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1. The PP2A phosphatase counteracts the function of the 9-1-1 axis in checkpoint activation

Author

Casari, E, Pizzul, P, Rinaldi, C, Gnugnoli, M, Clerici, M, Longhese, M, Casari E., Pizzul P., Rinaldi C., Gnugnoli M., Clerici M., Longhese M. P., Casari, E, Pizzul, P, Rinaldi, C, Gnugnoli, M, Clerici, M, Longhese, M, Casari E., Pizzul P., Rinaldi C., Gnugnoli M., Clerici M., and Longhese M. P.

Abstract

DNA damage elicits a checkpoint response depending on the Mec1/ATR kinase, which detects the presence of single-stranded DNA and activates the effector kinase Rad53/CHK2. In Saccharomyces cerevisiae, one of the signaling circuits leading to Rad53 activation involves the evolutionarily conserved 9-1-1 complex, which acts as a platform for the binding of Dpb11 and Rad9 (referred to as the 9-1-1 axis) to generate a protein complex that allows Mec1 activation. By examining the effects of both loss-of-function and hypermorphic mutations, here, we show that the Cdc55 and Tpd3 subunits of the PP2A phosphatase counteract activation of the 9-1-1 axis. The lack of this inhibitory function results in DNA-damage sensitivity, sustained checkpoint-mediated cell-cycle arrest, and impaired resection of DNA double-strand breaks. This PP2A anti-checkpoint role depends on the capacity of Cdc55 to interact with Ddc1 and to counteract Ddc1-Dpb11 complex formation by preventing Dpb11 recognition of Ddc1 phosphorylated on Thr602

Published
2023

2. Efficacy of intraventricular amikacin treatment in pan-resistant Pseudomonas aeruginosa postsurgical meningitis

Author

Molinaro M, Morelli P, De Gregori M, De Gregori S, Giardini I, Tordato F, Monzillo V, Pocaterra D, and Casari E

Subjects
Pan- resistant meningitis, Pseudomonas aeruginosa, amikacin, Infectious and parasitic diseases, RC109-216
Abstract

Mariadelfina Molinaro,1 Paola Morelli,2 Manuela De Gregori,1,3,4 Simona De Gregori,1 Ilaria Giardini,1 Federica Tordato,2 Vincenzina Monzillo,5,6 Daria Pocaterra,2 Erminia Casari7 1Clinical and Experimental Pharmacokinetics Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, 2Infectious Diseases Unit, Hospital Health Direction, Humanitas Clinical and Research Center, Milan, 3Pain Therapy Service, Fondazione IRCCS Policlinico San Matteo, Pavia, 4Study in Multidisciplinary Pain Research Group, Parma, 5Microbiology and Virology Unit, Fondazione IRCCS Policlinico San Matteo, 6Infectious Diseases Unit, Internal Medicine and Medical Therapy Department, University of Pavia, Pavia, 7Microbiology Unit, Analysis Laboratory, Humanitas Clinical and Research Center, Milan, Italy Background: We describe a case of pan-resistant Pseudomonas aeruginosa postsurgical meningitis associated with the presence of an external ventricular device. We changed therapy twice; finally, by using amikacin and a continuous infusion of cefepime, we obtained clinical improvement. Case presentation: A female patient, who underwent surgery for a cavernous angioma, presented with meningitis. Cerebrospinal fluid culture revealed a multidrug-resistant Pseudomonas aeruginosa, initially sensitive only to colistin. We successfully used intrathecal amikacin and intravenous cefepime continuous infusion plus intravenous amikacin after two previous ineffective therapeutic approaches. Conclusion: The evaluation of the antibiotic concentration and the bactericidal activity in cerebrospinal fluid may contribute to the choice of the drug in cases of multidrug-resistant meningitis. Keywords: pan-resistant meningitis, Pseudomonas aeruginosa, amikacin

Published
2018

3. Multicenter prospective study on the prevalence of colistin resistance in Escherichia coli: relevance of mcr-1-positive clinical isolates in Lombardy, Northern Italy

Author

Principe L, Piazza A, Mauri C, Anesi A, Bracco S, Brigante G, Casari E, Agrappi C, Caltagirone M, Novazzi F, Migliavacca R, Pagani L, and Luzzaro F

Subjects
MCR-1, colistin, Escherichia coli, prevalence, surveillance, epidemiology, Infectious and parasitic diseases, RC109-216
Abstract

Luigi Principe,1 Aurora Piazza,2,3 Carola Mauri,1 Adriano Anesi,4 Silvia Bracco,5 Gioconda Brigante,6 Erminia Casari,7 Carlo Agrappi,8 Mariasofia Caltagirone,2 Federica Novazzi,2 Roberta Migliavacca,2 Laura Pagani,2 Francesco Luzzaro1 1Microbiology and Virology Unit, A. Manzoni Hospital, Lecco, Italy; 2Clinical-Surgical, Diagnostic and Pediatric Sciences Department, Unit of Microbiology and Clinical Microbiology, University of Pavia, Pavia, Italy; 3Romeo and Enrica Invernizzi Pediatric Research Center, Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy; 4Clinical Pathology Laboratory, ASST Lodi, Lodi, Italy; 5Clinical Pathology Laboratory, ASST Vimercate, Vimercate, Italy; 6Clinical Pathology Laboratory, ASST Valle Olona, Busto Arsizio, Italy; 7Clinical Pathology Laboratory, IRCCS “Humanitas,” Rozzano, Italy; 8Microbiology and Virology Unit, ASST Ovest Milanese, Legnano, Italy Background: The emergence of the plasmid-mediated colistin resistance mechanism in Escherichia coli has raised concern among public health experts as colistin is a last-line antimicrobial resort. The primary aim of the study was to investigate the prevalence of this resistance trait in E. coli isolates circulating in the Lombardy region, Northern Italy. The presence of mcr-type genes and their genetic relationship were also studied.Materials and methods: A prospective study was performed during a 4-month period (May to August, 2016) in six acute care Hospitals. Consecutive nonduplicate clinical isolates of E. coli from any type of clinical specimen, with the exception of rectal swabs, were included in the study. Isolates that exhibited MIC values for colistin >2 mg/L were further investigated. Bacterial identification was obtained by matrix-assisted laser desorption ionization-time of flight mass spectrometry. Amplification of mcr-type genes (−1 to −5 variants) and microarray analysis were accomplished. Repetitive sequence-based PCR (Rep-PCR) and multilocus sequence typing (MLST) analysis were used for genotyping.Results: Overall, 3,902 consecutive E. coli isolates (2,342 from outpatients, 1,560 from inpatients) were evaluated during the study period. Of them, 18/3,902 (0.5%), collected from 4/6 centers, showed resistance to colistin. These isolates were mostly obtained from urine of both outpatients (n=12) and inpatients (n=6). Colistin MIC values ranged from 4 to 8 mg/L. The mcr-1 gene was detected in 10/18 isolates (7 from outpatients, 3 from inpatients). Rep-PCR and MLST analysis revealed the presence of nine different clusters. Further mcr-type genes were not detected.Conclusion: Resistance to colistin in E. coli clinical isolates appears low in our geographic area. With regard to mcr-1-positive isolates, they accounted for approximately 50% of colistin-resistant E. coli isolates, thus representing a relevant resistance mechanism in this context. Although overall limited, the presence of mcr-1 determinant in our region should not be ignored and great concern should be given to the continuous surveillance. Keywords: MCR-1, colistin, Escherichia coli, prevalence, surveillance, epidemiology

Published
2018

5. The chromatin remodeler Chd1 supports MRX and Exo1 functions in resection of DNA double-strand breaks

Author

Gnugnoli, M, Casari, E, Longhese, M, Gnugnoli M., Casari E., Longhese M. P., Gnugnoli, M, Casari, E, Longhese, M, Gnugnoli M., Casari E., and Longhese M. P.

Abstract

Repair of DNA double-strand breaks (DSBs) by homologous recombination (HR) requires that the 5’-terminated DNA strands are resected to generate single-stranded DNA overhangs. This process is initiated by a short-range resection catalyzed by the MRX (Mre11-Rad50-Xrs2) complex, which is followed by a long-range step involving the nuclease Exo1 or Dna2. Here we show that the Saccharomyces cerevisiae ATP-dependent chromatin-remodeling protein Chd1 participates in both short- and long-range resection by promoting MRX and Exo1 association with the DSB ends. Furthermore, Chd1 reduces histone occupancy near the DSB ends and promotes DSB repair by HR. All these functions require Chd1 ATPase activity, supporting a role for Chd1 in the opening of chromatin at the DSB site to facilitate MRX and Exo1 processing activities.

