Subsequent implementation of a three-phase nationwide lockdown strategy greatly reduced infection numbers and hospitalizations. Yet we present evidence of sustained viral spread among sporadic clusters acting as "hidden reservoirs" during summer 2020. Mathematical modelling shows that increased mobility among residents eventually catalyzed the coalescence of such clusters, thus driving up the number of infections and initiating a new epidemic wave. Our results suggest that the efficacy of public health interventions is, ultimately, limited by the size and structure of epidemic reservoirs, which may warrant prioritization during vaccine deployment.Giovanetti et al. examine SARS-CoV-2 transmission dynamics in Italy using phylodynamic analysis of viral genetic and epidemiological data. They present evidence to suggest that the efficacy of public health interventions is limited by the size and structure of epidemic reservoirs, which may influence vaccination programmes.
Published: 2021

8. People Living with HIV in the COVID-19 Era: A Case Report

Author: Farinacci, Damiano, Ciccullo, Arturo, Borghetti, Alberto, Visconti, Elena, Tamburrini, Enrica, Izzi, Immacolata Maria, Cauda, Roberto, Di Giambenedetto, Simona, Pallavicini, Federico, Tamburrini, Enrica (ORCID:0000-0003-4930-426X), Cauda, Roberto (ORCID:0000-0002-1498-4229), Di Giambenedetto, Simona (ORCID:0000-0001-6990-5076), Pallavicini, Federico (ORCID:0000-0001-6874-0302), Farinacci, Damiano, Ciccullo, Arturo, Borghetti, Alberto, Visconti, Elena, Tamburrini, Enrica, Izzi, Immacolata Maria, Cauda, Roberto, Di Giambenedetto, Simona, Pallavicini, Federico, Tamburrini, Enrica (ORCID:0000-0003-4930-426X), Cauda, Roberto (ORCID:0000-0002-1498-4229), Di Giambenedetto, Simona (ORCID:0000-0001-6990-5076), and Pallavicini, Federico (ORCID:0000-0001-6874-0302)
Abstract: inglese
Published: 2021

9. SARS-CoV-2 shifting transmission dynamics and hidden reservoirs potentially limit efficacy of public health interventions in Italy

Author: Giovanetti, Marta, Cella, Eleonora, Benedetti, Francesca, Rife Magalis, Brittany, Fonseca, Vagner, Fabris, Silvia, Campisi, Giovanni, Ciccozzi, Alessandra, Angeletti, Silvia, Borsetti, Alessandra, Tambone, Vittoradolfo, Sagnelli, Caterina, Pascarella, Stefano, Riva, Alberto, Ceccarelli, Giancarlo, Marcello, Alessandro, Azarian, Taj, Wilkinson, Eduan, de Oliveira, Tulio, Alcantara, Luiz Carlos Junior, Cauda, Roberto, Caruso, Arnaldo, Dean, Natalie E, Browne, Cameron, Lourenco, Jose, Salemi, Marco, Zella, Davide, Ciccozzi, Massimo, Cauda, Roberto (ORCID:0000-0002-1498-4229), Giovanetti, Marta, Cella, Eleonora, Benedetti, Francesca, Rife Magalis, Brittany, Fonseca, Vagner, Fabris, Silvia, Campisi, Giovanni, Ciccozzi, Alessandra, Angeletti, Silvia, Borsetti, Alessandra, Tambone, Vittoradolfo, Sagnelli, Caterina, Pascarella, Stefano, Riva, Alberto, Ceccarelli, Giancarlo, Marcello, Alessandro, Azarian, Taj, Wilkinson, Eduan, de Oliveira, Tulio, Alcantara, Luiz Carlos Junior, Cauda, Roberto, Caruso, Arnaldo, Dean, Natalie E, Browne, Cameron, Lourenco, Jose, Salemi, Marco, Zella, Davide, Ciccozzi, Massimo, and Cauda, Roberto (ORCID:0000-0002-1498-4229)
Abstract: We investigated SARS-CoV-2 transmission dynamics in Italy, one of the countries hit hardest by the pandemic, using phylodynamic analysis of viral genetic and epidemiological data. We observed the co-circulation of multiple SARS-CoV-2 lineages over time, which were linked to multiple importations and characterized by large transmission clusters concomitant with a high number of infections. Subsequent implementation of a three-phase nationwide lockdown strategy greatly reduced infection numbers and hospitalizations. Yet we present evidence of sustained viral spread among sporadic clusters acting as "hidden reservoirs" during summer 2020. Mathematical modelling shows that increased mobility among residents eventually catalyzed the coalescence of such clusters, thus driving up the number of infections and initiating a new epidemic wave. Our results suggest that the efficacy of public health interventions is, ultimately, limited by the size and structure of epidemic reservoirs, which may warrant prioritization during vaccine deployment.Giovanetti et al. examine SARS-CoV-2 transmission dynamics in Italy using phylodynamic analysis of viral genetic and epidemiological data. They present evidence to suggest that the efficacy of public health interventions is limited by the size and structure of epidemic reservoirs, which may influence vaccination programmes.
Published: 2021

10. A machine-learning parsimonious multivariable predictive model of mortality risk in patients with Covid-19

Author: Murri, Rita, Lenkowicz, Jacopo, Masciocchi, Carlotta, Iacomini, Chiara, Fantoni, Massimo, Damiani, Andrea, Marchetti, Antonio, Sergi, Paolo Domenico Angelo, Arcuri, Giovanni, Cesario, Alfredo, Patarnello, Stefano, Antonelli, Massimo, Bellantone, Rocco Domenico Alfonso, Bernabei, Roberto, Boccia, Stefania, Calabresi, Paolo, Cambieri, Andrea, Cauda, Roberto, Colosimo, Cesare, Crea, Filippo, De Maria Marchiano, Ruggero, De Stefano, Valerio, Franceschi, Francesco, Gasbarrini, Antonio, Parolini, Ornella, Richeldi, Luca, Sanguinetti, Maurizio, Urbani, Andrea, Zega, Maurizio, Scambia, Giovanni, Valentini, Vincenzo, Armuzzi, Alessandro, Barba, Marta, Baroni, Silvia, Bellesi, Silvia, Bentivoglio, Annarita, Biasucci, Luigi Marzio, Biscetti, Federico, Candelli, Marcello, Capalbo, Gennaro, Cattani Franchi, Paola, Chiusolo, Patrizia, Cingolani, Antonella, Corbo, Giuseppe Maria, Covino, Marcello, Cozzolino, Angela Maria, D’Alfonso, Marilena, De Angelis, Giulia, De Pascale, Gennaro, Frisullo, Giovanni, Gabrielli, Maurizio, Gambassi, Giovanni, Garcovich, Matteo, Gremese, Elisa, Grieco, Domenico Luca, Iaconelli, Amerigo, Iorio, Raffaele, Landi, Francesco, Larici, Annarita, Liuzzo, Giovanna, Maviglia, Riccardo, Miele, Luca, Montalto, Massimo, Natale, Luigi, Nicolotti, Nicola, Ojetti, Veronica, Pompili, Maurizio, Posteraro, Brunella, Rapaccini, Gianni, Rinaldi, Riccardo, Rossi, Elena, Santoliquido, Angelo, Sica, Simona, Tamburrini, Enrica, Teofili, Luciana, Testa, Antonia Carla, Tosoni, Alberto, Trani, Carlo, Varone, Francesco, Zileri Dal Verme, Lorenzo, Null, Null, Murri, Rita (ORCID:0000-0003-4263-7854), Fantoni, Massimo (ORCID:0000-0001-6913-8460), Cesario, Alfredo (ORCID:0000-0003-4687-0709), Antonelli, Massimo (ORCID:0000-0003-3007-1670), Bellantone, Rocco (ORCID:0000-0002-0844-3469), Bernabei, Roberto (ORCID:0000-0002-9197-004X), Boccia, Stefania (ORCID:0000-0002-1864-749X), Calabresi, Paolo (ORCID:0000-0003-0326-5509), Cauda, Roberto (ORCID:0000-0002-1498-4229), Colosimo, Cesare (ORCID:0000-0003-3800-3648), Crea, Filippo (ORCID:0000-0001-9404-8846), De Maria, Ruggero (ORCID:0000-0003-2255-0583), De Stefano, Valerio (ORCID:0000-0002-5178-5827), Gasbarrini, Antonio (ORCID:0000-0002-7278-4823), Parolini, Ornella (ORCID:0000-0002-5211-6430), Richeldi, Luca (ORCID:0000-0001-8594-1448), Sanguinetti, Maurizio (ORCID:0000-0002-9780-7059), Zega, Maurizio (ORCID:0000-0002-7821-2615), Scambia, Giovanni (ORCID:0000-0003-2758-1063), Valentini, Vincenzo (ORCID:0000-0003-4637-6487), Armuzzi, Alessandro (ORCID:0000-0003-1572-0118), Barba, Marta (ORCID:0000-0001-6084-7666), Baroni, Silvia (ORCID:0000-0002-3410-2617), Biasucci, Luigi Marzio (ORCID:0000-0002-6921-6497), Biscetti, Federico (ORCID:0000-0001-7449-657X), Candelli, Marcello (ORCID:0000-0001-8443-7880), Cattani, Paola (ORCID:0000-0003-4678-4763), Chiusolo, Patrizia (ORCID:0000-0002-1355-1587), Cingolani, Antonella (ORCID:0000-0002-3793-2755), Corbo, Giuseppe (ORCID:0000-0002-8104-4659), Covino, Marcello (ORCID:0000-0002-6709-2531), De Angelis, Giulia (ORCID:0000-0002-7087-7399), De Pascale, Gennaro (ORCID:0000-0002-8255-0676), Gambassi, Giovanni (ORCID:0000-0002-7030-9359), Gremese, Elisa (ORCID:0000-0002-2248-1058), Grieco, Domenico Luca (ORCID:0000-0002-4557-6308), Iorio, Raffaele (ORCID:0000-0002-6270-0956), Landi, Francesco (ORCID:0000-0002-3472-1389), Liuzzo, Giovanna (ORCID:0000-0002-5714-0907), Miele, Luca (ORCID:0000-0003-3464-0068), Montalto, Massimo (ORCID:0000-0001-8819-3684), Natale, Luigi (ORCID:0000-0002-7949-5119), Ojetti, Veronica (ORCID:0000-0002-8953-0707), Pompili, Maurizio (ORCID:0000-0001-6699-7980), Posteraro, Brunella (ORCID:0000-0002-1663-7546), Rossi, Elena (ORCID:0000-0002-7572-9379), Santoliquido, Angelo (ORCID:0000-0003-1539-4017), Tamburrini, Enrica (ORCID:0000-0003-4930-426X), Teofili, Luciana (ORCID:0000-0002-7214-1561), Testa, Antonia (ORCID:0000-0003-2217-8726), Trani, Carlo (ORCID:0000-0001-9777-013X), Verme, Lorenzo Zileri Dal, Murri, Rita, Lenkowicz, Jacopo, Masciocchi, Carlotta, Iacomini, Chiara, Fantoni, Massimo, Damiani, Andrea, Marchetti, Antonio, Sergi, Paolo Domenico Angelo, Arcuri, Giovanni, Cesario, Alfredo, Patarnello, Stefano, Antonelli, Massimo, Bellantone, Rocco Domenico Alfonso, Bernabei, Roberto, Boccia, Stefania, Calabresi, Paolo, Cambieri, Andrea, Cauda, Roberto, Colosimo, Cesare, Crea, Filippo, De Maria Marchiano, Ruggero, De Stefano, Valerio, Franceschi, Francesco, Gasbarrini, Antonio, Parolini, Ornella, Richeldi, Luca, Sanguinetti, Maurizio, Urbani, Andrea, Zega, Maurizio, Scambia, Giovanni, Valentini, Vincenzo, Armuzzi, Alessandro, Barba, Marta, Baroni, Silvia, Bellesi, Silvia, Bentivoglio, Annarita, Biasucci, Luigi Marzio, Biscetti, Federico, Candelli, Marcello, Capalbo, Gennaro, Cattani Franchi, Paola, Chiusolo, Patrizia, Cingolani, Antonella, Corbo, Giuseppe Maria, Covino, Marcello, Cozzolino, Angela Maria, D’Alfonso, Marilena, De Angelis, Giulia, De Pascale, Gennaro, Frisullo, Giovanni, Gabrielli, Maurizio, Gambassi, Giovanni, Garcovich, Matteo, Gremese, Elisa, Grieco, Domenico Luca, Iaconelli, Amerigo, Iorio, Raffaele, Landi, Francesco, Larici, Annarita, Liuzzo, Giovanna, Maviglia, Riccardo, Miele, Luca, Montalto, Massimo, Natale, Luigi, Nicolotti, Nicola, Ojetti, Veronica, Pompili, Maurizio, Posteraro, Brunella, Rapaccini, Gianni, Rinaldi, Riccardo, Rossi, Elena, Santoliquido, Angelo, Sica, Simona, Tamburrini, Enrica, Teofili, Luciana, Testa, Antonia Carla, Tosoni, Alberto, Trani, Carlo, Varone, Francesco, Zileri Dal Verme, Lorenzo, Null, Null, Murri, Rita (ORCID:0000-0003-4263-7854), Fantoni, Massimo (ORCID:0000-0001-6913-8460), Cesario, Alfredo (ORCID:0000-0003-4687-0709), Antonelli, Massimo (ORCID:0000-0003-3007-1670), Bellantone, Rocco (ORCID:0000-0002-0844-3469), Bernabei, Roberto (ORCID:0000-0002-9197-004X), Boccia, Stefania (ORCID:0000-0002-1864-749X), Calabresi, Paolo (ORCID:0000-0003-0326-5509), Cauda, Roberto (ORCID:0000-0002-1498-4229), Colosimo, Cesare (ORCID:0000-0003-3800-3648), Crea, Filippo (ORCID:0000-0001-9404-8846), De Maria, Ruggero (ORCID:0000-0003-2255-0583), De Stefano, Valerio (ORCID:0000-0002-5178-5827), Gasbarrini, Antonio (ORCID:0000-0002-7278-4823), Parolini, Ornella (ORCID:0000-0002-5211-6430), Richeldi, Luca (ORCID:0000-0001-8594-1448), Sanguinetti, Maurizio (ORCID:0000-0002-9780-7059), Zega, Maurizio (ORCID:0000-0002-7821-2615), Scambia, Giovanni (ORCID:0000-0003-2758-1063), Valentini, Vincenzo (ORCID:0000-0003-4637-6487), Armuzzi, Alessandro (ORCID:0000-0003-1572-0118), Barba, Marta (ORCID:0000-0001-6084-7666), Baroni, Silvia (ORCID:0000-0002-3410-2617), Biasucci, Luigi Marzio (ORCID:0000-0002-6921-6497), Biscetti, Federico (ORCID:0000-0001-7449-657X), Candelli, Marcello (ORCID:0000-0001-8443-7880), Cattani, Paola (ORCID:0000-0003-4678-4763), Chiusolo, Patrizia (ORCID:0000-0002-1355-1587), Cingolani, Antonella (ORCID:0000-0002-3793-2755), Corbo, Giuseppe (ORCID:0000-0002-8104-4659), Covino, Marcello (ORCID:0000-0002-6709-2531), De Angelis, Giulia (ORCID:0000-0002-7087-7399), De Pascale, Gennaro (ORCID:0000-0002-8255-0676), Gambassi, Giovanni (ORCID:0000-0002-7030-9359), Gremese, Elisa (ORCID:0000-0002-2248-1058), Grieco, Domenico Luca (ORCID:0000-0002-4557-6308), Iorio, Raffaele (ORCID:0000-0002-6270-0956), Landi, Francesco (ORCID:0000-0002-3472-1389), Liuzzo, Giovanna (ORCID:0000-0002-5714-0907), Miele, Luca (ORCID:0000-0003-3464-0068), Montalto, Massimo (ORCID:0000-0001-8819-3684), Natale, Luigi (ORCID:0000-0002-7949-5119), Ojetti, Veronica (ORCID:0000-0002-8953-0707), Pompili, Maurizio (ORCID:0000-0001-6699-7980), Posteraro, Brunella (ORCID:0000-0002-1663-7546), Rossi, Elena (ORCID:0000-0002-7572-9379), Santoliquido, Angelo (ORCID:0000-0003-1539-4017), Tamburrini, Enrica (ORCID:0000-0003-4930-426X), Teofili, Luciana (ORCID:0000-0002-7214-1561), Testa, Antonia (ORCID:0000-0003-2217-8726), Trani, Carlo (ORCID:0000-0001-9777-013X), and Verme, Lorenzo Zileri Dal
Abstract: The COVID-19 pandemic is impressively challenging the healthcare system. Several prognostic models have been validated but few of them are implemented in daily practice. The objective of the study was to validate a machine-learning risk prediction model using easy-to-obtain parameters to help to identify patients with COVID-19 who are at higher risk of death. The training cohort included all patients admitted to Fondazione Policlinico Gemelli with COVID-19 from March 5, 2020, to November 5, 2020. Afterward, the model was tested on all patients admitted to the same hospital with COVID-19 from November 6, 2020, to February 5, 2021. The primary outcome was in-hospital case-fatality risk. The out-of-sample performance of the model was estimated from the training set in terms of Area under the Receiving Operator Curve (AUROC) and classification matrix statistics by averaging the results of fivefold cross validation repeated 3-times and comparing the results with those obtained on the test set. An explanation analysis of the model, based on the SHapley Additive exPlanations (SHAP), is also presented. To assess the subsequent time evolution, the change in paO2/FiO2 (P/F) at 48 h after the baseline measurement was plotted against its baseline value. Among the 921 patients included in the training cohort, 120 died (13%). Variables selected for the model were age, platelet count, SpO2, blood urea nitrogen (BUN), hemoglobin, C-reactive protein, neutrophil count, and sodium. The results of the fivefold cross-validation repeated 3-times gave AUROC of 0.87, and statistics of the classification matrix to the Youden index as follows: sensitivity 0.840, specificity 0.774, negative predictive value 0.971. Then, the model was tested on a new population (n=1463) in which the case-fatality rate was 22.6%. The test model showed AUROC 0.818, sensitivity 0.813, specificity 0.650, negative predictive value 0.922. Considering the first quartile of the predicted risk score (low-risk score gro
Published: 2021

