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360 results on '"Baiocchi, M."'

1. The High Energy Light Isotope eXperiment program of direct cosmic-ray studies

Author

HELIX Collaboration, Coutu, S., Allison, P. S., Baiocchi, M., Beatty, J. J., Beaufore, L., Calderon, D. H., Castano, A. G., Chen, Y., Green, N., Hanna, D., Jeon, H. B., Klein, S. B., Kunkler, B., Lang, M., Mbarek, R., McBride, K., Mognet, S. I., Musser, J., Nutter, S., OBrien, S., Park, N., Powledge, K. M., Sakai, K., Tabata, M., Tarle, G., Tuttle, J. M., Visser, G., Wakely, S. P., and Yu, M.

Subjects
Astrophysics - Instrumentation and Methods for Astrophysics, Physics - Instrumentation and Detectors
Abstract

HELIX is a new NASA-sponsored instrument aimed at measuring the spectra and composition of light cosmic-ray isotopes from hydrogen to neon nuclei, in particular the clock isotopes 10Be (radioactive, with 1.4 Myr lifetime) and 9Be (stable). The latter are unique markers of the production and Galactic propagation of secondary cosmic-ray nuclei, and are needed to resolve such important mysteries as the proportion of secondary positrons in the excess of antimatter observed by the AMS-02 experiment. By using a combination of a 1 T superconducting magnet spectrometer (with drift-chamber tracker) with a high-resolution time-of-flight detector system and ring-imaging Cherenkov detector, mass-resolved isotope measurements of light cosmic-ray nuclei will be possible up to 3 GeV/n in a first stratospheric balloon flight from Kiruna, Sweden to northern Canada, anticipated to take place in early summer 2024. An eventual longer Antarctic balloon flight of HELIX will yield measurements up to 10 GeV/n, sampling production from a larger volume of the Galaxy extending into the halo. We review the instrument design, testing, status and scientific prospects., Comment: Presented at the 16th Topical Seminar on Innovative Particle and Radiation Detectors (IPRD23), Siena, Italy, to appear in JINST Proc

Published
2023

2. Electron-beam Calibration of Aerogel Tiles for the HELIX RICH Detector

Author

Allison, P., Baiocchi, M., Beatty, J. J., Beaufore, L., Calderone, D. H., Chen, Y., Coutu, S., Ellingwood, E., Green, N., Hanna, D., Jeon, H. B., Mbarek, R., McBride, K., Mognet, I., Musser, J., Nutter, S., O'Brien, S., Park, N., Rosin, T., Tabata, M., Tarlé, G., Visser, G., Wakely, S. P., and Yu, M.

Subjects
Astrophysics - Instrumentation and Methods for Astrophysics, High Energy Physics - Experiment
Abstract

The HELIX cosmic-ray detector is a balloon-borne instrument designed to measure the flux of light isotopes in the energy range from 0.2 GeV/n to beyond 3 GeV/n. It will rely on a ring-imaging Cherenkov (RICH) detector for particle identification at energies greater than 1 GeV/n and will use aerogel tiles with refractive index near 1.15 as the radiator. To achieve the performance goals of the experiment it is necessary to know the refractive index and its position dependence over the lateral extent of the tiles to a precision of O(10$^{-4}). In this paper we describe the apparatus and methods developed to calibrate the HELIX tiles in an electron beam, in order to meet this requirement., Comment: 27 pages and 16 figures. Accepted for publication in Nuclear Instruments and Methods A

Published
2023
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3. Feasibility, preliminary efficacy, and accessibility of a twitter-based social support group vs Fitbit only to decrease sedentary behavior in women

Author

Oppezzo, MA, Tremmel, JA, Kapphahn, K, Desai, M, Baiocchi, M, Sanders, M, and Prochaska, JJ

Subjects
Clinical Research, Prevention, Clinical Trials and Supportive Activities, Behavioral and Social Science, 3.1 Primary prevention interventions to modify behaviours or promote wellbeing, Prevention of disease and conditions, and promotion of well-being, Cardiovascular, Cancer, Metabolic and endocrine, Stroke, Good Health and Well Being, Communications Technologies, Clinical Sciences, Public Health and Health Services
Abstract

BackgroundHealth behavior change interventions delivered by social media allow for real-time, dynamic interaction, peer social support, and experimenter-provided content.AimsWe tested the feasibility, acceptability, and preliminary efficacy of a novel Twitter-based walking break intervention with daily behavior change strategies and prompts for social support, combined with a Fitbit, vs. Fitbit alone.MethodsIn a 2-group pilot, 45 sedentary women from a heart clinic were randomized to Twitter + Fitbit activity tracker (Tweet4Wellness, n = 23) or Fitbit-only (control, n = 22). All received a Fitbit and 13 weeks of tailored weekly step goals. Tweet4Wellness consisted of a private Twitter support group, with daily automated behavior change "tweets" informed by behavior change theory, and encouragement to communicate within the group. Feasibility outcomes included recruitment and enrollment numbers, implementation challenges, and number and type of help requests from participants throughout the study period. Preliminary efficacy outcomes provided by Fitbit data were sedentary minutes, number of hours with >250 steps, maximum sitting bout, weighted sedentary median bout length, total steps, intensity minutes (>3.0 METS), and ratio of time spent sitting-to-moving. Acceptability outcomes included level of Twitter participation within Tweet4Wellness, and Likert scale plus open-ended survey questions on enjoyment and perceived effectiveness of intervention components. Survey data on acceptability of the features of the intervention were collected at 13 weeks (end-of-treatment [EOT]) and 22 weeks (follow-up).ResultsThe study was feasible, with addressable implementation challenges. Tweet4Wellness participants changed significantly from baseline to EOT relative to control participants on number of active hours p = .018, total steps p = .028, and ratio of sitting-to-moving, p = .014. Only sitting-to-moving was significant at follow-up (p = .047). Among Tweet4Wellness participants, each tweet sent during treatment was associated with a 0.11 increase in active hours per day (p = .04) and a 292-step increase per day (p

Published
2021

5. The High Energy Light Isotope eXperiment program of direct cosmic-ray studies

Author

Coutu, S., primary, Allison, P.S., additional, Baiocchi, M., additional, Beatty, J.J., additional, Beaufore, L., additional, Calderón, D.H., additional, Castano, A.G., additional, Chen, Y., additional, Green, N., additional, Hanna, D., additional, Jeon, H.B., additional, Klein, S.B., additional, Kunkler, B., additional, Lang, M., additional, Mbarek, R., additional, McBride, K., additional, Mognet, S.I., additional, Musser, J., additional, Nutter, S., additional, O'Brien, S., additional, Park, N., additional, Powledge, K.M., additional, Sakai, K., additional, Tabata, M., additional, Tarlé, G., additional, Tuttle, J.M., additional, Visser, G., additional, Wakely, S.P., additional, and Yu, M., additional

Published
2024
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6. Electron-beam calibration of aerogel tiles for the HELIX RICH detector

Author

Allison, P., primary, Baiocchi, M., additional, Beatty, J.J., additional, Beaufore, L., additional, Calderone, D.H., additional, Chen, Y., additional, Coutu, S., additional, Ellingwood, E., additional, Green, N., additional, Hanna, D., additional, Jeon, H.B., additional, Mbarek, R., additional, McBride, K., additional, Mognet, I., additional, Musser, J., additional, Nutter, S., additional, O’Brien, S., additional, Park, N., additional, Rosin, T., additional, Tabata, M., additional, Tarlé, G., additional, Visser, G., additional, Wakely, S.P., additional, and Yu, M., additional

Published
2023
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8. Use of critical care resources during the first 2 weeks (February 24–March 8, 2020) of the Covid-19 outbreak in Italy

Author

Tonetti T., Grasselli G., Zanella A., Pizzilli G., Fumagalli R., Piva S., Lorini L., Iotti G., Foti G., Colombo S., Vivona L., Rossi S., Girardis M., Agnoletti V., Campagna A., Gordini G., Navalesi P., Boscolo A., Graziano A., Valeri I., Vianello A., Cereda D., Filippini C., Cecconi M., Locatelli F., Bartoletti M., Giannella M., Viale P., Antonelli M., Nava S., Pesenti A., Ranieri V. M., Albano G., Alborghetti A., Aldegheri G., Antonini B., Belgiorno N., Bellani G., Beretta E., Bonazzi S., Borelli M., Cabrini L., Carnevale L., Carnevale S., Castelli G., Catena E., Chiumello D., Coluccello A., Coppini D., Covello D., DeFilippi G., DeiPoli M., Dughi P., Gallioli G., Gnesin P., Greco S., Guatteri L., Guzzon D., Keim R., Landoni G., Langer T., Lombardo A., Marino G., Merli G., Merlo D., Mojoli F., Muttini S., Natalini G., Petrucci N., Pezzi A., Radrizzani D., Raimondi M., Riccio M., Storti E., Tavola M., Vitale G., Bosco E., Calo M. A., Danzi V., DeRosa S., Farnia A., Lazzari F., Meggiolaro M., Munari M., Saia M., Sella N., Serra E., Tiberio I., Baiocchi M., Benedetto M., Bordini M., Caramelli F., Cilloni N., DellaGiovampaola M., Fanelli A., Frascaroli G., Fusari M., Maitan S., Martino C., Melotti R. M., Merola R., Minardi F., Moro F., Nardi G., Nolli M., Pierucci E., Potalivo A., Repetti F., Salsi P., Terzitta M., Tosi M., Venturi S., Volta C. A., Zani G., Zanoni A (COVID-19 Northern Italian ICU Network), Landoni G, Tonetti, Tommaso, Grasselli, Giacomo, Zanella, Alberto, Pizzilli, Giacinto, Fumagalli, Roberto, Piva, Simone, Lorini, Luca, Iotti, Giorgio, Foti, Giuseppe, Colombo, Sergio, Vivona, Luigi, Rossi, Sandra, Girardis, Massimo, Agnoletti, Vanni, Campagna, Anselmo, Gordini, Giovanni, Navalesi, Paolo, Boscolo, Annalisa, Graziano, Alessandro, Valeri, Ilaria, Vianello, Andrea, Cereda, Danilo, Filippini, Claudia, Cecconi, Maurizio, Locatelli, Franco, Bartoletti, Michele, Giannella, Maddalena, Viale, Pierluigi, Antonelli, Massimo, Nava, Stefano, Pesenti, Antonio, Ranieri, V Marco, Tonetti, T, Grasselli, G, Zanella, A, Pizzilli, G, Fumagalli, R, Piva, S, Lorini, L, Iotti, G, Foti, G, Colombo, S, Vivona, L, Rossi, S, Girardis, M, Agnoletti, V, Campagna, A, Gordini, G, Navalesi, P, Boscolo, A, Graziano, A, Valeri, I, Vianello, A, Cereda, D, Filippini, C, Cecconi, M, Locatelli, F, Bartoletti, M, Giannella, M, Viale, P, Antonelli, M, Nava, S, Pesenti, A, Ranieri, V, Langer, T, Tonetti, T., Grasselli, G., Zanella, A., Pizzilli, G., Fumagalli, R., Piva, S., Lorini, L., Iotti, G., Foti, G., Colombo, S., Vivona, L., Rossi, S., Girardis, M., Agnoletti, V., Campagna, A., Gordini, G., Navalesi, P., Boscolo, A., Graziano, A., Valeri, I., Vianello, A., Cereda, D., Filippini, C., Cecconi, M., Locatelli, F., Bartoletti, M., Giannella, M., Viale, P., Antonelli, M., Nava, S., Pesenti, A., Ranieri, V. M., Albano, G., Alborghetti, A., Aldegheri, G., Antonini, B., Belgiorno, N., Bellani, G., Beretta, E., Bonazzi, S., Borelli, M., Cabrini, L., Carnevale, L., Carnevale, S., Castelli, G., Catena, E., Chiumello, D., Coluccello, A., Coppini, D., Covello, D., Defilippi, G., Deipoli, M., Dughi, P., Gallioli, G., Gnesin, P., Greco, S., Guatteri, L., Guzzon, D., Keim, R., Landoni, G., Langer, T., Lombardo, A., Marino, G., Merli, G., Merlo, D., Mojoli, F., Muttini, S., Natalini, G., Petrucci, N., Pezzi, A., Radrizzani, D., Raimondi, M., Riccio, M., Storti, E., Tavola, M., Vitale, G., Bosco, E., Calo, M. A., Danzi, V., Derosa, S., Farnia, A., Lazzari, F., Meggiolaro, M., Munari, M., Saia, M., Sella, N., Serra, E., Tiberio, I., Baiocchi, M., Benedetto, M., Bordini, M., Caramelli, F., Cilloni, N., Dellagiovampaola, M., Fanelli, A., Frascaroli, G., Fusari, M., Maitan, S., Martino, C., Melotti, R. M., Merola, R., Minardi, F., Moro, F., Nardi, G., Nolli, M., Pierucci, E., Potalivo, A., Repetti, F., Salsi, P., Terzitta, M., Tosi, M., Venturi, S., Volta, C. A., Zani, G., Zanoni, A (COVID-19 Northern Italian ICU Network), and Landoni, G