Published
2021

6. The 9-1-1 Complex Controls Mre11 Nuclease and Checkpoint Activation during Short-Range Resection of DNA Double-Strand Breaks

Author

Gobbini, E, Casari, E, Colombo, C, Bonetti, D, Longhese, M, Gobbini E., Casari E., Colombo C. V., Bonetti D., Longhese M. P., Gobbini, E, Casari, E, Colombo, C, Bonetti, D, Longhese, M, Gobbini E., Casari E., Colombo C. V., Bonetti D., and Longhese M. P.

Abstract

Resection of DNA double-strand breaks is a two-step process that relies on short and long-range nucleases. Gobbini et al. show that the 9-1-1 complex plays a dual function during short-range resection, promoting checkpoint activation by recruiting Rad9 at damaged sites and negatively regulating short-range resection in a Rad9-independent manner by restricting Mre11 nuclease. © 2020 The Author(s) Homologous recombination is initiated by nucleolytic degradation (resection) of DNA double-strand breaks (DSBs). DSB resection is a two-step process in which an initial short-range step is catalyzed by the Mre11-Rad50-Xrs2 (MRX) complex and limited to the vicinity of the DSB end. Then the two long-range resection Exo1 and Dna2-Sgs1 nucleases extend the resected DNA tracts. How short-range resection is regulated and contributes to checkpoint activation remains to be determined. Here, we show that abrogation of long-range resection induces a checkpoint response that decreases DNA damage resistance. This checkpoint depends on the 9-1-1 complex, which recruits Dpb11 and Rad9 at damaged DNA. Furthermore, the 9-1-1 complex, independently of Dpb11 and Rad9, restricts short-range resection by negatively regulating Mre11 nuclease. We propose that 9-1-1, which is loaded at the leading edge of resection, plays a key function in regulating Mre11 nuclease and checkpoint activation once DSB resection is initiated.

Published
2020

7. Resection of DNA double-strand breaks: novel regulatory mechanisms by checkpoint proteins and chromatin remodelers

Author

CLERICI, MICHELA, Casari, E, LONGHESE, MARIA PIA, CASARI, ERIKA, CLERICI, MICHELA, Casari, E, LONGHESE, MARIA PIA, and CASARI, ERIKA

Abstract

L'instabilità genomica è una delle caratteristiche delle cellule tumorali e può essere dovuta a difetti nella riparazione dei danni al DNA. Tra le differenti tipologie di danno al DNA, le rotture della doppia elica di DNA sono lesioni citotossiche che devono essere riparate per garantire stabilità genomica ed evitare la morte cellulare. Le cellule eucariotiche affrontano questi danni attivando una risposta con differenti vie molecolari. Tra esse il meccanismo NHEJ lega direttamente le estremità rotte del DNA. Oppure il meccanismo HR utilizza il cromatidio fratello/il cromosoma omologo come templato per riparare la rottura. HR è avviata dalla degradazione nucleolitica (resection) delle estremità 5' del DSB. La resection è un processo a due fasi: la prima fase, short-range, è catalizzata dal complesso MRX/MRN che, insieme a Sae2/CtIP catalizza un taglio endonucleolitico alle estremità 5’ del DNA rotto. Dopo di che, la seconda fase, long-range, prevede l’intervento delle nucleasi Exo1 e Dna2/Sgs1. Esse sono necessarie per generare code di 3’ssDNA. In seguito a una rottura della doppia elica di DNA, le cellule attivano anche un’altra via chiamata checkpoint da danno al DNA, che coordina la riparazione del danno con la progressione del ciclo cellulare. Tra i principali attori del checkpoint ci sono le chinasi Mec1/ATR e Tel1/ATM. Tel1 riconosce le rotture del doppio filamento di DNA non processate, mentre Mec1 è attivato dal DNA a singolo filamento, prodotto dal processo di resection. Una volta stimolate, queste due chinasi apicali attivano per fosforilazione le chinasi effettrici Rad53/CHK2 e Chk1/CHK1. Questa attivazione richiede anche la proteina conservata Rad9/53BP1 la cui associazione al DNA coinvolge diverse vie. Resta da determinare come la short-range resection sia regolata e contribuisca all'attivazione del checkpoint. In questa tesi, ho contribuito a dimostrare che l’inibizione della long-range resection induce una risposta di checkpoint che dipende, Genome instability is one of the hallmarks of cancer cells and can be due to DNA repair defects. Among different types of DNA damage, DNA DSBs are cytotoxic lesions that must be repaired to ensure genomic stability and avoid cell death. Eukaryotic cells deal with DSBs by activating the DNA damage response, that comprises pathways devoted to repair DNA breaks. DSBs can be repaired by NHEJ, which directly ligates the broken DNA ends, or by HR, which uses sister chromatids/homologous chromosomes as a template to repair the DNA break. HR is initiated by nucleolytic degradation (resection) of the 5’-terminated strands at both DSB ends. DSB resection is a two-step process, in which an initial short-range step is catalyzed by Mre11-Rad50-Xrs2/NBS1 (MRX/MRN) complex that, together with Sae2 (CtIP in mammals), catalyzes an endonucleolytic cleavage of the 5’strands. Then, a long-range resection step is carried out by the nucleases Exo1 and Dna2/Sgs1 to generate long 3’ssDNA tails. The DDR comprises also surveillance mechanisms, called DNA damage checkpoint, that couple DSB repair with cell cycle progression. Major checkpoint players include the apical protein kinases Mec1/ATR and Tel1/ATM. Tel1 recognizes unprocessed DSBs, while Mec1 is activated by RPA-coated ssDNA that is generated during the resection process. Once activated, these protein kinases activate by phosphorylation the effector kinases Rad53/CHK2 and Chk1/CHK1. This activation requires the conserved adaptor protein Rad9/53BP1, whose association to chromatin involves multiple pathways. How short-range resection is regulated and contributes to checkpoint activation remains to be determined. In this thesis, I contributed to show that abrogation of long-range resection induces a checkpoint response that depends on the checkpoint complex 9-1-1, which recruits Rad9 at damaged DNA. Furthermore, the 9-1-1 complex, independently of Rad9, restricts short-range resection by negatively regulating Mre11 nuclease. We propose t

Published
2022

8. The DNA damage checkpoint: A tale from budding yeast

Author

Pizzul, P, Casari, E, Gnugnoli, M, Rinaldi, C, Corallo, F, Longhese, M, Pizzul, Paolo, Casari, Erika, Gnugnoli, Marco, Rinaldi, Carlo, Corallo, Flavio, Longhese, Maria Pia, Pizzul, P, Casari, E, Gnugnoli, M, Rinaldi, C, Corallo, F, Longhese, M, Pizzul, Paolo, Casari, Erika, Gnugnoli, Marco, Rinaldi, Carlo, Corallo, Flavio, and Longhese, Maria Pia

Abstract

Studies performed in the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe have led the way in defining the DNA damage checkpoint and in identifying most of the proteins involved in this regulatory network, which turned out to have structural and functional equivalents in humans. Subsequent experiments revealed that the checkpoint is an elaborate signal transduction pathway that has the ability to sense and signal the presence of damaged DNA and transduce this information to influence a multifaceted cellular response that is essential for cancer avoidance. This review focuses on the work that was done in Saccharomyces cerevisiae to articulate the checkpoint concept, to identify its players and the mechanisms of activation and deactivation.

