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2. Extensive activation, tissue trafficking, turnover and functional impairment of NK cells in COVID-19 patients at disease onset associates with subsequent disease severity

Author

Bozzano, F., Dentone, C., Perrone, C., Di Biagio, A., Fenoglio, D., Parodi, A., Mikulska, M., Bruzzone, B., Giacobbe, D. R., Vena, A., Taramasso, L., Nicolini, L., Patroniti, N., Pelosi, P., Gratarola, A., de Palma, R., Filaci, G., Bassetti, M., de Maria, A., Alessandrini, A., Camera, M., Delfino, E., Dodi, F., Ferrazin, A., Mazzarello, G., Toscanini, F., Balletto, E., Portunato, F., Schenone, E., Rosseti, N., Baldi, F., Berruti, M., Briano, F., Dettori, S., Labate, L., Magnasco, L., Mirabella, M., Pincino, R., Russo, C., Sarteschi, G., Sepulcri, C., Tutino, S., Pontremoli, R., Beccati, V., Casciaro, S., Casu, M., Gavaudan, F., Ghinatti, M., Gualco, E., Leoncini, G., Pitto, P., Salam, K., Bixio, M., Amelia, A., Balestra, A., Ballarino, P., Bardi, N., Boccafogli, R., Caserza, F., Calzolari, E., Castelli, M., Cenni, E., Cortese, P., Cuttone, G., Feltrin, S., Giovinazzo, S., Giuntini, P., Natale, L., Orsi, D., Pastorino, M., Perazzo, T., Pescetelli, F., Schenone, F., Serra, M. G., Sottano, M., Brunetti, I., Robba, C., Ball, L., Loconte, M., Battaglini, D., de Rito, M. R., Cerana, M., Fasce, R., Insorsi, A., Molin, A., Tallone, R., Amelotti, M., Majabo, M. J., Merlini, M., Perazzo, F., Ahamd, N., Barbera, P., Bovio, M., Cam-Podonico, P., Collida, A., Cutuli, O., Lomeo, A., Fezza, F., Genti-Lucci, N., Hussein, N., Malvezzi, E., Massobrio, L., Motta, G., Pastorino, L., Pollicardo, N., Sartini, S., Virga, P. V. V., Porto, I., Bezante, G. P., Bona, R. D., Malfa, G. L., Valbusa, A., V. G., Ad, Barisione, E., Bellotti, M., Teresita, A., Blanco, A., Grosso, M., Piroddi, M. G., Moscatelli, P., Caiti, M., Magnani, O., Sukkar, S., Cogorno, L., Gradaschi, R., Guiddo, E., Martino, E., Pisciotta, L., Cavagliere, B., Cristina, R., Francesca, F., Garibotto, G., Esposito, P., Passalacqua, G., Bagnasco, D., Braido, F., Riccio, A., Tagliabue, E., Gustavino, C., Ferraiolo, A., Giuffrida, S., Rosso, N., Morando, A., Papalia, R., Passerini, D., Tiberio, G., Orengo, G., Battaglini, A., Ruffoni, S., and Caglieris, S.

Subjects
RNA viruses, Male, Viral Diseases, Coronaviruses, medicine.medical_treatment, Cytotoxicity, Cell, NK cells, Aged, Aged, 80 and over, COVID-19, Cohort Studies, Female, Flow Cytometry, Humans, Interferon-gamma, Italy, Killer Cells, Natural, Lymphocyte Activation, Middle Aged, Severity of Illness Index, Toxicology, 0302 clinical medicine, Medical Conditions, Spectrum Analysis Techniques, Cellular types, 80 and over, Killer Cells, Lymphocytes, Biology (General), Receptor, Immune Response, Pathology and laboratory medicine, 0303 health sciences, medicine.diagnostic_test, Immune cells, hemic and immune systems, Medical microbiology, Cytokine, medicine.anatomical_structure, Infectious Diseases, Spectrophotometry, Viruses, Natural, White blood cells, Cytophotometry, medicine.symptom, SARS CoV 2, Pathogens, Research Article, Cell biology, Blood cells, SARS coronavirus, Precursor Cells, QH301-705.5, Immunology, Inflammation, chemical and pharmacologic phenomena, Biology, Research and Analysis Methods, Microbiology, Flow cytometry, 03 medical and health sciences, Immune system, Signs and Symptoms, Virology, Genetics, medicine, Molecular Biology, 030304 developmental biology, Medicine and health sciences, Biology and life sciences, Organisms, Viral pathogens, Covid 19, RC581-607, NKG2D, Microbial pathogens, Perforin, Animal cells, biology.protein, Parasitology, Clinical Medicine, Immunologic diseases. Allergy, 030215 immunology
Abstract

The SARS-CoV-2 infection causes severe respiratory involvement (COVID-19) in 5–20% of patients through initial immune derangement, followed by intense cytokine production and vascular leakage. Evidence of immune involvement point to the participation of T, B, and NK cells in the lack of control of virus replication leading to COVID-19. NK cells contribute to early phases of virus control and to the regulation of adaptive responses. The precise mechanism of NK cell dysregulation is poorly understood, with little information on tissue margination or turnover. We investigated these aspects by multiparameter flow cytometry in a cohort of 28 patients hospitalized with early COVID-19. Relevant decreases in CD56brightCD16+/- NK subsets were detected, with a shift of circulating NK cells toward more mature CD56dimCD16+KIR+NKG2A+ and “memory” KIR+CD57+CD85j+ cells with increased inhibitory NKG2A and KIR molecules. Impaired cytotoxicity and IFN-γ production were associated with conserved expression of natural cytotoxicity receptors and perforin. Moreover, intense NK cell activation with increased HLA-DR and CD69 expression was associated with the circulation of CD69+CD103+ CXCR6+ tissue-resident NK cells and of CD34+DNAM-1brightCXCR4+ inflammatory precursors to mature functional NK cells. Severe disease trajectories were directly associated with the proportion of CD34+DNAM-1brightCXCR4+ precursors and inversely associated with the proportion of NKG2D+ and of CD103+ NK cells. Intense NK cell activation and trafficking to and from tissues occurs early in COVID-19, and is associated with subsequent disease progression, providing an insight into the mechanism of clinical deterioration. Strategies to positively manipulate tissue-resident NK cell responses may provide advantages to future therapeutic and vaccine approaches., Author summary This is a detailed study of activating and inhibitory receptors in NK cells of COVID-19 patients when first admitted to the hospital for respiratory insufficiency. NK cells are known to be the first line of defense against invading viruses, and regulate downstream B and T cell responses, including antibody production. We observed intense NK cell activation with decreased functional activity, as well as intense circulation of putative tissue resident CD69+CD103+CXCR6+ NK cells, with a related surge in inflammatory CD34+ precursors from the bone marrow. The findings suggest that there is unprecedented trafficking of NK cells from peripheral tissues, their increased death with recruitment of emergency precursors from the bone marrow, and a relationship with the subsequent course of the disease of the patients. This in turn suggests possible areas of treatment and prevention.