Subjects
medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Respiratory rate, Socio-culturale, Critical Care and Intensive Care Medicine, Acute respiratory failure, acute respiratory failure, COVID-19, ICU, non-invasive ventilation, rationing, 03 medical and health sciences, 0302 clinical medicine, Anesthesiology, Intensive care, Retrospective analysis, Medicine, 030212 general & internal medicine, Non-invasive ventilation, Rationing, Case report form, business.industry, Research, lcsh:Medical emergencies. Critical care. Intensive care. First aid, Outbreak, lcsh:RC86-88.9, Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA, 030228 respiratory system, Emergency medicine, Base excess, business
Abstract

Background A Covid-19 outbreak developed in Lombardy, Veneto and Emilia-Romagna (Italy) at the end of February 2020. Fear of an imminent saturation of available ICU beds generated the notion that rationing of intensive care resources could have been necessary. Results In order to evaluate the impact of Covid-19 on the ICU capacity to manage critically ill patients, we performed a retrospective analysis of the first 2 weeks of the outbreak (February 24–March 8). Data were collected from regional registries and from a case report form sent to participating sites. ICU beds increased from 1545 to 1989 (28.7%), and patients receiving respiratory support outside the ICU increased from 4 (0.6%) to 260 (37.0%). Patients receiving respiratory support outside the ICU were significantly older [65 vs. 77 years], had more cerebrovascular (5.8 vs. 13.1%) and renal (5.3 vs. 10.0%) comorbidities and less obesity (31.4 vs. 15.5%) than patients admitted to the ICU. PaO2/FiO2 ratio, respiratory rate and arterial pH were higher [165 vs. 244; 20 vs. 24 breath/min; 7.40 vs. 7.46] and PaCO2 and base excess were lower [34 vs. 42 mmHg; 0.60 vs. 1.30] in patients receiving respiratory support outside the ICU than in patients admitted to the ICU, respectively. Conclusions Increase in ICU beds and use of out-of-ICU respiratory support allowed effective management of the first 14 days of the Covid-19 outbreak, avoiding resource rationing.