Published
2022

9. To Fix or Not to Fix: Maintenance of Chromosome Ends Versus Repair of DNA Double-Strand Breaks

Author

Casari, E, Gnugnoli, M, Rinaldi, C, Pizzul, P, Colombo, C, Bonetti, D, Longhese, M, Casari, Erika, Gnugnoli, Marco, Rinaldi, Carlo, Pizzul, Paolo, Colombo, Chiara Vittoria, Bonetti, Diego, Longhese, Maria Pia, Casari, E, Gnugnoli, M, Rinaldi, C, Pizzul, P, Colombo, C, Bonetti, D, Longhese, M, Casari, Erika, Gnugnoli, Marco, Rinaldi, Carlo, Pizzul, Paolo, Colombo, Chiara Vittoria, Bonetti, Diego, and Longhese, Maria Pia

Abstract

Early work by Muller and McClintock discovered that the physical ends of linear chromosomes, named telomeres, possess an inherent ability to escape unwarranted fusions. Since then, extensive research has shown that this special feature relies on specialized proteins and structural properties that confer identity to the chromosome ends, thus allowing cells to distinguish them from intrachromosomal DNA double-strand breaks. Due to the inability of conventional DNA replication to fully replicate the chromosome ends and the downregulation of telomerase in most somatic human tissues, telomeres shorten as cells divide and lose this protective capacity. Telomere attrition causes the activation of the DNA damage checkpoint that leads to a cell-cycle arrest and the entering of cells into a nondividing state, called replicative senescence, that acts as a barrier against tumorigenesis. However, downregulation of the checkpoint overcomes this barrier and leads to further genomic instability that, if coupled with re-stabilization of telomeres, can drive tumorigenesis. This review focuses on the key experiments that have been performed in the model organism Saccharomyces cerevisiae to uncover the mechanisms that protect the chromosome ends from eliciting a DNA damage response, the conservation of these pathways in mammals, as well as the consequences of their loss in human cancer.

Published
2022

12. Resection of a DNA Double-Strand Break by Alkaline Gel Electrophoresis and Southern Blotting

Author

Casari, E, Gobbini, E, Clerici, M, Longhese, M, Longhese, MP, Casari, E, Gobbini, E, Clerici, M, Longhese, M, and Longhese, MP

Abstract

Generation of 3' single-stranded DNA (ssDNA) at the ends of a double-strand break (DSB) is essential to initiate repair by homology-directed mechanisms. Here we describe a Southern blot-based method to visualize the generation of ssDNA at the ends of site-specific DSBs generated in the Saccharomyces cerevisiae genome.

Published
2021

15. Processing of DNA double-strand breaks by the MRX complex in a chromatin context

Author

Casari, E, Rinaldi, C, Marsella, A, Gnugnoli, M, Colombo, C, Bonetti, D, Longhese, M, Colombo, CV, Longhese, MP, Casari, E, Rinaldi, C, Marsella, A, Gnugnoli, M, Colombo, C, Bonetti, D, Longhese, M, Colombo, CV, and Longhese, MP

Abstract

DNA double-strand breaks (DSBs) are highly cytotoxic lesions that must be repaired to ensure genomic stability and avoid cell death. The cellular response to DSBs is initiated by the evolutionarily conserved Mre11-Rad50-Xrs2/NBS1 (MRX/MRN) complex that has structural and catalytic functions. Furthermore, it is responsible for DSB signaling through the activation of the checkpoint kinase Tel1/ATM. Here, we review functions and regulation of the MRX/MRN complex in DSB processing in a chromatin context, as well as its interplay with Tel1/ATM.

Published
2019

16. Structure–function relationships of the Mre11 protein in the control of DNA end bridging and processing

Author

Marsella, A, Cassani, C, Casari, E, Tisi, R, Longhese, M, Longhese, MP, Marsella, A, Cassani, C, Casari, E, Tisi, R, Longhese, M, and Longhese, MP

Abstract

The evolutionarily conserved Mre11–Rad50–Xrs2 (MRX) complex cooperates with the Sae2 protein in initiating resection of DNA double-strand breaks (DSBs) and in maintaining the DSB ends tethered to each other for their accurate repair. How these MRX–Sae2 functions contribute to DNA damage resistance is not understood. By taking advantage of mre11 alleles that suppress the hypersensitivity of sae2∆ cells to genotoxic agents, we have recently found that Mre11 can be divided in two structurally distinct domains that support resistance to genotoxic agents by mediating different processes. While the Mre11 N-terminal domain impacts on the resection activity of long-range resection nucleases by mediating MRX and Tel1/ATM association to DNA DSBs, the C-terminus influences the MRX-tethering activity by its virtue to interact with Rad50. Given the evolutionary conservation of the MRX complex, our results have implications for understanding the consequences of its dysfunctions in human diseases