Published
2021

3. The role of the intensive care unit in real-time surveillance of emerging pandemics: the Italian GiViTI experience

Author

Bertolini, G, Nattino, G, Langer, M, Tavola, M, Crespi, D, Mondini, M, Rossi, C, Previtali, C, Marshall, J, Poole, D, Abascià, A, Acquarolo, A, Adorni, A, Agnelli, V, Agostini, F, Alampi, D, Alberti, A, Alborghetti, A, Alleva, S, Ambrosoni, S, Antonini, B, Arditi, E, Avalli, L, Babini, M, Bagalini, G, Balata, A, Balicco, B, Barbagallo, M, Bartoli, T, Bassi, G, Becarelli, S, Beck, E, Bellin, M, Bellonzi, A, Bellorini, M, Benanti, C, Bensi, M, Bernasconi, Mo, Berruto, F, Bertolini, R, Besozzi, A, Biamino, C, Bianchi, T, Bianchin, A, Boccalatte, D, Bocchi, A, Bonaccorso, G, Bonazzi, M, Balsamo, C, Bonicalzi, V, Boniotti, C, Bonizzoli, M, Bottazzi, A, Breschi, C, Brizio, E, Brunetti, B, Brunori, E, Bubbico, G, Buscaglia, G, Calicchio, G, Calligaro, P, Calva, S, Candido, M, Capitanio, G, Caroleo, S, Casagli, S, Casalini, P, Castiglione, G, Cerana, M, Chiani, C, Chierego, G, Ciani, A, Ciceri, R, Cigada, Mg, Cima, M, Cingolani, E, Cinque, E, Coletta, Rp, Colombo, L, Colombo, R, Converso, M, Corrado, A, Cortis, G, Costagli, V, Crema, L, Crestan, E, Da, D, Cero, Pd, Ferro, Md, De Blasi RA, De Blasio, E, De Cristofaro MG, De Luca, A, Di Pasquale, D, Doroni, L, Fabi, Mc, Facondini, F, Fagoni, Nazzareno, Falzetti, G, Faraldi, L, Fiore, G, Fiume, C, Galeotti, E, Galleschi, N, Gallo, M, Gamberini, E, Garelli, A, Giacomello, S, Gianni, M, Giudici, R, Giuntini, R, Gnesin, P, Gorietti, A, Grassitelli, S, Greco, M, Irpino, A, Guadagna, A, Guadagnucci, A, Guagliardi, C, Laici, C, Lain, G, Lanza, G, Lefons, U, Leggieri, C, Lembo, R, Librenti, M, Liverani, C, Longobardo, A, Madeira, Sm, Madonna, R, Magatti, Mf, Mamprin, F, Mannolini, G, Marafon, S, Marchesi, G, Marifoglou, D, Martinelli, P, Martinelli, S, Escobar, Rm, Mastroianni, A, Mastropierro, R, Mediani, Ts, Messina, M, Milan, B, Molesi, A, Alberto, Cm, Mongelli, P, Morigi, A, Mosti, G, Muttini, S, Nardini, M, Nascimben, E, Natalini, G, Negri, G, Negro, G, Neri, M, Netto, R, Nonini, S, Odetto, L, Olivieri, C, Candida, Mo, Osti, D, Palmer, M, Parnigotto, A, Parrini, V, Pasculli, M, Pasetti, G, Passafiume, M, Pastorini, S, Patrignani, L, Pedeferri, M, Pegoraro, M, Pelati, E, Pelosi, G, Pera, L, Perino, P, Pero, A, Perzolla, D, Peta, M, Pinna, C, Pizzali, M, Postiglione, M, Potalivo, A, Raffaeli, M, Randellini, R, Rech, A, Renda, B, Ricciardi, G, Rizzi, S, Romagnoli, S, Rossi, G, Rossi, M, Rutta, C, Sagliaschi, U, Salcuni, R, Salvi, G, Scalera, M, Scarrone, S, Schiavuzzi, M, Aurelio, Ps, Selvaggi, P, Sicignano, A, Sorbara, C, Spagarino, E, Sparicio, D, Spinazzola, Ar, Sucre, Mj, Terzitta, M, Tetamo, R, Tibaldi, G, Todesco, L, Tomaselli, P, Torta, M, Turriziani, I, Ughi, L, Vaccari, C, Vaj, M, Vanzino, R, Vardanega, A, Vecchiarelli, P, Vedovati, S, Zanni, V, Zappa, S, Zardin, M, Zaro, G, Zuccaro, F, Barattini, M, Chieregato, A, Fumagalli, R, Livigni, S, Mengoli, F, Nardi, G, Palma, D, Portolani, L, Radrizzani, D, Terzitta, M., Bertolini, G, Nattino, G, Langer, M, Tavola, M, Crespi, D, Mondini, M, Rossi, C, Previtali, C, Marshall, J, Poole, D, Abascia, A, Acquarolo, A, Adorni, A, Agnelli, V, Agostini, F, Alampi, D, Alberti, A, Alborghetti, A, Alleva, S, Ambrosoni, S, Antonini, B, Arditi, E, Avalli, L, Babini, M, Bagalini, G, Balata, A, Balicco, B, Barbagallo, M, Bartoli, T, Bassi, G, Becarelli, S, Beck, E, Bellin, M, Bellonzi, A, Bellorini, M, Benanti, C, Bensi, M, Bernasconi, M, Berruto, F, Besozzi, A, Biamino, C, Bianchi, T, Bianchin, A, Boccalatte, D, Bocchi, A, Bonaccorso, G, Bonazzi, M, Balsamo, C, Bonicalzi, V, Boniotti, C, Bonizzoli, M, Bottazzi, A, Breschi, C, Brizio, E, Brunetti, B, Brunori, E, Bubbico, G, Buscaglia, G, Calicchio, G, Calligaro, P, Calva, S, Candido, M, Capitanio, G, Caroleo, S, Casagli, S, Casalini, P, Castiglione, G, Cerana, M, Chiani, C, Chierego, G, Ciani, A, Ciceri, R, Cigada, M, Cima, M, Cingolani, E, Cinque, E, Coletta, R, Colombo, L, Colombo, R, Converso, M, Corrado, A, Cortis, G, Costagli, V, Crema, L, Crestan, E, Da, D, Cero, P, Ferro, M, De Blasi, R, De Blasio, E, De Cristofaro, M, De Luca, A, Di Pasquale, D, Doroni, L, Fabi, M, Facondini, F, Fagoni, N, Falzetti, G, Faraldi, L, Fiore, G, Fiume, C, Galeotti, E, Galleschi, N, Gallo, M, Gamberini, E, Garelli, A, Giacomello, S, Gianni, M, Giudici, R, Giuntini, R, Gnesin, P, Gorietti, A, Grassitelli, S, Greco, M, Irpino, A, Guadagna, A, Guadagnucci, A, Guagliardi, C, Laici, C, Lain, G, Lanza, G, Lefons, U, Leggieri, C, Lembo, R, Librenti, M, Liverani, C, Longobardo, A, Madeira, S, Madonna, R, Magatti, M, Mamprin, F, Mannolini, G, Marafon, S, Marchesi, G, Marifoglou, D, Martinelli, P, Martinelli, S, Escobar, R, Mastroianni, A, Mastropierro, R, Mediani, T, Messina, M, Milan, B, Molesi, A, Alberto, C, Mongelli, P, Morigi, A, Mosti, G, Muttini, S, Nardini, M, Nascimben, E, Natalini, G, Negri, G, Negro, G, Neri, M, Netto, R, Nonini, S, Odetto, L, Olivieri, C, Candida, M, Osti, D, Palmer, M, Parnigotto, A, Parrini, V, Pasculli, M, Pasetti, G, Passafiume, M, Pastorini, S, Patrignani, L, Pedeferri, M, Pegoraro, M, Pelati, E, Pelosi, G, Pera, L, Perino, P, Pero, A, Perzolla, D, Peta, M, Pinna, C, Pizzali, M, Postiglione, M, Potalivo, A, Raffaeli, M, Randellini, R, Rech, A, Renda, B, Ricciardi, G, Rizzi, S, Romagnoli, S, Rossi, G, Rossi, M, Rutta, C, Sagliaschi, U, Salcuni, R, Salvi, G, Scalera, M, Scarrone, S, Schiavuzzi, M, Aurelio, P, Selvaggi, P, Sicignano, A, Sorbara, C, Spagarino, E, Sparicio, D, Spinazzola, A, Sucre, M, Terzitta, M, Tetamo, R, Tibaldi, G, Todesco, L, Tomaselli, P, Torta, M, Turriziani, I, Ughi, L, Vaccari, C, Vaj, M, Vanzino, R, Vardanega, A, Vecchiarelli, P, Vedovati, S, Zanni, V, Zappa, S, Zardin, M, Zaro, G, Zuccaro, F, Barattini, M, Chieregato, A, Fumagalli, R, Livigni, S, Mengoli, F, Nardi, G, Palma, D, Portolani, L, and Radrizzani, D