Published
2020

9. ECMO for COVID-19 patients in Europe and Israel

Author

Lorusso, R, Combes, A, Coco, V, De Piero, M, Belohlavek, J, Delnoij, T, van der Horst, I, Miranda, D, van der Linden, M, van der Heijden, J, Scholten, E, van Belle-van Haren, N, Lagrand, W, de Jong, S, Candura, D, Maas, J, van den Berg, M, Malfertheiner, M, Dreier, E, Mueller, T, Boeken, U, Akhyari, P, Lichtenberg, A, Saeed, D, Thiele, H, Baumgaertel, M, Schmitto, J, Mariani, S, Thielmann, M, Brenner, T, Benk, C, Czerny, M, Kalbhenn, J, Maier, S, Schibilsky, D, Staudacher, D, Henn, P, Iuliu, T, Muellenbach, R, Reyher, C, Rolfes, C, Zacharowski, K, Lotz, G, Sonntagbauer, M, Kersten, A, Karagiannidis, C, Schafer, S, Fichte, J, Hopf, H, Samalavicius, R, Lorini, L, Ghitti, D, Grazioli, L, Loforte, A, Baiocchi, M, Checco, E, Pacini, D, Meani, P, Cappai, A, Russo, C, Bottiroli, M, Mondino, M, Ranucci, M, Fina, D, Ballotta, A, Scandroglio, A, Zangrillo, A, Pieri, M, Nardelli, P, Fominskiy, E, Landoni, G, Fanelli, V, Brazzi, L, Montrucchio, G, Sales, G, Simonetti, U, Urbino, R, Livigni, S, Degani, A, Raffa, G, Pilato, M, Martucci, G, Arcadipane, A, Chiarini, G, Latronico, N, Cattaneo, S, Puglia, C, Reina, G, Sponga, S, Livi, U, Foti, G, Giani, M, Rona, R, Avalli, L, Bombino, M, Costa, M, Carozza, R, Donati, A, Piciche, M, Favaro, A, Salvador, L, Danzi, V, Zanin, A, Condello, I, Fiore, F, Moscarelli, M, Nasso, G, Speziale, G, Sandrelli, L, Montalto, A, Musumeci, F, Circelli, A, Gamberini, E, Russo, E, Benni, M, Agnoletti, V, Rociola, R, Milano, A, Grasso, S, Civita, A, Murgolo, F, Pilato, E, Comentale, G, Montisci, A, Alessandri, F, Tosi, A, Pugliese, F, Carelli, S, Grieco, D, Antonelli, M, Ramoni, E, Di Nardo, M, Maisano, F, Bettex, D, Weber, A, Grunenfelder, J, Consiglio, J, Hansjoerg, J, Haenggi, M, Agus, G, Doeble, T, Zenklusen, U, Bechtold, X, Stockman, B, De Backer, D, Giglioli, S, Meyns, B, Vercaemst, L, Herman, G, Meersseman, P, Vandenbriele, C, Dauwe, D, Vlasselaers, D, Raes, M, Debeuckelaere, G, Rodrigus, I, Biston, P, Piagnerelli, M, Peperstraete, H, Germay, O, Vandewiele, K, Vandeweghe, D, Witters, I, Havrin, S, Bourgeois, M, Taccone, F, Nobile, L, Lheureux, O, Brasseur, A, Creteur, J, Defraigne, J, Misset, B, Courcelle, R, Timmermans, P, Lehaen, J, Frederik, B, Riera, J, Castro, M, Gallart, E, Martinez-Martinez, M, Argudo, E, Garcia-de-Acilu, M, de Pablo Sanchez, R, Ortiz, A, Cabanes, M, Higa, K, Cassina, A, Berbel, D, Sanchez-Salado, J, Arnau, B, de Gopegui, P, Ricart, P, Sandoval, E, Veganzones, J, Millan, P, de la Sota, P, Santa Teresa, P, Alcantara, S, Alvarez, J, Gonzalez, A, Lopez, M, Gordillo, A, Naranjo-Izurieta, J, Costa, R, Albacete Moreno, C, de Ayala, J, Blanco-Schweizer, P, Andres, N, Boado, V, Martinez, J, Casal, V, Garcia, E, Martin-Villen, L, Climent, J, Pinto, L, Leprince, P, Lebreton, G, Juvin, C, Schmidt, M, Pineton, M, Folliguet, T, Saiydoun, G, Gaudard, P, Colson, P, Obadia, J, Pozzi, M, Fellahi, J, Yonis, H, Richard, J, Parasido, A, Verhoye, J, Flecher, E, Ajrhourh, L, Nesseler, N, Mansour, A, Guinot, P, Zarka, J, Besserve, P, Makhoul, M, Bolotin, G, Kassif, Y, Soufleris, D, Schellongowski, P, Bonaros, N, Krapf, C, Ebert, K, Mair, P, Kothleutner, F, Kowalewsky, M, Christensen, S, Pedersen, F, Balik, M, Blaha, J, Lips, M, Otahal, M, Camporota, L, Daly, K, Agnew, N, Barker, J, Head, L, Garcia, M, Ledot, S, Aquino, V, Lewis, R, Worthy, J, Noor, H, Scott, I, O'Brien, S, Conrick-Martin, I, Carton, E, Gillon, S, Flemming, L, Broman, L, Grins, E, Ketskalo, M, Tsarenko, S, Popugaev, K, Minin, S, Kornilov, I, Skopets, A, Kornelyuk, R, Turchaninov, A, Gorjup, V, Shelukhin, D, Dsouki, Y, Sargin, M, Kaygin, M, Liana, S, Puss, S, Soerensen, G, Magnus, R, Kanetoft, M, Watson, P, Redfors, B, Krenner, N, Velia Antonini, M, Barrett, N, Belliato, M, Davidson, M, Finney, S, Fowles, J, Halbe, M, Hennig, F, Jones, T, Smith, J, Roeleveld, P, Swol, J, Lorusso R., Combes A., Coco V. L., De Piero M. E., Belohlavek J., Delnoij T., van der Horst I., Miranda D. R., van der Linden M., van der Heijden J. J., Scholten E., van Belle-van Haren N., Lagrand W., de Jong S., Candura D., Maas J., van den Berg M. J. G., Malfertheiner M., Dreier E., Mueller T., Boeken U., Akhyari P., Lichtenberg A., Saeed D., Thiele H., Baumgaertel M., Schmitto J. D., Mariani S., Thielmann M., Brenner T., Benk C., Czerny M., Kalbhenn J., Maier S., Schibilsky D., Staudacher D. L., Henn P., Iuliu T., Muellenbach R., Reyher C., Rolfes C., Zacharowski K., Lotz G., Sonntagbauer M., Kersten A., Karagiannidis C., Schafer S., Fichte J., Hopf H. -B., Samalavicius R., Lorini L., Ghitti D., Grazioli L., Loforte A., Baiocchi M., Checco E. D., Pacini D., Meani P., Cappai A., Russo C. F., Bottiroli M., Mondino M., Ranucci M., Fina D., Ballotta A., Scandroglio A. M., Zangrillo A., Pieri M., Nardelli P., Fominskiy E., Landoni G., Fanelli V., Brazzi L., Montrucchio G., Sales G., Simonetti U., Urbino R., Livigni S., Degani A., Raffa G., Pilato M., Martucci G., Arcadipane A., Chiarini G., Latronico N., Cattaneo S., Puglia C., Reina G., Sponga S., Livi U., Foti G., Giani M., Rona R., Avalli L., Bombino M., Costa M. C., Carozza R., Donati A., Piciche M., Favaro A., Salvador L., Danzi V., Zanin A., Condello I., Fiore F., Moscarelli M., Nasso G., Speziale G., Sandrelli L., Montalto A., Musumeci F., Circelli A., Gamberini E., Russo E., Benni M., Agnoletti V., Rociola R., Milano A. D., Grasso S., Civita A., Murgolo F., Pilato E., Comentale G., Montisci A., Alessandri F., Tosi A., Pugliese F., Carelli S., Grieco D. L., Antonelli M., Ramoni E., Di Nardo M., Maisano F., Bettex D., Weber A., Grunenfelder J., Consiglio J., Hansjoerg J., Haenggi M., Agus G., Doeble T., Zenklusen U., Bechtold X., Stockman B., De Backer D., Giglioli S., Meyns B., Vercaemst L., Herman G., Meersseman P., Vandenbriele C., Dauwe D., Vlasselaers D., Raes M., Debeuckelaere G., Rodrigus I., Biston P., Piagnerelli M., Peperstraete H., Germay O., Vandewiele K., Vandeweghe D., Witters I., Havrin S., Bourgeois M., Taccone F. S., Nobile L., Lheureux O., Brasseur A., Creteur J., Defraigne J. -O., Misset B., Courcelle R., Timmermans P. J., Lehaen J., Frederik B., Riera J., Castro M. A., Gallart E., Martinez-Martinez M., Argudo E., Garcia-de-Acilu M., de Pablo Sanchez R., Ortiz A. B., Cabanes M. -P. F., Higa K. O., Cassina A. M., Berbel D. O., Sanchez-Salado J. C., Arnau B. -L., de Gopegui P. R., Ricart P., Sandoval E., Veganzones J., Millan P., de la Sota P., Santa Teresa P., Alcantara S., Alvarez J. D., Gonzalez A. V., Lopez M., Gordillo A., Naranjo-Izurieta J., Costa R. G., Albacete Moreno C. L., de Ayala J. A., Blanco-Schweizer P., Andres N. H., Boado V., Martinez J. M. N., Casal V. G., Garcia E. F., Martin-Villen L., Climent J. C., Pinto L. F., Leprince P., Lebreton G., Juvin C., Schmidt M., Pineton M., Folliguet T., Saiydoun G., Gaudard P., Colson P., Obadia J. -F., Pozzi M., Fellahi J. L., Yonis H., Richard J. C., Parasido A., Verhoye J. -P., Flecher E., Ajrhourh L., Nesseler N., Mansour A., Guinot P. -G., Zarka J., Besserve P., Makhoul M., Bolotin G., Kassif Y., Soufleris D., Schellongowski P., Bonaros N., Krapf C., Ebert K., Mair P., Kothleutner F., Kowalewsky M., Christensen S., Pedersen F. M., Balik M., Blaha J., Lips M., Otahal M., Camporota L., Daly K., Agnew N., Barker J., Head L., Garcia M., Ledot S., Aquino V., Lewis R., Worthy J., Noor H., Scott I., O'Brien S., Conrick-Martin I., Carton E., Gillon S., Flemming L., Broman L. M., Grins E., Ketskalo M., Tsarenko S., Popugaev K., Minin S., Kornilov I., Skopets A., Kornelyuk R., Turchaninov A., Gorjup V., Shelukhin D., Dsouki Y. E., Sargin M., Kaygin M. A., Liana S., Puss S., Soerensen G., Magnus R., Kanetoft M., Watson P., Redfors B., Krenner N., Velia Antonini M., Barrett N. A., Belliato M., Davidson M., Finney S., Fowles J. -A., Halbe M., Hennig F., Jones T., Pinto L., Smith J., Roeleveld P., Swol J., Lorusso, R, Combes, A, Coco, V, De Piero, M, Belohlavek, J, Delnoij, T, van der Horst, I, Miranda, D, van der Linden, M, van der Heijden, J, Scholten, E, van Belle-van Haren, N, Lagrand, W, de Jong, S, Candura, D, Maas, J, van den Berg, M, Malfertheiner, M, Dreier, E, Mueller, T, Boeken, U, Akhyari, P, Lichtenberg, A, Saeed, D, Thiele, H, Baumgaertel, M, Schmitto, J, Mariani, S, Thielmann, M, Brenner, T, Benk, C, Czerny, M, Kalbhenn, J, Maier, S, Schibilsky, D, Staudacher, D, Henn, P, Iuliu, T, Muellenbach, R, Reyher, C, Rolfes, C, Zacharowski, K, Lotz, G, Sonntagbauer, M, Kersten, A, Karagiannidis, C, Schafer, S, Fichte, J, Hopf, H, Samalavicius, R, Lorini, L, Ghitti, D, Grazioli, L, Loforte, A, Baiocchi, M, Checco, E, Pacini, D, Meani, P, Cappai, A, Russo, C, Bottiroli, M, Mondino, M, Ranucci, M, Fina, D, Ballotta, A, Scandroglio, A, Zangrillo, A, Pieri, M, Nardelli, P, Fominskiy, E, Landoni, G, Fanelli, V, Brazzi, L, Montrucchio, G, Sales, G, Simonetti, U, Urbino, R, Livigni, S, Degani, A, Raffa, G, Pilato, M, Martucci, G, Arcadipane, A, Chiarini, G, Latronico, N, Cattaneo, S, Puglia, C, Reina, G, Sponga, S, Livi, U, Foti, G, Giani, M, Rona, R, Avalli, L, Bombino, M, Costa, M, Carozza, R, Donati, A, Piciche, M, Favaro, A, Salvador, L, Danzi, V, Zanin, A, Condello, I, Fiore, F, Moscarelli, M, Nasso, G, Speziale, G, Sandrelli, L, Montalto, A, Musumeci, F, Circelli, A, Gamberini, E, Russo, E, Benni, M, Agnoletti, V, Rociola, R, Milano, A, Grasso, S, Civita, A, Murgolo, F, Pilato, E, Comentale, G, Montisci, A, Alessandri, F, Tosi, A, Pugliese, F, Carelli, S, Grieco, D, Antonelli, M, Ramoni, E, Di Nardo, M, Maisano, F, Bettex, D, Weber, A, Grunenfelder, J, Consiglio, J, Hansjoerg, J, Haenggi, M, Agus, G, Doeble, T, Zenklusen, U, Bechtold, X, Stockman, B, De Backer, D, Giglioli, S, Meyns, B, Vercaemst, L, Herman, G, Meersseman, P, Vandenbriele, C, Dauwe, D, Vlasselaers, D, Raes, M, Debeuckelaere, G, Rodrigus, I, Biston, P, Piagnerelli, M, Peperstraete, H, Germay, O, Vandewiele, K, Vandeweghe, D, Witters, I, Havrin, S, Bourgeois, M, Taccone, F, Nobile, L, Lheureux, O, Brasseur, A, Creteur, J, Defraigne, J, Misset, B, Courcelle, R, Timmermans, P, Lehaen, J, Frederik, B, Riera, J, Castro, M, Gallart, E, Martinez-Martinez, M, Argudo, E, Garcia-de-Acilu, M, de Pablo Sanchez, R, Ortiz, A, Cabanes, M, Higa, K, Cassina, A, Berbel, D, Sanchez-Salado, J, Arnau, B, de Gopegui, P, Ricart, P, Sandoval, E, Veganzones, J, Millan, P, de la Sota, P, Santa Teresa, P, Alcantara, S, Alvarez, J, Gonzalez, A, Lopez, M, Gordillo, A, Naranjo-Izurieta, J, Costa, R, Albacete Moreno, C, de Ayala, J, Blanco-Schweizer, P, Andres, N, Boado, V, Martinez, J, Casal, V, Garcia, E, Martin-Villen, L, Climent, J, Pinto, L, Leprince, P, Lebreton, G, Juvin, C, Schmidt, M, Pineton, M, Folliguet, T, Saiydoun, G, Gaudard, P, Colson, P, Obadia, J, Pozzi, M, Fellahi, J, Yonis, H, Richard, J, Parasido, A, Verhoye, J, Flecher, E, Ajrhourh, L, Nesseler, N, Mansour, A, Guinot, P, Zarka, J, Besserve, P, Makhoul, M, Bolotin, G, Kassif, Y, Soufleris, D, Schellongowski, P, Bonaros, N, Krapf, C, Ebert, K, Mair, P, Kothleutner, F, Kowalewsky, M, Christensen, S, Pedersen, F, Balik, M, Blaha, J, Lips, M, Otahal, M, Camporota, L, Daly, K, Agnew, N, Barker, J, Head, L, Garcia, M, Ledot, S, Aquino, V, Lewis, R, Worthy, J, Noor, H, Scott, I, O'Brien, S, Conrick-Martin, I, Carton, E, Gillon, S, Flemming, L, Broman, L, Grins, E, Ketskalo, M, Tsarenko, S, Popugaev, K, Minin, S, Kornilov, I, Skopets, A, Kornelyuk, R, Turchaninov, A, Gorjup, V, Shelukhin, D, Dsouki, Y, Sargin, M, Kaygin, M, Liana, S, Puss, S, Soerensen, G, Magnus, R, Kanetoft, M, Watson, P, Redfors, B, Krenner, N, Velia Antonini, M, Barrett, N, Belliato, M, Davidson, M, Finney, S, Fowles, J, Halbe, M, Hennig, F, Jones, T, Smith, J, Roeleveld, P, Swol, J, Lorusso R., Combes A., Coco V. L., De Piero M. E., Belohlavek J., Delnoij T., van der Horst I., Miranda D. R., van der Linden M., van der Heijden J. J., Scholten E., van Belle-van Haren N., Lagrand W., de Jong S., Candura D., Maas J., van den Berg M. J. G., Malfertheiner M., Dreier E., Mueller T., Boeken U., Akhyari P., Lichtenberg A., Saeed D., Thiele H., Baumgaertel M., Schmitto J. D., Mariani S., Thielmann M., Brenner T., Benk C., Czerny M., Kalbhenn J., Maier S., Schibilsky D., Staudacher D. L., Henn P., Iuliu T., Muellenbach R., Reyher C., Rolfes C., Zacharowski K., Lotz G., Sonntagbauer M., Kersten A., Karagiannidis C., Schafer S., Fichte J., Hopf H. -B., Samalavicius R., Lorini L., Ghitti D., Grazioli L., Loforte A., Baiocchi M., Checco E. D., Pacini D., Meani P., Cappai A., Russo C. F., Bottiroli M., Mondino M., Ranucci M., Fina D., Ballotta A., Scandroglio A. M., Zangrillo A., Pieri M., Nardelli P., Fominskiy E., Landoni G., Fanelli V., Brazzi L., Montrucchio G., Sales G., Simonetti U., Urbino R., Livigni S., Degani A., Raffa G., Pilato M., Martucci G., Arcadipane A., Chiarini G., Latronico N., Cattaneo S., Puglia C., Reina G., Sponga S., Livi U., Foti G., Giani M., Rona R., Avalli L., Bombino M., Costa M. C., Carozza R., Donati A., Piciche M., Favaro A., Salvador L., Danzi V., Zanin A., Condello I., Fiore F., Moscarelli M., Nasso G., Speziale G., Sandrelli L., Montalto A., Musumeci F., Circelli A., Gamberini E., Russo E., Benni M., Agnoletti V., Rociola R., Milano A. D., Grasso S., Civita A., Murgolo F., Pilato E., Comentale G., Montisci A., Alessandri F., Tosi A., Pugliese F., Carelli S., Grieco D. L., Antonelli M., Ramoni E., Di Nardo M., Maisano F., Bettex D., Weber A., Grunenfelder J., Consiglio J., Hansjoerg J., Haenggi M., Agus G., Doeble T., Zenklusen U., Bechtold X., Stockman B., De Backer D., Giglioli S., Meyns B., Vercaemst L., Herman G., Meersseman P., Vandenbriele C., Dauwe D., Vlasselaers D., Raes M., Debeuckelaere G., Rodrigus I., Biston P., Piagnerelli M., Peperstraete H., Germay O., Vandewiele K., Vandeweghe D., Witters I., Havrin S., Bourgeois M., Taccone F. S., Nobile L., Lheureux O., Brasseur A., Creteur J., Defraigne J. -O., Misset B., Courcelle R., Timmermans P. J., Lehaen J., Frederik B., Riera J., Castro M. A., Gallart E., Martinez-Martinez M., Argudo E., Garcia-de-Acilu M., de Pablo Sanchez R., Ortiz A. B., Cabanes M. -P. F., Higa K. O., Cassina A. M., Berbel D. O., Sanchez-Salado J. C., Arnau B. -L., de Gopegui P. R., Ricart P., Sandoval E., Veganzones J., Millan P., de la Sota P., Santa Teresa P., Alcantara S., Alvarez J. D., Gonzalez A. V., Lopez M., Gordillo A., Naranjo-Izurieta J., Costa R. G., Albacete Moreno C. L., de Ayala J. A., Blanco-Schweizer P., Andres N. H., Boado V., Martinez J. M. N., Casal V. G., Garcia E. F., Martin-Villen L., Climent J. C., Pinto L. F., Leprince P., Lebreton G., Juvin C., Schmidt M., Pineton M., Folliguet T., Saiydoun G., Gaudard P., Colson P., Obadia J. -F., Pozzi M., Fellahi J. L., Yonis H., Richard J. C., Parasido A., Verhoye J. -P., Flecher E., Ajrhourh L., Nesseler N., Mansour A., Guinot P. -G., Zarka J., Besserve P., Makhoul M., Bolotin G., Kassif Y., Soufleris D., Schellongowski P., Bonaros N., Krapf C., Ebert K., Mair P., Kothleutner F., Kowalewsky M., Christensen S., Pedersen F. M., Balik M., Blaha J., Lips M., Otahal M., Camporota L., Daly K., Agnew N., Barker J., Head L., Garcia M., Ledot S., Aquino V., Lewis R., Worthy J., Noor H., Scott I., O'Brien S., Conrick-Martin I., Carton E., Gillon S., Flemming L., Broman L. M., Grins E., Ketskalo M., Tsarenko S., Popugaev K., Minin S., Kornilov I., Skopets A., Kornelyuk R., Turchaninov A., Gorjup V., Shelukhin D., Dsouki Y. E., Sargin M., Kaygin M. A., Liana S., Puss S., Soerensen G., Magnus R., Kanetoft M., Watson P., Redfors B., Krenner N., Velia Antonini M., Barrett N. A., Belliato M., Davidson M., Finney S., Fowles J. -A., Halbe M., Hennig F., Jones T., Pinto L., Smith J., Roeleveld P., and Swol J.