Published
2019

17. Strategies for preventing group B streptococcal infections in newborns: A nation-wide survey of Italian policies

Author

Tzialla, C, berardi, A, farina, C, clerici, P, borghesi, A, viora, E, scollo, P, stronati, M, Task Force for group B streptococcal infections for the Italian Society of Neonatology including Stival, G, barbaglia, Ma, guala, A, giunta, E, parola, L, grossignani, Mr, perri, P, tubaldi, L, alletto, G, daidone, S, flacco, V, dani, C, sterpa, A, rapisardi, G, elicio, Mr, faldella, G, capretti, Mg, messner, H, bandiera, M, achille, C, azzali, A, montrasio, G, mariani, S, galvagno, G, giacosa, E, de Angelis, F, spandrio, M, serra, A, garofalo, F, perona, A, porcelli, F, ferrero, F, De Franco, S, paollilo, P, picone, S, besana, R, varisco, T, farina, M, memo, L, nicolini, G, lietti, D, Di Chiara, G, rottoli, A, Bonabitacola, T, Cortis, E, Neri, E, Martinelli, S, Ilardi, L, Rondanini, Gf, Calzi, P, Gatta, A, Quntadamo, Pa, Ivaldi, M, Terenzani, L, Di Lascio, N, Travaglio, Md, Vetrano, G, Furcolo, G, Vitacco, V, Intini, C, Frigerio, M, Stroppiana, P, Policicchio, G, Mesirca, P, Gianino, P, Audenio, E, Paludetto, R, Raimondi, F, Pugliese, A, Valentino, L, Nosari, N, Marchesano, G, Chirico, G, Bellù, R, Menchini, M, Poletti, A, E T, Vacchiano, Pinto, L, E D, Perri, Coppola, R, Perini, R, Vetrella, A, De Luca, G, Lista, G, Cavigioli, F, Bettinelli, A, Massironi, E, Franco, C, Bernardo, L, Poli, S, Palladini, M, Tota, V, Spadavecchia, F, Zuccotti, Gv, Pogliani, L, Bracaglia, G, Mancini, Al, Zocco, F, Iozzia, G, Auriemma, A, Teani, M, Mangilli, G, Tempra, Am, Di Terlizi, L, Bottino, R, Salvi, C, Fortunato, V, Musaico, R, Gargantini, G, Carrera, G, Magaldi, R, Taurino, L, D'Onofrio, Am, Buffone, E, Tempera, A, Agosti, M, Garzia, P, Mosca, F, Pugni, L, Tagliabue, P, Colombo, C, Demi, M, Picco, G, Carlucci, A, Zorzi, G, Padula, D, Cardone, Ml, Buonocore, G, Muraca, Mc, Boldrini, A, Ciantelli, M, Lanari, M, Serra, L, Felici, L, Banderalli, G, Brambilla, C, Dall'Agnola, A, Viviani, E, Zonca, Mc, Licardi, G, Chiara, A, Ancora, G, Papa, I, Gancia, P, Pomero, G, Deloglu, A, Villani, P, Mussini, P, Canidio, E, Migliavacca, D, Di Fabio, S, Cipollone, I, Biasucci, G, Rubbi, P, Piepoli, M, Guastaferro, N, Infriccioli, F, Bertino, E, Perathoner, C, Parmigiani, S, Suriano, G, Ianniello, C, Biasini, A, Azzalli, M, Timpani, G, Barresi, S, Caoci, G, Ciccotti, R, De Curtis, M, Natale, F, Finocchi, M, Haass, C, Milillo, F, Lucieri, S, Guercio, E, Canepa, Sa, Scozia, G, Antonucci, R, Limongelli, O, Macciò, S, Mongelli, F, Colonna, F, Dragovic, D, Calipa, Mt, Cohen, A, Moresco, L, Italian Society of Obstetricians and Gynecologists including La Spina, R, Ruggeri, R, Luehwink, A, Brattoli, M, Fedi, A, Lacchi, L, Ettore, G, Pappalardo, E, Conoscenti, G, Zeni, B, Spellecchia, D, Favretti, L, Spagna, L, Zaglio, S, Bresciani, D, Bandini, A, Mancini, R, Mustoni, P, Dodero, D, Grimaldi, M, Di Mario, M, Migliorini, P, Kemeny, A, Anastasio, Ps, Riccardi, T, Maggino, T, Cerri, G, Puggina, P, Marconi, Am, Morgia, S, Bellia, G, D'Anna, Mr, Catania, M, Bacchi Modena, A, Franchi, L, Calonaci, N, Schettini, S, Paradiso, R, Saccucci, P, Ioppi, M, Zorzi, M, Stellin, G, Patacchiola, F, Carrata, L, Bassini, D, San Marco, L, Todros, T, Tibadi, C, Liborio, M, Italian Association of Clinical Microbiologists including Laricchia, R, Tauro, L, Ferrara, F, Nuara, C, Ghiraldi, E, Molinari, F, Comessatti, A, Rocchetti, A, Di Matteo, L, Miconi, V, Calvi, P, Pernigotti, A, Fabozzi, F, Micca, G, Monticone, G, Sarti, M, Da Rin, G, Zoppelletto, M, Modolo, E, Landini, Mp, Furlini, G, Galluppi, E, Pagani, E, Aschbacher, R, Innocenti, P, Bresolin, N, Raggi, Me, Bonfanti, C, De Francesco, M, Santer, P, Griessmaier, A, De Francesco, D, Pirali, A, Prasciolu, C, Usai, F, Cuzzone, G, Scutellà, M, Tramacere, P, Fossati, D, Piaserico, G, Bordignon, G, Sciacca, A, Di Vincenzo, F, Imbriani, A, Melotti, D, Catanoso, G, Rivetti, I, Neri, G, Bruno, R, Bacelle, L, Sartore, P, Giana, G, Sala, E, Giraldi, C, Cavalcanti, P, Perugini, M, Perugini, A, Ginardi, C, Maritano, D, Ferrini, A, Bonettini, A, Avanzini, A, Gasperoni, S, Pieretti, B, Montanari, E, Carillo, C, Rossi, Mr, Laureti, A, Baldoni, Ml, Serra, D, Melioli, G, Bandettini, R, Oneto, F, Colla, R, Storchi Incerti, S, Lanzini, F, Pauri, P, Tili, E, Leone, Ra, Verdastro, G, Megha, M, Luzzaro, F, Conti, A, Busulini, L, Mirri, P, Diodati, R, Vettori, C, Pittalis, S, Anesi, A, Fiore, A, Goglia, L, Vitullo, E, Sinno, A, Platzgummer, S, Spitaler, C, Trabucchi, Mc, Besozzi, M, Cesana, E, Inghilleri, G, Grosso, S, D'Angelo, R, Fogato, E, Lavarda, F, Ortisi, G, Clementi, M, Cichero, P, Rumpianesi, F, Venturelli, C, Mortillaro, F, Daffara, S, Catania, Mr, Iula, D, Andreoni, S, Politi, A, Agostinelli, C, Paparella, C, Capozzi, D, Notaris, P, Bistoni, F, Mencacci, A, Valentini, M, Filippetti, A, Confalonieri, M, Novarese, O, Bonini, F, Salamone, D, Camporese, A, De Rosa, R, Casprini, P, Degl'Innocenti, R, Giordano, R, Allù, Mt, Zanella, D, Malandrino, M, Tronci, M, Valmarin, M, Leonetti, G, Falco, S, Meledandri, M, Ballardini, M, Spanò, A, Cava, Mc, Mascellino, Mt, Schinella, M, Gualdi, P, Casari, E, Scattolo, N, Motta, C, Perfetti, C, Bassano, M, Cera, G, Iafisco, P, Mura, I, Palmieri, A, Migliardi, M, Ferlini, M, Grandi, G, Giardini, F, Albano, F, Latino, M, Ferrero, Mp, Bellizia, L, Russolo, M, Russolo, S, Pesenti, A, Fasano, Ma, Previato, S, Radillo, O, Busetti, M, Ferrari, P, Siderini, V, Puzzolante, L, Scarparo, C, Arzese, A, Cappuccia, N, Lodolo, L, Delledonne, L, Gramoni, A, Maiolo, V, Gheller, A, Spadaro, S, Balzaretti, M, Tzialla, C., Berardi, A., Farina, C., Clerici, P., Borghesi, A., Viora, E., Scollo, P., Stronati, M., Stival, G., Barbaglia, M. A., Guala, A., Giunta, E., Parola, L., Grossignani, M. R., Perri, P., Tubaldi, L., Alletto, G., Daidone, S., Flacco, V., Dani, C., Sterpa, A., Rapisardi, G., Elicio, M. R., Faldella, G., Capretti, M. G., Messner, H., Bandiera, M., Achille, C., Azzali, A., Montrasio, G., Mariani, S., Galvagno, G., Giacosa, E., de Angelis, F., Spandrio, M., Serra, A., Garofalo, F., Perona, A., Porcelli, F., Ferrero, F., De Franco, S., Paollilo, P., Picone, S., Besana, R., Varisco, T., Farina, M., Memo, L., Nicolini, G., Lietti, D., Di Chiara, G., Rottoli, A., Bonabitacola, T., Cortis, E., Neri, E., Martinelli, S., Ilardi, L., Rondanini, G. F., Calzi, P., Gatta, A., Quntadamo, P. A., Ivaldi, M., Terenzani, L., Di Lascio, N., Travaglio, M. D., Vetrano, G., Furcolo, G., Vitacco, V., Intini, C., Frigerio, M., Stroppiana, P., Policicchio, G., Mesirca, P., Gianino, P., Audenio, E., Paludetto, R., Raimondi, F., Pugliese, A., Valentino, L., Nosari, N., Marchesano, G., Chirico, G., Bell(`u), R., Menchini, M., Poletti, A., Vacchiano, T., Pinto, L., Perri, D., Coppola, R., Perini, R., Vetrella, A., De Luca, G., Lista, G., Cavigioli, F., Bettinelli, A., Massironi, E., Franco, C., Bernardo, L., Poli, S., Palladini, M., Tota, V., Spadavecchia, F., Zuccotti, G. V., Pogliani, L., Bracaglia, G., Mancini, A. L., Zocco, F., Iozzia, G., Auriemma, A., Teani, M., Mangilli, G., Tempra, A. M., Di Terlizi, L., Bottino, R., Salvi, C., Fortunato, V., Musaico, R., Gargantini, G., Carrera, G., Magaldi, R., Taurino, L., D?onofrio, A. M., Buffone, E., Tempera, A., Agosti, M., Garzia, P., Mosca, F., Pugni, L., Tagliabue, P., Colombo, C., Demi, M., Picco, G., Carlucci, A., Zorzi, G., Padula, D., Cardone, M. L., Buonocore, G., Muraca, M. C., Boldrini, A., Ciantelli, M., Lanari, M., Serra, L., Felici, L., Banderalli, G., Brambilla, C., Dall?agnola, A., Viviani, E., Zonca, M. C., Licardi, G., Chiara, A., Ancora, G., Papa, I., Gancia, P., Pomero, G., Deloglu, A., Villani, P., Mussini, P., Canidio, E., Migliavacca, D., Di Fabio, S., Cipollone, I., Biasucci, G., Rubbi, P., Piepoli, M., Guastaferro, N., Infriccioli, F., Bertino, E., Perathoner, C., Parmigiani, S., Suriano, G., Ianniello, C., Biasini, A., Azzalli, M., Timpani, G., Barresi, S., Caoci, G., Ciccotti, R., De Curtis, M., Natale, F., Finocchi, M., Haass, C., Milillo, F., Lucieri, S., Guercio, E., Canepa, S. A., Scozia, G., Antonucci, R., Limongelli, O., Macci(`o), S., Mongelli, F., Colonna, F., Dragovic, D., Calipa, M. T., Cohen, A., Moresco, L., La Spina, R., Ruggeri, R., Luehwink, A., Brattoli, M., Fedi, A., Lacchi, L., Ettore, G., Pappalardo, E., Conoscenti, G., Zeni, B., Spellecchia, D., Favretti, L., Spagna, L., Zaglio, S., Bresciani, D., Bandini, A., Mancini, R., Mustoni, P., Dodero, D., Grimaldi, M., Di Mario, M., Migliorini, P., Kemeny, A., Anastasio, P. S., Riccardi, T., Maggino, T., Cerri, G., Puggina, P., Marconi, A. M., Morgia, S., Bellia, G., D?anna, M. R., Catania, M., Bacchi Modena, A., Franchi, L., Calonaci, N., Schettini, S., Paradiso, R., Saccucci, P., Ioppi, M., Zorzi, M., Stellin, G., Patacchiola, F., Carrata, L., Bassini, D., San Marco, L., Todros, T., Tibadi, C., Liborio, M., Laricchia, R., Tauro, L., Ferrara, F., Nuara, C., Ghiraldi, E., Molinari, F., Comessatti, A., Rocchetti, A., Di Matteo, L., Miconi, V., Calvi, P., Pernigotti, A., Fabozzi, F., Micca, G., Monticone, G., Sarti, M., Da Rin, G., Zoppelletto, M., Modolo, E., Landini, M. P., Furlini, G., Galluppi, E., Pagani, E., Aschbacher, R., Innocenti, P., Bresolin, N., Raggi, M. E., Bonfanti, C., De Francesco, M., Santer, P., Griessmaier, A., De Francesco, D., Pirali, A., Prasciolu, C., Usai, F., Cuzzone, G., Scutell(`a), M., Tramacere, P., Fossati, D., Piaserico, G., Bordignon, G., Sciacca, A., Di Vincenzo, F., Imbriani, A., Melotti, D., Catanoso, G., Rivetti, I., Neri, G., Bruno, R., Bacelle, L., Sartore, P., Giana, G., Sala, E., Giraldi, C., Cavalcanti, P., Perugini, M., Perugini, A., Ginardi, C., Maritano, D., Ferrini, A., Bonettini, A., Avanzini, A., Gasperoni, S., Pieretti, B., Montanari, E., Carillo, C., Rossi, M. R., Laureti, A., Baldoni, M. L., Serra, D., Melioli, G., Bandettini, R., Oneto, F., Colla, R., Storchi Incerti, S., Lanzini, F., Pauri, P., Tili, E., Leone, R. A., Verdastro, G., Megha, M., Luzzaro, F., Conti, A., Busulini, L., Mirri, P., Diodati, R., Vettori, C., Pittalis, S., Anesi, A., Fiore, A., Goglia, L., Vitullo, E., Sinno, A., Platzgummer, S., Spitaler, C., Trabucchi, M. C., Besozzi, M., Cesana, E., Inghilleri, G., Grosso, S., D?angelo, R., Fogato, E., Lavarda, F., Ortisi, G., Clementi, M., Cichero, P., Rumpianesi, F., Venturelli, C., Mortillaro, F., Daffara, S., Catania, M. R., Iula, D., Andreoni, S., Politi, A., Agostinelli, C., Paparella, C., Capozzi, D., Notaris, P., Bistoni, F., Mencacci, A., Valentini, M., Filippetti, A., Confalonieri, M., Novarese, O., Bonini, F., Salamone, D., Camporese, A., De Rosa, R., Casprini, P., Degl?innocenti, R., Giordano, R., All(`u), M. T., Zanella, D., Malandrino, M., Tronci, M., Valmarin, M., Leonetti, G., Falco, S., Meledandri, M., Ballardini, M., Span(`o), A., Cava, M. C., Mascellino, M. T., Schinella, M., Gualdi, P., Casari, E., Scattolo, N., Motta, C., Perfetti, C., Bassano, M., Cera, G., Iafisco, P., Mura, I., Palmieri, A., Migliardi, M., Ferlini, M., Grandi, G., Giardini, F., Albano, F., Latino, M., Ferrero, M. P., Bellizia, L., Russolo, M., Russolo, S., Pesenti, A., Fasano, M. A., Previato, S., Radillo, O., Busetti, M., Ferrari, P., Siderini, V., Puzzolante, L., Scarparo, C., Arzese, A., Cappuccia, N., Lodolo, L., Delledonne, L., Gramoni, A., Maiolo, V., Gheller, A., Spadaro, S., Balzaretti, M., Tzialla, Chryssoula, Berardi, Alberto, Farina, Claudio, Clerici, Pierangelo, Borghesi, Alessandro, Viora, Elsa, Scollo, Paolo, Stronati, Mauro, [.., Lanari, Marcello, Faldella, Giacomo, and ]