Subjects
medicine.medical_specialty, Epidemiology, surveillance system, law.invention, 03 medical and health sciences, Influenza A Virus, H1N1 Subtype, 0302 clinical medicine, Public health surveillance, law, Infectious disease epidemiology, influenza, pandemic, Humans, Influenza, Human, Intensive Care Units, Italy, Public Health Surveillance, Pandemics, Pandemic, medicine, human, 030212 general & internal medicine, medicine (all), Intensive care medicine, business.industry, Public health, Outbreak, 030208 emergency & critical care medicine, Monitoring system, medicine.disease, Intensive care unit, infectious disease epidemiology, humans, influenza a virus, h1n1 subtype, intensive care units, italy, public health surveillance, pandemics, infectious diseases, epidemiology, Infectious Diseases, Human mortality from H5N1, Medical emergency, business
Abstract

SUMMARYThe prompt availability of reliable epidemiological information on emerging pandemics is crucial for public health policy-makers. Early in 2013, a possible new H1N1 epidemic notified by an intensive care unit (ICU) to GiViTI, the Italian ICU network, prompted the re-activation of the real-time monitoring system developed during the 2009–2010 pandemic. Based on data from 216 ICUs, we were able to detect and monitor an outbreak of severe H1N1 infection, and to compare the situation with previous years. The timely and correct assessment of the severity of an epidemic can be obtained by investigating ICU admissions, especially when historical comparisons can be made.

Published
2015
Full Text
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4. The role of the intensive care unit in real-time surveillance of emerging pandemics: The Italian GiViTI experience