Published
2021

10. A regional-based newborn hearing screening program: the Emilia-Romagna model after ten years of legislation.

Author

Bianchin, G., Palma, S., Polizzi, V., Kaleci, S., Stagi, P., Cappai, M., Baiocchi, M. P., Benincasa, P., Brandolini, C., Casadio, L., Di Sarro, S., Farneti, D., Galli, A., Ghiselli, S., Iadicicco, P., Landuzzi, E., Limarzi, M., Locatelli, C., Murri, A., and Nanni, L.

Subjects
NEWBORN infants, CONGENITAL disorders, HEALTH outcome assessment, EPIDEMIOLOGY, DEAFNESS
Abstract

Copyright of Annali di Igiene, Medicina Preventiva e di Comunità is the property of Societa Editrice Universo s.r.l. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Published
2023
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12. One-Year Outcomes and Trends over Two Eras of Transcatheter Aortic Valve Implantation in Real-World Practice

Author

Costa, G, D'Errigo, P, Rosato, S, Biancari, F, Marcellusi, A, Tarantini, G, Santoro, G, Baiocchi, M, Maffeo, D, Fiorina, C, Cerza, F, Baglio, G, Juvonen, T, Badoni, G, Valvo, R, Seccareccia, F, Barbanti, M, Tamburino, C, Appendix, Ruvolo, G, Nardi, P, Pisano, C, HUS Heart and Lung Center, and University of Helsinki

Subjects
trends, REPLACEMENT, Settore MED/23, OBSERVANT, Outcomes, Transcatheter aortic valve implantation, Trends, TRANSFEMORAL TRANSCATHETER, 3121 General medicine, internal medicine and other clinical medicine, NEW-GENERATION DEVICES, General Medicine, transcatheter aortic valve implantation, outcomes, NEXT-DAY DISCHARGE
Abstract

Background: Data reflecting the benefit of procedural improvements in real-world transcatheter aortic valve implantation (TAVI) practice are sparse. Aims: To compare outcomes and trends of two TAVI eras from real Italian practice. Methods: A total of 1811 and 2939 TAVI patients enrolled in the national, prospective OBSERVANT and OBSERVANT II studies in 2010–2012 and 2016–2018, respectively, were compared in a cohort study. Outcomes were adjusted using inverse propensity of treatment weighting and propensity score matching. Results: The median age (83.0 (79.0–86.0) vs. 83.0 (79.0–86.0)) and EuroSCORE II (5.2 (3.2–7.7) vs. 5.1 (3.1–8.1)) of OBSERVANT and OBSERVANT II patients were similar. At 1 year, patients of the OBSERVANT II study had a significantly lower risk of all-cause death (10.6% vs. 16.3%, Hazard Ratio (HR) 0.63 (95% Confidence Interval (CI) 0.52–0.76)) and rehospitalization for heart failure (HF) (14.3% vs. 19.5%, Sub-distribution HR 0.71 (95%CI 0.60–0.84)), whereas rates of stroke (3.1% vs. 3.6%) and permanent pacemaker implantation (PPI) (16.6% vs. 18.0%) were comparable between study groups. Conclusions: Age and risk profile among patients undergoing TAVI in Italy remained substantially unchanged between the 2010–2012 and 2016–2018 time periods. After adjustment, patients undergoing TAVI in the most recent era had lower risk of all-cause death and rehospitalization for HF at 1 year, whereas rates of stroke and PPI did not differ significantly.

Published
2022
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13. An organoid model of colorectal circulating tumor cells with stem cell features, hybrid EMT state and distinctive therapy response profile

Author

De Angelis, M. L., Francescangeli, F., Nicolazzo, C., Signore, M., Giuliani, Alessandro, Colace, L., Boe, A., Magri, V., Baiocchi, M., Ciardi, A., Scarola, F., Spada, M., La Torre, F., Gazzaniga, P., Biffoni, M., De Maria Marchiano, Ruggero, Zeuner, A., Giuliani A., De Maria R. (ORCID:0000-0003-2255-0583), De Angelis, M. L., Francescangeli, F., Nicolazzo, C., Signore, M., Giuliani, Alessandro, Colace, L., Boe, A., Magri, V., Baiocchi, M., Ciardi, A., Scarola, F., Spada, M., La Torre, F., Gazzaniga, P., Biffoni, M., De Maria Marchiano, Ruggero, Zeuner, A., Giuliani A., and De Maria R. (ORCID:0000-0003-2255-0583)

Abstract

Background: Circulating tumor cells (CTCs) are responsible for the metastatic dissemination of colorectal cancer (CRC) to the liver, lungs and lymph nodes. CTCs rarity and heterogeneity strongly limit the elucidation of their biological features, as well as preclinical drug sensitivity studies aimed at metastasis prevention. Methods: We generated organoids from CTCs isolated from an orthotopic CRC xenograft model. CTCs-derived organoids (CTCDOs) were characterized through proteome profiling, immunohistochemistry, immunofluorescence, flow cytometry, tumor-forming capacity and drug screening assays. The expression of intra- and extracellular markers found in CTCDOs was validated on CTCs isolated from the peripheral blood of CRC patients. Results: CTCDOs exhibited a hybrid epithelial-mesenchymal transition (EMT) state and an increased expression of stemness-associated markers including the two homeobox transcription factors Goosecoid and Pancreatic Duodenal Homeobox Gene-1 (PDX1), which were also detected in CTCs from CRC patients. Functionally, CTCDOs showed a higher migratory/invasive ability and a different response to pathway-targeted drugs as compared to xenograft-derived organoids (XDOs). Specifically, CTCDOs were more sensitive than XDOs to drugs affecting the Survivin pathway, which decreased the levels of Survivin and X-Linked Inhibitor of Apoptosis Protein (XIAP) inducing CTCDOs death. Conclusions: These results indicate that CTCDOs recapitulate several features of colorectal CTCs and may be used to investigate the features of metastatic CRC cells, to identify new prognostic biomarkers and to devise new potential strategies for metastasis prevention.

Published
2022

14. Tryptophan and Atherosclerosis

Author

Baldo-Enzi, G., Baiocchi, M. R., Bertazzo, A., Costa, C. V. L., Allegri, G., Filippini, Graziella Allegri, editor, Costa, Carlo V. L., editor, and Bertazzo, Antonella, editor

Published
1996
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16. Static compliance and driving pressure are associated with ICU mortality in intubated COVID-19 ARDS

Author

Boscolo, A., Sella, N., Lorenzoni, G., Pasin, L., Pretto, C., Tocco, M., Tamburini, E., De Cassai, A., Rosi, P., Polati, E., Donadello, K., Gottin, L., De Rosa, S., Baratto, F., Toffoletto, F., Ranieri, V. M., Gregori, D., Navalesi, P., Valeri, I., Andreatta, G., Gandolfi, L., Gadaldi, A., Brumana, N., Forin, E., Correale, C., Pesenti, E., Fregolent, D., Pirelli, P. F., Marchesin, D., Perona, M., Franchetti, N., Della Paolera, M., Simoni, C., Falcioni, T., Tresin, A., Schiavolin, C., Schiavi, A., Vathi, S., Sartori, D., Sorgato, A., Pistollato, E., Serra, E., Pittarello, D., Tiberio, I., Bond, O., Michieletto, E., Muraro, L., Peralta, A., Persona, P., Petranzan, E., Zarantonello, F., Graziano, A., Piasentini, E., Bernardi, L., Pianon, R., Badii, F., Bosco, E., Agostini, M., Farnia, A., Peta, M., Calo, M. A., Meggiolaro, M., Lazzari, F., Martinello, I., Fullin, G., Papaccio, F., Bonato, A., Sgarabotto, C., Montacciani, F., Alessandra, P., Gagliardi, G., Ferraro, G., Ongaro, L., Baiocchi, M., Danzi, V., Zanatta, P., Marchiotto, S., Bassanini, S., Zamperini, M., Daroui, I., Linassi, F., and Pettenuzzo, T.