Subjects
Male, Pediatrics, Group B, 0302 clinical medicine, Neonate, Pregnancy, Surveys and Questionnaires, Prevalence, Mass Screening, Blood culture, 030212 general & internal medicine, Antibiotic prophylaxis, Survey, GBS, Group B streptococcus, Infection, Newborn infant, Adult, Antibiotic Prophylaxis, Female, Health Surveys, Humans, Infant, Newborn, Italy, Neonatal Screening, Pregnancy Complications, Infectious, Prenatal Care, Primary Prevention, Risk Assessment, Streptococcal Infections, Streptococcus agalactiae, reproductive and urinary physiology, Group B streptococcu, medicine.diagnostic_test, lcsh:RJ1-570, Infectious, Perinatology and Child Health, Pediatrics, Perinatology and Child Health, medicine.medical_specialty, Antibiotic sensitivity, Group B Streptococcal Infection, Prenatal care, 03 medical and health sciences, 030225 pediatrics, medicine, Intensive care medicine, Mass screening, business.industry, Public health, Infant, lcsh:Pediatrics, Newborn, Pregnancy Complications, business
Abstract

Background There are no Italian data regarding the strategies for preventing neonatal group B streptococcal (GBS) infection. We conducted a national survey in order to explore obstetrical, neonatal and microbiological practices for the GBS prevention. Methods Three distinct questionnaires were sent to obstetricians, neonatologists and microbiologists. Questionnaires included data on prenatal GBS screening, maternal risk factors, intrapartum antibiotic prophylaxis, microbiological information concerning specimen processing and GBS antimicrobial susceptibility. Results All respondent obstetrical units used the culture-based screening approach to identify women who should receive intrapartum antibiotic prophylaxis, and more than half of the microbiological laboratories (58%) reported using specimen processing consistent with CDC guidelines. Most neonatal units (89 out of 107, 82%) reported using protocols for preventing GBS early-onset sepsis consistent with CDC guidelines. Conclusions The screening-based strategy is largely prevalent in Italy, and most protocols for preventing GBS early-onset sepsis are consistent with CDC guidelines. However, we found discrepancies in practices among centers that may reflect the lack of Italian guidelines issued by public health organizations.

Published
2017

19. The MRX complex regulates Exo1 resection activity by altering DNA end structure

Author

Gobbini, E, Cassani, C, Vertemara, J, Wang, W, Mambretti, F, Casari, E, Sung, P, Tisi, R, Zampella, G, Longhese, M, Gobbini, Elisa, Cassani, Corinne, Vertemara, Jacopo, Wang, Weibin, Mambretti, Fabiana, CASARI, ERIKA, Sung, Patrick, Tisi, Renata, Zampella, Giuseppe, Longhese, Maria Pia, Gobbini, E, Cassani, C, Vertemara, J, Wang, W, Mambretti, F, Casari, E, Sung, P, Tisi, R, Zampella, G, Longhese, M, Gobbini, Elisa, Cassani, Corinne, Vertemara, Jacopo, Wang, Weibin, Mambretti, Fabiana, CASARI, ERIKA, Sung, Patrick, Tisi, Renata, Zampella, Giuseppe, and Longhese, Maria Pia

Abstract

Homologous recombination is triggered by nucleolytic degradation (resection) of DNA double-strand breaks (DSBs). DSB resection requires the Mre11-Rad50-Xrs2 (MRX) complex, which promotes the activity of Exo1 nuclease through a poorly understood mechanism. Here, we describe the Mre11-R10T mutant variant that accelerates DSB resection compared to wild-type Mre11 by potentiating Exo1-mediated processing. This increased Exo1 resection activity leads to a decreased association of the Ku complex to DSBs and an enhanced DSB resection in G1, indicating that Exo1 has a direct function in preventing Ku association with DSBs. Molecular dynamics simulations show that rotation of the Mre11 capping domains is able to induce unwinding of double-strand DNA (dsDNA). The R10T substitution causes altered orientation of the Mre11 capping domain that leads to persistent melting of the dsDNA end. We propose that MRX creates a specific DNA end structure that promotes Exo1 resection activity by facilitating the persistence of this nuclease on the DSB ends, uncovering a novel MRX function in DSB resection

Published
2018

20. Incidence, Risk Factors and Outcome of Pre-engraftment Gram-Negative Bacteremia After Allogeneic and Autologous Hematopoietic Stem Cell Transplantation: An Italian Prospective Multicenter Survey