11. Evolution of cellular HIV DNA levels in virologically suppressed patients switching to dolutegravir/lamivudine versus maintaining a triple regimen: a prospective, longitudinal, matched, controlled study

Author: Lombardi, Francesca, Belmonti, Simone, Borghetti, Alberto, Fabbiani, Massimiliano, Marchetti, Simona, Tamburrini, Enrica, Cauda, Roberto, Di Giambenedetto, Simona, Tamburrini, Enrica (ORCID:0000-0003-4930-426X), Cauda, Roberto (ORCID:0000-0002-1498-4229), di Giambenedetto, Simona (ORCID:0000-0001-6990-5076), Lombardi, Francesca, Belmonti, Simone, Borghetti, Alberto, Fabbiani, Massimiliano, Marchetti, Simona, Tamburrini, Enrica, Cauda, Roberto, Di Giambenedetto, Simona, Tamburrini, Enrica (ORCID:0000-0003-4930-426X), Cauda, Roberto (ORCID:0000-0002-1498-4229), and di Giambenedetto, Simona (ORCID:0000-0001-6990-5076)
Abstract: Objectives: To assess the impact of switching to dolutegravir plus lamivudine maintenance therapy on the HIV cellular reservoir size.Patients and methods: This was a prospective, longitudinal, matched, controlled study. We enrolled virologically suppressed patients on stable three-drug ART who switched at baseline (BL) to dolutegravir/lamivudine (DT group) or maintained triple therapy (TT group); subjects in the TT group were matched 1:1 with those in the DT group according to age, gender, years since HIV diagnosis, years on ART and anchor drug. Total blood-associated HIV DNA levels were assessed by droplet digital PCR at BL and after 48weeks (T48). Results were expressed as log(10)HIV DNAcopies/10(6) leucocytes.Results: We enrolled 40 patients in the DT group and 40 in the TT group; the two groups were homogeneous for all main characteristics except nadir CD4 cell count. At BL, HIV DNA levels were comparable between the DT and TT groups: 2.27 (IQR 1.97-2.47) and 2.26 (IQR 2.05-2.61) log(10)HIV DNAcopies/10(6) leucocytes, respectively. Change in HIV DNA load from BL to T48 was -0.105 (IQR -0.384 to 0.121, P=0.041) in the DT group and -0.132 (IQR -0.362 to 0.046, P=0.005) in the TT group, with a comparable decline observed between the two groups (P=0.821). A higher HIV DNA decline was associated with higher BL CD4/CD8 ratio.Conclusions: Maintenance therapy with dolutegravir/lamivudine had the same impact as the triple regimen on HIV DNA levels after 48weeks of treatment. These data seem to support the effectiveness of a dolutegravir/lamivudine dual regimen in controlling the magnitude of the cellular reservoir (www.clinicaltrials.gov, number NCT02836782).
Published: 2020

12. Ethical Criteria for the Admission and Management of Patients in the ICU Under Conditions of Limited Medical Resources: A Shared International Proposal in View of the COVID-19 Pandemic

Author: Tambone, Vittoradolfo, Boudreau, Donald, Ciccozzi, Massimo, Sanders, Karen, Campanozzi, Laura Leondina, Wathuta, Jane, Violante, Luciano, Cauda, Roberto, Petrini, Carlo, Abbate, Antonio, Alloni, Rossana, Argemi, Josepmaria, Argemí Renom, Josep, De Benedictis, Anna, Galerneau, France, García-Sánchez, Emilio, Ghilardi, Giampaolo, Hafler, Janet Palmer, Linden, Magdalena, Marcos, Alfredo, Onetti Muda, Andrea, Pandolfi, Marco, Pelaccia, Thierry, Picozzi, Mario, Revello, Ruben Oscar, Ricci, Giovanna, Rohrbaugh, Robert, Rossi, Patrizio, Sirignano, Ascanio, Spagnolo, Antonio Gioacchino, Stammers, Trevor, Velázquez, Lourde, Agazzi, Evandro, Mercurio, Mark, Cauda, Roberto (ORCID:0000-0002-1498-4229), Spagnolo, Antonio Gioacchino (ORCID:0000-0002-5762-2164), Tambone, Vittoradolfo, Boudreau, Donald, Ciccozzi, Massimo, Sanders, Karen, Campanozzi, Laura Leondina, Wathuta, Jane, Violante, Luciano, Cauda, Roberto, Petrini, Carlo, Abbate, Antonio, Alloni, Rossana, Argemi, Josepmaria, Argemí Renom, Josep, De Benedictis, Anna, Galerneau, France, García-Sánchez, Emilio, Ghilardi, Giampaolo, Hafler, Janet Palmer, Linden, Magdalena, Marcos, Alfredo, Onetti Muda, Andrea, Pandolfi, Marco, Pelaccia, Thierry, Picozzi, Mario, Revello, Ruben Oscar, Ricci, Giovanna, Rohrbaugh, Robert, Rossi, Patrizio, Sirignano, Ascanio, Spagnolo, Antonio Gioacchino, Stammers, Trevor, Velázquez, Lourde, Agazzi, Evandro, Mercurio, Mark, Cauda, Roberto (ORCID:0000-0002-1498-4229), and Spagnolo, Antonio Gioacchino (ORCID:0000-0002-5762-2164)
Abstract: inglese, inglese
Published: 2020

13. People Living with HIV in the COVID-19 Era: A Case Report

Author: Farinacci, Damiano, Ciccullo, Arturo, Borghetti, Alberto, Visconti, Elena, Tamburrini, Enrica, Izzi, Immacolata Maria, Cauda, Roberto, Di Giambenedetto, Simona, Pallavicini, Federico, Tamburrini, Enrica (ORCID:0000-0003-4930-426X), Cauda, Roberto (ORCID:0000-0002-1498-4229), Di Giambenedetto, Simona (ORCID:0000-0001-6990-5076), Pallavicini, Federico (ORCID:0000-0001-6874-0302), Farinacci, Damiano, Ciccullo, Arturo, Borghetti, Alberto, Visconti, Elena, Tamburrini, Enrica, Izzi, Immacolata Maria, Cauda, Roberto, Di Giambenedetto, Simona, Pallavicini, Federico, Tamburrini, Enrica (ORCID:0000-0003-4930-426X), Cauda, Roberto (ORCID:0000-0002-1498-4229), Di Giambenedetto, Simona (ORCID:0000-0001-6990-5076), and Pallavicini, Federico (ORCID:0000-0001-6874-0302)
Abstract: Not available
Published: 2020

14. Knowing more about chloroquine/hydroxycloroquine in COVID-19 patients

Author: Cassone, Antonio, Iacoviello, Licia, Cauda, Roberto, Cauda, Roberto (ORCID:0000-0002-1498-4229), Cassone, Antonio, Iacoviello, Licia, Cauda, Roberto, and Cauda, Roberto (ORCID:0000-0002-1498-4229)
Abstract: Not available
Published: 2020

15. No evidence of SARS-CoV-2 circulation in HIV-infected patients between December 2019 and February 2020 in Rome, Italy

Author: Lombardi, Francesca, Belmonti, Simone, Ricci, Rosalba, Borghetti, Alberto, Fabbiani, Massimiliano, Ciccullo, Arturo, Cauda, Roberto, Di Giambenedetto, Simona, Lombardi, Francesca (ORCID:0000-0001-5757-8346), Cauda, Roberto (ORCID:0000-0002-1498-4229), Di Giambenedetto, Simona (ORCID:0000-0001-6990-5076), Lombardi, Francesca, Belmonti, Simone, Ricci, Rosalba, Borghetti, Alberto, Fabbiani, Massimiliano, Ciccullo, Arturo, Cauda, Roberto, Di Giambenedetto, Simona, Lombardi, Francesca (ORCID:0000-0001-5757-8346), Cauda, Roberto (ORCID:0000-0002-1498-4229), and Di Giambenedetto, Simona (ORCID:0000-0001-6990-5076)
Abstract: Not available
Published: 2020

16. Effectiveness of switching to darunavir/cobicistat in virologically-suppressed HIV-positive patients receiving ritonavir-boosted protease inhibitor-based regimen: the 'STORE' Study

Author: Gori, Andrea, Antinori, Andrea, Vergori, Alessandra, Cossu, Maria Vittoria, Menzaghi, Barbara, Sterrantino, Gaetana, Rusconi, Stefano, Cattelan, Annamaria, Castelli, Francesco, Gianotti, Nicola, Orofino, Giancarlo, Ripamonti, Diego, Savinelli, Stefano, Manzillo, Elio, Santantonio, Teresa Antonia, Celesia, Benedetto Maurizio, Cauda, Roberto, Maserati, Renato, Dʼarminio Monforte, Antonella, Stingone, Christof, Bonora, Stefano, Uglietti, Alessia, Termini, Roberta, Rucci, Francesco, Mancusi, Daniela, Cauda, Roberto (ORCID:0000-0002-1498-4229), Gori, Andrea, Antinori, Andrea, Vergori, Alessandra, Cossu, Maria Vittoria, Menzaghi, Barbara, Sterrantino, Gaetana, Rusconi, Stefano, Cattelan, Annamaria, Castelli, Francesco, Gianotti, Nicola, Orofino, Giancarlo, Ripamonti, Diego, Savinelli, Stefano, Manzillo, Elio, Santantonio, Teresa Antonia, Celesia, Benedetto Maurizio, Cauda, Roberto, Maserati, Renato, Dʼarminio Monforte, Antonella, Stingone, Christof, Bonora, Stefano, Uglietti, Alessia, Termini, Roberta, Rucci, Francesco, Mancusi, Daniela, and Cauda, Roberto (ORCID:0000-0002-1498-4229)
Abstract: OBJECTIVE: This study investigates the effectiveness and tolerability of switching to darunavir/cobicistat (DRV/c)-based antiretroviral regimen (ART) from a ritonavir-boosted protease inhibitor (PI/r)-based regimen in virologically suppressed human immunodeficiency virus (HIV)-positive patients. DRV trough values were also investigated. SETTING: Prospective, multicenter, single-country, non-interventional, cohort study. METHODS: This study included patients on a PI/r-based ART for at least twelve months having plasma HIV-1 RNA <50 copies/mL for at least six months. Primary endpoint: HIV-1 RNA <50 copies/mL at 48 ± 6 weeks from baseline. A secondary analysis was performed using the time to loss of virological response (TLOVR) algorithm. Biochemical parameters including DRV trough samples were collected as per clinical practice and measured using high-performance liquid chromatography. RESULTS: Of 336 patients enrolled, 282 completed the study: 70.8% had plasma HIV-1 RNA <50 copies/mL at 48 weeks; using the TLOVR algorithm, 82.7% maintained virological suppression. Virological failure (VF) was observed in 6 patients (1.8%). Adverse event (AE)-related discontinuations were 4.5%. After 48 weeks, we found a significant improvement in both triglycerides (median, 130.0 mg/dL to 113.5 mg/dL, p=0.0254) and HDL cholesterol (48 to 49 mg/dL, p<0.0001) but no change in other biomarkers. DRV trough concentrations in 56 subjects showed a median value of 2862.5 (1469.5-4439.0) ng/mL, higher in females than in males (4221 ng/mL vs. 2634 ng/mL, p=0.046). CONCLUSIONS: In stable HIV-1 positive virologically suppressed patients, the switch to DRV/c-based ART was beneficial in terms of low rates of VF and AEs due to its high tolerability and improvement in triglycerides.
Published: 2020

17. Evolution of cellular HIV DNA levels in virologically suppressed patients switching to dolutegravir/lamivudine versus maintaining a triple regimen: a prospective, longitudinal, matched, controlled study

Author: Lombardi, Francesca, Belmonti, Simone, Borghetti, Alberto, Fabbiani, Massimiliano, Marchetti, Simona, Tamburrini, Enrica, Cauda, Roberto, Di Giambenedetto, Simona, Lombardi, Francesca (ORCID:0000-0001-5757-8346), Tamburrini, Enrica (ORCID:0000-0003-4930-426X), Cauda, Roberto (ORCID:0000-0002-1498-4229), di Giambenedetto, Simona (ORCID:0000-0001-6990-5076), Lombardi, Francesca, Belmonti, Simone, Borghetti, Alberto, Fabbiani, Massimiliano, Marchetti, Simona, Tamburrini, Enrica, Cauda, Roberto, Di Giambenedetto, Simona, Lombardi, Francesca (ORCID:0000-0001-5757-8346), Tamburrini, Enrica (ORCID:0000-0003-4930-426X), Cauda, Roberto (ORCID:0000-0002-1498-4229), and di Giambenedetto, Simona (ORCID:0000-0001-6990-5076)
Abstract: OBJECTIVES: To assess the impact of switching to dolutegravir plus lamivudine maintenance therapy on the HIV cellular reservoir size. PATIENTS AND METHODS: This was a prospective, longitudinal, matched, controlled study. We enrolled virologically suppressed patients on stable three-drug ART who switched at baseline (BL) to dolutegravir/lamivudine (DT group) or maintained triple therapy (TT group); subjects in the TT group were matched 1:1 with those in the DT group according to age, gender, years since HIV diagnosis, years on ART and anchor drug. Total blood-associated HIV DNA levels were assessed by droplet digital PCR at BL and after 48 weeks (T48). Results were expressed as log10 HIV DNA copies/106 leucocytes. RESULTS: We enrolled 40 patients in the DT group and 40 in the TT group; the two groups were homogeneous for all main characteristics except nadir CD4 cell count. At BL, HIV DNA levels were comparable between the DT and TT groups: 2.27 (IQR 1.97-2.47) and 2.26 (IQR 2.05-2.61) log10 HIV DNA copies/106 leucocytes, respectively. Change in HIV DNA load from BL to T48 was -0.105 (IQR -0.384 to 0.121, P = 0.041) in the DT group and -0.132 (IQR -0.362 to 0.046, P = 0.005) in the TT group, with a comparable decline observed between the two groups (P = 0.821). A higher HIV DNA decline was associated with higher BL CD4/CD8 ratio. CONCLUSIONS: Maintenance therapy with dolutegravir/lamivudine had the same impact as the triple regimen on HIV DNA levels after 48 weeks of treatment. These data seem to support the effectiveness of a dolutegravir/lamivudine dual regimen in controlling the magnitude of the cellular reservoir (www.clinicaltrials.gov, number NCT02836782). © The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.
Published: 2020

18. Cognitive impairment and cardiovascular disease related to alexithymia in a well-controlled HIV-infected population

Author: Ciccarelli, Nicoletta, Baldonero, Eleonora, Milanini, Benedetta, Fabbiani, Massimiliano, Cauda, Roberto, Di Giambenedetto, Simona, Silveri, Maria Caterina, Ciccarelli, Nicoletta (ORCID:0000-0002-7582-9142), Cauda, Roberto (ORCID:0000-0002-1498-4229), Di Giambenedetto, Simona (ORCID:0000-0001-6990-5076), Silveri, Maria Caterina (ORCID:0000-0001-5012-0682), Ciccarelli, Nicoletta, Baldonero, Eleonora, Milanini, Benedetta, Fabbiani, Massimiliano, Cauda, Roberto, Di Giambenedetto, Simona, Silveri, Maria Caterina, Ciccarelli, Nicoletta (ORCID:0000-0002-7582-9142), Cauda, Roberto (ORCID:0000-0002-1498-4229), Di Giambenedetto, Simona (ORCID:0000-0001-6990-5076), and Silveri, Maria Caterina (ORCID:0000-0001-5012-0682)
Abstract: Both cognitive diseases and alexithymia may be associated with HIV. Moreover, alexithymia has been linked to cardiovascular (CV) diseases. Our aim was to explore the prevalence of alexithymia and its associations with neurocognitive disorders (HAND) and CV risk factors in a well-controlled HIV-positive population. We consecutively enrolled 140 HIV-positive individuals on antiretroviral therapy and 35 healthy subjects matched for age, education and gender. In all participants alexithymia was explored by the 20-item Toronto Alexithymia Scale. For HIV-positive subjects also data about CV risk factors were collected, and a comprehensive neuropsychological examination was administered; HAND was defined according to Frascati criteria. Patients and controls did not differ in the proportion of alexithymic status (10% vs. 11%; p=0.761). Among HIV-positive patients, alexithymic participants presented a higher prevalence of diabetes (21% vs. 3%, p=0.035) and hypertension (36% vs. 13%, p= 0.037) compared to non-alexithymic. About 30% (n=41) of HIV-positive patients met criteria for asymptomatic HAND. Alexithymia was not independently associated with a higher risk of HAND (p=0.189). Analyzing each cognitive domain, alexithymia showed an independent association with an abnormal performance (OR 1.08; p=0.037) only in psychomotor speed. In conclusion, in the context of a well-controlled HIV infection, we found a low prevalence of alexithymia comparable to healthy controls. Alexithymia was linked to higher risk of CV disease in the HIV-positive population, but with a rate similar to that previously estimated in the HIV-negative alexithymic. Finally, alexithymia was clearly associated to cognitive impairment only in the psychomotor speed domain, suggesting a common fronto-striatal system dysregulation.
Published: 2019

19. Incidence of Bloodstream Infections, Length of Hospital Stay, and Survival in Patients With Recurrent Clostridioides difficile Infection Treated With Fecal Microbiota Transplantation or Antibiotics: A Prospective Cohort Study