Author

Bertolini, G, Nattino, G, Langer, M, Tavola, M, Crespi, D, Mondini, M, Rossi, C, Previtali, C, Marshall, J, Poole, D, Abascia, A, Acquarolo, A, Adorni, A, Agnelli, V, Agostini, F, Alampi, D, Alberti, A, Alborghetti, A, Alleva, S, Ambrosoni, S, Antonini, B, Arditi, E, Avalli, L, Babini, M, Bagalini, G, Balata, A, Balicco, B, Barbagallo, M, Bartoli, T, Bassi, G, Becarelli, S, Beck, E, Bellin, M, Bellonzi, A, Bellorini, M, Benanti, C, Bensi, M, Bernasconi, M, Berruto, F, Besozzi, A, Biamino, C, Bianchi, T, Bianchin, A, Boccalatte, D, Bocchi, A, Bonaccorso, G, Bonazzi, M, Balsamo, C, Bonicalzi, V, Boniotti, C, Bonizzoli, M, Bottazzi, A, Breschi, C, Brizio, E, Brunetti, B, Brunori, E, Bubbico, G, Buscaglia, G, Calicchio, G, Calligaro, P, Calva, S, Candido, M, Capitanio, G, Caroleo, S, Casagli, S, Casalini, P, Castiglione, G, Cerana, M, Chiani, C, Chierego, G, Ciani, A, Ciceri, R, Cigada, M, Cima, M, Cingolani, E, Cinque, E, Coletta, R, Colombo, L, Colombo, R, Converso, M, Corrado, A, Cortis, G, Costagli, V, Crema, L, Crestan, E, Da, D, Cero, P, Ferro, M, De Blasi, R, De Blasio, E, De Cristofaro, M, De Luca, A, Di Pasquale, D, Doroni, L, Fabi, M, Facondini, F, Fagoni, N, Falzetti, G, Faraldi, L, Fiore, G, Fiume, C, Galeotti, E, Galleschi, N, Gallo, M, Gamberini, E, Garelli, A, Giacomello, S, Gianni, M, Giudici, R, Giuntini, R, Gnesin, P, Gorietti, A, Grassitelli, S, Greco, M, Irpino, A, Guadagna, A, Guadagnucci, A, Guagliardi, C, Laici, C, Lain, G, Lanza, G, Lefons, U, Leggieri, C, Lembo, R, Librenti, M, Liverani, C, Longobardo, A, Madeira, S, Madonna, R, Magatti, M, Mamprin, F, Mannolini, G, Marafon, S, Marchesi, G, Marifoglou, D, Martinelli, P, Martinelli, S, Escobar, R, Mastroianni, A, Mastropierro, R, Mediani, T, Messina, M, Milan, B, Molesi, A, Alberto, C, Mongelli, P, Morigi, A, Mosti, G, Muttini, S, Nardini, M, Nascimben, E, Natalini, G, Negri, G, Negro, G, Neri, M, Netto, R, Nonini, S, Odetto, L, Olivieri, C, Candida, M, Osti, D, Palmer, M, Parnigotto, A, Parrini, V, Pasculli, M, Pasetti, G, Passafiume, M, Pastorini, S, Patrignani, L, Pedeferri, M, Pegoraro, M, Pelati, E, Pelosi, G, Pera, L, Perino, P, Pero, A, Perzolla, D, Peta, M, Pinna, C, Pizzali, M, Postiglione, M, Potalivo, A, Raffaeli, M, Randellini, R, Rech, A, Renda, B, Ricciardi, G, Rizzi, S, Romagnoli, S, Rossi, G, Rossi, M, Rutta, C, Sagliaschi, U, Salcuni, R, Salvi, G, Scalera, M, Scarrone, S, Schiavuzzi, M, Aurelio, P, Selvaggi, P, Sicignano, A, Sorbara, C, Spagarino, E, Sparicio, D, Spinazzola, A, Sucre, M, Terzitta, M, Tetamo, R, Tibaldi, G, Todesco, L, Tomaselli, P, Torta, M, Turriziani, I, Ughi, L, Vaccari, C, Vaj, M, Vanzino, R, Vardanega, A, Vecchiarelli, P, Vedovati, S, Zanni, V, Zappa, S, Zardin, M, Zaro, G, Zuccaro, F, Barattini, M, Chieregato, A, Fumagalli, R, Livigni, S, Mengoli, F, Nardi, G, Palma, D, Portolani, L, Radrizzani, D, Bertolini G., Nattino G., Langer M., Tavola M., Crespi D., Mondini M., Rossi C., Previtali C., Marshall J., Poole D., Abascia A., Acquarolo A., Adorni A., Agnelli V., Agostini F., Alampi D., Alberti A., Alborghetti A., Alleva S., Ambrosoni S., Antonini B., Arditi E., Avalli L., Babini M., Bagalini G., Balata A., Balicco B., Barbagallo M., Bartoli T., Bassi G., Becarelli S., Beck E., Bellin M., Bellonzi A., Bellorini M., Benanti C., Bensi M., Bernasconi M. O., Berruto F., Besozzi A., Biamino C., Bianchi T., Bianchin A., Boccalatte D., Bocchi A., Bonaccorso G., Bonazzi M., Balsamo C., Bonicalzi V., Boniotti C., Bonizzoli M., Bottazzi A., Breschi C., Brizio E., Brunetti B., Brunori E., Bubbico G., Buscaglia G., Calicchio G., Calligaro P., Calva S., Candido M., Capitanio G., Caroleo S., Casagli S., Casalini P., Castiglione G., Cerana M., Chiani C., Chierego G., Ciani A., Ciceri R., Cigada M. G., Cima M., Cingolani E., Cinque E., Coletta R. P., Colombo L., Colombo R., Converso M., Corrado A., Cortis G., Costagli V., Crema L., Crestan E., Da D., Cero P. D., Ferro M. D., De Blasi R. A., De Blasio E., De Cristofaro M. G., De Luca A., Di Pasquale D., Doroni L., Fabi M. C., Facondini F., Fagoni N., Falzetti G., Faraldi L., Fiore G., Fiume C., Galeotti E., Galleschi N., Gallo M., Gamberini E., Garelli A., Giacomello S., Gianni M., Giudici R., Giuntini R., Gnesin P., Gorietti A., Grassitelli S., Greco M., Irpino A., Guadagna A., Guadagnucci A., Guagliardi C., Laici C., Lain G., Lanza G., Lefons U., Leggieri C., Lembo R., Librenti M., Liverani C., Longobardo A., Madeira S. M., Madonna R., Magatti M. F., Mamprin F., Mannolini G., Marafon S., Marchesi G., Marifoglou D., Martinelli P., Martinelli S., Escobar R. M., Mastroianni A., Mastropierro R., Mediani T. S., Messina M., Milan B., Molesi A., Alberto C. M., Mongelli P., Morigi A., Mosti G., Muttini S., Nardini M., Nascimben E., Natalini G., Negri G., Negro G., Neri M., Netto R., Nonini S., Odetto L., Olivieri C., Candida M. O., Osti D., Palmer M., Parnigotto A., Parrini V., Pasculli M., Pasetti G., Passafiume M., Pastorini S., Patrignani L., Pedeferri M., Pegoraro M., Pelati E., Pelosi G., Pera L., Perino P., Pero A., Perzolla D., Peta M., Pinna C., Pizzali M., Postiglione M., Potalivo A., Raffaeli M., Randellini R., Rech A., Renda B., Ricciardi G., Rizzi S., Romagnoli S., Rossi G., Rossi M., Rutta C., Sagliaschi U., Salcuni R., Salvi G., Scalera M., Scarrone S., Schiavuzzi M., Aurelio P. S., Selvaggi P., Sicignano A., Sorbara C., Spagarino E., Sparicio D., Spinazzola A. R., Sucre M. J., Terzitta M., Tetamo R., Tibaldi G., Todesco L., Tomaselli P., Torta M., Turriziani I., Ughi L., Vaccari C., Vaj M., Vanzino R., Vardanega A., Vecchiarelli P., Vedovati S., Zanni V., Zappa S., Zardin M., Zaro G., Zuccaro F., Barattini M., Chieregato A., Fumagalli R., Livigni S., Mengoli F., Nardi G., Palma D., Portolani L., Radrizzani