Author

Girmenia, C, Bertaina, A, Piciocchi, A, Perruccio, K, Algarotti, A, Busca, A, Cattaneo, C, Raiola, Am, Guidi, S, Iori, Ap, Candoni, A, Irrera, G, Milone, G, Marcacci, G, Scimè, R, Musso, M, Cudillo, L, Sica, S, Castagna, L, Corradini, P, Marchesi, F, Pastore, D, Alessandrino, Ep, Annaloro, C, Ciceri, F, Santarone, S, Nassi, L, Farina, C, Viscoli, C, Rossolini, Gm, Bonifazi, F, Rambaldi, A, Capria, S, Mastronuzzi, A, Pagliara, D, Bernaschi, P, Amico, L, Carotti, A, Mencacci, A, Bruno, B, Costa, C, Passi, A, Ravizzola, G, Angelucci, E, Marchese, A, Pecile, P, Ventura, G, Fanin, R, Scarparo, C, Barbaro, A, Leotta, S, Marchese, Ae, Becchimanzi, C, Donnarumma, D, Tringali, S, Baldi, Mt, Scalone, R, Picardi, A, Arcese, W, Fontana, C, Giammarco, S, Spanu, T, Crocchiolo, R, Casari, E, Mussetti, A, Conte, E, Ensoli, F, Miragliotta, G, Marone, P, Arghittu, M, Greco, R, Forcina, A, Chichero, P, Di Bartolomeo, P, Fazii, P, Kroumova, V, Decembrino, N, Zecca, M, Pisapia, G, Palazzo, G, Lanino, E, Faraci, M, Castagnola, E, Bandettini, R, Pastano, R, Sammassimo, S, Passerini, R, Stefani, Pm, Gherlinzoni, F, Rigoli, R, Prezioso, L, Cambò, B, Calderaro, A, Carella, Am, Cascavilla, N, Labonia, Mt, Celeghini, I, Mordini, N, Piana, F, Vacca, A, Sanna, M, Podda, G, Corsetti, Mt, Rocchetti, A, Cilloni, D, De Gobbi, M, Bianco, O, Fagioli, F, Carraro, F, De Intinis, G, Severino, A, Proia, A, Parisi, G, Vallisa, D, Confalonieri, M, Russo, D, Malagola, M, Galieni, P, Falcioni, S, Travaglini, V, Raimondi, R, Borghero, C, Pavan, G, Prete, A, Belotti, T, Ambretti, S, Imola, M, Mianulli, Am, Pedna, Mf, Cesaro, S, Lo Cascio, G, Ferrari, A, Piedimonte, M, Santino, I, Calandrelli, M, Olivieri, A, Orecchioni, F, Mirabile, M, Centurioni, R, Gironacci, L, Caravelli, D, Gallo, S, De Filippi, M, Cupelli, L, Dentamaro, T, Falco, S, Eugenio, Os, Marotta, S, Risitano, A, Lula, D, Musto, P, Pietrantuono, G, Traficante, A, Cerchiara, E, Tirindelli, Mc, Dicuonzo, G, Chierichini, A, Anaclerico, B, and Placanica, P.

Published
2017

21. Incidence, Risk Factors and Outcome of Pre-engraftment Gram-Negative Bacteremia after Allogeneic and Autologous Hematopoietic Stem Cell Transplantation: An Italian Prospective Multicenter Survey

Author

Girmenia, C., Bertaina, A., Piciocchi, A., Perruccio, K., Algarotti, A., Busca, A., Cattaneo, C., Raiola, A. M., Guidi, S., Iori, A. P., Candoni, A., Irrera, G., Milone, G., Marcacci, G., Scime, R., Musso, M., Cudillo, L., Sica, Simona, Castagna, Luigi, Corradini, P., Marchesi, F., Pastore, D., Alessandrino, E. P., Annaloro, C., Ciceri, F., Santarone, S., Nassi, L., Farina, C., Viscoli, C., Rossolini, G. M., Bonifazi, F., Rambaldi, A., Capria, S., Mastronuzzi, A., Pagliara, D., Bernaschi, P., Amico, L., Carotti, A., Mencacci, A., Bruno, Brunella, Costa, C., Passi, A., Ravizzola, G., Angelucci, E., Marchese, Alessandra Maria, Pecile, P., Ventura, Giulio, Fanin, R., Scarparo, C., Barbaro, A., Leotta, Salvatore Nuccio, Marchese, A. E., Becchimanzi, C., Donnarumma, D., Tringali, S., Baldi, M. T., Scalone, R., Picardi, A., Arcese, W., Fontana, Cecilia Alejandra, Giammarco, S., Spanu, Teresa, Crocchiolo, R., Casari, E., Mussetti, A., Conte, Eliana, Ensoli, F., Miragliotta, G., Marone, P., Arghittu, M., Greco, R., Forcina, A., Chichero, P., Di Bartolomeo, P., Fazii, P., Kroumova, V., Decembrino, N., Zecca, M., Pisapia, Giovanni, Palazzo, G., Lanino, E., Faraci, M., Castagnola, E., Bandettini, R., Pastano, R., Sammassimo, S., Passerini, R., Stefani, P. M., Gherlinzoni, F., Rigoli, R., Prezioso, L., Cambo, B., Calderaro, A., Carella, A. M., Cascavilla, N., Labonia, M. T., Celeghini, I., Mordini, N., Piana, F., Vacca, A., Sanna, Maria Maddalena, Podda, G., Corsetti, M. T., Rocchetti, A., Cilloni, D., De Gobbi, M., Bianco, O., Fagioli, F., Carraro, F., De Intinis, G., Severino, A., Proia, Anna Silvia, Parisi, G., Vallisa, D., Confalonieri, Marco, Russo, D., Malagola, M., Galieni, P., Falcioni, S., Travaglini, V., Raimondi, Maria Rosa, Borghero, C., Pavan, Giuseppe, Prete, A., Belotti, T., Ambretti, S., Imola, M., Mianulli, A. M., Pedna, M. F., Cesaro, S., Lo Cascio, G., Ferrari, A., Piedimonte, M., Santino, I., Calandrelli, M., Olivieri, Alessandra, Orecchioni, F., Mirabile, M., Centurioni, R., Gironacci, L., Caravelli, D., Gallo, S., De Filippi, M., Cupelli, L., Dentamaro, T., Falco, S., Eugenio, O. S., Marotta, S., Risitano, A., Lula, D., Musto, P., Pietrantuono, G., Traficante, A., Cerchiara, E., Tirindelli, M. C., Dicuonzo, G., Chierichini, A., Anaclerico, B., Placanica, P., Sica S. (ORCID:0000-0003-2426-3465), Castagna L., Bruno B., Marchese A., Ventura G. (ORCID:0000-0002-0304-7264), Leotta S., Fontana C., Spanu T. (ORCID:0000-0003-1864-5184), Conte E., Pisapia G., Sanna M., Proia A., Confalonieri M. (ORCID:0000-0002-3708-379X), Raimondi R., Pavan G., Olivieri A., Girmenia, C., Bertaina, A., Piciocchi, A., Perruccio, K., Algarotti, A., Busca, A., Cattaneo, C., Raiola, A. M., Guidi, S., Iori, A. P., Candoni, A., Irrera, G., Milone, G., Marcacci, G., Scime, R., Musso, M., Cudillo, L., Sica, Simona, Castagna, Luigi, Corradini, P., Marchesi, F., Pastore, D., Alessandrino, E. P., Annaloro, C., Ciceri, F., Santarone, S., Nassi, L., Farina, C., Viscoli, C., Rossolini, G. M., Bonifazi, F., Rambaldi, A., Capria, S., Mastronuzzi, A., Pagliara, D., Bernaschi, P., Amico, L., Carotti, A., Mencacci, A., Bruno, Brunella, Costa, C., Passi, A., Ravizzola, G., Angelucci, E., Marchese, Alessandra Maria, Pecile, P., Ventura, Giulio, Fanin, R., Scarparo, C., Barbaro, A., Leotta, Salvatore Nuccio, Marchese, A. E., Becchimanzi, C., Donnarumma, D., Tringali, S., Baldi, M. T., Scalone, R., Picardi, A., Arcese, W., Fontana, Cecilia Alejandra, Giammarco, S., Spanu, Teresa, Crocchiolo, R., Casari, E., Mussetti, A., Conte, Eliana, Ensoli, F., Miragliotta, G., Marone, P., Arghittu, M., Greco, R., Forcina, A., Chichero, P., Di Bartolomeo, P., Fazii, P., Kroumova, V., Decembrino, N., Zecca, M., Pisapia, Giovanni, Palazzo, G., Lanino, E., Faraci, M., Castagnola, E., Bandettini, R., Pastano, R., Sammassimo, S., Passerini, R., Stefani, P. M., Gherlinzoni, F., Rigoli, R., Prezioso, L., Cambo, B., Calderaro, A., Carella, A. M., Cascavilla, N., Labonia, M. T., Celeghini, I., Mordini, N., Piana, F., Vacca, A., Sanna, Maria Maddalena, Podda, G., Corsetti, M. T., Rocchetti, A., Cilloni, D., De Gobbi, M., Bianco, O., Fagioli, F., Carraro, F., De Intinis, G., Severino, A., Proia, Anna Silvia, Parisi, G., Vallisa, D., Confalonieri, Marco, Russo, D., Malagola, M., Galieni, P., Falcioni, S., Travaglini, V., Raimondi, Maria Rosa, Borghero, C., Pavan, Giuseppe, Prete, A., Belotti, T., Ambretti, S., Imola, M., Mianulli, A. M., Pedna, M. F., Cesaro, S., Lo Cascio, G., Ferrari, A., Piedimonte, M., Santino, I., Calandrelli, M., Olivieri, Alessandra, Orecchioni, F., Mirabile, M., Centurioni, R., Gironacci, L., Caravelli, D., Gallo, S., De Filippi, M., Cupelli, L., Dentamaro, T., Falco, S., Eugenio, O. S., Marotta, S., Risitano, A., Lula, D., Musto, P., Pietrantuono, G., Traficante, A., Cerchiara, E., Tirindelli, M. C., Dicuonzo, G., Chierichini, A., Anaclerico, B., Placanica, P., Sica S. (ORCID:0000-0003-2426-3465), Castagna L., Bruno B., Marchese A., Ventura G. (ORCID:0000-0002-0304-7264), Leotta S., Fontana C., Spanu T. (ORCID:0000-0003-1864-5184), Conte E., Pisapia G., Sanna M., Proia A., Confalonieri M. (ORCID:0000-0002-3708-379X), Raimondi R., Pavan G., and Olivieri A.