Author: Ianiro, Gianluca, Murri, Rita, Sciumè, Giusi Desirè, Impagnatiello, Michele, Masucci, Luca, Ford, Alexander C, Law, Graham R, Tilg, Herbert, Sanguinetti, Maurizio, Cauda, Roberto, Gasbarrini, Antonio, Fantoni, Massimo, Cammarota, Giovanni, Ianiro, Gianluca (ORCID:0000-0002-8318-0515), Murri, Rita (ORCID:0000-0003-4263-7854), Masucci, Luca (ORCID:0000-0002-8358-6726), Sanguinetti, Maurizio (ORCID:0000-0002-9780-7059), Cauda, Roberto (ORCID:0000-0002-1498-4229), Gasbarrini, Antonio (ORCID:0000-0002-7278-4823), Fantoni, Massimo (ORCID:0000-0001-6913-8460), Cammarota, Giovanni (ORCID:0000-0002-3626-6148), Ianiro, Gianluca, Murri, Rita, Sciumè, Giusi Desirè, Impagnatiello, Michele, Masucci, Luca, Ford, Alexander C, Law, Graham R, Tilg, Herbert, Sanguinetti, Maurizio, Cauda, Roberto, Gasbarrini, Antonio, Fantoni, Massimo, Cammarota, Giovanni, Ianiro, Gianluca (ORCID:0000-0002-8318-0515), Murri, Rita (ORCID:0000-0003-4263-7854), Masucci, Luca (ORCID:0000-0002-8358-6726), Sanguinetti, Maurizio (ORCID:0000-0002-9780-7059), Cauda, Roberto (ORCID:0000-0002-1498-4229), Gasbarrini, Antonio (ORCID:0000-0002-7278-4823), Fantoni, Massimo (ORCID:0000-0001-6913-8460), and Cammarota, Giovanni (ORCID:0000-0002-3626-6148)
Abstract: Background: Clostridioides difficile infection (CDI) is a risk factor for bloodstream infection (BSI). Fecal microbiota transplantation (FMT) is more effective than antibiotics in treating recurrent CDI, but its efficacy in preventing CDI-related BSI is uncertain. Objective: To assess incidence of primary BSI in patients with recurrent CDI treated with FMT versus antibiotics. Design: Prospective cohort study. Patients treated with FMT and those treated with antibiotics were matched on propensity score. Setting: Single academic medical center. Patients: 290 inpatients with recurrent CDI (57 patients per treatment in matched cohort). Intervention: FMT or antibiotics. Measurements: The primary outcome was primary BSI within 90 days. Secondary outcomes were length of hospitalization and overall survival (OS) at 90 days. Results: Of the 290 patients, 109 were treated with FMT and 181 received antibiotics. Five patients in the FMT group and 40 in the antibiotic group developed BSI. Because of differences in the patients treated with FMT versus antibiotics in many baseline characteristics, including number of recurrences and CDI severity, comparative analyses were limited to the matched cohort. Risk for BSI was 23 percentage points (95% CI, 10 to 35 percentage points) lower in the FMT group; the FMT group also had 14 fewer days of hospitalization (CI, 9 to 20 fewer days) and a 32-percentage point increase in OS (CI, 16 to 47 percentage points) compared with the antibiotic group. Limitation: Nonrandomized study with potential for unmeasured or residual confounding; limited generalizability of the propensity score-matched cohort. Conclusion: In a propensity score-matched cohort, patients with recurrent CDI treated with FMT were less likely to develop primary BSI.
Published: 2019

20. Case Report: Multifocal Tubercular Osteomyelitis of the Spine and Bilateral Dactylitis

Author: Taccari, Francesco, Baldin, Gianmaria, Emiliozzi, Arianna, Campana, Lara, Tamburrini, Enrica, Leone, Edoardo, Delogu, Giovanni, Sali, Michela, Cauda, Roberto, Leone, Antonio, Pallavicini, Federico, Tamburrini, Enrica (ORCID:0000-0003-4930-426X), Delogu, Giovanni (ORCID:0000-0003-0182-8267), Sali, Michela (ORCID:0000-0003-3609-2990), Cauda, Roberto (ORCID:0000-0002-1498-4229), Leone, Antonio (ORCID:0000-0003-3669-6321), Pallavicini, Federico (ORCID:0000-0001-6874-0302), Taccari, Francesco, Baldin, Gianmaria, Emiliozzi, Arianna, Campana, Lara, Tamburrini, Enrica, Leone, Edoardo, Delogu, Giovanni, Sali, Michela, Cauda, Roberto, Leone, Antonio, Pallavicini, Federico, Tamburrini, Enrica (ORCID:0000-0003-4930-426X), Delogu, Giovanni (ORCID:0000-0003-0182-8267), Sali, Michela (ORCID:0000-0003-3609-2990), Cauda, Roberto (ORCID:0000-0002-1498-4229), Leone, Antonio (ORCID:0000-0003-3669-6321), and Pallavicini, Federico (ORCID:0000-0001-6874-0302)
Abstract: We report a case of a 13-year-old immunocompetent male with multifocal tubercular osteomyelitis involving several spinal segments, small bones of the hands, and the scalp, who started with progressively back pain and enlarging painful swelling on the palms of hands, fatigue, and irregular fever. All the hand lesions were firm, mildly tender, and covered by ulcerated skin with serous discharge from the site. Magnetic resonance showed lesions of the right fifth metacarpal, of the right intermediate phalanx of the fourth finger, of the left second metacarpal, and of most vertebral bodies of the cervical, dorsal, lumbar, and sacral spine. The nucleic acid amplification test and the final culture from the drainage of the hands' lesion were positive for Mycobacterium tuberculosis. The patient received a standard antitubercular treatment for 12 months with clinical improvement.
Published: 2019

21. Reduced soluble CD14 levels after switching from a dual regimen with lamivudine plus boosted protease inhibitors to lamivudine plus dolutegravir in virologically suppressed HIV-infected patients

Author: Lombardi, Francesca, Belmonti, Simone, Borghetti, Alberto, Ciccullo, Arturo, Baldin, Gianmaria, Cauda, Roberto, Fabbiani, Massimiliano, Di Giambenedetto, Simona, Lombardi, Francesca (ORCID:0000-0001-5757-8346), Cauda, Roberto (ORCID:0000-0002-1498-4229), Di Giambenedetto, Simona (ORCID:0000-0001-6990-5076), Lombardi, Francesca, Belmonti, Simone, Borghetti, Alberto, Ciccullo, Arturo, Baldin, Gianmaria, Cauda, Roberto, Fabbiani, Massimiliano, Di Giambenedetto, Simona, Lombardi, Francesca (ORCID:0000-0001-5757-8346), Cauda, Roberto (ORCID:0000-0002-1498-4229), and Di Giambenedetto, Simona (ORCID:0000-0001-6990-5076)
Abstract: Background: HIV-induced systemic immune activation and inflammation have been associated with morbidity and mortality in virologically suppressed patients. Objective: To evaluate the impact of treatment switch from a dual regimen with lamivudine (3TC) plus ritonavir-boosted protease inhibitors (PI/r) to 3TC plus dolutegravir (DTG) on the monocyte activation marker soluble CD14 (sCD14) and other inflammatory biomarkers, interleukin-6 (IL-6), C-reactive protein (CRP), intestinal fatty acid-binding protein (I-FABP) and D-dimer. Methods: We performed a retrospective case-crossover study on integrase inhibitors-naïve virologically suppressed patients while on 3TC + PI/r dual maintenance therapy for ≥48 weeks who switched to 3TC + DTG and maintained this regimen for ≥48 weeks. Biomarkers plasma levels were tested by ELISA assays on stored samples at three time points: at switch (BL), 48 weeks before (-48 W) and 48 weeks after switch (+48 W). Results: A total of 67 patients were included. Median sCD14 levels were stable from -48 W to BL (from 6.07 to 6.04 log10 pg/mL, p = 0.235) but showed a statistically significant decrease after switch: from 6.04 (IQR 5.92-6.12) at BL to 5.95 (IQR 5.84-6.07) log10 pg/mL at + W48 (p < 0.001). Concurrently, an improvement in lipid profile was observed, even thought it was not correlated to the change in sCD14. The levels of IL-6, CRP, I-FABP and D-dimer remained stable before and after the switch to 3TC + DTG. Conclusions: In virologically suppressed HIV-infected patients on a 3TC + PI/r dual therapy, switching to 3TC + DTG was associated with a significant decline in sCD14. These data suggest reduced monocyte activation following substitution of boosted PI with DTG, which could have important clinical implications.
Published: 2019

22. Liver fibrosis is associated with cognitive impairment in people living with HIV

Author: Ciccarelli, Nicoletta, Fabbiani, Massimiliano, Brita, Anna C., De Marco, Ramona, Grima, Pierfrancesco, Gagliardini, Roberta, Borghetti, Alberto, Cauda, Roberto, Di Giambenedetto, Simona, Ciccarelli, Nicoletta (ORCID:0000-0002-7582-9142), Cauda, Roberto (ORCID:0000-0002-1498-4229), Di Giambenedetto, Simona (ORCID:0000-0001-6990-5076), Ciccarelli, Nicoletta, Fabbiani, Massimiliano, Brita, Anna C., De Marco, Ramona, Grima, Pierfrancesco, Gagliardini, Roberta, Borghetti, Alberto, Cauda, Roberto, Di Giambenedetto, Simona, Ciccarelli, Nicoletta (ORCID:0000-0002-7582-9142), Cauda, Roberto (ORCID:0000-0002-1498-4229), and Di Giambenedetto, Simona (ORCID:0000-0001-6990-5076)
Abstract: Purpose: Our aim was to better explore the association between liver fibrosis (LF) and neurocognitive impairment (NCI) in people living with HIV (PLWH). Methods: We performed a cross-sectional cohort study by consecutively enrolling PLWH at two clinical centers. All subjects underwent a comprehensive neuropsychological battery; NCI was defined as having a pathological performance (1.5 SD below the normative mean) on at least two cognitive domains. LF was explored using FIB4 index; in a subgroup of PLWH, LF was also assessed by transient elastography. Results: A total of 386 subjects were enrolled, of whom 17 (4.4%) had FIB4 > 3.25. In the subgroup of PLWH (N = 127) performing also liver transient elastography, 14 (11%) had liver stiffness > 14 kPa. Overall, 47 subjects (12%) were diagnosed with NCI. At multivariate regression analyses, participants with FIB4 > 1.45 showed a higher risk of NCI in comparison with those with lower values (aOR 3.04, p = 0.044), after adjusting for education (aOR 0.71, p < 0.001), past AIDS-defining events (aOR 2.91, p = 0.014), CD4 cell count, past injecting drug use (IDU), HIV-RNA < 50 copies/mL, and HCV co-infection. Also a liver stiffness > 14 kPa showed an independent association with a higher risk of NCI (aOR 10.13, p = 0.041). Analyzing any single cognitive domain, a higher risk of abnormal psychomotor speed was associated with a liver stiffness > 14 kPa (aOR 223.17, p = 0.019) after adjusting for education (aOR 0.57, p = 0.018), HIV-RNA < 50 copies/mL (aOR 0.01, p = 0.007), age, past IDU, and HCV co-infection. Conclusions: In PLWH, increased LF, estimated through non-invasive methods, was associated to a higher risk of NCI independently from HCV status.
Published: 2019

23. A pilot experience of common European infectious diseases curriculum for medical students: the IDEAL summer school

Author: Charlier, Caroline, Wolf, Federica, Vlieghe, Erika, Planquette, Benjamin, Damme, Pierre Van, De Gaetano Donati, Katleen, Buffet, Pierre, Henry, Benoît, Cevik, Muge, Leen, Clifford, Laurenson, Ian, Cameron, Helen, Ogavu, Joseph, Nabankema, Evelyn, Omona, Venice, Valnaud, Pauline, Mackintosh, Claire, Johannessen, Ingólfur, Geertruyden, Jean-Pierre Van, Jeunne, Claire Le, Cauda, Roberto, Wolf, Federica (ORCID:0000-0003-1361-1049), Cauda, Roberto (ORCID:0000-0002-1498-4229), Charlier, Caroline, Wolf, Federica, Vlieghe, Erika, Planquette, Benjamin, Damme, Pierre Van, De Gaetano Donati, Katleen, Buffet, Pierre, Henry, Benoît, Cevik, Muge, Leen, Clifford, Laurenson, Ian, Cameron, Helen, Ogavu, Joseph, Nabankema, Evelyn, Omona, Venice, Valnaud, Pauline, Mackintosh, Claire, Johannessen, Ingólfur, Geertruyden, Jean-Pierre Van, Jeunne, Claire Le, Cauda, Roberto, Wolf, Federica (ORCID:0000-0003-1361-1049), and Cauda, Roberto (ORCID:0000-0002-1498-4229)
Abstract: We demonstrated our ability as European medical educators to overcome language and organizational barriers moving towards a paradigm of Euorpean-wide teaching that better addresses students' needs and underpins high quality, safe exchange of information across the continents; thereby promoting excellent patient care by tomorrow's physicians.
Published: 2019

24. Efficacy of Ceftazidime-avibactam Salvage Therapy in Patients with Infections Caused by KPC-producing Klebsiella pneumoniae

Author: Tumbarello, Mario, Trecarichi, Enrico Maria, Corona, Alberto, De Rosa, Francesco Giuseppe, Bassetti, Matteo, Mussini, Cristina, Menichetti, Francesco, Viscoli, Claudio, Campoli, Caterina, Venditti, Mario, De Gasperi, Andrea, Mularoni, Alessandra, Tascini, Carlo, Parruti, Giustino, Pallotto, Carlo, Sica, Simona, Concia, Ercole, Cultrera, Rosario, De Pascale, Gennaro, Capone, Alessandro, Antinori, Spinello, Corcione, Silvia, Righi, Elda, Losito, Angela Raffaella, Digaetano, Margherita, Amadori, Francesco, Giacobbe, Daniele Roberto, Ceccarelli, Giancarlo, Mazza, Ernestina, Raffaelli, Francesca, Spanu, Teresa, Cauda, Roberto, Viale, Pierluigi, Tumbarello, Mario (ORCID:0000-0002-9519-8552), Sica, Simona (ORCID:0000-0003-2426-3465), De Pascale, Gennaro (ORCID:0000-0002-8255-0676), Spanu, Teresa (ORCID:0000-0003-1864-5184), Cauda, Roberto (ORCID:0000-0002-1498-4229), Tumbarello, Mario, Trecarichi, Enrico Maria, Corona, Alberto, De Rosa, Francesco Giuseppe, Bassetti, Matteo, Mussini, Cristina, Menichetti, Francesco, Viscoli, Claudio, Campoli, Caterina, Venditti, Mario, De Gasperi, Andrea, Mularoni, Alessandra, Tascini, Carlo, Parruti, Giustino, Pallotto, Carlo, Sica, Simona, Concia, Ercole, Cultrera, Rosario, De Pascale, Gennaro, Capone, Alessandro, Antinori, Spinello, Corcione, Silvia, Righi, Elda, Losito, Angela Raffaella, Digaetano, Margherita, Amadori, Francesco, Giacobbe, Daniele Roberto, Ceccarelli, Giancarlo, Mazza, Ernestina, Raffaelli, Francesca, Spanu, Teresa, Cauda, Roberto, Viale, Pierluigi, Tumbarello, Mario (ORCID:0000-0002-9519-8552), Sica, Simona (ORCID:0000-0003-2426-3465), De Pascale, Gennaro (ORCID:0000-0002-8255-0676), Spanu, Teresa (ORCID:0000-0003-1864-5184), and Cauda, Roberto (ORCID:0000-0002-1498-4229)
Abstract: Ceftazidime-avibactam (CAZ-AVI) has been approved in Europe for the treatment of complicated intra-abdominal and urinary-tract infections, as well as hospital-acquired pneumonia, and for Gram-negative infections with limited treatment options. CAZ-AVI displays in vitro activity against KPC-enzyme producers, but clinical-trial data on its efficacy in this setting are lacking. Methods: We retrospectively reviewed 138 cases of infections caused by Klebsiella pneumoniae carbapenemase-producing (KPC-Kp) in adults who received CAZ-AVI in compassionate-use programs in Italy. Case features and outcomes were analyzed, and survival was then specifically explored in the large subcohort whose infections were bacteremic. Results: The 138 patients started CAZ-AVI salvage therapy after a first line treatment (median: 7 days) with other antimicrobials. CAZ-AVI was administered with at least one other active antibiotic in 109 (78.9%) cases. Thirty days after infection onset, 47 (34.1%) of the 138 patients had died. Thirty-day mortality among the 104 patients with bacteremic KPC-Kp infections was significantly lower than that of a matched cohort whose KPC-Kp bacteremia had been treated with drugs other than CAZ-AVI (36.5% vs. 55.7%, p=0.005). Multivariate analysis of the 208 cases of KPC-Kp bacteremia identified septic shock, neutropenia, Charlson comorbidity index >3, and recent mechanical ventilation as independent predictors of mortality, whereas receipt of CAZ-AVI was the sole independent predictor of survival. Conclusions: CAZ-AVI appears to be a promising drug for treatment of severe KPC-Kp infections, especially those involving bacteremia.
Published: 2019

25. Safety and efficacy of ombitasvir/paritaprevir/ritonavir/dasabuvir plus ribavirin in patients over 65 years with HCV genotype 1 cirrhosis