D., Bertolini, G, Nattino, G, Langer, M, Tavola, M, Crespi, D, Mondini, M, Rossi, C, Previtali, C, Marshall, J, Poole, D, Abascia, A, Acquarolo, A, Adorni, A, Agnelli, V, Agostini, F, Alampi, D, Alberti, A, Alborghetti, A, Alleva, S, Ambrosoni, S, Antonini, B, Arditi, E, Avalli, L, Babini, M, Bagalini, G, Balata, A, Balicco, B, Barbagallo, M, Bartoli, T, Bassi, G, Becarelli, S, Beck, E, Bellin, M, Bellonzi, A, Bellorini, M, Benanti, C, Bensi, M, Bernasconi, M, Berruto, F, Besozzi, A, Biamino, C, Bianchi, T, Bianchin, A, Boccalatte, D, Bocchi, A, Bonaccorso, G, Bonazzi, M, Balsamo, C, Bonicalzi, V, Boniotti, C, Bonizzoli, M, Bottazzi, A, Breschi, C, Brizio, E, Brunetti, B, Brunori, E, Bubbico, G, Buscaglia, G, Calicchio, G, Calligaro, P, Calva, S, Candido, M, Capitanio, G, Caroleo, S, Casagli, S, Casalini, P, Castiglione, G, Cerana, M, Chiani, C, Chierego, G, Ciani, A, Ciceri, R, Cigada, M, Cima, M, Cingolani, E, Cinque, E, Coletta, R, Colombo, L, Colombo, R, Converso, M, Corrado, A, Cortis, G, Costagli, V, Crema, L, Crestan, E, Da, D, Cero, P, Ferro, M, De Blasi, R, De Blasio, E, De Cristofaro, M, De Luca, A, Di Pasquale, D, Doroni, L, Fabi, M, Facondini, F, Fagoni, N, Falzetti, G, Faraldi, L, Fiore, G, Fiume, C, Galeotti, E, Galleschi, N, Gallo, M, Gamberini, E, Garelli, A, Giacomello, S, Gianni, M, Giudici, R, Giuntini, R, Gnesin, P, Gorietti, A, Grassitelli, S, Greco, M, Irpino, A, Guadagna, A, Guadagnucci, A, Guagliardi, C, Laici, C, Lain, G, Lanza, G, Lefons, U, Leggieri, C, Lembo, R, Librenti, M, Liverani, C, Longobardo, A, Madeira, S, Madonna, R, Magatti, M, Mamprin, F, Mannolini, G, Marafon, S, Marchesi, G, Marifoglou, D, Martinelli, P, Martinelli, S, Escobar, R, Mastroianni, A, Mastropierro, R, Mediani, T, Messina, M, Milan, B, Molesi, A, Alberto, C, Mongelli, P, Morigi, A, Mosti, G, Muttini, S, Nardini, M, Nascimben, E, Natalini, G, Negri, G, Negro, G, Neri, M, Netto, R, Nonini, S, Odetto, L, Olivieri, C, Candida, M, Osti, D, Palmer, M, Parnigotto, A, Parrini, V, Pasculli, M, Pasetti, G, Passafiume, M, Pastorini, S, Patrignani, L, Pedeferri, M, Pegoraro, M, Pelati, E, Pelosi, G, Pera, L, Perino, P, Pero, A, Perzolla, D, Peta, M, Pinna, C, Pizzali, M, Postiglione, M, Potalivo, A, Raffaeli, M, Randellini, R, Rech, A, Renda, B, Ricciardi, G, Rizzi, S, Romagnoli, S, Rossi, G, Rossi, M, Rutta, C, Sagliaschi, U, Salcuni, R, Salvi, G, Scalera, M, Scarrone, S, Schiavuzzi, M, Aurelio, P, Selvaggi, P, Sicignano, A, Sorbara, C, Spagarino, E, Sparicio, D, Spinazzola, A, Sucre, M, Terzitta, M, Tetamo, R, Tibaldi, G, Todesco, L, Tomaselli, P, Torta, M, Turriziani, I, Ughi, L, Vaccari, C, Vaj, M, Vanzino, R, Vardanega, A, Vecchiarelli, P, Vedovati, S, Zanni, V, Zappa, S, Zardin, M, Zaro, G, Zuccaro, F, Barattini, M, Chieregato, A, Fumagalli, R, Livigni, S, Mengoli, F, Nardi, G, Palma, D, Portolani, L, Radrizzani, D, Bertolini G., Nattino G., Langer M., Tavola M., Crespi D., Mondini M., Rossi C., Previtali C., Marshall J., Poole D., Abascia A., Acquarolo A., Adorni A., Agnelli V., Agostini F., Alampi D., Alberti A., Alborghetti A., Alleva S., Ambrosoni S., Antonini B., Arditi E., Avalli L., Babini M., Bagalini G., Balata A., Balicco B., Barbagallo M., Bartoli T., Bassi G., Becarelli S., Beck E., Bellin M., Bellonzi A., Bellorini M., Benanti C., Bensi M., Bernasconi M. O., Berruto F., Besozzi A., Biamino C., Bianchi T., Bianchin A., Boccalatte D., Bocchi A., Bonaccorso G., Bonazzi M., Balsamo C., Bonicalzi V., Boniotti C., Bonizzoli M., Bottazzi A., Breschi C., Brizio E., Brunetti B., Brunori E., Bubbico G., Buscaglia G., Calicchio G., Calligaro P., Calva S., Candido M., Capitanio G., Caroleo S., Casagli S., Casalini P., Castiglione G., Cerana M., Chiani C., Chierego G., Ciani A., Ciceri R., Cigada M. G., Cima M., Cingolani E., Cinque E., Coletta R. P., Colombo L., Colombo R., Converso M., Corrado A., Cortis G., Costagli V., Crema L., Crestan E., Da D., Cero P. D., Ferro M. D., De Blasi R. A., De Blasio E., De Cristofaro M. G., De Luca A., Di Pasquale D., Doroni L., Fabi M. C., Facondini F., Fagoni N., Falzetti G., Faraldi L., Fiore G., Fiume C., Galeotti E., Galleschi N., Gallo M., Gamberini E., Garelli A., Giacomello S., Gianni M., Giudici R., Giuntini R., Gnesin P., Gorietti A., Grassitelli S., Greco M., Irpino A., Guadagna A., Guadagnucci A., Guagliardi C., Laici C., Lain G., Lanza G., Lefons U., Leggieri C., Lembo R., Librenti M., Liverani C., Longobardo A., Madeira S. M., Madonna R., Magatti M. F., Mamprin F., Mannolini G., Marafon S., Marchesi G., Marifoglou D., Martinelli P., Martinelli S., Escobar R. M., Mastroianni A., Mastropierro R., Mediani T. S., Messina M., Milan B., Molesi A., Alberto C. M., Mongelli P., Morigi A., Mosti G., Muttini S., Nardini M., Nascimben E., Natalini G., Negri G., Negro G., Neri M., Netto R., Nonini S., Odetto L., Olivieri C., Candida M. O., Osti D., Palmer M., Parnigotto A., Parrini V., Pasculli M., Pasetti G., Passafiume M., Pastorini S., Patrignani L., Pedeferri M., Pegoraro M., Pelati E., Pelosi G., Pera L., Perino P., Pero A., Perzolla D., Peta M., Pinna C., Pizzali M., Postiglione M., Potalivo A., Raffaeli M., Randellini R., Rech A., Renda B., Ricciardi G., Rizzi S., Romagnoli S., Rossi G., Rossi M., Rutta C., Sagliaschi U., Salcuni R., Salvi G., Scalera M., Scarrone S., Schiavuzzi M., Aurelio P. S., Selvaggi P., Sicignano A., Sorbara C., Spagarino E., Sparicio D., Spinazzola A. R., Sucre M. J., Terzitta M., Tetamo R., Tibaldi G., Todesco L., Tomaselli P., Torta M., Turriziani I., Ughi L., Vaccari C., Vaj M., Vanzino R., Vardanega A., Vecchiarelli P., Vedovati S., Zanni V., Zappa S., Zardin M., Zaro G., Zuccaro F., Barattini M., Chieregato A., Fumagalli R., Livigni S., Mengoli F., Nardi G., Palma D., Portolani L., and Radrizzani D.