Abstract

Background Gram-negative bacteremia (GNB) is a major cause of illness and death after hematopoietic stem cell transplantation (HSCT), and updated epidemiological investigation is advisable. Methods We prospectively evaluated the epidemiology of pre-engraftment GNB in 1118 allogeneic HSCTs (allo-HSCTs) and 1625 autologous HSCTs (auto-HSCTs) among 54 transplant centers during 2014 (SIGNB-GITMO-AMCLI study). Using logistic regression methods. we identified risk factors for GNB and evaluated the impact of GNB on the 4-month overall-survival after transplant. Results The cumulative incidence of pre-engraftment GNB was 17.3% in allo-HSCT and 9% in auto-HSCT. Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa were the most common isolates. By multivariate analysis, variables associated with GNB were a diagnosis of acute leukemia, a transplant from a HLA-mismatched donor and from cord blood, older age, and duration of severe neutropenia in allo-HSCT, and a diagnosis of lymphoma, older age, and no antibacterial prophylaxis in auto-HSCT. A pretransplant infection by a resistant pathogen was significantly associated with an increased risk of posttransplant infection by the same microorganism in allo-HSCT. Colonization by resistant gram-negative bacteria was significantly associated with an increased rate of infection by the same pathogen in both transplant procedures. GNB was independently associated with increased mortality at 4 months both in allo-HSCT (hazard ratio, 2.13; 95% confidence interval, 1.45-3.13; P <.001) and auto-HSCT (2.43; 1.22-4.84; P =.01). Conclusions Pre-engraftment GNB is an independent factor associated with increased mortality rate at 4 months after auto-HSCT and allo-HSCT. Previous infectious history and colonization monitoring represent major indicators of GNB. Clinical Trials registration NCT02088840.

Published
2017

24. Infections by carbapenem-resistant Klebsiella pneumoniae in SCT recipients: a nationwide retrospective survey from Italy

Author

Girmenia, C, Rossolini, Gm, Piciocchi, A, Bertaina, A, Pisapia, G, Pastore, D, Sica, S, Severino, A, Cudillo, L, Ciceri, F, Scimè, R, Lombardini, L, Viscoli, C, Rambaldi, A, the Gruppo Italiano Trapianto Midollo Osseo (GITMO), Frigeni, M, Corti, C, Mometto, G, Annaloro, C, Casari, E, Castagna, L, Rossi, G, Cattaneo, C, Russo, D, Cancelli, V, Alessandrino, Ep, Ripamonti, F, Pavan, F, Rovelli, A, Pecoraro, C, Busca, A, Carraro, F, Fagioli, F, Gallo, S, Caravelli, D, De Gobbi, M, Saglio, G, Castellino, C, Mordini, N, Gaidano, G, Nassi, L, Raimondi, R, Vespignani, M, Scattolin, Am, Panizzolo, Is, Cesaro, S, Candoni, A, Patriarca, F, Bacigalupo, A, Raiola, A, Castagnola, E, Lanino, E, Stanzani, M, Bandini, G, Massaccesi, E, Prete, A, Bassi, S, Vallisa, D, Caramatti, C, Aversa, F, Zuffa, E, Guidi, S, Bosi, A, Tintori, V, Iori, Ap, Capria, S, Arcese, W, Dentamaro, T, Fabritiis, Pd, Anaclerico, B, Chierichini, A, Piedimonte, M, Ferrari, A, Marchesi, F, Mengarelli, A, Cerchiara, E, Tirindelli, Mc, Gaziev, J, Majolino, I, Chiusolo, P, Lucarelli, B, Massei, Ms, Carotti, A, Perruccio, K, Caniglia, M, Santarone, S, Bartolomeo, Pd, Mazzotta, S, Galieni, P, Olivieri, A, Rosa, Gd, Risitano, A, Delia, M, Specchia, G, Palazzo, G, Messina, G, Irrera, G, Angelucci, E, Baronciani, D, Vacca, A, Crescimanno, A, Musso, M, Imbriani, A, Milone, G., Girmenia, C, Rossolini, Gm, Piciocchi, A, Bertaina, A, Pisapia, G, Pastore, D, Sica, S, Severino, A, Cudillo, L, Ciceri, Fabio, Scime, R, Lombardini, L, Viscoli, C, Rambaldi, A, and and the Gruppo Italiano Trapianto Midollo Osseo, (GITMO)

Subjects
Male, Klebsiella pneumoniae, Carbapenem resistant Klebsiella pneumoniae, Drug Resistance, carbapenem-resistant Klebsiella pneumoniae, colonization, sepsis, Allogeneic Hematopoietic Stem Cell Transplantation, Hematologic Diseases, hemic and lymphatic diseases, polycyclic compounds, Medicine, Adolescent, Adult, Aged, Allografts, Autografts, Female, Humans, Italy, Klebsiella Infections, Middle Aged, Retrospective Studies, Carbapenems, Drug Resistance, Bacterial, Stem Cell Transplantation, Hematology, Transplantation, biology, Bacterial, humanities, surgical procedures, operative, medicine.medical_specialty, Retrospective survey, Internal medicine, business.industry, Retrospective cohort study, Klebsiella infections, biology.organism_classification, Settore MED/15, infection, body regions, Settore MED/15 - MALATTIE DEL SANGUE, Immunology, business
Abstract

Infections by carbapenem-resistant Klebsiella pneumoniae (CRKp) represent a challenging problem after SCT. A retrospective survey (January 2010 to July 2013) involving 52 Italian centers was performed to assess the epidemiology and the prognostic factors of CRKp infections in auto- and allo-SCT. Cases of CRKp infection were reported in 53.4% of centers. CRKp infections were documented in 25 auto-SCTs and 87 allo-SCTs, with an incidence of 0.4% (from 0.1% in 2010 to 0.7% in 2013) and 2% (from 0.4% in 2010 to 2.9% in 2013), respectively. A CRKp colonization documented before or after transplant was followed by an infection in 25.8% of auto-SCT and 39.2% of allo-SCT patients. The infection-related mortality rates were 16% and 64.4%, respectively. A pre-transplant CRKp infection (hazard ratio (HR) 0.33, 95% confidence intervals (CIs) 0.15-0.74; P = 0.007) and a not CRKp-targeted first-line treatment (HR 2.67, 95% CI 1.43-4.99; P = 0.002) were independent factors associated with an increased mortality in allo-SCT patients who developed a CRKp infection. Our study shows challenging findings of CRKp infections in SCT patients in Italy particularly after allo-SCT. The detection of carriers and the definition of early therapeutic strategies represent critical aspects of the management of CRKp infections after SCT. OI Aversa, Franco/0000-0002-8871-6817; de Fabritiis, Paolo/0000-0002-1835-0581; TIRINDELLI, MARIA CRISTINA/0000-0003-4645-4465; cudillo, laura/0000-0002-6828-9707