Subjects
Male, ARDS, Supine position, COVID-19, Driving pressure, Mechanical ventilation, Respiratory system compliance, medicine.medical_treatment, Pulmonary compliance, Critical Care and Intensive Care Medicine, Hypoxemia, law.invention, 03 medical and health sciences, 0302 clinical medicine, law, Tidal Volume, Humans, Medicine, Tidal volume, Aged, Respiratory Distress Syndrome, RC86-88.9, business.industry, Respiration, Research, Medical emergencies. Critical care. Intensive care. First aid, 030208 emergency & critical care medicine, Middle Aged, medicine.disease, Respiration, Artificial, Intensive care unit, Intensive Care Units, Female, Intubation, Italy, 030228 respiratory system, Anesthesia, Artificial, medicine.symptom, business, Cohort study
Abstract

Background Pathophysiological features of coronavirus disease 2019-associated acute respiratory distress syndrome (COVID-19 ARDS) were indicated to be somewhat different from those described in nonCOVID-19 ARDS, because of relatively preserved compliance of the respiratory system despite marked hypoxemia. We aim ascertaining whether respiratory system static compliance (Crs), driving pressure (DP), and tidal volume normalized for ideal body weight (VT/kg IBW) at the 1st day of controlled mechanical ventilation are associated with intensive care unit (ICU) mortality in COVID-19 ARDS. Methods Observational multicenter cohort study. All consecutive COVID-19 adult patients admitted to 25 ICUs belonging to the COVID-19 VENETO ICU network (February 28th–April 28th, 2020), who received controlled mechanical ventilation, were screened. Only patients fulfilling ARDS criteria and with complete records of Crs, DP and VT/kg IBW within the 1st day of controlled mechanical ventilation were included. Crs, DP and VT/kg IBW were collected in sedated, paralyzed and supine patients. Results A total of 704 COVID-19 patients were screened and 241 enrolled. Seventy-one patients (29%) died in ICU. The logistic regression analysis showed that: (1) Crs was not linearly associated with ICU mortality (p value for nonlinearity = 0.01), with a greater risk of death for values 2O; (2) the association between DP and ICU mortality was linear (p value for nonlinearity = 0.68), and increasing DP from 10 to 14 cmH2O caused significant higher odds of in-ICU death (OR 1.45, 95% CI 1.06–1.99); (3) VT/kg IBW was not associated with a significant increase of the risk of death (OR 0.92, 95% CI 0.55–1.52). Multivariable analysis confirmed these findings. Conclusions Crs 2O was associated with ICU mortality, while DP was linearly associated with mortality. DP should be kept as low as possible, even in the case of relatively preserved Crs, irrespective of VT/kg IBW, to reduce the risk of death.

Published
2021

17. A survey on apolipoprotein A-I and B: the CNR study

Author

Roma, P., Fantappie, S., Baiocchi, M. R., Fellin, R., Avogaro, P., Cazzolato, G., Muntoni, S., Pintus, F., Giacchi, M., Salvi, M., Strano, A., Avellone, G., Mancini, M., Farinaro, E., Oriente, P., Postiglione, L., Urbinati, G., Antonini, R., Tenconi, M. T., Sottocornola, L., Catapano, A. L., Descovich, Giancarlo, editor, Gaddi, Antonio, editor, Magri, Gianluigi, editor, and Lenzi, Sergio, editor

Published
1990
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19. Correction to: Tocilizumab for patients with COVID-19 pneumonia. The single-arm TOCIVID-19 prospective trial (Journal of Translational Medicine, (2020), 18, 1, (405), 10.1186/s12967-020-02573-9)

Author

Perrone, F., Piccirillo, M. C., Ascierto, P. A., Salvarani, C., Parrella, R., Marata, A. M., Popoli, P., Ferraris, L., Marrocco-Trischitta, M. M., Ripamonti, D., Binda, F., Bonfanti, P., Squillace, N., Castelli, F., Muiesan, M. L., Lichtner, M., Calzetti, C., Salerno, N. D., Atripaldi, L., Cascella, M., Costantini, M., Dolci, G., Facciolongo, N. C., Fraganza, F., Massari, M., Montesarchio, V., Mussini, C., Negri, E. A., Botti, G., Cardone, C., Gargiulo, P., Gravina, A., Schettino, C., Arenare, L., Chiodini, P., Gallo, C., Vitale, M. G., Trojaniello, C., Palla, M., Bianchi, A. A. M., De Feo, G., Miscio, L., Chiodiniy, P., Froldi, M., Menicanti, L., Cuppone, M. T., Gobbo, G., Baldessari, C., Valenti, V., Castelvecchio, S., Poli, F., Giacomazzi, F., Piccinni, R., Annnunziata, M. L., Biondi, A., Bussolari, C., Mazzoleni, M., Giachi, A., Filtz, A., Manini, A., Poletti, E., Masserini, F., Conforti, F., Gaudiano, G., Favero, V., Moroni, A., Viva, T., Fancoli, F., Ferrari, D., Niro, D., Resta, M., Ballotta, A., Poli, M. D., Ranucci, M., Tebaldi, A., Gritti, G., Pasulo, L., Gaglio, L., Del Fabbro, R., Alborghetti, L., Giustinetti, G., Columpsi, P., Cazzaniga, M., Capici, S., Sala, L., Di Sciacca, R., Mosca, G., Pirozzi, M. R., Franceschini, F., Roccaro, A., Salvetti, M., Paini, A., Corda, L., Ricci, C., Tomasoni, L., Nasta, P., Lorenzotti, S., Odolini, S., Foca, E., Roldan, E. Q., Metra, M., Magrini, S., Borghetti, P., Latronico, N., Piva, S., Filippini, M., Tomasi, G., Zuccala, F., Cattaneo, S., Scolari, F., Bossini, N., Gaggiotti, M., Properzi, M., Del Borgo, C., Marocco, R., Belvisi, V., Tieghi, T., De Masi, M., Zuccala, P., Fabietti, P., Vetica, A., Mercurio, V. S., Carraro, A., Fondaco, L., Kertusha, B., Curtolo, A., Del Giudice, E., Lubrano, R., Zotti, M. 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G., Casella, O., Chiereleson, F., Costa, C., De Franco, D., Germana, G., Messina, A., Musumeci, D., Noto, C., Valenti, M., Sorrentino, C., Panico, R., Schettino, G., Piccoli, J., Pepe, A., De Rosa, F., Ottaviano, M., Marrazzo, G., Raponi, G., Diberardino, S., Bausi, S., Marini, S. F., Giubellino, E., Innocenti, G., Gugliemi, G., Maccari, D., and Baciu, I.

Subjects
tocilizumab, covid 19, pneumonia
Published
2021

20. Outcomes of COVID-19 patients intubated after failure of non-invasive ventilation: a multicenter observational study

Author

Boscolo, A., Pasin, L., Sella, N., Pretto, C., Tocco, M., Tamburini, E., Rosi, P., Polati, E., Donadello, K., Gottin, L., Vianello, A., Landoni, G., Navalesi, P., Valeri, I., Andreatta, G., Gandolfi, L., Gadaldi, A., Brumana, N., Forin, E., Correale, C., Fregolent, D., Pirelli, P. F., Marchesin, D., Perona, M., Franchetti, N., Paolera, M. D., Simoni, C., Falcioni, T., Tresin, A., Schiavolin, C., Schiavi, A., Vathi, S., Sartori, D., Sorgato, A., Pistollato, E., Golino, G. L., Frigo, L., Serra, E., Pittarello, D., Tiberio, I., Bond, O., Michieletto, E., Muraro, L., Peralta, A., Persona, P., Petranzan, E., Zarantonello, F., Graziano, A., De Cassai, A., Bernardi, L., Pianon, R., Badii, F., Bosco, E., Agostini, M., Trevisiol, P., Farnia, A., Peta, M., Altafini, L., Calo, M. A., Meggiolaro, M., Lazzari, F., Martinello, I., Fullin, G., Papaccio, F., Toffoletto, F., Bonato, A., Sgarabotto, C., Baratto, F., Montacciani, F., Parnigotto, A., Gagliardi, G., Gioconda, F., Ongaro, L., Baiocchi, M., Danzi, V., De Rosa, S., Zanatta, P., Sinigaglia, E., da Ros, A., Marchiotto, S., Bassanini, S., Zamperini, M., Daroui, I., Mosaner, W., Lembo, R., Linassi, F., and Pettenuzzo, T.

Subjects
Male, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Respiratory distress syndrome, Outcome Assessment, Science, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Endotracheal intubation, Article, law.invention, law, Risk Factors, Outcome Assessment, Health Care, medicine, Intubation, Intratracheal, Humans, Hospital Mortality, Aged, COVID-19, Female, Intensive Care Units, Logistic Models, Middle Aged, Multivariate Analysis, Noninvasive Ventilation, Respiratory Insufficiency, SARS-CoV-2, Multidisciplinary, business.industry, Intensive care unit, Icu admission, Health Care, Intratracheal, Multicenter study, Emergency medicine, Breathing, Medicine, Observational study, business, Intubation
Abstract

IntroductionThe efficacy of non-invasive ventilation (NIV) in acute respiratory failure secondary to SARS-CoV-2 infection remains controversial. Current literature mainly examined efficacy, safety and potential predictors of NIV failure provided out of the Intensive Care Unit (ICU). On the contrary, the outcomes of ICU patients, intubated after NIV failure, remain to be explored. The aims of the present study are: 1) investigating in-hospital mortality in coronavirus disease 2019 (COVID-19) ICU patients receiving endotracheal intubation after NIV failure and 2) assessing whether the length of NIV application affects patient survival. MethodsThis observational multicenter study included all consecutive COVID-19 adult patients, admitted into the twenty-five ICUs of the COVID-19 VENETO ICU network (February-April 2020), who underwent endotracheal intubation after NIV failure. ResultsAmong the 704 patients admitted to ICU during the study period, 280 (40%) presented the inclusion criteria and were enrolled. The median age was 69 [60-76] years; 219 patients (78%) were male. In-hospital mortality was 43%. Only the length of NIV application before ICU admission (OR 2.03 (95% CI 1.06 - 4.98), p = 0.03) and age (OR 1.18 (95% CI 1.04 - 1.33), p < 0.01) were identified as independent risk factors of in-hospital mortality; whilst the length of NIV after ICU admission did not affect patient outcome. ConclusionsIn-hospital mortality of ICU patients intubated after NIV failure was 43%. Days on NIV before ICU admission and age were assessed to be potential risk factors of greater in-hospital mortality.