Abstract

The prompt availability of reliable epidemiological information on emerging pandemics is crucial for public health policy-makers. Early in 2013, a possible new H1N1 epidemic notified by an intensive care unit (ICU) to GiViTI, the Italian ICU network, prompted the re-activation of the real-time monitoring system developed during the 2009-2010 pandemic. Based on data from 216 ICUs, we were able to detect and monitor an outbreak of severe H1N1 infection, and to compare the situation with previous years. The timely and correct assessment of the severity of an epidemic can be obtained by investigating ICU admissions, especially when historical comparisons can be made.

Published
2016

5. The prognostic importance of chronic end-stage diseases in geriatric patients admitted to 163 Italian ICUs

Author

Poole, D., Finazzi, S., Nattino, G., Radrizzani, D., Gristina, G., Malacarne, P., Livigni, S., Bertolini, G., Sorgato, C., Mannoni, R., Agnelli, V., Chiani, C., Lanza, G., Venturini, E., Gianni, M., Olivieri, M. C., Guerriero, B., Della Mora, E., Palmer, M., Blasetti, A., Coletta, R., Covani Frigieri, F., Guarducci, M. D., Caracciolo, A., Lain, G., Bernard, M., DE Blasio, E., Zanni, V., Marchesi, G., Madeira, S. M., Spagarino, E., Potalivo, A., Mengoli, F., Parrini, V., Sagliaschi, U., Prandini, A., Rosano, A., Natalini, G., Piccioni, G., Schiavuzzi, M., Bronzini, N., Piva, S., Besozzi, A., Napoleone, A., Patrignani, L., Pisu, M., Mancosu, S., Chiarello, M., Pastorini, S., Bassi, G., Negro, G., Orsini, I., Marifoglou, D., Pota, V., Pegoraro, M., Sucre, M. J., DI Masi, P., Castiglione, G., Morello, G., Garofalo, G., Caroleo, S., Visconti, M. G., Gamberini, E., Mastroianni, A., Liccardi, M. M., Anelati, D., Martinelli, S., Bonato, A., Adorni, A., Colombo, D., Dal Cero, P., Crema, L., Petrucci, N., Beck, E., Alleva, S., Giuntini, R., DA Re, D., Casalini, P., Fabi, M. C., Galeotti, E., Bagalini, G., Bellonzi, A., Zoppellari, R., Lamborghini, S., Pera, L., Doni, L., Bonizzoli, M., Librenti, M., Barattini, M., Mangani, V., Terzitta, M., Guagliardi, C., Bruzzone, C., Arditi, E., Cerana, M., Tavola, M., Falini, S., Vespignani, M. G., Salvi, G., Ramello, P. L., Molesi, A., Ceradelli, M., Buonanno, R., Righini, E., DI Cocco, A., DI Martino, R., Cinque, E., Bonfiglio, M., Ciceri, R., Colombo, L., Nardini, M., Rossi, G., Boccalatte-Rosa, D. L., Babini, M., Zompanti, V., Negri, G., Antonini, B., Baratta, A., Zuccaro, F., Rossi, M., Pedeferri, M., Bellin, M., Sicignano, A., Pezzi, A., Leggieri, C., Fontana, G., Faraldi, L., Cigada, M. G., Magenta, P., Colombo, R., Colombo, S., Gonzi, S., Pizzali, M., Girardis, M., Piccinini, P., Bignone, P., Padovan, L., Bianchin, A., Caria, F. C., Randellini, R., Roticiani, V., Grassi, M., Belluomo Anello, C., Decristofaro, M., Postiglione, M., Giacomello, S., Olivieri, C., Vaccari, C., Dal Ferro, M., Messina, M., Belgiorno, N., Odetto, L., Pasetti, G. S., Balicco, B., Pizzaballa, M. L., Muraro, L., Pignataro, A., Guadagna, A., Fabbri, P. G., Tetamo, R., Bottazzi, A., Mediani, T. S., Gorietti, A., Breschi, C., Ciani, A., Segalini, P., Codeluppi, V., Berruto, F., Pastorelli, M., Comite, C., Pelati, E., Bertolini, R., Lefons, U., DI Pasquale, D. A., Mannolini, G., Vlassich, F., Becarelli, S., Garelli, A., Salsi, P., Rossi, S., Facondini, F., Alampi, D., Cingolani, E., Molino, F. M., Nardi, G., Casula, M., DE Blasi, R. A., Vulcano, G. A., Azzolini, M., Bernasconi, M. O., Bellato, V., Calicchio, G., Righetti, F., Turati, M., Dei Poli, M., Zaro, G., Brizio, E., Coaloa, M., Falzetti, G., Mamprin, F., Liverani, C. M., Clementi, S., Bonucci, P., Varesio, V., Pannacci, R., Fiore, G., Gallo, M., Torta, M., Selvaggi, P., Bert, P. P., Segala, V., Pettazzi, G., Bensi, M., Bocchi, A., Cima, M., Morbelli, M., Peta, M., DI Stella, R., Maggiolo, C., Lembo, R., Pero, A., Marafon, S., Carnevale, L., Vanzino, R., Vecchiarelli, P., and Marino, G.