Author: Ascione, Antonio, De Luca, Massimo, Melazzini, Mario, Montilla, Simona, Trotta, Maria Paola, Petta, Salvatore, Puoti, Massimo, Sangiovanni, Vincenzo, Messina, Vincenzo, Bruno, Savino, Izzi, Antonio, Villa, Erica, Aghemo, Alessio, Zignego, Anna Linda, Orlandini, Alessandra, Fontanella, Luca, Gasbarrini, Antonio, Marzioni, Marco, Giannini, Edoardo G., Craxì, Antonio, Abbati, Giuseppe, Alberti, Alfredo, Andreone, Pietro, Andreoni, Massimo, Angeli, Paolo, Angelico, Mario, Angarano, Gioacchino, Angrisani, Debora, Antinori, Andrea, Antonini, Cinzia, Avancini, Ivo, Barone, Michele, Bruno, Raffaele, Benedetti, Antonio, Bernabucci, Veronica, Blanc, Pier, Boarini, Chiara, Boffa, Nicola, Boglione, Lucio, Borghi, Vanni, Borgia, Guglielmo, Brancaccio, Giuseppina, Brunetto, Maurizia, Cacciola, Irene, Calabrese, Paolo, Calvaruso, Vincenza, Campagnolo, Davide, Canovari, Benedetta, Caporaso, Nicola, Capra, Franco, Carolo, Giada, Cassola, Giovanni, Castelli, Francesco, Cauda, Roberto, Silberstein, Francesca Ceccherini, Cecere, Roberto, Chessa, Luchino, Chiodera, Alessandro, Chirianni, Antonio, Ciancio, Alessia, Cima, Serena, Coco, Barbara, Colombo, Massimo, Coppola, Nicola, Corti, Giampaolo, Cosco, Lucio, Corradori, Silvia, Cozzolongo, Raffaele, Cristaudo, Antonio, Danieli, Elena, Monforte, Antonella D’Arminio, Monache, Marco delle, Del Poggio, Paolo, de Luca, Andrea, Dentone, Chiara, Di Biagio, Antonio, Di Leo, Alfredo, Di Perri, Giovanni, Di Stefano, Marco, D’Offizi, Giampiero, Donato, Francesca, Durante, Emanuele, Erne, Elke, Fagiuoli, Stefano, Falasca, Katia, Federico, Alessandro, Felder, Martina, Ferrari, Carlo, Gaeta, Giovanni Battista, Ganga, Roberto, Gatti, Pietro, Giacomet, Vania, Giacometti, Andrea, Gianstefani, Alice, Giordani, Maria, Giorgini, Alessia, Grieco, Antonio, Guerra, Michele, Gulminetti, Roberto, Ieluzzi, Donatella, Imparato, Michele, Iodice, Valentina, La Monica, Silvia, Lazzarin, Adriano, Lenzi, Marco, Levrero, Massimo, Lichtner, Myriam, Lionetti, Raffaella, Guercio, Carmela Lo, Madonna, Salvatore, Magnani, Silvia, Maida, Ivana, Marignani, Massimo, Marrone, Aldo, Marsetti, Fabio, Martini, Silvia, Masarone, Mario, Maserati, Renato, Mastroianni, Claudio Maria, Memoli, Massimo, Menzaghi, Barbara, Merli, Manuela, Miele, Luca, Milella, Michele, Mondelli, Mario, Montalbano, Marzia, Monti, Monica, Morelli, Olivia, Morisco, Filomena, Nardone, Gaetano, Novara, Sergio, Onnelli, Giovanna, Onofrio, Mirella, Paganin, Simona, Pani, Luca, Parisi, Maria Rita, Parruti, Giustino, Pasquazzi, Caterina, Pasulo, Luisa, Perno, Carlo Federico, Persico, Marcello, Piai, Guido, Picciotto, Antonino, Pigozzi, Grazielle Marie, Piovesan, Sara, Piras, Maria Chiara, Pirisi, Massimo, Piscaglia, Anna Maria, Ponti, Laura, Potenza, Domenico, Pravadelli, Cecilia, Quartini, Mariano, Quirino, Tiziana, Raimondo, Giovanni, Rapaccini, Gian Ludovico, Rendina, Maria, Rizzardini, Giuliano, Rizzetto, Mario, Rizzo, Salvatore, Romagnoli, Dante, Romano, Antonietta, Rossi, Cristina, Rumi, Maria Grazia, Russello, Maurizio, Russo, Francesca Paolo, Russo, Maria Luisa, Sansonno, Domenico Ettore, Santantonio, Teresa Antonia, Saracco, Giorgio, Schimizzi, Anna Maria, Serviddio, Gaetano, Simeone, Filomena, Solinas, Attilio, Soria, Alessandro, Tabone, Marco, Taliani, Gloria, Tarantino, Giuseppe, Tarquini, Pierluigi, Tavio, Marcello, Termite, Antonio, Teti, Elisabetta, Toniutto, Pierluigi, Torti, Carlo, Tundi, Paolo, Vecchiet, Giacomo, Verucchi, Gabriella, Gentilucci, Umberto Vespasiani, Vinci, Maria, Vullo, Vincenzo, Zolfino, Teresa, Zuin, Massimo, Gasbarrini, Antonio (ORCID:0000-0002-7278-4823), Cauda, Roberto (ORCID:0000-0002-1498-4229), de Luca, Andrea (ORCID:0000-0002-8311-6935), Grieco, Antonio (ORCID:0000-0002-0544-8993), Miele, Luca (ORCID:0000-0003-3464-0068), Rapaccini, Gian Ludovico (ORCID:0000-0002-6467-857X), Ascione, Antonio, De Luca, Massimo, Melazzini, Mario, Montilla, Simona, Trotta, Maria Paola, Petta, Salvatore, Puoti, Massimo, Sangiovanni, Vincenzo, Messina, Vincenzo, Bruno, Savino, Izzi, Antonio, Villa, Erica, Aghemo, Alessio, Zignego, Anna Linda, Orlandini, Alessandra, Fontanella, Luca, Gasbarrini, Antonio, Marzioni, Marco, Giannini, Edoardo G., Craxì, Antonio, Abbati, Giuseppe, Alberti, Alfredo, Andreone, Pietro, Andreoni, Massimo, Angeli, Paolo, Angelico, Mario, Angarano, Gioacchino, Angrisani, Debora, Antinori, Andrea, Antonini, Cinzia, Avancini, Ivo, Barone, Michele, Bruno, Raffaele, Benedetti, Antonio, Bernabucci, Veronica, Blanc, Pier, Boarini, Chiara, Boffa, Nicola, Boglione, Lucio, Borghi, Vanni, Borgia, Guglielmo, Brancaccio, Giuseppina, Brunetto, Maurizia, Cacciola, Irene, Calabrese, Paolo, Calvaruso, Vincenza, Campagnolo, Davide, Canovari, Benedetta, Caporaso, Nicola, Capra, Franco, Carolo, Giada, Cassola, Giovanni, Castelli, Francesco, Cauda, Roberto, Silberstein, Francesca Ceccherini, Cecere, Roberto, Chessa, Luchino, Chiodera, Alessandro, Chirianni, Antonio, Ciancio, Alessia, Cima, Serena, Coco, Barbara, Colombo, Massimo, Coppola, Nicola, Corti, Giampaolo, Cosco, Lucio, Corradori, Silvia, Cozzolongo, Raffaele, Cristaudo, Antonio, Danieli, Elena, Monforte, Antonella D’Arminio, Monache, Marco delle, Del Poggio, Paolo, de Luca, Andrea, Dentone, Chiara, Di Biagio, Antonio, Di Leo, Alfredo, Di Perri, Giovanni, Di Stefano, Marco, D’Offizi, Giampiero, Donato, Francesca, Durante, Emanuele, Erne, Elke, Fagiuoli, Stefano, Falasca, Katia, Federico, Alessandro, Felder, Martina, Ferrari, Carlo, Gaeta, Giovanni Battista, Ganga, Roberto, Gatti, Pietro, Giacomet, Vania, Giacometti, Andrea, Gianstefani, Alice, Giordani, Maria, Giorgini, Alessia, Grieco, Antonio, Guerra, Michele, Gulminetti, Roberto, Ieluzzi, Donatella, Imparato, Michele, Iodice, Valentina, La Monica, Silvia, Lazzarin, Adriano, Lenzi, Marco, Levrero, Massimo, Lichtner, Myriam, Lionetti, Raffaella, Guercio, Carmela Lo, Madonna, Salvatore, Magnani, Silvia, Maida, Ivana, Marignani, Massimo, Marrone, Aldo, Marsetti, Fabio, Martini, Silvia, Masarone, Mario, Maserati, Renato, Mastroianni, Claudio Maria, Memoli, Massimo, Menzaghi, Barbara, Merli, Manuela, Miele, Luca, Milella, Michele, Mondelli, Mario, Montalbano, Marzia, Monti, Monica, Morelli, Olivia, Morisco, Filomena, Nardone, Gaetano, Novara, Sergio, Onnelli, Giovanna, Onofrio, Mirella, Paganin, Simona, Pani, Luca, Parisi, Maria Rita, Parruti, Giustino, Pasquazzi, Caterina, Pasulo, Luisa, Perno, Carlo Federico, Persico, Marcello, Piai, Guido, Picciotto, Antonino, Pigozzi, Grazielle Marie, Piovesan, Sara, Piras, Maria Chiara, Pirisi, Massimo, Piscaglia, Anna Maria, Ponti, Laura, Potenza, Domenico, Pravadelli, Cecilia, Quartini, Mariano, Quirino, Tiziana, Raimondo, Giovanni, Rapaccini, Gian Ludovico, Rendina, Maria, Rizzardini, Giuliano, Rizzetto, Mario, Rizzo, Salvatore, Romagnoli, Dante, Romano, Antonietta, Rossi, Cristina, Rumi, Maria Grazia, Russello, Maurizio, Russo, Francesca Paolo, Russo, Maria Luisa, Sansonno, Domenico Ettore, Santantonio, Teresa Antonia, Saracco, Giorgio, Schimizzi, Anna Maria, Serviddio, Gaetano, Simeone, Filomena, Solinas, Attilio, Soria, Alessandro, Tabone, Marco, Taliani, Gloria, Tarantino, Giuseppe, Tarquini, Pierluigi, Tavio, Marcello, Termite, Antonio, Teti, Elisabetta, Toniutto, Pierluigi, Torti, Carlo, Tundi, Paolo, Vecchiet, Giacomo, Verucchi, Gabriella, Gentilucci, Umberto Vespasiani, Vinci, Maria, Vullo, Vincenzo, Zolfino, Teresa, Zuin, Massimo, Gasbarrini, Antonio (ORCID:0000-0002-7278-4823), Cauda, Roberto (ORCID:0000-0002-1498-4229), de Luca, Andrea (ORCID:0000-0002-8311-6935), Grieco, Antonio (ORCID:0000-0002-0544-8993), Miele, Luca (ORCID:0000-0003-3464-0068), and Rapaccini, Gian Ludovico (ORCID:0000-0002-6467-857X)
Abstract: Purpose: To analyse safety and efficacy of treatment based on ombitasvir/paritaprevir/ritonavir/dasabuvir plus ribavirin in the sub-group of GT1 patients older than 65 years. Methods: We collected data extracted from the ABACUS compassionate-use nationwide Italian programme, in patients with cirrhosis due to hepatitis C virus (HCV) Genotype-1 (GT1) or 4 and at high risk of decompensation. GT1-HCV-infected patients received once-daily ombitasvir/paritaprevir, with the pharmacokinetic enhancer ritonavir (25/150/100 mg) and twice-daily dasabuvir (250 mg) plus Ribavirin (RBV) (OBV/PTV/r + DSV + RBV) for 12 (GT1b) or 24 (GT1a) weeks. Endpoints were to evaluate safety and efficacy, the latter defined as HCV RNA negative 12 weeks after the end of treatment (SVR12). Results: Patients who suffered any adverse event (AE) were 74/240 (30.8%); 13/240 (5.4%) discontinued the treatment. A multivariate analysis found albumin < 3.5 g/dL (OR 2.04: 95% CI 1.0–4.2, p < 0.05) and hypertension (OR 4.6: 95% CI 2.3–9.2, p < 0.001) as variables independently associated with AE occurrence. The SVR12 was 95% (228/240). Multivariate analysis identified baseline bilirubin < 2 mg/dL (OR 4.9: 95% CI 1.17–20.71, p = 0.029) as the only variable independently associated with SVR12. Conclusion: Our findings suggest that OBV/PTV/r + DSV + RBV is safe and effective in real-life use in patients with compensated cirrhosis, HCV-GT1 infection, and age over 65.
Published: 2018

26. Systematic clinical management of patients with candidemia improves survival

Author: Murri, Rita, Giovannenze, Francesca, Camici, Marta, Torelli, Riccardo, Ventura, Giulio, Scoppettuolo, Giancarlo, Sanguinetti, Maurizio, Cauda, Roberto, Fantoni, Massimo, Murri, Rita (ORCID:0000-0003-4263-7854), Ventura, Giulio (ORCID:0000-0002-0304-7264), Sanguinetti, Maurizio (ORCID:0000-0002-9780-7059), Cauda, Roberto (ORCID:0000-0002-1498-4229), Fantoni, Massimo (ORCID:0000-0001-6913-8460), Murri, Rita, Giovannenze, Francesca, Camici, Marta, Torelli, Riccardo, Ventura, Giulio, Scoppettuolo, Giancarlo, Sanguinetti, Maurizio, Cauda, Roberto, Fantoni, Massimo, Murri, Rita (ORCID:0000-0003-4263-7854), Ventura, Giulio (ORCID:0000-0002-0304-7264), Sanguinetti, Maurizio (ORCID:0000-0002-9780-7059), Cauda, Roberto (ORCID:0000-0002-1498-4229), and Fantoni, Massimo (ORCID:0000-0001-6913-8460)
Abstract: Objectives: Taking into account the significant morbidity, mortality, and hospital costs related to Candidemia, our objective is to define if improving appropriateness in candidemia management was associated with better clinical outcomes. Methods: A prospective observational monocentric cohort study was conducted. Adherence to five main elements was examined: appropriate selection of initial therapy; follow-up blood culture; echocardiography; ophthalmological examination; and removal of a central venous catheter. The correlation between the number of appropriate elements achieved and 30 day survival was examined. Results: Patients with candidemia (n = 213) were enrolled. Adherence to all five elements was achieved in 36 cases (16.9%), while the majority adhered to three or four elements (28.2% and 37.1%, respectively). Multivariable Cox regression analysis revealed that the number of elements achieved was associated with survival [HR: 0.39 (0.30–0.52); p < 0.001]. Also, the number of elements achieved correlated positively with duration of therapy (p = 0.01), but not length of hospital stay (p = 0.56). Conclusions: Five elements, including therapeutic and non-therapeutic-related aspects, of care were good indicators of appropriate management of patients with candidemia. Implementation of evidence-based practice regarding optimal clinical management is crucial for any antimicrobial stewardship program.
Published: 2018

27. Atazanavir/ritonavir with lamivudine as maintenance therapy in virologically suppressed HIV-infected patients: 96 week outcomes of a randomized trial

Author: Fabbiani, Massimiliano, Gagliardini, Roberta, Ciccarelli, Nicoletta, Quiros Roldan, Eugenia, Latini, Alessandra, D'Ettorre, Gabriella, Antinori, Andrea, Castagna, Antonella, Orofino, Giancarlo, Francisci, Daniela, Chinello, Pierangelo, Madeddu, Giordano, Grima, Pierfrancesco, Rusconi, Stefano, Del Pin, Barbara, Lombardi, Francesca, D'Avino, Alessandro, Focà, Emanuele, Colafigli, Manuela, Cauda, Roberto, Di Giambenedetto, Simona, De Luca, Andrea, Ciccarelli, Nicoletta (ORCID:0000-0002-7582-9142), Lombardi, Francesca (ORCID:0000-0001-5757-8346), Cauda, Roberto (ORCID:0000-0002-1498-4229), Di Giambenedetto, Simona (ORCID:0000-0001-6990-5076), De Luca, Andrea (ORCID:0000-0002-8311-6935), Fabbiani, Massimiliano, Gagliardini, Roberta, Ciccarelli, Nicoletta, Quiros Roldan, Eugenia, Latini, Alessandra, D'Ettorre, Gabriella, Antinori, Andrea, Castagna, Antonella, Orofino, Giancarlo, Francisci, Daniela, Chinello, Pierangelo, Madeddu, Giordano, Grima, Pierfrancesco, Rusconi, Stefano, Del Pin, Barbara, Lombardi, Francesca, D'Avino, Alessandro, Focà, Emanuele, Colafigli, Manuela, Cauda, Roberto, Di Giambenedetto, Simona, De Luca, Andrea, Ciccarelli, Nicoletta (ORCID:0000-0002-7582-9142), Lombardi, Francesca (ORCID:0000-0001-5757-8346), Cauda, Roberto (ORCID:0000-0002-1498-4229), Di Giambenedetto, Simona (ORCID:0000-0001-6990-5076), and De Luca, Andrea (ORCID:0000-0002-8311-6935)
Abstract: Objectives: To investigate the long-term safety and efficacy of a treatment switch to dual ART with atazanavir/ritonavir + lamivudine versus continuing a standard regimen with atazanavir/ritonavir + 2NRTI in virologically suppressed patients. Methods: ATLAS-M is a 96 week open-label, randomized, non-inferiority (margin -12%) trial enrolling HIV-infected adults on atazanavir/ritonavir + 2NRTI, with stable HIV-RNA <50 copies/mL and CD4 counts >200 cells/mm3. At baseline, patients were randomized 1:1 to switch to atazanavir/ritonavir + lamivudine or to continue the previous regimen. Here, we report the 96 week efficacy and safety data. The study was registered with ClinicalTrials.gov, number NCT01599364. Results: Overall, 266 subjects were enrolled (133 in each arm). At 96 weeks, in the ITT population, patients free of treatment failure totalled 103 (77.4%) with atazanavir/ritonavir + lamivudine and 87 (65.4%) with triple therapy (difference +12.0%, 95% CI +1.2/+22.8, P = 0.030), demonstrating the superiority of dual therapy. Two (1.5%) and 9 (6.8%) virological failures occurred in the dual-therapy arm and the triple-therapy arm, respectively, without development of resistance to any study drug. Clinical adverse events occurred at similar rates in both arms. A higher frequency of grade 3-4 hyperbilirubinemia (66.9% versus 50.4%, P = 0.006) and hypertriglyceridaemia (6.8% versus 1.5%, P = 0.031) occurred with dual therapy, although this never led to treatment discontinuation. A significant improvement in renal function and lumbar spine bone mineral density occurred in the dual-therapy arm. The evolution of CD4, HIV-DNA levels and neurocognitive performance was similar in both arms. Conclusions: In this randomized study, a treatment switch to atazanavir/ritonavir + lamivudine was superior over the continuation of atazanavir/ritonavir + 2NRTI in virologically suppressed patients, with a sustained benefit in terms of improved renal function and bone mineral density.
Published: 2018

28. Systemic inflammation markers after simplification to atazanavir/ritonavir plus lamivudine in virologically suppressed HIV-1-infected patients: ATLAS-M substudy