Published
2021

21. Control of replication stress and mitosis in colorectal cancer stem cells through the interplay of PARP1, MRE11 and RAD51

Author

Manic, G., Musella, Martina, Corradi, F., Sistigu, Antonella, Vitale, Sara, Soliman Abdel Rehim, S., Mattiello, L., Malacaria, E., Galassi, Claudia, Signore, M., Pallocca, M., Scalera, S., Goeman, F., De Nicola, F., Guarracino, A., Pennisi, Riccardo, Antonangeli, F., Sperati, F., Baiocchi, M., Biffoni, M., Fanciulli, M., Maugeri-Sacca, M., Franchitto, A., Pichierri, P., De Maria Marchiano, Ruggero, Vitale, I., Musella M., Sistigu A. (ORCID:0000-0002-2528-1238), Vitale S., Galassi C., Pennisi R., De Maria R. (ORCID:0000-0003-2255-0583), Manic, G., Musella, Martina, Corradi, F., Sistigu, Antonella, Vitale, Sara, Soliman Abdel Rehim, S., Mattiello, L., Malacaria, E., Galassi, Claudia, Signore, M., Pallocca, M., Scalera, S., Goeman, F., De Nicola, F., Guarracino, A., Pennisi, Riccardo, Antonangeli, F., Sperati, F., Baiocchi, M., Biffoni, M., Fanciulli, M., Maugeri-Sacca, M., Franchitto, A., Pichierri, P., De Maria Marchiano, Ruggero, Vitale, I., Musella M., Sistigu A. (ORCID:0000-0002-2528-1238), Vitale S., Galassi C., Pennisi R., and De Maria R. (ORCID:0000-0003-2255-0583)

Abstract

Cancer stem cells (CSCs) are tumor subpopulations driving disease development, progression, relapse and therapy resistance, and their targeting ensures tumor eradication. CSCs display heterogeneous replication stress (RS), but the functionality/relevance of the RS response (RSR) centered on the ATR-CHK1 axis is debated. Here, we show that the RSR is efficient in primary CSCs from colorectal cancer (CRC-SCs), and describe unique roles for PARP1 and MRE11/RAD51. First, we demonstrated that PARP1 is upregulated in CRC-SCs resistant to several replication poisons and RSR inhibitors (RSRi). In these cells, PARP1 modulates replication fork speed resulting in low constitutive RS. Second, we showed that MRE11 and RAD51 cooperate in the genoprotection and mitosis execution of PARP1-upregulated CRC-SCs. These roles represent therapeutic vulnerabilities for CSCs. Indeed, PARP1i sensitized CRC-SCs to ATRi/CHK1i, inducing replication catastrophe, and prevented the development of resistance to CHK1i. Also, MRE11i + RAD51i selectively killed PARP1-upregulated CRC-SCs via mitotic catastrophe. These results provide the rationale for biomarker-driven clinical trials in CRC using distinct RSRi combinations.

Published
2021

23. Use of critical care resources during the first 2 weeks (February 24–March 8, 2020) of the Covid-19 outbreak in Italy

Author

Tonetti, T., Grasselli, G., Zanella, A., Pizzilli, G., Fumagalli, R., Piva, S., Lorini, L., Iotti, G., Foti, G., Colombo, S., Vivona, L., Rossi, S., Girardis, M., Agnoletti, V., Campagna, A., Gordini, G., Navalesi, P., Boscolo, A., Graziano, A., Valeri, I., Vianello, A., Cereda, D., Filippini, C., Cecconi, M., Locatelli, Franco, Bartoletti, M., Giannella, M., Viale, P., Antonelli, M., Nava, S., Pesenti, A., Ranieri, V. M., Albano, G., Alborghetti, A., Aldegheri, G., Antonini, B., Belgiorno, N., Bellani, G., Beretta, E., Bonazzi, S., Borelli, M., Cabrini, L., Carnevale, L., Carnevale, S., Castelli, G., Catena, E., Chiumello, D., Coluccello, A., Coppini, D., Covello, D., Defilippi, G., Deipoli, M., Dughi, P., Gallioli, G., Gnesin, P., Greco, S., Guatteri, L., Guzzon, D., Keim, R., Landoni, G., Langer, T., Lombardo, A., Marino, G., Merli, G., Merlo, D., Mojoli, F., Muttini, S., Natalini, G., Petrucci, N., Pezzi, A., Radrizzani, D., Raimondi, M., Riccio, M., Storti, E., Tavola, M., Vitale, G., Bosco, E., Calo, M. A., Danzi, V., Derosa, S., Farnia, A., Lazzari, F., Meggiolaro, M., Munari, M., Saia, M., Sella, N., Serra, E., Tiberio, I., Baiocchi, M., Benedetto, M., Bordini, M., Caramelli, F., Cilloni, N., Dellagiovampaola, M., Fanelli, A., Frascaroli, G., Fusari, M., Maitan, S., Martino, C., Melotti, R. M., Merola, R., Minardi, F., Moro, F., Nardi, G., Nolli, M., Pierucci, E., Potalivo, A., Repetti, F., Salsi, P., Terzitta, M., Tosi, M., Venturi, S., Volta, C. A., Zani, G., Zanoni, A., Locatelli F. (ORCID:0000-0002-7976-3654), Tonetti, T., Grasselli, G., Zanella, A., Pizzilli, G., Fumagalli, R., Piva, S., Lorini, L., Iotti, G., Foti, G., Colombo, S., Vivona, L., Rossi, S., Girardis, M., Agnoletti, V., Campagna, A., Gordini, G., Navalesi, P., Boscolo, A., Graziano, A., Valeri, I., Vianello, A., Cereda, D., Filippini, C., Cecconi, M., Locatelli, Franco, Bartoletti, M., Giannella, M., Viale, P., Antonelli, M., Nava, S., Pesenti, A., Ranieri, V. M., Albano, G., Alborghetti, A., Aldegheri, G., Antonini, B., Belgiorno, N., Bellani, G., Beretta, E., Bonazzi, S., Borelli, M., Cabrini, L., Carnevale, L., Carnevale, S., Castelli, G., Catena, E., Chiumello, D., Coluccello, A., Coppini, D., Covello, D., Defilippi, G., Deipoli, M., Dughi, P., Gallioli, G., Gnesin, P., Greco, S., Guatteri, L., Guzzon, D., Keim, R., Landoni, G., Langer, T., Lombardo, A., Marino, G., Merli, G., Merlo, D., Mojoli, F., Muttini, S., Natalini, G., Petrucci, N., Pezzi, A., Radrizzani, D., Raimondi, M., Riccio, M., Storti, E., Tavola, M., Vitale, G., Bosco, E., Calo, M. A., Danzi, V., Derosa, S., Farnia, A., Lazzari, F., Meggiolaro, M., Munari, M., Saia, M., Sella, N., Serra, E., Tiberio, I., Baiocchi, M., Benedetto, M., Bordini, M., Caramelli, F., Cilloni, N., Dellagiovampaola, M., Fanelli, A., Frascaroli, G., Fusari, M., Maitan, S., Martino, C., Melotti, R. M., Merola, R., Minardi, F., Moro, F., Nardi, G., Nolli, M., Pierucci, E., Potalivo, A., Repetti, F., Salsi, P., Terzitta, M., Tosi, M., Venturi, S., Volta, C. A., Zani, G., Zanoni, A., and Locatelli F. (ORCID:0000-0002-7976-3654)

Abstract

Background: A Covid-19 outbreak developed in Lombardy, Veneto and Emilia-Romagna (Italy) at the end of February 2020. Fear of an imminent saturation of available ICU beds generated the notion that rationing of intensive care resources could have been necessary. Results: In order to evaluate the impact of Covid-19 on the ICU capacity to manage critically ill patients, we performed a retrospective analysis of the first 2 weeks of the outbreak (February 24–March 8). Data were collected from regional registries and from a case report form sent to participating sites. ICU beds increased from 1545 to 1989 (28.7%), and patients receiving respiratory support outside the ICU increased from 4 (0.6%) to 260 (37.0%). Patients receiving respiratory support outside the ICU were significantly older [65 vs. 77 years], had more cerebrovascular (5.8 vs. 13.1%) and renal (5.3 vs. 10.0%) comorbidities and less obesity (31.4 vs. 15.5%) than patients admitted to the ICU. PaO2/FiO2 ratio, respiratory rate and arterial pH were higher [165 vs. 244; 20 vs. 24 breath/min; 7.40 vs. 7.46] and PaCO2 and base excess were lower [34 vs. 42 mmHg; 0.60 vs. 1.30] in patients receiving respiratory support outside the ICU than in patients admitted to the ICU, respectively. Conclusions: Increase in ICU beds and use of out-of-ICU respiratory support allowed effective management of the first 14 days of the Covid-19 outbreak, avoiding resource rationing.

Published
2020

24. A pre-existing population of ZEB2+ quiescent cells with stemness and mesenchymal features dictate chemoresistance in colorectal cancer

Author

Francescangeli, F., Contavalli, Paola, De Angelis, M. L., Careccia, Silvia, Signore, M., Haas, Tobias Longin, Salaris, F., Baiocchi, M., Boe, A., Giuliani, A., Tcheremenskaia, O., Pagliuca, A., Guardiola, O., Minchiotti, G., Colace, L., Ciardi, A., D'Andrea, V., La Torre, F., Medema, J., De Maria Marchiano, Ruggero, Zeuner, A., Contavalli P., Careccia S., Haas T. L. (ORCID:0000-0003-2336-0263), De Maria R. (ORCID:0000-0003-2255-0583), Francescangeli, F., Contavalli, Paola, De Angelis, M. L., Careccia, Silvia, Signore, M., Haas, Tobias Longin, Salaris, F., Baiocchi, M., Boe, A., Giuliani, A., Tcheremenskaia, O., Pagliuca, A., Guardiola, O., Minchiotti, G., Colace, L., Ciardi, A., D'Andrea, V., La Torre, F., Medema, J., De Maria Marchiano, Ruggero, Zeuner, A., Contavalli P., Careccia S., Haas T. L. (ORCID:0000-0003-2336-0263), and De Maria R. (ORCID:0000-0003-2255-0583)

Abstract

Background : Quiescent/slow cycling cells have been identified in several tumors and correlated with therapy resistance. However, the features of chemoresistant populations and the molecular factors linking quiescence to chemoresistance are largely unknown. Methods: A population of chemoresistant quiescent/slow cycling cells was isolated through PKH26 staining (which allows to separate cells on the basis of their proliferation rate) from colorectal cancer (CRC) xenografts and subjected to global gene expression and pathway activation analyses. Factors expressed by the quiescent/slow cycling population were analyzed through lentiviral overexpression approaches for their ability to induce a dormant chemoresistant state both in vitro and in mouse xenografts. The correlation between quiescence-associated factors, CRC consensus molecular subtype and cancer prognosis was analyzed in large patient datasets. Results: Untreated colorectal tumors contain a population of quiescent/slow cycling cells with stem cell features (quiescent cancer stem cells, QCSCs) characterized by a predetermined mesenchymal-like chemoresistant phenotype. QCSCs expressed increased levels of ZEB2, a transcription factor involved in stem cell plasticity and epithelial-mesenchymal transition (EMT), and of antiapototic factors pCRAF and pASK1. ZEB2 overexpression upregulated pCRAF/pASK1 levels resulting in increased chemoresistance, enrichment of cells with stemness/EMT traits and proliferative slowdown of tumor xenografts. In parallel, chemotherapy treatment of tumor xenografts induced the prevalence of QCSCs with a stemness/EMT phenotype and activation of the ZEB2/pCRAF/pASK1 axis, resulting in a chemotherapy-unresponsive state. In CRC patients, increased ZEB2 levels correlated with worse relapse-free survival and were strongly associated to the consensus molecular subtype 4 (CMS4) characterized by dismal prognosis, decreased proliferative rates and upregulation of EMT genes. Conclusions: These resul