Subjects
Male, medicine.medical_specialty, Cirrhosis, Disease, Severity of Illness Index, law.invention, 03 medical and health sciences, 0302 clinical medicine, Patient Admission, Postoperative Complications, law, Internal medicine, 80 and over, aged, critical care, prognosis, Medicine, Dementia, Humans, Hospital Mortality, Elective surgery, Aged, Retrospective Studies, Aged, 80 and over, business.industry, Critical care, Prognosis, Female, Intensive Care Units, Italy, Chronic Disease, 030208 emergency & critical care medicine, Odds ratio, medicine.disease, Comorbidity, Intensive care unit, Anesthesiology and Pain Medicine, 030228 respiratory system, Cohort, business
Abstract

BACKGROUND The number of elderly patients undergoing major surgical interventions and then needing admission to intensive care unit (ICU) grows steadily. We investigated this issue in a cohort of 232,278 patients admitted in five years (2011-2015) to 163 Italian general ICUs. METHODS Surgical patients older than 75 registered in the GiViTI MargheritaPROSAFE project were analyzed. The impact on hospital mortality of important chronic conditions (severe COPD, NYHA class IV, dementia, end-stage renal disease, cirrhosis with portal hypertension) was investigated with two prognostic models developed yearly on patients staying in the ICU less or more than 24 hours. RESULTS 44,551 elderly patients (19.2%) underwent emergency (47.3%) or elective surgery (52.7%). At least one severe comorbidity was present in 14.6% of them, yielding a higher hospital mortality (32.4%, vs. 21.1% without severe comorbidity). In the models for patients staying in the ICU 24 hours or more, cirrhosis, NYHA class IV, and severe COPD were constant independent predictors of death (adjusted odds ratios [ORs] range 1.67-1.97, 1.54-1.91, and 1.34-1.50, respectively), while dementia was statistically significant in four out of five models (adjusted ORs 1.23-1.28). End-stage renal disease, instead, never resulted to be an independent prognostic factor. For patients staying in the ICU less than 24 hours, chronic comorbidities were only occasionally independent predictors of death. CONCLUSIONS Our study confirms that elderly surgical patients represent a relevant part of all ICUs admissions. About one of seven bear at least one severe chronic comorbidity, that, excluding end-stage renal disease, are all strong independent predictors of hospital death.

Published
2017

14. Involvement of the Plasma Membrane Ca2+‐ATPase in the Short‐Term Response of Arabidopsis thalianaCultured Cells to Oligogalacturonides

Author

Romani, G., Bonza, M. C., Filippini, I., Cerana, M., Beffagna, N., and Michelis, M. I.

Abstract

Abstract: Treatment of Arabidopsis thalianacells with oligogalacturonides (OG) initiates a transient production of reactive oxygen species (ROS), the concentration of which in the medium peaks after about 20 min of treatment. The analysis of OG effects on Ca2+fluxes shows that OG influence both Ca2+influx and Ca2+efflux (measured as 45Ca2+fluxes) in a complex way. During the first 10 ‐ 15 min, OG stimulate Ca2+influx and decrease its efflux, while at successive times of treatment, OG cause an increase of Ca2+efflux and a slight decrease of its influx. Treatment with sub‐μM concentrations of eosin yellow (EY), which selectively inhibits the Ca2+‐ATPase of plasma membrane (PM), completely prevents the OG‐induced increase in Ca2+efflux. EY also suppresses the transient feature of OG‐induced ROS accumulation, keeping the level of ROS in the medium high. The biochemical analysis of PM purified from OG‐treated cells indicates that treatment with OG for 15 to 45 min induces a significant decrease in Ca2+‐ATPase activation by exogenous calmodulin (CaM), and markedly increases the amount of CaM associated with the PM. During the same time span, OG do not influence the expression of At‐ACA8, the main isoform of PM Ca2+‐ATPase in suspension‐cultured A. thalianacells, and of CaM genes. Overall, the reported results demonstrate that the PM Ca2+‐ATPase is involved in the response of plant cells to OG and is essential in regulation of the oxidative burst.

Published
2004
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16. Mortality and long-term quality of life after percutaneous tracheotomy in Intensive Care Unit: a prospective observational study.