Published
2015

25. La clinica psicologica. Fondamenti e linee di sviluppo

Author

Fava, G. A., Rafanelli, C., Baldaro, B., Battaglia, M., Caracciolo, S., Carlomagno, S., Casari, E., Dettore, D., Fulcheri, M., Grandi, S., Menoni, E., Michielin, Paolo, Palomba, Daniela, Pruneti, C., Reda, M. A., Rezzonico, G., Strepparava, M. G., Uguzzoni, U., Violani, C., Sirigatti, S., Fava, G, Rafanelli, C, Baldaro, B, Battaglia, M, Caracciolo, S, Carlomagno, S, Casari, E, Dettore, D, Fulcheri, M, Grandi, S, Menoni, E, Michielin, P, Palomba, D, Pruneti, C, Reda, M, Rezzonico, G, Strepparava, M, Uguzzoni, U, Violani, C, Sirigatti, S, GA. Fava, C. Rafanelli, B. Baldaro, M. Battaglia, S. Caracciolo, S. Carlomagno, E. Casari, D. Dettore, M. Fulcheri, S. Grandi, E. Menoni, P. Michielin, D. Palomba, C. Pruneti, MA. Reda, G. Rezzonico, MG. Strepparava, U. Uguzzoni, C. Violani, and S. Sirigatti

Subjects
Psicologia Clinica, Pedagogia Medica, Clinica psicologica, clinica psicologica, psicologia clinica, valutazione, M-PSI/08 - PSICOLOGIA CLINICA
Abstract

La clinica psicologica può essere definita come l’applicazione di strumenti psicologici alla valutazione, con un approccio clinimetrico, anziché psicometrico. La clinica psicologica utilizza l’osservazione, la descrizione e la classificazione; confronta le varie metodiche di registrazione delle osservazioni (etero, auto-valutative, psicofisiologiche, ecc.); formula e testa ipotesi esplicative di natura pragmatica (l’articolazione delle componenti terapeutiche). È legata ad una concezione realistica, e non idealistica della clinica, e ad un concetto dinamico della salute e della malattia. Richiede una profonda conoscenza della clinica, della psicopatologia, della ricerca e della pratica in psicoterapia. Prescinde da rigidi steccati determinati da gruppi di potere ed influenza. Costituisce il naturale presupposto per l’accesso a trattamenti psicoterapeutici basati sull’evidenza nell’ambito della medicina generale e di quella specialistica. È in grado di operare un profondo rinnovamento nella psicologia clinica, che può esercitare importanti influenze anche in altre aree psicologiche, nella psichiatria e nella medicina clinica.

Published
2009

27. La clinica psicologica. Fondamenti e linee di sviluppo

Author

Fava, G., Rafanelli, C., Baldaro, B., Battaglia, M., Caracciolo, S., Carlomagno, S., Casari, E., Dettore, D., Fulcheri, M., Menoni, S. G. r. a. n. d. i. S., Michielini, P., Palomba, D., Pruneti, C., Reda, M., Rezzonico, G., Strepparava, M., Uguzzoni, Ugo, Violani, C., and Sirigatti, S.

Subjects
valutazione clinica, modelli psicometrici, clinica psicologica, clinimetria
Published
2009

30. La clinica psicologica. Fondamenti e linee di sviluppo

Author

Fava, G, Rafanelli, C, Baldaro, B, Battaglia, M, Caracciolo, S, Carlomagno, S, Casari, E, Dettore, D, Fulcheri, M, Grandi, S, Menoni, E, Michielin, P, Palomba, D, Pruneti, C, Reda, M, Rezzonico, G, Strepparava, M, Uguzzoni, U, Violani, C, Sirigatti, S, Fava, GA, Reda, MA, Sirigatti, S., REZZONICO, GIORGIO FRANCO AUGUSTO, STREPPARAVA, MARIA GRAZIA, Fava, G, Rafanelli, C, Baldaro, B, Battaglia, M, Caracciolo, S, Carlomagno, S, Casari, E, Dettore, D, Fulcheri, M, Grandi, S, Menoni, E, Michielin, P, Palomba, D, Pruneti, C, Reda, M, Rezzonico, G, Strepparava, M, Uguzzoni, U, Violani, C, Sirigatti, S, Fava, GA, Reda, MA, Sirigatti, S., REZZONICO, GIORGIO FRANCO AUGUSTO, and STREPPARAVA, MARIA GRAZIA

Abstract

La clinica psicologica può essere definita come l’applicazione di strumenti psicologici alla valutazione, con un approccio clinimetrico, anziché psicometrico. La clinica psicologica utilizza l’osservazione, la descrizione e la classificazione; confronta le varie metodiche di registrazione delle osservazioni (etero, auto-valutative, psicofisiologiche, ecc.); formula e testa ipotesi esplicative di natura pragmatica (l’articolazione delle componenti terapeutiche). È legata ad una concezione realistica, e non idealistica della clinica, e ad un concetto dinamico della salute e della malattia. Richiede una profonda conoscenza della clinica, della psicopatologia, della ricerca e della pratica in psicoterapia. Prescinde da rigidi steccati determinati da gruppi di potere ed influenza. Costituisce il naturale presupposto per l’accesso a trattamenti psicoterapeutici basati sull’evidenza nell’ambito della medicina generale e di quella specialistica. È in grado di operare un profondo rinnovamento nella psicologia clinica, che può esercitare importanti influenze anche in altre aree psicologiche, nella psichiatria e nella medicina clinica.

Published
2009

39. The Impact-on-Family Scale: a test of invariance across culture.

Author

Kolk, Annemarie M., Schipper, Janine L., Hanewald, Gerrit J. F. P., Casari, Ezio F., Fantino, Alga G., Kolk, A M, Schipper, J L, Hanewald, G J, Casari, E F, and Fantino, A G

Subjects
PSYCHOLOGY of mothers, CHRONIC diseases in children
Abstract

Objective: To test the cultural invariance of the Impact-on-Family Scale in order to make cross-cultural comparisons.Methods: The Italian version of the scale was administered to mothers of children with chronic illnesses. Factorial invariance was examined to investigate whether the four factors found with the original United States (U.S.) scale could be replicated.Results: The results clearly demonstrate the replicability of the first three factors, Financial Burden, Familial/Social Impact, and Personal Strain. In addition, internal consistency and the homogeneity of the items of the corresponding scales are satisfactory. However, the fourth factor, Mastery, could not be replicated, and the reliability of the corresponding scale is poor. Italian mothers scored significantly lower on the Financial Burden and on the Familial/Social Impact dimension, compared to the American sample.Conclusions: Three of the four factors of the Impact-on-Family Scale are useful for cross-cultural comparisons between U.S. and Italian samples. [ABSTRACT FROM AUTHOR]

Published
2000
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44. Aspergillus left ventricular assist device endocarditis

Author

Alessandro BARBONE, Pini D, Grossi P, Bandera A, Manasse E, Citterio E, Eusebio A, Silvaggio G, Settepani F, Municinò A, Colombo P, Casari E, Ornaghi D, Gronda E, and Gallotti R

Subjects
Fungal infection, Heart failure, Left ventricular assist device

50. Reducing rates of <italic>Clostridium difficile</italic> infection by switching to a stand-alone NAAT with clear sampling criteria.

Author

Casari, E., De Luca, C., Calabrò, M., Scuderi, C., Daleno, C., and Ferrario, A.

Subjects
CLOSTRIDIOIDES difficile, IMMUNOASSAY, PATIENTS, DIAGNOSIS
Abstract

Background: Clostridium difficile infection is an important cause of morbidity and mortality but the optimal method of diagnosis for both patient management and infection prevention remains controversial. Methods: Our hospital made a decision to switch from the use of toxin immunoassay to a stand-alone nucleic acid test. This change was accompanied by the provision of clear sampling guidance and rejection criteria and this study aimed to assess the impact of that change. We analysed sample numbers, numbers of positive results, and the proportion of cases assessed as healthcare acquired over a 6-year period during which the testing method was changed from a toxin A/B immunoassay to a stand-alone commercial nucleic acid test after the first two years. Results: Sample numbers and numbers of cases assessed as healthcare acquired fell following the introduction of the nucleic acid test and sampling guidance, while infection rates in other hospitals in the same region remained relatively stable. Conclusions: It is our opinion that the use of a highly sensitive assay together with clear sampling guidance offers the optimal approach to patient management and best use of isolation facilities. [ABSTRACT FROM AUTHOR]

Published
2018
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