Published
2020

26. MortalitY in caRdIAc surgery (MYRIAD): A randomizeD controlled trial of volatile anesthetics. Rationale and design

Author

Landoni, G, Lomivorotov, V, Pisano, A, Nigro Neto, C, Benedetto, U, Biondi Zoccai, G, Gemma, M, Frassoni, S, Agro, F, Baiocchi, M, Barbosa Gomes Galas, F, Bautin, A, Bradic, N, Carollo, C, Crescenzi, G, Elnakera, A, El-Tahan, M, Fominskiy, E, Farag, A, Gazivoda, G, Gianni, S, Grigoryev, E, Guarracino, F, Hanafi, S, Huang, W, Kunst, G, Kunstyr, J, Lei, C, Lembo, R, Li, Z, Likhvantsev, V, Lozovskiy, A, Ma, J, Monaco, F, Navalesi, P, Nazar, B, Pasyuga, V, Porteri, E, Royse, C, Ruggeri, L, Riha, H, Santos Silva, F, Severi, L, Shmyrev, V, Uvaliev, N, Wang, C, Winterton, D, Yong, C, Yu, J, Bellomo, R, Zangrillo, A, Landoni G., Lomivorotov V., Pisano A., Nigro Neto C., Benedetto U., Biondi Zoccai G., Gemma M., Frassoni S., Agro F. E., Baiocchi M., Barbosa Gomes Galas F. R., Bautin A., Bradic N., Carollo C., Crescenzi G., Elnakera A. M., El-Tahan M. R., Fominskiy E., Farag A. G., Gazivoda G., Gianni S., Grigoryev E., Guarracino F., Hanafi S., Huang W., Kunst G., Kunstyr J., Lei C., Lembo R., Li Z. -J., Likhvantsev V., Lozovskiy A., Ma J., Monaco F., Navalesi P., Nazar B., Pasyuga V., Porteri E., Royse C., Ruggeri L., Riha H., Santos Silva F., Severi L., Shmyrev V., Uvaliev N., Wang C. B., Wang C. -Y., Winterton D., Yong C. -Y., Yu J., Bellomo R., Zangrillo A., Landoni, G, Lomivorotov, V, Pisano, A, Nigro Neto, C, Benedetto, U, Biondi Zoccai, G, Gemma, M, Frassoni, S, Agro, F, Baiocchi, M, Barbosa Gomes Galas, F, Bautin, A, Bradic, N, Carollo, C, Crescenzi, G, Elnakera, A, El-Tahan, M, Fominskiy, E, Farag, A, Gazivoda, G, Gianni, S, Grigoryev, E, Guarracino, F, Hanafi, S, Huang, W, Kunst, G, Kunstyr, J, Lei, C, Lembo, R, Li, Z, Likhvantsev, V, Lozovskiy, A, Ma, J, Monaco, F, Navalesi, P, Nazar, B, Pasyuga, V, Porteri, E, Royse, C, Ruggeri, L, Riha, H, Santos Silva, F, Severi, L, Shmyrev, V, Uvaliev, N, Wang, C, Winterton, D, Yong, C, Yu, J, Bellomo, R, Zangrillo, A, Landoni G., Lomivorotov V., Pisano A., Nigro Neto C., Benedetto U., Biondi Zoccai G., Gemma M., Frassoni S., Agro F. E., Baiocchi M., Barbosa Gomes Galas F. R., Bautin A., Bradic N., Carollo C., Crescenzi G., Elnakera A. M., El-Tahan M. R., Fominskiy E., Farag A. G., Gazivoda G., Gianni S., Grigoryev E., Guarracino F., Hanafi S., Huang W., Kunst G., Kunstyr J., Lei C., Lembo R., Li Z. -J., Likhvantsev V., Lozovskiy A., Ma J., Monaco F., Navalesi P., Nazar B., Pasyuga V., Porteri E., Royse C., Ruggeri L., Riha H., Santos Silva F., Severi L., Shmyrev V., Uvaliev N., Wang C. B., Wang C. -Y., Winterton D., Yong C. -Y., Yu J., Bellomo R., and Zangrillo A.

Abstract

Objective There is initial evidence that the use of volatile anesthetics can reduce the postoperative release of cardiac troponin I, the need for inotropic support, and the number of patients requiring prolonged hospitalization following coronary artery bypass graft (CABG) surgery. Nevertheless, small randomized controlled trials have failed to demonstrate a survival advantage. Thus, whether volatile anesthetics improve the postoperative outcome of cardiac surgical patients remains uncertain. An adequately powered randomized controlled trial appears desirable. Design Single blinded, international, multicenter randomized controlled trial with 1:1 allocation ratio. Setting Tertiary and University hospitals. Interventions Patients (n = 10,600) undergoing coronary artery bypass graft will be randomized to receive either volatile anesthetic as part of the anesthetic plan, or total intravenous anesthesia. Measurements and main results The primary end point of the study will be one-year mortality (any cause). Secondary endpoints will be 30-day mortality; 30-day death or non-fatal myocardial infarction (composite endpoint); cardiac mortality at 30 day and at one year; incidence of hospital re-admission during the one year follow-up period and duration of intensive care unit, and hospital stay. The sample size is based on the hypothesis that volatile anesthetics will reduce 1-year unadjusted mortality from 3% to 2%, using a two-sided alpha error of 0.05, and a power of 0.9. Conclusions The trial will determine whether the simple intervention of adding a volatile anesthetic, an intervention that can be implemented by all anesthesiologists, can improve one-year survival in patients undergoing coronary artery bypass graft surgery.

Published
2017

28. A new bioavailable fenretinide formulation with antiproliferative, antimetabolic, and cytotoxic effects on solid tumors

Author

Orienti, I., Francescangeli, F., De Angelis, M. L., Fecchi, K., Bongiorno-Borbone, L., Signore, M., Peschiaroli, A., Boe, A., Bruselles, A., Costantino, A., Eramo, A., Salvati, V., Sette, G., Contavalli, P., Zolla, L., Oki, T., Kitamura, T., Spada, M., Giuliani, A., Baiocchi, M., La Torre, F., Melino, G., Tartaglia, M., De Maria, R., Zeuner, A., Salvati V., Sette G., Contavalli P., Spada M., De Maria R. (ORCID:0000-0003-2255-0583), Orienti, I., Francescangeli, F., De Angelis, M. L., Fecchi, K., Bongiorno-Borbone, L., Signore, M., Peschiaroli, A., Boe, A., Bruselles, A., Costantino, A., Eramo, A., Salvati, V., Sette, G., Contavalli, P., Zolla, L., Oki, T., Kitamura, T., Spada, M., Giuliani, A., Baiocchi, M., La Torre, F., Melino, G., Tartaglia, M., De Maria, R., Zeuner, A., Salvati V., Sette G., Contavalli P., Spada M., and De Maria R. (ORCID:0000-0003-2255-0583)

Abstract

Fenretinide is a synthetic retinoid characterized by anticancer activity in preclinical models and favorable toxicological profile, but also by a low bioavailability that hindered its clinical efficacy in former clinical trials. We developed a new formulation of fenretinide complexed with 2-hydroxypropyl-beta-cyclodextrin (nanofenretinide) characterized by an increased bioavailability and therapeutic efficacy. Nanofenretinide was active in cell lines derived from multiple solid tumors, in primary spheroid cultures and in xenografts of lung and colorectal cancer, where it inhibited tumor growth independently from the mutational status of tumor cells. A global profiling of pathways activated by nanofenretinide was performed by reverse-phase proteomic arrays and lipid analysis, revealing widespread repression of the mTOR pathway, activation of apoptotic, autophagic and DNA damage signals and massive production of dihydroceramide, a bioactive lipid with pleiotropic effects on several biological processes. In cells that survived nanofenretinide treatment there was a decrease of factors involved in cell cycle progression and an increase in the levels of p16 and phosphorylated p38 MAPK with consequent block in G0 and early G1. The capacity of nanofenretinide to induce cancer cell death and quiescence, together with its elevated bioavailability and broad antitumor activity indicate its potential use in cancer treatment and chemoprevention.

Published
2019

29. A novel oral micellar fenretinide formulation with enhanced bioavailability and antitumour activity against multiple tumours from cancer stem cells

Author

Orienti, I., Salvati, Valentina, Sette, Giovanni, Zucchetti, M., Bongiorno-Borbone, L., Peschiaroli, A., Zolla, L., Francescangeli, F., Ferrari, M., Matteo, C., Bello, E., Di Virgilio, A., Falchi, M., De Angelis, M. L., Baiocchi, M., Melino, G., De Maria Marchiano, Ruggero, Zeuner, A., Eramo, A., Salvati V., Sette G., De Maria R. (ORCID:0000-0003-2255-0583), Orienti, I., Salvati, Valentina, Sette, Giovanni, Zucchetti, M., Bongiorno-Borbone, L., Peschiaroli, A., Zolla, L., Francescangeli, F., Ferrari, M., Matteo, C., Bello, E., Di Virgilio, A., Falchi, M., De Angelis, M. L., Baiocchi, M., Melino, G., De Maria Marchiano, Ruggero, Zeuner, A., Eramo, A., Salvati V., Sette G., and De Maria R. (ORCID:0000-0003-2255-0583)

Abstract

Background: An increasing number of anticancer agents has been proposed in recent years with the attempt to overcome treatment-resistant cancer cells and particularly cancer stem cells (CSC), the major culprits for tumour resistance and recurrence. However, a huge obstacle to treatment success is the ineffective delivery of drugs within the tumour environment due to limited solubility, short circulation time or inconsistent stability of compounds that, together with concomitant dose-limiting systemic toxicity, contribute to hamper the achievement of therapeutic drug concentrations. The synthetic retinoid Fenretinide (4-hydroxy (phenyl)retinamide; 4-HPR) formerly emerged as a promising anticancer agent based on pre-clinical and clinical studies. However, a major limitation of fenretinide is traditionally represented by its poor aqueous solubility/bioavailability due to its hydrophobic nature, that undermined the clinical success of previous clinical trials. Methods: Here, we developed a novel nano-micellar fenretinide formulation called bionanofenretinide (Bio-nFeR), based on drug encapsulation in an ion-pair stabilized lipid matrix, with the aim to raise fenretinide bioavailability and antitumour efficacy. Results: Bio-nFeR displayed marked antitumour activity against lung, colon and melanoma CSC both in vitro and in tumour xenografts, in absence of mice toxicity. Bio-nFeR is suitable for oral administration, reaching therapeutic concentrations within tumours and an unprecedented therapeutic activity in vivo as single agent. Conclusion: Altogether, our results indicate Bio-nFeR as a novel anticancer agent with low toxicity and high activity against tumourigenic cells, potentially useful for the treatment of solid tumours of multiple origin.