Author

Vargas M, Sutherasan Y, Brunetti I, Micalizzi C, Insorsi A, Ball L, Folentino M, Sileo R, De Lucia A, Cerana M, Accattatis A, De Lisi D, Gratarola A, Mora F, Peretti G, Servillo G, and Pelosi P

Subjects
Aged, Female, Hospital Mortality, Humans, Intensive Care Units, Male, Middle Aged, Prospective Studies, Time Factors, Tracheotomy methods, Quality of Life, Tracheotomy mortality
Abstract

Background: Quality of life and mortality after percutaneous dilatational tracheotomy (PDT) has been poorly investigated. The aims of this study were to evaluate the independent risk factors for Intensive Care Unit (ICU) mortality and investigate quality of life over the first year after PDT in critically ill patients., Methods: This was a prospective, single-center, cohort study performed in a tertiary care University Hospital, enrolling consecutive ICU patients requiring elective PDT, collecting data during the tracheotomy procedure and the ICU stay. Follow-up was performed at three, six and twelve months after PDT. The medical interview included the Euro Quality of Life questionnaire comprising five dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression)., Results: A total of 137 patients were included in the study. In the multivariate analysis, ICU mortality was independently associated with age (OR 1.089; P=0.003) and SAPS II (OR 1.047; P=0.003), and inversely with neurologic disease (OR 0.162; P=0.004). Mortality increased over time (ICU mortality 26.7%; in-hospital mortality 43.1%; 3-months mortality 47.4%; 6-months mortality 61.3%; and 1-year mortality 70.8%; P=0.0001). Tracheostomized patients due to respiratory disease had a higher ICU mortality (50%) compared to those with neurological disease (13.6%). quality of life (QoL) of tracheostomized patients was severely compromised at 3-months (QoL: 17, 15-19), 6-months (QoL: 17; 16-19), while moderately compromised at 1-year (QoL: 13; 9-16). A subgroup analysis showed better QoL at 3-months, 6-months and 1-year in respiratory compared to neurological tracheostomized patients (P=0.01)., Conclusions: Patients baseline characteristics and indication for PDT procedure are important determinants of in-ICU mortality and QoL in tracheostomized patients.

Published
2018
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17. Persistence of Candida albicans candidemia in non-neutropenic surgical patients: management of a representative patient in the absence of second-line treatment guidelines.

Author

Pacini D, Cerana M, Beltrame A, Di Biagio A, and De Maria A

Subjects
Amphotericin B therapeutic use, Caspofungin, Drug Combinations, Echinocandins, Female, Fluconazole therapeutic use, Humans, Ileostomy, Lipopeptides, Middle Aged, Peptides, Cyclic therapeutic use, Phosphatidylcholines therapeutic use, Phosphatidylglycerols therapeutic use, Practice Guidelines as Topic, Antifungal Agents therapeutic use, Candida albicans, Fungemia drug therapy, Postoperative Complications drug therapy
Abstract

Primary treatment failure and mortality in non-neutropenic patients with candidemia is high according to clinical trial experience. Current guidelines are mainly useful only for first line treatment strategies.We describe treatment failure and persistent protracted Candida albicans candidemia without clinically evident ocular involvement nor catheter recolonization in a malnourished non-neutropenic surgical patient with peritonitis. Primary antifungal treatment failure with fluconazole and secondary treatment failure with caspofungin occurred in the absence of evident Candida seeding the eye, valvular endocardium, or the intravascular catheter. Switch to liposomal amphotericin B was followed by clinical and microbiological cure. In patients with multiple risk factors for the acquisition of candidemia and life-threatening clinical conditions, the possibility of primary/secondary failure of new potent antifungal regimens may be initially neglected. Additional multicenter controlled clinical data are needed to guide the timing and choice of secondary antifungal treatment regimens in non-neutropenic candidemia patients.

Published
2007
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18. [Acute iatrogenic myopathy during treatment of status asthmaticus. Our experience and review of the literature].

Author

Pacini D, Ferretti M, Carletti A, Cerana M, De Rito M, Doveri A, Abbruzzese M, Primavera A, and Minetti C

Subjects
Adult, Heart Diseases physiopathology, Humans, Intraoperative Complications physiopathology, Male, Status Asthmaticus therapy, Heart Diseases etiology, Iatrogenic Disease, Intraoperative Complications etiology, Status Asthmaticus complications
Abstract

Case Report: A young man was admitted to the ICU for acute asthmatic respiratory failure. He was sedated with propofol, curarized with pancuronium and put on mechanical ventilation for 15 day because of the persistent asthmatics crisis. Drug therapy for asthma included high-dose corticosteroids. When sedation and paralysis were stopped, the patient, that was fully conscious, showed flaccid quadriplegia. A muscular biopsy showed elective loss of the myosin thick filaments. Electrophysiologic evaluation was compatible with both neurologic or muscular pathology. The evolution of the disease was good; a drop-out performed 5 months later showed a complete motor recovery., Discussion: This case report confirms that in some patients, intensive treatment of status asthmaticus may cause myopathy. Only recently this myopathy has been correlated to an interaction between steroids and neuromuscular blockers. Many experimental and clinical observations suggest a negative interaction between steroids and non-depolarizing curare derivatives. In the case reported here, diagnosis was based on electrophysiologic examination and above all on muscular biopsy., Conclusion: The occurrence of an acute toxic myopathy should always be taken into account, considering the high number of patients admitted with respiratory failure requiring steroid treatment and curare administrative for mechanical ventilation. It therefore seems reasonable to reduce steroid therapy as soon as possible with a periodic suspension of curare administration. Curare usage should be critically evaluated. Some basic examination such as serum CPK monitoring should allow early detection of muscular damage.

Published
1997

19. [Respiratory function tests and operative risk in thoracic surgery].

Author

Launo C, Palermo S, Riello R, Cammardella MP, Invitto V, and Cerana M

Subjects
Adult, Aged, Anesthesia, Female, Humans, Male, Middle Aged, Postoperative Complications blood, Retrospective Studies, Risk Factors, Lung Neoplasms surgery, Postoperative Complications epidemiology, Preoperative Care, Respiratory Function Tests
Abstract

In a retrospective study on 145 patients who underwent anesthesia for thoracic surgery, perioperative variables and preoperative pulmonary function tests influencing mortality and morbidity were evaluated. 3 patients (2.07%) died and 6 (4.14%) had cardiac, respiratory and other complications in postoperative 48 hours. Clinical-statistic analysis has shown the perioperative variables predictive on mortality and morbidity and operative risk: the operation type, FEV1, MVV (% theoretical), postexclusion gas analysis, Motley index (TLC/RV), intraoperative PaCO2, muscle-relaxant dose, preoperative myocardial infarction, weight, ASA, abnormal ECG, hypercreatininemia and loss of blood. MVV, FEV1, Motley index and residual FEV1 are the useful preoperative pulmonary function tests for evaluation of operative risk and surgical resection. Evaluation of operative risk in thoracic surgery shows the necessity of preoperative pulmonary function tests.

Published
1992

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