Author: Belmonti, Simone, Lombardi, Francesca, Quiros-Roldan, Eugenia, Latini, Alessandra, Castagna, Antonella, Borghetti, Alberto, Baldin, Gianmaria, Ciccullo, Arturo, Cauda, Roberto, De Luca, Andrea, Di Giambenedetto, Simona, Giacometti, Andrea, Di Pietro, Massimo, Mughini, Maria Teresa, Grima, Pierfrancesco, Viscoli, Claudio, Manconi, Paolo Emilio, Puoti, Massimo, Galli, Massimo, Viale, Pierluigi, Gori, Andrea, Rizzardini, Giuliano, Mineo, Maurizio, Antinori, Andrea, Petrosillo, Nicola, Vullo, Vincenzo, Stella Mura, Maria, Caramello, Pietro, Scotton, Pier Giorgio, Concia, Ercole, Lazzarin, Adriano, Francisci, Daniela, Sacchini, Daria, Lombardi, Francesca (ORCID:0000-0001-5757-8346), Cauda, Roberto (ORCID:0000-0002-1498-4229), De Luca, Andrea (ORCID:0000-0002-8311-6935), Di Giambenedetto, Simona (ORCID:0000-0001-6990-5076), Belmonti, Simone, Lombardi, Francesca, Quiros-Roldan, Eugenia, Latini, Alessandra, Castagna, Antonella, Borghetti, Alberto, Baldin, Gianmaria, Ciccullo, Arturo, Cauda, Roberto, De Luca, Andrea, Di Giambenedetto, Simona, Giacometti, Andrea, Di Pietro, Massimo, Mughini, Maria Teresa, Grima, Pierfrancesco, Viscoli, Claudio, Manconi, Paolo Emilio, Puoti, Massimo, Galli, Massimo, Viale, Pierluigi, Gori, Andrea, Rizzardini, Giuliano, Mineo, Maurizio, Antinori, Andrea, Petrosillo, Nicola, Vullo, Vincenzo, Stella Mura, Maria, Caramello, Pietro, Scotton, Pier Giorgio, Concia, Ercole, Lazzarin, Adriano, Francisci, Daniela, Sacchini, Daria, Lombardi, Francesca (ORCID:0000-0001-5757-8346), Cauda, Roberto (ORCID:0000-0002-1498-4229), De Luca, Andrea (ORCID:0000-0002-8311-6935), and Di Giambenedetto, Simona (ORCID:0000-0001-6990-5076)
Abstract: Background Biomarkers of systemic inflammation predict non-AIDS events and overall mortality in virologically suppressed HIV-1-infected patients. Objectives To determine whether switching to a dual antiretroviral maintenance therapy was associated with modification of biomarkers of systemic inflammation as compared with continuation of successful standard triple therapy. Methods In this substudy of the randomized ATLAS-M trial, we compared in virologically suppressed patients the impact at 1 year of simplification to a dual therapy with atazanavir/ritonavir plus lamivudine versus maintaining atazanavir/ritonavir plus two NRTI triple therapy on markers of systemic inflammation. Plasma levels of interleukin-6, C-reactive protein (CRP), soluble CD14 (sCD14) and D-dimer were quantified by ELISA at baseline and at 48 weeks. Results A subset of 139 of 266 randomized patients with available samples was analysed: 69 in the triple therapy arm and 70 in the dual therapy arm. The baseline biomarker levels were comparable between randomization arms. No significant differences in changes from baseline to week 48 were observed between arms (dual therapy versus triple therapy): IL-6, −0.030 versus −0.016 log10 pg/L; CRP, +0.022 versus +0.027 log10 pg/mL; sCD14, −0.016 versus +0.019 log10 pg/mL; and D-dimer, −0.031 versus +0.004 log10 pg/mL. A history of cancer was associated with higher baseline levels of IL-6 (P = 0.002) and CRP (P = 0.049). No relationship was observed between baseline biomarker level and persistent residual viraemia, HIV-1 DNA load, plasma lipids and other potential explanatory variables. Conclusions Simplification with atazanavir/ritonavir plus lamivudine does not affect plasma markers of systemic inflammation in virologically suppressed patients. The association between these findings and clinical outcomes requires further evaluation
Published: 2018

29. Idsa Did Not Endorse the Surviving Sepsis Campaign Guidelines

Author: Murri, Rita, Taccari, Francesco, Palazzolo, Claudia, Fantoni, Massimo, Cauda, Roberto, Murri, Rita (ORCID:0000-0003-4263-7854), Fantoni, Massimo (ORCID:0000-0001-6913-8460), Cauda, Roberto (ORCID:0000-0002-1498-4229), Murri, Rita, Taccari, Francesco, Palazzolo, Claudia, Fantoni, Massimo, Cauda, Roberto, Murri, Rita (ORCID:0000-0003-4263-7854), Fantoni, Massimo (ORCID:0000-0001-6913-8460), and Cauda, Roberto (ORCID:0000-0002-1498-4229)
Abstract: The SSC 2016 sepsis definition is based on some studies in which the rate of proven infection is very low or unknown. The new definition does not consider patients with <2 points at Sequential Organ Failure Assessment (SOFA) score but with bloodstream infection (BSI). Even though this population is not formally a “septic population,” patients may require intense care and appropriate therapy. To highlight this issue, we analyzed data on people with BSI seen in a large university hospital in Rome. Four hundred three patients were considered: mean age, 66.3 years, 56% were males, 36% were hospitalized within the previous 90 days before the BSI, and 29% received at least 1 antibiotic in the previous month. Forty percent had a central venous catheter at the onset. Sixty-five percent had no SIRS criteria and 35% only 1 criterion. The 30-day mortality was 11.2%; median of duration of antibiotic therapy was 17 days (interquartile range, 11–25 days). The 30-day mortality of people with Candida BSI was 24.7%. According to our results, the SSC 2016 sepsis definition, may omit diagnosis of infected patients who need appropriate therapy (such as Candida BSI) and who also have a high mortality. To manage the delicate balance between not starting useless therapy and not neglecting demanding conditions such as Candida BSI, we strongly suggest improving rate of diagnostic tests in patients with suspected infections to achieve the highest diagnostic sensitivity.
Published: 2018

30. Effect of combination therapy containing a high-dose carbapenem on mortality in patients with carbapenem-resistant Klebsiella pneumoniae bloodstream infection

Author: Giannella, Maddalena, Trecarichi, Enrico Maria, Giacobbe, Daniele Roberto, De Rosa, Francesco Giuseppe, Bassetti, Matteo, Bartoloni, Alessandro, Bartoletti, Michele, Losito, Angela Raffaella, del Bono, Valerio, Corcione, Silvia, Tedeschi, Sara, Raffaelli, Francesca, Saffioti, Carolina, Spanu, Teresa, Rossolini, Gian Maria, Marchese, Anna, Ambretti, Simone, Cauda, Roberto, Viscoli, Claudio, Lewis, Russell Edward, Viale, Pierluigi, Tumbarello, Mario, Spanu, Teresa (ORCID:0000-0003-1864-5184), Cauda, Roberto (ORCID:0000-0002-1498-4229), Tumbarello, Mario (ORCID:0000-0002-9519-8552), Giannella, Maddalena, Trecarichi, Enrico Maria, Giacobbe, Daniele Roberto, De Rosa, Francesco Giuseppe, Bassetti, Matteo, Bartoloni, Alessandro, Bartoletti, Michele, Losito, Angela Raffaella, del Bono, Valerio, Corcione, Silvia, Tedeschi, Sara, Raffaelli, Francesca, Saffioti, Carolina, Spanu, Teresa, Rossolini, Gian Maria, Marchese, Anna, Ambretti, Simone, Cauda, Roberto, Viscoli, Claudio, Lewis, Russell Edward, Viale, Pierluigi, Tumbarello, Mario, Spanu, Teresa (ORCID:0000-0003-1864-5184), Cauda, Roberto (ORCID:0000-0002-1498-4229), and Tumbarello, Mario (ORCID:0000-0002-9519-8552)
Abstract: Objectives: To evaluate the impact of high-dose (HD) carbapenem-based combination therapy on clinical outcome in patients with monomicrobial carbapenem-resistant Klebsiella pneumoniae (CR-KP) bloodstream-infection (BSI). Methods: Post hoc analysis of all adult patients with CR-KP BSI who were treated with a combination antibiotic regimen, collected over a six-year period in six large Italian teaching hospitals. To control for confounding effects of HD carbapenem combination on 14-day mortality, a multivariate Cox regression analysis was performed. Due to imbalances between patients, a propensity score for receiving HD carbapenem was added to the model. Results: 595 patients with CR-KP BSI were analysed, 77% of isolates showed a carbapenem MIC â¥16 mg/L, 428 (71.9%) received HD carbapenem-based combination therapy. Overall, 127 patients (21.3%) died within 14 days after BSI onset. Multivariate analysis showed the Charlson comorbidity index (HR 1.31, 95%CI 1.20â1.43, P < 0.001), septic shock at BSI onset (HR 3.14, 95%CI 2.19â4.50, P < 0.001), and colistin-resistant strain (HR 1.52, 95%CI 1.02â2.24, P = 0.03) were independently associated with 14-day mortality, whereas admission to surgical ward (HR 0.44, 95%CI 0.25â0.78, P = 0.005) and HD carbapenem use (HR 0.69, 95%CI 0.47â1.00, P = 0.05) were protective factors. When adjusted for the propensity score, HD carbapenem use showed a greater protective effect (HR 0.64, 95%CI 0.43â0.95, P = 0.03). Stratifying the model for carbapenem MIC, the benefit of HD carbapenem was also observed for strains with carbapenem MIC â¥16 mg/L. Conclusions: In patients receiving combination therapy for CR-KP BSI, the use of HD carbapenem seems to be associated with better outcome, even in the presence of high-level carbapenem resistance.
Published: 2018

31. Efficacy and tolerability of dolutegravir and two nucleos(t)ide reverse transcriptase inhibitors in HIV-1-positive, virologically suppressed patients

Author: Borghetti, Alberto, Baldin, Gianmaria, Capetti, Amedeo, Sterrantino, Gaetana, Rusconi, Stefano, Latini, Alessandra, Giacometti, Andrea, Madeddu, Giordano, Picarelli, Chiara, De Marco, Ramona, Cossu, Maria V., Lagi, Filippo, Cauda, Roberto, De Luca, Andrea, Di Giambenedetto, Simona, Cauda, Roberto (ORCID:0000-0002-1498-4229), De Luca, Andrea (ORCID:0000-0002-8311-6935), Di Giambenedetto, Simona (ORCID:0000-0001-6990-5076), Borghetti, Alberto, Baldin, Gianmaria, Capetti, Amedeo, Sterrantino, Gaetana, Rusconi, Stefano, Latini, Alessandra, Giacometti, Andrea, Madeddu, Giordano, Picarelli, Chiara, De Marco, Ramona, Cossu, Maria V., Lagi, Filippo, Cauda, Roberto, De Luca, Andrea, Di Giambenedetto, Simona, Cauda, Roberto (ORCID:0000-0002-1498-4229), De Luca, Andrea (ORCID:0000-0002-8311-6935), and Di Giambenedetto, Simona (ORCID:0000-0001-6990-5076)
Abstract: Not Available N/A
Published: 2017

32. 3-Year efficacy and durability of simplification to single tablet regimens: a comparison between co-formulated efavirenz/emtricitabine/tenofovir and rilpivirine/emtricitabine/tenofovir

Author: Gagliardini, Roberta, Bandera, Alessandra, Zaccarelli, Mauro, Sterrantino, Gaetana, Latini, Alessandra, D'Avino, Alessandro, Lapadula, Giuseppe, Antinori, Andrea, Cauda, Roberto, De Luca, Andrea, Gori, Andrea, Di Giambenedetto, Simona, Fabbiani, Massimiliano, Cauda, Roberto (ORCID:0000-0002-1498-4229), De Luca, Andrea (ORCID:0000-0002-8311-6935), Di Giambenedetto, Simona (ORCID:0000-0001-6990-5076), Gagliardini, Roberta, Bandera, Alessandra, Zaccarelli, Mauro, Sterrantino, Gaetana, Latini, Alessandra, D'Avino, Alessandro, Lapadula, Giuseppe, Antinori, Andrea, Cauda, Roberto, De Luca, Andrea, Gori, Andrea, Di Giambenedetto, Simona, Fabbiani, Massimiliano, Cauda, Roberto (ORCID:0000-0002-1498-4229), De Luca, Andrea (ORCID:0000-0002-8311-6935), and Di Giambenedetto, Simona (ORCID:0000-0001-6990-5076)
Abstract: BACKGROUND: Few data are available about efficacy and durability of simplification from multi-tablet antiretroviral regimens to co-formulated efavirenz (EFV)/emtricitabine (FTC)/tenofovir (TDF) versus rilpivirine (RPV)/FTC/TDF in virologically suppressed HIV-1-infected patients. METHODS: We retrospectively analysed HIV-infected patients with HIV RNA <50 copies/ml switching to co-formulated EFV/FTC/TDF or RPV/FTC/TDF at five Italian centres. Patients were followed from time of switch until regimen discontinuation or a maximum of 3-years follow-up. Time to treatment discontinuation (TD) and virological failure (VF; defined as two consecutive HIV RNA >50 copies/ml or a single determination >1,000 copies/ml) and their predictors were investigated. RESULTS: 1,560 patients were reviewed of which 1,097 (70%) switched to EFV/FTC/TDF and 463 (30%) to RPV/FTC/TDF. During follow-up, VF and TD occurred in 44 (4%) and 242 (22%) patients in EFV/FTC/TDF and in 29 (6%) and 50 (11%) patients in RPV/FTC/TDF, respectively. The 3-year estimated probability of remaining free from VF was 96.2% with EFV/FTC/TDF versus 92.7% with RPV/FTC/TDF (P=0.003). At multivariate analysis, regimen type (EFV/FTC/TDF versus RPV/FTC/TDF aHR 0.24; P=0.004) and time of virological suppression (aHR 0.85; P=0.048) were the only independent predictors of VF. The estimated 3-year probability of remaining free from TD was 77.4% with EFV/FTC/TDF versus 88.4% with RPV/FTC/TDF (P=0.001). Predictors of TD were female sex, switching from PI-based regimens, older age, shorter time of virological suppression and regimen type (EFV/FTC/TDF versus RPV/FTC/TDF aHR 2.48; P<0.001). RPV/FTC/TDF showed a safer lipid profile and a greater increase in creatinine. CONCLUSIONS: Both regimens showed good safety and efficacy in this real-life setting, although switch to RPV/FTC/TDF seemed better tolerated while EFV/FTC/TDF was associated with a lower probability of VF.
Published: 2017

33. Generic antiretrovirals for the treatment of HIV: A novel challenge for Western countries?

Author: Cattaneo, Dario, Andreoni, Massimo, Carosi, Gianpiero, Cauda, Roberto, Lazzarin, Adriano, Rizzardini, Giuliano, Cauda, Roberto (ORCID:0000-0002-1498-4229), Cattaneo, Dario, Andreoni, Massimo, Carosi, Gianpiero, Cauda, Roberto, Lazzarin, Adriano, Rizzardini, Giuliano, and Cauda, Roberto (ORCID:0000-0002-1498-4229)
Abstract: The introduction of generic antiretroviral medications in developing countries has resulted in significant CD4 cell restoration, HIV viral decline, and a noteworthy reduction in the time to initiation of therapy. Projection models have also predicted significant cost saving associated with the extensive diffusion of generic antiretrovirals in developed countries. However, some uncertainties on generics have recently been raised. These concerns mainly relate to the adequacy of the study design for bioequivalence testing, the potential for uncontrolled switching from one generic to another, and the loss of adherence if patients switched from fixed-dose coformulations to single components in order to incorporate the new generic drugs. In the present review, we deal with current evidence and potential controversial issues regarding generic antiretrovirals and their underlying economic implications and provide some proposals on how to favor the widespread diffusion of generics in HIV medicine. This may be particularly relevant considering that the safe, systematic switch from patented to generic antiretrovirals could potentially guarantee access to therapies for HIV-infected patients worldwide and lead to money savings that would compensate the expenditure increase resulting from new, innovative HIV drugs.
Published: 2017

34. Antibiotic stewardship from toolkit to local implementation: The 'gutta cavat lapidem' strategy

Author: Fantoni, Massimo, Murri, Rita, Cauda, Roberto, Fantoni, Massimo (ORCID:0000-0001-6913-8460), Murri, Rita (ORCID:0000-0003-4263-7854), Cauda, Roberto (ORCID:0000-0002-1498-4229), Fantoni, Massimo, Murri, Rita, Cauda, Roberto, Fantoni, Massimo (ORCID:0000-0001-6913-8460), Murri, Rita (ORCID:0000-0003-4263-7854), and Cauda, Roberto (ORCID:0000-0002-1498-4229)
Abstract: not available
Published: 2017

35. Ombitasvir, paritaprevir, and ritonavir, with or without dasabuvir, plus ribavirin for patients with hepatitis C virus genotype 1 or 4 infection with cirrhosis (ABACUS): a prospective observational study

Author: Petta, Salvatore, Marzioni, Marco, Russo, Pierluigi, Aghemo, Alessio, Alberti, Alfredo, Ascione, Antonio, Antinori, Andrea, Bruno, Raffaele, Bruno, Savino, Chirianni, Antonio, Gaeta, Giovanni Battista, Giannini, Edoardo G, Merli, Manuela, Messina, Vincenzo, Montilla, Simona, Perno, Carlo Federico, Puoti, Massimo, Raimondo, Giovanni, Rendina, Maria, Silberstein, Francesca Ceccherini, Villa, Erica, Zignego, Anna Linda, Pani, Luca, Craxã¬, Antonio, Tabone, Marco, Andreoni, Massimo, Teti, Elisabetta, Angelico, Mario, Persico, Marcello, Masarone, Mario, Chiodera, Aledssandro, Solinas, Attilio, delle Monache, Marco, Cecere, Roberto, Maria Schimizzi, Anna, Piovesan, Sara, Campagnolo, Davide, Chiara Piras, Maria, Zolfino, Teresa, Paolo Russo, Francesca, Morelli, Olivia, Sangiovanni, Vincenzo, Onofrio, Mirella, Iodice, Valentina, Izzi, Antonio, Pirisi, Massimo, Danieli, Elena, Vinci, Maria Rosaria, Rizzardini, Giuliano, Fagiuoli, Stefano, Pasulo, Luisa, D'Arminio Monforte, Antonella, Zuin, Massimo, Giorgini, Alessia, Simeone, Filomena, Piali, Guido, Lo Guercio, Carmela, Federico, Alessandro, Brancaccio, Giuseppina, Marrone, Aldo, Abbati, Giuseppe, Boarini, Chiara, Borghi, Vanni, Bernabucci, Veronica, Corti, Giampaolo, Monti, Monica, Rizzetto, Mario, Martini, Silvia, Andreone, Pietro, Gianstefani, Alice, Lenzi, Marco, Verucchi, Gabriella, Toniutto, Pierluigi, Borgia, Guglielmo, Caporaso, Nicola, Morisco, Filomena, Nardone, Gaetano, Angrisani, Debora, Giacometti, Andrea, Benedetti, Antonio, Tarantino, Giuseppe, Marsetti, Fabio, Tavio, Marcello, Novara, Sergio, Antonia Santantonio, Teresa, Serviddio, Gaetano, Brunetto, Maurizia, Coco, Barbara, Angarano, Gioacchino, Milella, Michele, Barone, Michele, Di Leo, Alfredo, Ettore Sansonno, Domenico, Cacciola, Irene, Boffa, Nicola, Saracco, Giorgio, Di Biagio, Antonio, Picciotto, Antonino, De Luca, Andrea, Calvaruso, Vincenza, Corradori, Silvia, Ferrari, Carlo, Orlandini, Alessandra, Maida, Ivana, Torti, Carlo, Chessa, Luchino, Felder, Martina, Vespasiani Gentilucci, Umberto, Angeli, Paolo, Romano, Antonietta, Rapaccini, Gian Ludovico, Miele, Luca, Cima, Serena, Russo, Maria Luisa, Cozzolongo, Raffaele, Onnelli, Giovanna, D'Offizi, Giampiero, Lionetti, Raffaella, Montalbano, Marzia, Guerra, Michele, Di Perri, Giovanni, Boglione, Lucio, Capra, Franco, Carolo, Giada, Ieluzzi, Donatella, Antonini, Cinzia, Termite, Antonio, Madonia, Salvatore, Tarquini, Pierluigi, Parruti, Giustino, Vecchiet, Giacomo, Falasca, Katia, Menzaghi, Barbara, Quirino, Tiziana, Dentone, Chiara, Maria Piscaglia, Anna, Rossi, Cristina, Giordani, Maria, Fontanella, Luca, Cassola, Giovanni, Russello, Maurizio, Cristaudo, Antonio, Giacomet, Vania, Colombo, Massimo, Donato, Francesca, Durante, Emanuele, Cosco, Lucio, Marignani, Massimo, Quartini, Mariano, Memoli, Massimo, Ganga, Roberto, Ponti, Laura, Soria, Alessandro, Grazia Rumi, Maria, Gulminetti, Roberto, Maserati, Renato, Mondelli, Mario, Lazzarin, Adriano, Rita Parisi, Maria, Canovari, Benedetta, Avancini, Ivo, Pravadelli, Cecilia, Blanc, Pier, Pasquazzi, Caterina, Maria Mastroianni, Claudio, Lichtner, Myriam, Distefano, Marco, Magnani, Silvia, Paganin, Simona, Erne, Elke, Gatti, Pietro, Tundi, Paolo, Calabrese, Paolo, Gasbarrini, Antonio, Grieco, Antonio, Coppola, Nicola, Del Poggio, Paolo, Levrero, Massimo, Talliani, Gloria, Vullo, Vincenzo, Cauda, Roberto, La Monica, Silvia, Potenza, Domenico, Rizzo, Salvatore, Castelli, Francesco, Marie Pigozzi, Grazielle, Ciancio, Alessia, Romagnoli, Dante, Barchetti, Federica, Ivanovic, Jelena, Longo, Olimpia, Petraglia, Sandra, Paola Trotta, Maria, Vinci, Maria, de Luca, Andrea (ORCID:0000-0002-8311-6935), Rapaccini, Gian Ludovico (ORCID:0000-0002-6467-857X), Miele, Luca (ORCID:0000-0003-3464-0068), Luisa Russo, Maria, Gasbarrini,Antonio (ORCID:0000-0002-7278-4823), Grieco,Antonio (ORCID:0000-0002-0544-8993), Cauda,Roberto (ORCID:0000-0002-1498-4229), Petta, Salvatore, Marzioni, Marco, Russo, Pierluigi, Aghemo, Alessio, Alberti, Alfredo, Ascione, Antonio, Antinori, Andrea, Bruno, Raffaele, Bruno, Savino, Chirianni, Antonio, Gaeta, Giovanni Battista, Giannini, Edoardo G, Merli, Manuela, Messina, Vincenzo, Montilla, Simona, Perno, Carlo Federico, Puoti, Massimo, Raimondo, Giovanni, Rendina, Maria, Silberstein, Francesca Ceccherini, Villa, Erica, Zignego, Anna Linda, Pani, Luca, Craxã¬, Antonio, Tabone, Marco, Andreoni, Massimo, Teti, Elisabetta, Angelico, Mario, Persico, Marcello, Masarone, Mario, Chiodera, Aledssandro, Solinas, Attilio, delle Monache, Marco, Cecere, Roberto, Maria Schimizzi, Anna, Piovesan, Sara, Campagnolo, Davide, Chiara Piras, Maria, Zolfino, Teresa, Paolo Russo, Francesca, Morelli, Olivia, Sangiovanni, Vincenzo, Onofrio, Mirella, Iodice, Valentina, Izzi, Antonio, Pirisi, Massimo, Danieli, Elena, Vinci, Maria Rosaria, Rizzardini, Giuliano, Fagiuoli, Stefano, Pasulo, Luisa, D'Arminio Monforte, Antonella, Zuin, Massimo, Giorgini, Alessia, Simeone, Filomena, Piali, Guido, Lo Guercio, Carmela, Federico, Alessandro, Brancaccio, Giuseppina, Marrone, Aldo, Abbati, Giuseppe, Boarini, Chiara, Borghi, Vanni, Bernabucci, Veronica, Corti, Giampaolo, Monti, Monica, Rizzetto, Mario, Martini, Silvia, Andreone, Pietro, Gianstefani, Alice, Lenzi, Marco, Verucchi, Gabriella, Toniutto, Pierluigi, Borgia, Guglielmo, Caporaso, Nicola, Morisco, Filomena, Nardone, Gaetano, Angrisani, Debora, Giacometti, Andrea, Benedetti, Antonio, Tarantino, Giuseppe, Marsetti, Fabio, Tavio, Marcello, Novara, Sergio, Antonia Santantonio, Teresa, Serviddio, Gaetano, Brunetto, Maurizia, Coco, Barbara, Angarano, Gioacchino, Milella, Michele, Barone, Michele, Di Leo, Alfredo, Ettore Sansonno, Domenico, Cacciola, Irene, Boffa, Nicola, Saracco, Giorgio, Di Biagio, Antonio, Picciotto, Antonino, De Luca, Andrea, Calvaruso, Vincenza, Corradori, Silvia, Ferrari, Carlo, Orlandini, Alessandra, Maida, Ivana, Torti, Carlo, Chessa, Luchino, Felder, Martina, Vespasiani Gentilucci, Umberto, Angeli, Paolo, Romano, Antonietta, Rapaccini, Gian Ludovico, Miele, Luca, Cima, Serena, Russo, Maria Luisa, Cozzolongo, Raffaele, Onnelli, Giovanna, D'Offizi, Giampiero, Lionetti, Raffaella, Montalbano, Marzia, Guerra, Michele, Di Perri, Giovanni, Boglione, Lucio, Capra, Franco, Carolo, Giada, Ieluzzi, Donatella, Antonini, Cinzia, Termite, Antonio, Madonia, Salvatore, Tarquini, Pierluigi, Parruti, Giustino, Vecchiet, Giacomo, Falasca, Katia, Menzaghi, Barbara, Quirino, Tiziana, Dentone, Chiara, Maria Piscaglia, Anna, Rossi, Cristina, Giordani, Maria, Fontanella, Luca, Cassola, Giovanni, Russello, Maurizio, Cristaudo, Antonio, Giacomet, Vania, Colombo, Massimo, Donato, Francesca, Durante, Emanuele, Cosco, Lucio, Marignani, Massimo, Quartini, Mariano, Memoli, Massimo, Ganga, Roberto, Ponti, Laura, Soria, Alessandro, Grazia Rumi, Maria, Gulminetti, Roberto, Maserati, Renato, Mondelli, Mario, Lazzarin, Adriano, Rita Parisi, Maria, Canovari, Benedetta, Avancini, Ivo, Pravadelli, Cecilia, Blanc, Pier, Pasquazzi, Caterina, Maria Mastroianni, Claudio, Lichtner, Myriam, Distefano, Marco, Magnani, Silvia, Paganin, Simona, Erne, Elke, Gatti, Pietro, Tundi, Paolo, Calabrese, Paolo, Gasbarrini, Antonio, Grieco, Antonio, Coppola, Nicola, Del Poggio, Paolo, Levrero, Massimo, Talliani, Gloria, Vullo, Vincenzo, Cauda, Roberto, La Monica, Silvia, Potenza, Domenico, Rizzo, Salvatore, Castelli, Francesco, Marie Pigozzi, Grazielle, Ciancio, Alessia, Romagnoli, Dante, Barchetti, Federica, Ivanovic, Jelena, Longo, Olimpia, Petraglia, Sandra, Paola Trotta, Maria, Vinci, Maria, de Luca, Andrea (ORCID:0000-0002-8311-6935), Rapaccini, Gian Ludovico (ORCID:0000-0002-6467-857X), Miele, Luca (ORCID:0000-0003-3464-0068), Luisa Russo, Maria, Gasbarrini,Antonio (ORCID:0000-0002-7278-4823), Grieco,Antonio (ORCID:0000-0002-0544-8993), and Cauda,Roberto (ORCID:0000-0002-1498-4229)
Abstract: Background We ran a compassionate use nationwide programme (ABACUS) to provide access to ombitasvir, paritaprevir, and ritonavir, with dasabuvir, plus ribavirin for hepatitis C virus (HCV) genotype 1 infection and ombitasvir, paritaprevir, and ritonavir, plus ribavirin for HCV genotype 4 infection in patients with cirrhosis at high risk of decompensation while approval of these regimens was pending in Italy. Methods In this prospective observational study, we collected data from a compassionate use nationwide programme from March 17, 2014, to May 28, 2015. Patients with HCV genotype 1 infection and cirrhosis at high risk of decompensation were given coformulated ombitasvir (25 mg), paritaprevir (150 mg), and ritonavir (100 mg) once daily and dasabuvir (250 mg) twice daily for 12 weeks (patients with HCV genotype 1b infection) or 24 weeks (patients with HCV genotype 1a infection). Patients with HCV genotype 4 infection were given coformulated ombitasvir (25 mg), paritaprevir (150 mg), and ritonavir (100 mg) once per day for 24 weeks. All patients were given weight-based ribavirin. The primary efficacy endpoint was sustained virological response at week 12 after the end of treatment (SVR12), analysed by intention-to-treat. Univariate and multivariate logistic regression analyses were used to identify baseline characteristics associated with SVR12. Adverse events were recorded throughout the study. Findings 728 (96%) of 762 patients with cirrhosis who were given ombitasvir, paritaprevir, and ritonavir, with or without dasabuvir, plus ribavirin therapy for 12 or 24 weeks achieved SVR12. Logistic regression analyses identified that bilirubin concentrations of less than 2 mg/dL were associated with SVR12 (odds ratio [OR] 4Â·76 [95% CI 1Â·83â12Â·3]; p=0Â·001). 166 (23%) of 734 patients included in safety analyses had an adverse event. 25 (3%) patients discontinued treatment because of adverse events. Asthenia was the most commonly reported adverse event, occurring i
Published: 2017

36. Efficacy and tolerability of switching to a dual therapy with darunavir/ritonavir plus raltegravir in HIV-infected patients with HIV-1 RNA ≤50 cp/mL

Author: Madeddu, Giordano, Rusconi, Stefano, Cozzi Lepri, Alessandro, Di Giambenedetto, Simona, Bonora, Stefano, Carbone, Alessia, De Luca, Andrea, Gianotti, Nicola, Di Biagio, Antonio, Antinori, Andrea, D’Arminio Monforte, A., Andreoni, M., Angarano, G., Antinori, A., Castelli, F., Cauda, Roberto, Di Perri, G., Galli, M., Iardino, R., Ippolito, G., Lazzarin, A., Perno, C. F., von Schloesser, F., Viale, P., Castagna, A., Ceccherini Silberstein, F., Cozzi Lepri, A., Girardi, E., Lo Caputo, S., Mussini, C., Puoti, M., Ammassari, A., Balotta, C., Bandera, A., Bonfanti, P., Borderi, M., Calcagno, A., Calza, L., Capobianchi, M. R., Cingolani, A., Cinque, P., Lichtner, A., Madeddu, G., Maggiolo, F., Marchetti, G., Marcotullio, S., Monno, L., Nozza, S., Quiros Roldan, E., Rossotti, R., Rusconi, S., Santoro, M. M., Saracino, A., Zaccarelli, M., Fanti, Iuri, Galli, L., Lorenzini, P., Rodano, A., Shanyinde, M., Tavelli, A., Carletti, F., Carrara, S., Di Caro, A., Graziano, S., Petrone, F., Prota, G., Quartu, S., Truffa, S., Giacometti, A., Costantini, A., Valeriani, C., Santoro, C., Suardi, C., Donati, V., Verucchi, G., Minardi, C., Quirino, T., Abeli, C., Manconi, P. E., Piano, P., Cacopardo, B., Celesia, B., Vecchiet, J., Falasca, K., Sighinolfi, L., Segala, D., Mazzotta, F., Vichi, F., Cassola, G., Viscoli, C., Alessandrini, A., Bobbio, N., Mazzarello, G., Mastroianni, C., Belvisi, V., Caramma, I., Chiodera, A., Castelli, A. P., Rizzardini, G., Ridolfo, A. L., Piolini, R., Salpietro, S., Carenzi, L., Moioli, M. C., Tincati, C., Puzzolante, C., Gori, A., Guaraldi, G., Lapadula, G., Abrescia, N., Chirianni, A., Borgia, G., Di Martino, F., Maddaloni, L., Gentile, I., Orlando, R., Cascio, A., Colomba, C., Baldelli, F., Francisci, D., Parruti, G., Ursini, T., Magnani, G., Ursitti, M. A., Vullo, V., Cristaudo, A., Baldin, Gianmaria, Cicalini, S., Gallo, L., Nicastri, E., Acinapura, R., Capozzi, M., Libertone, R., Savinelli, S., Latini, A., Iaiani, G., Fontanelli Sulekova, L., Cecchetto, M., Viviani, F., Mura, M. S., de Luca, A., Rossetti, Barbara, Caramello, P., Orofino, G. C., Bonora, S., Sciandra, M., Bassetti, M., Londero, A., Pellizzer, G., Manfrin, V., Di Giambenedetto, Simona (ORCID:0000-0001-6990-5076), De Luca, Andrea (ORCID:0000-0002-8311-6935), Cauda, Roberto (ORCID:0000-0002-1498-4229), Madeddu, Giordano, Rusconi, Stefano, Cozzi Lepri, Alessandro, Di Giambenedetto, Simona, Bonora, Stefano, Carbone, Alessia, De Luca, Andrea, Gianotti, Nicola, Di Biagio, Antonio, Antinori, Andrea, D’Arminio Monforte, A., Andreoni, M., Angarano, G., Antinori, A., Castelli, F., Cauda, Roberto, Di Perri, G., Galli, M., Iardino, R., Ippolito, G., Lazzarin, A., Perno, C. F., von Schloesser, F., Viale, P., Castagna, A., Ceccherini Silberstein, F., Cozzi Lepri, A., Girardi, E., Lo Caputo, S., Mussini, C., Puoti, M., Ammassari, A., Balotta, C., Bandera, A., Bonfanti, P., Borderi, M., Calcagno, A., Calza, L., Capobianchi, M. R., Cingolani, A., Cinque, P., Lichtner, A., Madeddu, G., Maggiolo, F., Marchetti, G., Marcotullio, S., Monno, L., Nozza, S., Quiros Roldan, E., Rossotti, R., Rusconi, S., Santoro, M. M., Saracino, A., Zaccarelli, M., Fanti, Iuri, Galli, L., Lorenzini, P., Rodano, A., Shanyinde, M., Tavelli, A., Carletti, F., Carrara, S., Di Caro, A., Graziano, S., Petrone, F., Prota, G., Quartu, S., Truffa, S., Giacometti, A., Costantini, A., Valeriani, C., Santoro, C., Suardi, C., Donati, V., Verucchi, G., Minardi, C., Quirino, T., Abeli, C., Manconi, P. E., Piano, P., Cacopardo, B., Celesia, B., Vecchiet, J., Falasca, K., Sighinolfi, L., Segala, D., Mazzotta, F., Vichi, F., Cassola, G., Viscoli, C., Alessandrini, A., Bobbio, N., Mazzarello, G., Mastroianni, C., Belvisi, V., Caramma, I., Chiodera, A., Castelli, A. P., Rizzardini, G., Ridolfo, A. L., Piolini, R., Salpietro, S., Carenzi, L., Moioli, M. C., Tincati, C., Puzzolante, C., Gori, A., Guaraldi, G., Lapadula, G., Abrescia, N., Chirianni, A., Borgia, G., Di Martino, F., Maddaloni, L., Gentile, I., Orlando, R., Cascio, A., Colomba, C., Baldelli, F., Francisci, D., Parruti, G., Ursini, T., Magnani, G., Ursitti, M. A., Vullo, V., Cristaudo, A., Baldin, Gianmaria, Cicalini, S., Gallo, L., Nicastri, E., Acinapura, R., Capozzi, M., Libertone, R., Savinelli, S., Latini, A., Iaiani, G., Fontanelli Sulekova, L., Cecchetto, M., Viviani, F., Mura, M. S., de Luca, A., Rossetti, Barbara, Caramello, P., Orofino, G. C., Bonora, S., Sciandra, M., Bassetti, M., Londero, A., Pellizzer, G., Manfrin, V., Di Giambenedetto, Simona (ORCID:0000-0001-6990-5076), De Luca, Andrea (ORCID:0000-0002-8311-6935), and Cauda, Roberto (ORCID:0000-0002-1498-4229)
Abstract: Background: Nucleos(t)ide reverse transcriptase inhibitors (NRTI) toxicity may represent a threat for long-term success of combined antiretroviral therapy. Some studies have suggested a possible improvement of NRTI-related toxicity after switching to NRTI-sparing regimens. Objectives: We aimed to explore the efficacy and tolerability of switching to darunavir/ritonavir (DRV/r) plus raltegravir (RAL) while having a viral load (VL) ≤50 copies/mL in the clinical setting. Study design: Treatment-experienced HIV 1-infected patients enrolled in the ICONA Foundation Study cohort were included if they switched their current regimen to DRV/r + RAL with a HIV-RNA ≤50 copies/mL. Different definitions of virological failure (VF) and treatment failure (TF) were employed. Kaplan–Meier curves and Cox regression models were performed to estimate time to event probability. Results: We included 72 HIV-infected patients, 22 (31%) of these were female, 31 (43%) men who have sex with men (MSM) amd 15 (21%) had hepatitis co-infections. Median age was 44 (IQR: 35-50) years amd CD4 count was 389 (IQR 283-606) cells/mmc. Median follow-up time for TF was 24 (IQR 9–31) months. Twenty-five discontinuations occurred (60% simplifications); only 2 (8%) were toxicity-driven (lipid elevations). The probability of VF (confirmed VL >50 copies/mL) was estimated at 7% [95% confidence interval (CI) 1–13%] by 12 and 9% (95% CI 2–16%) by 24 months. When considering TF, we found a probability of stop/intensification/single VL > 200 copies/mL of 13% (95% CI 1–17%) and 22% (95% CI 11–33%) by 12 and 24 months. Female gender (adjusted relative hazard, ARH = 0.10; 95% CI 0.01–0.74; p = 0.024) and older age (AHR = 0.50 per 10 years older; 95% CI 0.25–0.99; p = 0.045) were associated with a lower risk of TF. A previous PI failure was strongly associated with TF (AHR = 52.6, 95% CI 3.6–779; p = 0.004). Conclusions: DRV/r + RAL is a valuable NRTI-sparing option, especially in female and older patients, with a relat
Published: 2017

37. Recommendations for the inclusion of Fabry disease as a rare febrile condition in existing algorithms for fever of unknown origin

Author: Manna, Raffaele, Cauda, Roberto, Feriozzi, Sandro, Gambaro, Giovanni, Gasbarrini, Antonio, Lacombe, Didier, Livneh, Avi, Martini, Alberto, Ozdogan, Huri, Pisani, Antonio, Riccio, Eleonora, Verrecchia, Elena, Dagna, Lorenzo, Manna, Raffaele (ORCID:0000-0003-1560-3907), Cauda, Roberto (ORCID:0000-0002-1498-4229), Gambaro, Giovanni (ORCID:0000-0001-5733-2370), Gasbarrini, Antonio (ORCID:0000-0002-7278-4823), Manna, Raffaele, Cauda, Roberto, Feriozzi, Sandro, Gambaro, Giovanni, Gasbarrini, Antonio, Lacombe, Didier, Livneh, Avi, Martini, Alberto, Ozdogan, Huri, Pisani, Antonio, Riccio, Eleonora, Verrecchia, Elena, Dagna, Lorenzo, Manna, Raffaele (ORCID:0000-0003-1560-3907), Cauda, Roberto (ORCID:0000-0002-1498-4229), Gambaro, Giovanni (ORCID:0000-0001-5733-2370), and Gasbarrini, Antonio (ORCID:0000-0002-7278-4823)
Abstract: Fever of unknown origin (FUO) is a rather rare clinical syndrome representing a major diagnostic challenge. The occurrence of more than three febrile attacks with fever-free intervals of variable duration during 6 months of observation has recently been proposed as a subcategory of FUO, Recurrent FUO (RFUO). A substantial number of patients with RFUO have auto-inflammatory genetic fevers, but many patients remain undiagnosed. We hypothesize that this undiagnosed subgroup may be comprised of, at least in part, a number of rare genetic febrile diseases such as Fabry disease. We aimed to identify key features or potential diagnostic clues for Fabry disease as a model of rare genetic febrile diseases causing RFUO, and to develop diagnostic guidelines for RFUO, using Fabry disease as an example of inserting other rare diseases in the existing FUO algorithms. An international panel of specialists in recurrent fevers and rare diseases, including internists, infectious disease specialists, rheumatologists, gastroenterologists, nephrologists, and medical geneticists convened to review the existing diagnostic algorithms, and to suggest recommendations for arriving at accurate diagnoses on the basis of available literature and clinical experience. By combining specific features of rare diseases with other diagnostic considerations, guidelines have been designed to raise awareness and identify rare diseases among other causes of FUO. The proposed guidelines may be useful for the inclusion of rare diseases in the diagnostic algorithms for FUO. A wide spectrum of patients will be needed to validate the algorithm in different clinical settings.
Published: 2017

38. New classification for the treatment of pyogenic spondylodiscitis: validation study on a population of 250 patients with a follow-up of 2 years

Author: Pola, Enrico, Autore, G., Formica, V. M., Pambianco, V., Colangelo, Debora, Cauda, Roberto, Fantoni, Massimo, Pola, Enrico (ORCID:0000-0001-5350-3910), Cauda, Roberto (ORCID:0000-0002-1498-4229), Fantoni, Massimo (ORCID:0000-0001-6913-8460), Pola, Enrico, Autore, G., Formica, V. M., Pambianco, V., Colangelo, Debora, Cauda, Roberto, Fantoni, Massimo, Pola, Enrico (ORCID:0000-0001-5350-3910), Cauda, Roberto (ORCID:0000-0002-1498-4229), and Fantoni, Massimo (ORCID:0000-0001-6913-8460)
Abstract: Purpose: Pyogenic spondylodiscitis (PS) is still burdened by a high rate of orthopedic and neurological complications. Despite the rising incidence, the choice of a proper orthopedic treatment is often delayed by the lack of clinical data. The aim of this study was to propose a clinical-radiological classification of pyogenic spondylodiscitis to define a standard treatment algorithm. Methods: Based on data from 250 patients treated from 2008 to 2015, a clinical-radiological classification of pyogenic spondylodiscitis was developed. According to primary classification criteria (bone destruction or segmental instability, epidural abscesses and neurological impairment), three main classes were identified. Subclasses were defined according to secondary criteria. PS without segmental instability or neurological impairment was treated conservatively. When significant bone loss or neurological impairment occurred, surgical stabilization and/or decompression were performed. All patients underwent clinical and radiological 2-year follow-up. Results: Type A PS occurred in 84 patients, while 46 cases were classified as type B and 120 as type C. Average time of hospitalization was 51.94 days and overall healing rate was 92.80%. 140 patients (56.00%) were treated conservatively with average time of immobilization of 218.17 ± 9.89 days. Both VAS and SF-12 scores improved across time points in all classes. Residual chronic back pain occurred in 27 patients (10.80%). Overall observed mortality was 4.80%. Conclusions: Standardized treatment of PS is highly recommended to ensure patients a good quality of life. The proposed scheme includes all available orthopedic treatments and helps spine surgeons to significantly reduce complications and costs and to avoid overtreatment.
Published: 2017

39. Evolution of blood-associated HIV-1 DNA levels after 48 weeks of switching to atazanavir/ritonavir+lamivudine dual therapy versus continuing triple therapy in the randomized AtLaS-M trial

Author: Lombardi, Francesca, Belmonti, Simone, Quiros Roldan, Eugenia, Latini, Alessandra, Castagna, Antonella, D'Ettorre, Gabriella, Gagliardini, Roberta, Fabbiani, Massimiliano, Cauda, Roberto, De Luca, Andrea, Di Giambenedetto, Simona, Lombardi, Francesca (ORCID:0000-0001-5757-8346), Cauda, Roberto (ORCID:0000-0002-1498-4229), De Luca, Andrea (ORCID:0000-0002-8311-6935), Di Giambenedetto, Simona (ORCID:0000-0001-6990-5076), Lombardi, Francesca, Belmonti, Simone, Quiros Roldan, Eugenia, Latini, Alessandra, Castagna, Antonella, D'Ettorre, Gabriella, Gagliardini, Roberta, Fabbiani, Massimiliano, Cauda, Roberto, De Luca, Andrea, Di Giambenedetto, Simona, Lombardi, Francesca (ORCID:0000-0001-5757-8346), Cauda, Roberto (ORCID:0000-0002-1498-4229), De Luca, Andrea (ORCID:0000-0002-8311-6935), and Di Giambenedetto, Simona (ORCID:0000-0001-6990-5076)
Abstract: OBJECTIVES: The AtLaS-M randomized trial showed that in patients with HIV-1 RNA <50 copies/mL on atazanavir/ritonavir + two NRTIs, switching to a dual therapy with atazanavir/ritonavir+lamivudine had superior efficacy as compared with continuing the previous triple therapy. This substudy was designed to evaluate at 48 weeks the impact of the dual therapy versus the three-drug atazanavir/ritonavir-based therapy on the HIV-1 cellular reservoir as reflected by the quantification of blood-associated HIV-1 DNA levels. METHODS: In a representative subset of 201 of 266 randomized patients (104 in the dual-therapy arm and 97 in the triple-therapy arm) total HIV-1 DNA levels in whole blood at baseline and after 48 weeks and factors associated with the HIV-1 DNA levels were evaluated. RESULTS: The mean baseline HIV-1 DNA levels (2.47 log 10 copies/10 6 leucocytes) were comparable between arms. A significant mean decrease between baseline and week 48 was observed: -0.069 log 10 copies/10 6 leucocytes in the dual-therapy arm ( P = 0.046) and -0.078 in the triple-therapy arm ( P = 0.011); the mean difference between arms was -0.009 ( P = 0.842). Nadir CD4 count was inversely correlated with baseline HIV-1 DNA ( P = 0.009); longer duration of ART and lower nadir CD4 correlated with a less prominent HIV-1 DNA decrease (both P < 0.005). Higher baseline HIV-1 DNA was associated with residual viraemia at week 48 ( P = 0.031). CONCLUSIONS: When compared with continuing three-drug therapy, atazanavir/ritonavir+lamivudine dual therapy resulted in a similar decline in HIV-1 DNA levels in patients with sustained virological suppression. These data support the safety of this simplified treatment strategy in terms of its effect on the cellular HIV-1 reservoir
Published: 2017

40. International Infectious Diseases Teaching to Undergraduate medical Students: a Successful European Collaborative Experience

Author: Charlier, C., Johannessen, I., Mackintosh, C. L., Wilks, D., Cauda, Roberto, Wolf Minotti, Federica, Le Jeunne, C., Cauda, Roberto (ORCID:0000-0002-1498-4229), Wolf, Federica (ORCID:0000-0003-1361-1049), Charlier, C., Johannessen, I., Mackintosh, C. L., Wilks, D., Cauda, Roberto, Wolf Minotti, Federica, Le Jeunne, C., Cauda, Roberto (ORCID:0000-0002-1498-4229), and Wolf, Federica (ORCID:0000-0003-1361-1049)
Abstract: The emerging global-health paradigm requires medical teaching to be continuously refined and updated. To this end, transnational approaches should be encouraged, and medical training harmonized. Infectious diseases (ID) teaching in the current context of emerging infections, fast-increasing bacterial resistance, and large-scale human migration, was chosen to develop a common international course. We report the successful implementation of a joint European undergraduate course aiming to i) develop a common ID core curriculum among European medical students; ii) promote mobility among teachers and students; iii) promote international cooperation among European teachers. The course was built around teachers' mobility. It was delivered in English by a team of European medical educators from Paris Descartes University, Università Cattolica del Sacro Cuore in Rome and the University of Edinburgh to groups of 25-30 undergraduate medical students at each university. Partner institutions officially recognized the course as substitutive of, or additive to the regular curriculum. The course has been running for 3 years, and received excellent satisfaction scores from students and staff as regards to scientific content, pedagogy and international exchanges.This cooperative approach demonstrates the feasibility of a harmonized European undergraduate medical education, having ID as a test experiment for future developments.
Published: 2017

41. Trimethoprim-sulfamethoxazole therapy for patients with carbapenemase-producing Klebsiella pneumoniae infections: retrospective single-center case series

Author: Murri, Rita, Fiori, Barbara, Spanu, Teresa, Mastrorosa, Ilaria, Giovannenze, Francesca, Taccari, Francesco, Palazzolo, Claudia, Scoppettuolo, Giancarlo, Ventura, Giulio, Sanguinetti, Maurizio, Cauda, Roberto, Fantoni, Massimo, Murri, Rita (ORCID:0000-0003-4263-7854), Fiori, Barbara (ORCID:0000-0003-3318-5809), Spanu, Teresa (ORCID:0000-0003-1864-5184), Ventura, Giulio (ORCID:0000-0002-0304-7264), Sanguinetti, Maurizio (ORCID:0000-0002-9780-7059), Cauda, Roberto (ORCID:0000-0002-1498-4229), Fantoni, Massimo (ORCID:0000-0001-6913-8460), Murri, Rita, Fiori, Barbara, Spanu, Teresa, Mastrorosa, Ilaria, Giovannenze, Francesca, Taccari, Francesco, Palazzolo, Claudia, Scoppettuolo, Giancarlo, Ventura, Giulio, Sanguinetti, Maurizio, Cauda, Roberto, Fantoni, Massimo, Murri, Rita (ORCID:0000-0003-4263-7854), Fiori, Barbara (ORCID:0000-0003-3318-5809), Spanu, Teresa (ORCID:0000-0003-1864-5184), Ventura, Giulio (ORCID:0000-0002-0304-7264), Sanguinetti, Maurizio (ORCID:0000-0002-9780-7059), Cauda, Roberto (ORCID:0000-0002-1498-4229), and Fantoni, Massimo (ORCID:0000-0001-6913-8460)
Abstract: not available
Published: 2017

42. Characteristics of staphylococcus aureus bacteraemia and predictors of early and late mortality

Author: Bassetti, Matteo, Peghin, Maddalena, Trecarichi, Enrico Maria, Carnelutti, Alessia, Righi, Elda, Del Giacomo, Paola, Ansaldi, Filippo, Trucchi, Cecilia, Alicino, Cristiano, Cauda, Roberto, Sartor, Assunta, Spanu, Teresa, Scarparo, Claudio, Tumbarello, Mario, Cauda, Roberto (ORCID:0000-0002-1498-4229), Spanu, Teresa (ORCID:0000-0003-1864-5184), Tumbarello, Mario (ORCID:0000-0002-9519-8552), Bassetti, Matteo, Peghin, Maddalena, Trecarichi, Enrico Maria, Carnelutti, Alessia, Righi, Elda, Del Giacomo, Paola, Ansaldi, Filippo, Trucchi, Cecilia, Alicino, Cristiano, Cauda, Roberto, Sartor, Assunta, Spanu, Teresa, Scarparo, Claudio, Tumbarello, Mario, Cauda, Roberto (ORCID:0000-0002-1498-4229), Spanu, Teresa (ORCID:0000-0003-1864-5184), and Tumbarello, Mario (ORCID:0000-0002-9519-8552)
Abstract: We aimed to describe the characteristics of patients with Staphylococcus aureus bacteremia and to evaluate the risk factors associated with early (7-day) and late (30-day) mortality. We performed an observational study including all consecutive episodes of Staphylococcus aureus bacteremia diagnosed at two Italian university hospitals during 2010±2014. A total of 337 patients were included. Mean age was 69 years (range, 57±78) and 65% were males. Methicillin-resistant S. aureus (MRSA) was identified in 132/337 (39%)cases. Overall 7-And 30-day mortality were 13% and 26%, respectively. Early mortality was associated with increased Charlson scores (OR 1.3, 95% CI 1.1±1.5), MRSA bacteremia (OR 3.2, 95% CI 1.4±8.1), presentation with septic shock (OR 13.5, 95% CI 5.4±36.4), and occurrence of endocarditis (OR 4.5, 95%CI 1.4±14.6). Similar risk factors were identified for late mortality, including increased Charlson scores (OR 1.2, 95% CI 1.1±1.4), MRSA bacteremia (OR 2.1, 95% CI 1.2±3.9), presentation with septic shock (OR 4, 95%CI 1.7±9.7), occurrence of endocarditis (OR 3.8, 95% CI 1.4±10.2) as well as Child C cirrhosis (OR 3.9, 95% CI 1.1±14.4) and primary bacteremia (OR 2.5, 95%CI 1.3±5). Infectious disease consultation resulted in better outcomes both at 7 (OR 0.1, 95% CI 0.05±0.4) and at 30 days (OR 0.4, 95% CI 0.2± 0.7). In conclusion, our study highlighted high rates of MRSA infection in nosocomial Staphylococcus aureus bacteremia. Multiple comorbidities, disease severity and methicillin-resistance are key factors for early and late mortality in this group. In patients with Staphylococcus aureus bacteremia, infectious disease consultation remains a valuable tool to improve clinical outcome.
Published: 2017

43. Efficacy and tolerability of dolutegravir and two nucleos(t)ide reverse transcriptase inhibitors in HIV-1-positive, virologically suppressed patients

Author: Borghetti, Alberto, Baldin, Gianmaria, Capetti, Amedeo, Sterrantino, Gaetana, Rusconi, Stefano, Latini, Alessandra, Giacometti, Andrea, Madeddu, Giordano, Picarelli, Chiara, De Marco, Ramona, Cossu, Maria V., Lagi, Filippo, Cauda, Roberto, De Luca, Andrea, Di Giambenedetto, Simona, Cauda, Roberto (ORCID:0000-0002-1498-4229), De Luca, Andrea (ORCID:0000-0002-8311-6935), Di Giambenedetto, Simona (ORCID:0000-0001-6990-5076), Borghetti, Alberto, Baldin, Gianmaria, Capetti, Amedeo, Sterrantino, Gaetana, Rusconi, Stefano, Latini, Alessandra, Giacometti, Andrea, Madeddu, Giordano, Picarelli, Chiara, De Marco, Ramona, Cossu, Maria V., Lagi, Filippo, Cauda, Roberto, De Luca, Andrea, Di Giambenedetto, Simona, Cauda, Roberto (ORCID:0000-0002-1498-4229), De Luca, Andrea (ORCID:0000-0002-8311-6935), and Di Giambenedetto, Simona (ORCID:0000-0001-6990-5076)
Abstract: Not Available
Published: 2017

44. Treatment simplification to atazanavir/ritonavir + lamivudine versus maintenance of atazanavir/ritonavir + two NRTIs in virologically suppressed HIV-1-infected patients: 48 week results from a randomized trial (ATLAS-M)

Author: Di Giambenedetto, Simona, Fabbiani, Massimiliano, Quiros Roldan, Eugenia, Latini, Alessandra, D'Ettorre, Gabriella, Antinori, Andrea, Castagna, Antonella, Orofino, Giancarlo, Francisci, Daniela, Chinello, Pierangelo, Madeddu, Giordano, Grima, Pierfrancesco, Rusconi, Stefano, Di Pietro, Massimo, Mondi, Annalisa, Ciccarelli, Nicoletta, Borghetti, Alberto, Focà, Emanuele, Colafigli, Manuela, De Luca, Andrea, Cauda, Roberto, Di Giambenedetto, Simona (ORCID:0000-0001-6990-5076), Ciccarelli, Nicoletta (ORCID:0000-0002-7582-9142), De Luca, Andrea (ORCID:0000-0002-8311-6935), Cauda, Roberto (ORCID:0000-0002-1498-4229), Di Giambenedetto, Simona, Fabbiani, Massimiliano, Quiros Roldan, Eugenia, Latini, Alessandra, D'Ettorre, Gabriella, Antinori, Andrea, Castagna, Antonella, Orofino, Giancarlo, Francisci, Daniela, Chinello, Pierangelo, Madeddu, Giordano, Grima, Pierfrancesco, Rusconi, Stefano, Di Pietro, Massimo, Mondi, Annalisa, Ciccarelli, Nicoletta, Borghetti, Alberto, Focà, Emanuele, Colafigli, Manuela, De Luca, Andrea, Cauda, Roberto, Di Giambenedetto, Simona (ORCID:0000-0001-6990-5076), Ciccarelli, Nicoletta (ORCID:0000-0002-7582-9142), De Luca, Andrea (ORCID:0000-0002-8311-6935), and Cauda, Roberto (ORCID:0000-0002-1498-4229)
Abstract: not available
Published: 2017

45. Simplification to a dual regimen with darunavir/ritonavir plus lamivudine or emtricitabine in virologically-suppressed HIV-infected patients

Author: Fabbiani, Massimiliano, Di Giambenedetto, Simona (ORCID:0000-0001-6990-5076), Poli, Andrea, Borghetti, Alberto, Castagna, Antonella, Mondi, Annalisa, Galizzi, Nadia, Maillard, Myriam, Gori, Andrea, Cauda, Roberto (ORCID:0000-0002-1498-4229), De Luca, Andrea (ORCID:0000-0002-8311-6935), Gianotti, Nicola, Fabbiani, Massimiliano, Di Giambenedetto, Simona (ORCID:0000-0001-6990-5076), Poli, Andrea, Borghetti, Alberto, Castagna, Antonella, Mondi, Annalisa, Galizzi, Nadia, Maillard, Myriam, Gori, Andrea, Cauda, Roberto (ORCID:0000-0002-1498-4229), De Luca, Andrea (ORCID:0000-0002-8311-6935), and Gianotti, Nicola
Abstract: not available
Published: 2016

46. Discontinuation of initial antiretroviral therapy in clinical practice: Moving toward individualized therapy

Author: Di Biagio, Antonio, Cozzi Lepri, Alessandro, Prinapori, Roberta, Angarano, Gioacchino, Gori, Andrea, Quirino, Tiziana, De Luca, Andrea, Costantini, Andrea, Mussini, Cristina, Rizzardini, Giuliano, Castagna, Antonella, Antinori, Andrea, Monforte, Antonella D'arminio, Moroni, M., Andreoni, M., Angarano, G., Antinori, A., D'Arminio Monforte, A., Castelli, F., Cauda, Roberto, Di Perri, G., Galli, M., Iardino, R., Ippolito, G., Lazzarin, A., Perno, C. F., Von Schloesser, F., Viale, P., Castagna, A., Ceccherini Silberstein, F., Cozzi Lepri, A., Girardi, E., Lo Caputo, S., Mussini, C., Puoti, M., Ammassari, A., Balotta, C., Bandera, A., Bonfanti, P., Bonora, S., Borderi, M., Calcagno, A., Calza, L., Capobianchi, M. R., Cingolani, Antonella, Cinque, P., De Luca, A., Di Biagio, A., Gianotti, N., Gori, A., Guaraldi, G., Lapadula, G., Lichtner, M., Madeddu, G., Maggiolo, F., Marchetti, G., Marcotullio, S., Monno, L., Quiros Roldan, E., Rossotti, R., Rusconi, S., Santoro, M., Saracino, A., Zaccarelli, M., Fanti, Iuri, Galli, L., Lorenzini, P., Rodano, A., Shanyinde, M., Tavelli, A., Giacometti, A., Costantini, A., Mazzoccato, S., Santoro, C., Suardi, C., Vanino, E., Verucchi, G., Minardi, C., Quirino, T., Abeli, C., Manconi, P. E., Piano, P., Vecchiet, J., Falasca, K., Sighinolfi, L., Segala, D., Mazzotta, F., Cassola, G., Viscoli, C., Alessandrini, A., Piscopo, R., Mazzarello, G., Mastroianni, C., Belvisi, V., Caramma, I., Chiodera, A., Castelli, A. P., Rizzardini, G., Ridolfo, A. L., Piolini, R., Salpietro, S., Carenzi, L., Moioli, M. C., Tincati, C., Puzzolante, C., Abrescia, N., Chirianni, A., Borgia, G., Guida, M. G., Gargiulo, M., Gentile, I., Orlando, R., Baldelli, F., Francisci, D., Parruti, G., Ursini, T., Magnani, G., Ursitti, M. A., Cauda, R., Vullo, V., Cingolani, A., D'Avino, Alessandro, Gallo, L., Nicastri, E., Acinapura, R., Capozzi, M., Libertone, R., Tebano, G., Viviani, F., Sasset, L., Mura, M. S., Rossetti, Barbara, Caramello, P., Orofino, G. C., Sciandra, M., Bassetti, M., Londero, A., Pellizzer, G., Manfrin, V., De Luca, Andrea (ORCID:0000-0002-8311-6935), Cauda, Roberto (ORCID:0000-0002-1498-4229), Cingolani, Antonella (ORCID:0000-0002-3793-2755), Di Biagio, Antonio, Cozzi Lepri, Alessandro, Prinapori, Roberta, Angarano, Gioacchino, Gori, Andrea, Quirino, Tiziana, De Luca, Andrea, Costantini, Andrea, Mussini, Cristina, Rizzardini, Giuliano, Castagna, Antonella, Antinori, Andrea, Monforte, Antonella D'arminio, Moroni, M., Andreoni, M., Angarano, G., Antinori, A., D'Arminio Monforte, A., Castelli, F., Cauda, Roberto, Di Perri, G., Galli, M., Iardino, R., Ippolito, G., Lazzarin, A., Perno, C. F., Von Schloesser, F., Viale, P., Castagna, A., Ceccherini Silberstein, F., Cozzi Lepri, A., Girardi, E., Lo Caputo, S., Mussini, C., Puoti, M., Ammassari, A., Balotta, C., Bandera, A., Bonfanti, P., Bonora, S., Borderi, M., Calcagno, A., Calza, L., Capobianchi, M. R., Cingolani, Antonella, Cinque, P., De Luca, A., Di Biagio, A., Gianotti, N., Gori, A., Guaraldi, G., Lapadula, G., Lichtner, M., Madeddu, G., Maggiolo, F., Marchetti, G., Marcotullio, S., Monno, L., Quiros Roldan, E., Rossotti, R., Rusconi, S., Santoro, M., Saracino, A., Zaccarelli, M., Fanti, Iuri, Galli, L., Lorenzini, P., Rodano, A., Shanyinde, M., Tavelli, A., Giacometti, A., Costantini, A., Mazzoccato, S., Santoro, C., Suardi, C., Vanino, E., Verucchi, G., Minardi, C., Quirino, T., Abeli, C., Manconi, P. E., Piano, P., Vecchiet, J., Falasca, K., Sighinolfi, L., Segala, D., Mazzotta, F., Cassola, G., Viscoli, C., Alessandrini, A., Piscopo, R., Mazzarello, G., Mastroianni, C., Belvisi, V., Caramma, I., Chiodera, A., Castelli, A. P., Rizzardini, G., Ridolfo, A. L., Piolini, R., Salpietro, S., Carenzi, L., Moioli, M. C., Tincati, C., Puzzolante, C., Abrescia, N., Chirianni, A., Borgia, G., Guida, M. G., Gargiulo, M., Gentile, I., Orlando, R., Baldelli, F., Francisci, D., Parruti, G., Ursini, T., Magnani, G., Ursitti, M. A., Cauda, R., Vullo, V., Cingolani, A., D'Avino, Alessandro, Gallo, L., Nicastri, E., Acinapura, R., Capozzi, M., Libertone, R., Tebano, G., Viviani, F., Sasset, L., Mura, M. S., Rossetti, Barbara, Caramello, P., Orofino, G. C., Sciandra, M., Bassetti, M., Londero, A., Pellizzer, G., Manfrin, V., De Luca, Andrea (ORCID:0000-0002-8311-6935), Cauda, Roberto (ORCID:0000-0002-1498-4229), and Cingolani, Antonella (ORCID:0000-0002-3793-2755)
Abstract: Background: Study aim was to estimate the rate and identify predictors of discontinuation of first combination antiretroviral therapy (cART) in recent years. Methods: Patients who initiated first cART between January 2008 and October 2014 were included. Discontinuation was defined as stop of at least 1 drug of the regimen, regardless of the reason. All causes of discontinuation were evaluated and 3 main endpoints were considered: toxicity, intolerance, and simplification. Predictors of discontinuation were examined separately for all 3 endpoints. Kaplan-Meier analysis was used for the outcome discontinuation of ≥1 drug regardless of the reason. Cox regression analysis was used to identify factors associated with treatment discontinuation because of the 3 reasons considered. Results: A total of 4052 patients were included. Main reason for stopping at least 1 drug were simplification (29%), intolerance (21%), toxicity (19%), other causes (18%), failure (8%), planned discontinuation (4%), and nonadherence (2%). In a multivariable Cox model, predictors of discontinuation for simplification were heterosexual transmission (P = 0.007), being immigrant (P = 0.017), higher nadir lymphocyte T CD4+cell (P = 0.011), and higher lymphocyte T CD8+cell count (P = 0.025); for discontinuation due to intolerance: the use of statins (P = 0.029), higher blood glucose levels (P = 0.050). About toxicity: higher blood glucose levels (P = 0.010) and the use of zidovudine/lamivudine as backbone (P = 0.044). Conclusions: In the late cART era, the main reason for stopping the initial regimen is simplification. This scenario reflects the changes in recommendations aimed to enhance adherence and quality of life, and minimize drug toxicity.
Published: 2016

47. Simplification to a dual regimen with darunavir/ritonavir plus lamivudine or emtricitabine in virologically-suppressed HIV-infected patients

Author: Fabbiani, Massimiliano, Di Giambenedetto, Simona, Poli, Andrea, Borghetti, Alberto, Castagna, Antonella, Mondi, Annalisa, Galizzi, Nadia, Maillard, Myriam, Gori, Andrea, Cauda, Roberto, De Luca, Andrea, Gianotti, Nicola, Di Giambenedetto, Simona (ORCID:0000-0001-6990-5076), Cauda, Roberto (ORCID:0000-0002-1498-4229), De Luca, Andrea (ORCID:0000-0002-8311-6935), Fabbiani, Massimiliano, Di Giambenedetto, Simona, Poli, Andrea, Borghetti, Alberto, Castagna, Antonella, Mondi, Annalisa, Galizzi, Nadia, Maillard, Myriam, Gori, Andrea, Cauda, Roberto, De Luca, Andrea, Gianotti, Nicola, Di Giambenedetto, Simona (ORCID:0000-0001-6990-5076), Cauda, Roberto (ORCID:0000-0002-1498-4229), and De Luca, Andrea (ORCID:0000-0002-8311-6935)
Abstract: not available
Published: 2016

48. Relationship between self-reported adherence, antiretroviral drug concentration measurement and self-reported symptoms in patients treated for HIV-1 infection

Author: Fabbiani, Massimiliano, Di Giambenedetto, Simona, Cingolani, Antonella, Fanti, Iuri, Colafigli, Manuela, Tamburrini, Enrica, Cauda, Roberto, Navarra, Pierluigi, De Luca, Andrea, Murri, Rita, Di Giambenedetto, Simona (ORCID:0000-0001-6990-5076), Cingolani, Antonella (ORCID:0000-0002-3793-2755), Tamburrini, Enrica (ORCID:0000-0003-4930-426X), Cauda, Roberto (ORCID:0000-0002-1498-4229), Navarra, Pierluigi (ORCID:0000-0002-4424-650X), De Luca, Andrea (ORCID:0000-0002-8311-6935), Murri, Rita (ORCID:0000-0003-4263-7854), Fabbiani, Massimiliano, Di Giambenedetto, Simona, Cingolani, Antonella, Fanti, Iuri, Colafigli, Manuela, Tamburrini, Enrica, Cauda, Roberto, Navarra, Pierluigi, De Luca, Andrea, Murri, Rita, Di Giambenedetto, Simona (ORCID:0000-0001-6990-5076), Cingolani, Antonella (ORCID:0000-0002-3793-2755), Tamburrini, Enrica (ORCID:0000-0003-4930-426X), Cauda, Roberto (ORCID:0000-0002-1498-4229), Navarra, Pierluigi (ORCID:0000-0002-4424-650X), De Luca, Andrea (ORCID:0000-0002-8311-6935), and Murri, Rita (ORCID:0000-0003-4263-7854)
Abstract: The aim of the study was to explore relationships between self-reported adherence, antiretroviral drug concentration measurement (TDM) and self-reported symptoms.
Published: 2016

49. Risk of chronic kidney disease among patients developing mild renal impairment during tenofovir-containing antiretroviral treatment

Author: Lapadula, Giuseppe, Bernasconi, Davide Paolo, Casari, Salvatore, Maggiolo, Franco, Cauda, Roberto, Di Pietro, Massimo, Ladisa, Nicoletta, Sighinolfi, Laura, Zoppo, Sarah Dal, Sabbatini, Francesca, Soria, Alessandro, Pezzoli, Chiara, Mondi, Annalisa, Costarelli, Silvia, Valsecchi, Maria Grazia, Torti, Carlo, Gori, Andrea, Castelli, F., Carosi, G., Quiros, E., Nasta, P., Torti, C., Cauda, R., Di Giambenedetto, Simona, Maggiolo, F., Scalzini, A., Castelnuovo, F., Mazzotta, F., Di Pietro, M., Sighinolfi, L., Angarano, G., Ladisa, N., Monno, L., Saracino, A., Pan, A., Lorenzotti, S., Gori, A., Costarelli, S., Cauda, Roberto (ORCID:0000-0002-1498-4229), Di Giambenedetto, Simona (ORCID:0000-0001-6990-5076), Lapadula, Giuseppe, Bernasconi, Davide Paolo, Casari, Salvatore, Maggiolo, Franco, Cauda, Roberto, Di Pietro, Massimo, Ladisa, Nicoletta, Sighinolfi, Laura, Zoppo, Sarah Dal, Sabbatini, Francesca, Soria, Alessandro, Pezzoli, Chiara, Mondi, Annalisa, Costarelli, Silvia, Valsecchi, Maria Grazia, Torti, Carlo, Gori, Andrea, Castelli, F., Carosi, G., Quiros, E., Nasta, P., Torti, C., Cauda, R., Di Giambenedetto, Simona, Maggiolo, F., Scalzini, A., Castelnuovo, F., Mazzotta, F., Di Pietro, M., Sighinolfi, L., Angarano, G., Ladisa, N., Monno, L., Saracino, A., Pan, A., Lorenzotti, S., Gori, A., Costarelli, S., Cauda, Roberto (ORCID:0000-0002-1498-4229), and Di Giambenedetto, Simona (ORCID:0000-0001-6990-5076)
Abstract: Background: Tenofovir (TDF) can cause kidney injury through tubular dysfunction, with or without drop of estimated glomerular filtration rate (eGFR). Whether mild eGFR reductions during treatment should be considered a reason for prompt TDF discontinuation, however, remains unclear. Methods: Patients with normal pre-TDF eGFR levels, who had developed mild renal impairment (i.e., two consecutive eGFR results between 89-60 ml/min) on TDF, were observed until onset of chronic kidney disease (CKD), defined as two eGFR<60 ml/min 3 to 6 months apart. Multivariable Poisson regression analysis was used to investigate whether outcome was associated with current and cumulative use of TDF (modeled as time-varying covariates). Results: 2023 (29%) out of 6984 patients developed mild renal impairment on TDF. Among them, 191 progressed to CKD. The incidence of CKD did not significantly differ during TDF treatment (2.6 per 100 PYFU; 95%CI 2.2-3.2) or after its discontinuation (2.2 per 100 PYFU; 95%CI 1.8-2.6). However, the rate of CKD was significantly higher among patients continuing with TDF treatment compared to those who had discontinued it within 6 months of occurrence of mild renal impairment (aIRR 4, 95%CI 2.4-6.8). In contrast, among patients who had maintained TDF >6 months despite mild renal impairment, current TDF use was not associated with a significantly higher rate of CKD. Other significant predictors of CKD were older age, intravenous drug use, diabetes, hypertension, lower pre-TDF eGFR, higher eGFR drop since TDF introduction and longer exposure to TDF. Conclusions: Prompt discontinuation of TDF among patients developing mild renal impairmentmay prevent further progression of renal damage.
Published: 2016

50. Impact of 48 weeks of atazanavir/ritonavir plus lamivudine dual therapy on cellular HIV-DNA levels in the AtLaS pilot study

Author: Lombardi, Francesca, Belmonti, Simone, Fabbiani, Massimiliano, Borghetti, Alberto, Cauda, Roberto, De Luca, Andrea, Di Giambenedetto, Simona, Lombardi, Francesca (ORCID:0000-0001-5757-8346), Cauda, Roberto (ORCID:0000-0002-1498-4229), De Luca, Andrea (ORCID:0000-0002-8311-6935), Di Giambenedetto, Simona (ORCID:0000-0001-6990-5076), Lombardi, Francesca, Belmonti, Simone, Fabbiani, Massimiliano, Borghetti, Alberto, Cauda, Roberto, De Luca, Andrea, Di Giambenedetto, Simona, Lombardi, Francesca (ORCID:0000-0001-5757-8346), Cauda, Roberto (ORCID:0000-0002-1498-4229), De Luca, Andrea (ORCID:0000-0002-8311-6935), and Di Giambenedetto, Simona (ORCID:0000-0001-6990-5076)
Abstract: not available
Published: 2016

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