Published
2019

31. A Specific Mutational Signature Associated with DNA 8-Oxoguanine Persistence in MUTYH-defective Colorectal Cancer.

Author

Viel, A, Bruselles, A, Meccia, E, Fornasarig, M, Quaia, M, Canzonieri, V, Policicchio, E, Urso, Ed, Agostini, M, Genuardi, Maurizio, Lucci Cordisco, Emanuela, Venesio, T, Martayan, Aline, Diodoro, Mg, Sanchez-Mete, L, Stigliano, V, Mazzei, Francesca, Grasso, F, Giuliani, Alessandro, Baiocchi, M, Maestro, R, Giannini, G, Tartaglia, Marco, Alexandrov, Lb, Bignami, M., Genuardi M (ORCID:0000-0002-7410-8351), Lucci-Cordisco E (ORCID:0000-0002-6279-7604), Martayan A, Tartaglia M, Viel, A, Bruselles, A, Meccia, E, Fornasarig, M, Quaia, M, Canzonieri, V, Policicchio, E, Urso, Ed, Agostini, M, Genuardi, Maurizio, Lucci Cordisco, Emanuela, Venesio, T, Martayan, Aline, Diodoro, Mg, Sanchez-Mete, L, Stigliano, V, Mazzei, Francesca, Grasso, F, Giuliani, Alessandro, Baiocchi, M, Maestro, R, Giannini, G, Tartaglia, Marco, Alexandrov, Lb, Bignami, M., Genuardi M (ORCID:0000-0002-7410-8351), Lucci-Cordisco E (ORCID:0000-0002-6279-7604), Martayan A, and Tartaglia M

Abstract

8-Oxoguanine, a common mutagenic DNA lesion, generates G:C>T:A transversions via mispairing with adenine during DNA replication. When operating normally, the MUTYH DNA glycosylase prevents 8-oxoguanine-related mutagenesis by excising the incorporated adenine. Biallelic MUTYH mutations impair this enzymatic function and are associated with colorectal cancer (CRC) in MUTYH-Associated Polyposis (MAP) syndrome. Here, we perform whole-exome sequencing that reveals a modest mutator phenotype in MAP CRCs compared to sporadic CRC stem cell lines or bulk tumours. The excess G:C>T:A transversion mutations in MAP CRCs exhibits a novel mutational signature, termed Signature 36, with a strong sequence dependence. The MUTYH mutational signature reflecting persistent 8-oxoG:A mismatches occurs frequently in the APC, KRAS, PIK3CA, FAT4, TP53, FAT1, AMER1, KDM6A, SMAD4 and SMAD2 genes that are associated with CRC. The occurrence of Signature 36 in other types of human cancer indicates that DNA 8-oxoguanine-related mutations might contribute to the development of cancer in other organs.

Published
2017

32. CHK1-targeted therapy to deplete DNA replication- stressed, p53-deficient, hyperdiploid colorectal cancer stem cells

Author

Manic, G, Signore, M, Sistigu, Antonella, Russo, Giorgio, Corradi, F, Siteni, S, Musella, Marco, Vitale, Sara, De Angelis, Maria Laura, Pallocca, M, Amoreo, Ca, Sperati, F, Di Franco, S, Barresi, S, Policicchio, E, De Luca, G, De Nicola, F, Mottolese, M, Zeuner, A, Fanciulli, M, Stassi, G, Maugeri-Saccà, M, Baiocchi, M, Tartaglia, Marco, Vitale, Ilio, De Maria Marchiano, Ruggero, Sistigu A (ORCID:0000-0002-2528-1238), Russo G, Musella M, Vitale S, De Angelis ML, Tartaglia M, Vitale I, De Maria Marchiano (ORCID:0000-0003-2255-0583), Manic, G, Signore, M, Sistigu, Antonella, Russo, Giorgio, Corradi, F, Siteni, S, Musella, Marco, Vitale, Sara, De Angelis, Maria Laura, Pallocca, M, Amoreo, Ca, Sperati, F, Di Franco, S, Barresi, S, Policicchio, E, De Luca, G, De Nicola, F, Mottolese, M, Zeuner, A, Fanciulli, M, Stassi, G, Maugeri-Saccà, M, Baiocchi, M, Tartaglia, Marco, Vitale, Ilio, De Maria Marchiano, Ruggero, Sistigu A (ORCID:0000-0002-2528-1238), Russo G, Musella M, Vitale S, De Angelis ML, Tartaglia M, Vitale I, and De Maria Marchiano (ORCID:0000-0003-2255-0583)

Abstract

Objective Cancer stem cells (CSCs) are responsible for tumour formation and spreading, and their targeting is required for tumour eradication. There are limited therapeutic options for advanced colorectal cancer (CRC), particularly for tumours carrying RAS-activating mutations. The aim of this study was to identify novel CSC-targeting strategies. Design To discover potential therapeutics to be clinically investigated as single agent, we performed a screening with a panel of FDA-approved or investigational drugs on primary CRC cells enriched for CSCs (CRC-SCs) isolated from 27 patients. Candidate predictive biomarkers of efficacy were identified by integrating genomic, reverse-phase protein microarray (RPPA) and cytogenetic analyses, and validated by immunostainings. DNA replication stress (RS) was increased by employing DNA replication-perturbing or polyploidising agents. Results The drug-library screening led to the identification of LY2606368 as a potent anti-CSC agent acting in vitro and in vivo in tumour cells from a considerable number of patients (∼36%). By inhibiting checkpoint kinase (CHK)1, LY2606368 affected DNA replication in most CRC-SCs, including RAS-mutated ones, forcing them into premature, lethal mitoses. Parallel genomic, RPPA and cytogenetic analyses indicated that CRC-SCs sensitive to LY2606368 displayed signs of ongoing RS response, including the phosphorylation of RPA32 and ataxia telangiectasia mutated serine/threonine kinase (ATM). This was associated with mutation(s) in TP53 and hyperdiploidy, and made these CRC-SCs exquisitely dependent on CHK1 function. Accordingly, experimental increase of RS sensitised resistant CRC-SCs to LY2606368. Conclusions LY2606368 selectively eliminates replication-stressed, p53-deficient and hyperdiploid CRC-SCs independently of RAS mutational status. These results provide a strong rationale for biomarker-driven clinical trials with LY2606368 in patients with CRC.

Published
2017

34. The natural history of the normal/mild elevated TSH serum levels in children and adolescents with Hashimoto's thyroiditis and isolated hyperthyrotropinaemia: a three year follow-up

Author

Radetti G., Maselli M., Buzi F., Corrias A., Mussa A., Cambiaso P., Cappa M., Baiocchi M., Gastaldi R., Minerba L., Loche S., SALERNO, MARIACAROLINA, Radetti, G., Maselli, M., Buzi, F., Corrias, A., Mussa, A., Cambiaso, P., Salerno, Mariacarolina, Cappa, M., Baiocchi, M., Gastaldi, R., Minerba, L., and Loche, S.

Subjects
Hashimoto's Thyroiditi, TSH, Hyperthyrotropinaemia
Abstract

Objective: The natural history of Hashimoto's thyroiditis (HT), and of isolated hyperthyrotropinaemia (IH) is not well defined. We therefore studied the natural course of patients with HT and IH and looked for possible prognostic factors. Design: Retrospective cross-sectional study Patients: 323 patients with HT (88 m and 235 f,), and 59 with IH (30 m, 29 f), mean age 9.9 ± 3.8 yrs were included in the study. When first examined, 236 of the children with HT had a normal TSH (G0) and in 87, it was elevated but

Published
2012

38. Dynamic regulation of the cancer stem cell compartment by Cripto-1 in colorectal cancer

Author

Francescangeli, Federica, Contavalli, Paola, De Angelis, Maria Laura, Baiocchi, M., Gambara, G., Pagliuca, Alfredo, Fiorenzano, A., Prezioso, C., Boe, A., Todaro, M., Stassi, G., Castro, N. P., Watanabe, K., Salomon, D. S., De Maria Marchiano, Ruggero, Minchiotti, G., Zeuner, A., Francescangeli, F., Contavalli, P., De Angelis, M. L., Pagliuca, A., De Maria Marchiano, R. (ORCID:0000-0003-2255-0583), Francescangeli, Federica, Contavalli, Paola, De Angelis, Maria Laura, Baiocchi, M., Gambara, G., Pagliuca, Alfredo, Fiorenzano, A., Prezioso, C., Boe, A., Todaro, M., Stassi, G., Castro, N. P., Watanabe, K., Salomon, D. S., De Maria Marchiano, Ruggero, Minchiotti, G., Zeuner, A., Francescangeli, F., Contavalli, P., De Angelis, M. L., Pagliuca, A., and De Maria Marchiano, R. (ORCID:0000-0003-2255-0583)

Abstract

Stemness was recently depicted as a dynamic condition in normal and tumor cells. We found that the embryonic protein Cripto-1 (CR1) was expressed by normal stem cells at the bottom of colonic crypts and by cancer stem cells (CSCs) in colorectal tumor tissues. CR1-positive populations isolated from patient-derived tumor spheroids exhibited increased clonogenic capacity and expression of stem-cell-related genes. CR1 expression in tumor spheroids was variable over time, being subject to a complex regulation of the intracellular, surface and secreted protein, which was related to changes of the clonogenic capacity at the population level. CR1 silencing induced CSC growth arrest in vitro with a concomitant decrease of SrcAkt signaling, while in vivo it inhibited the growth of CSC-derived tumor xenografts and reduced CSC numbers. Importantly, CR1 silencing in established xenografts through an inducible expression system decreased CSC growth in both primary and metastatic tumors, indicating an essential role of CR1 in the regulation the CSC compartment. These results point to CR1 as a novel and dynamically regulated effector of stem cell functions in colorectal cancer.

Published
2015

41. Dynamic regulation of the cancer stem cell compartment by Cripto-1 in colorectal cancer

Author

Francescangeli, F, primary, Contavalli, P, additional, De Angelis, M L, additional, Baiocchi, M, additional, Gambara, G, additional, Pagliuca, A, additional, Fiorenzano, A, additional, Prezioso, C, additional, Boe, A, additional, Todaro, M, additional, Stassi, G, additional, Castro, N P, additional, Watanabe, K, additional, Salomon, D S, additional, De Maria, R, additional, Minchiotti, G, additional, and Zeuner, A, additional

Published
2015
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43. Elimination of quiescent/slow-proliferating cancer stem cells by Bcl-XL inhibition in non-small cell lung cancer

Author

Zeuner, A., Francescangeli, F., Contavalli, P., Zapparelli, G., Apuzzo, T., Eramo, A., Baiocchi, M., De Angelis, M. L., Biffoni, M., Sette, G., Todaro, M., Stassi, G., De Maria Marchiano, R., De Maria Marchiano, R. (ORCID:0000-0003-2255-0583), Zeuner, A., Francescangeli, F., Contavalli, P., Zapparelli, G., Apuzzo, T., Eramo, A., Baiocchi, M., De Angelis, M. L., Biffoni, M., Sette, G., Todaro, M., Stassi, G., De Maria Marchiano, R., and De Maria Marchiano, R. (ORCID:0000-0003-2255-0583)

Abstract

Lung cancer is the most common cause of cancer-related mortality worldwide, urging the discovery of novel molecular targets and therapeutic strategies. Stem cells have been recently isolated from non-small cell lung cancer (NSCLC), thus allowing the investigation of molecular pathways specifically active in the tumorigenic population. We have found that Bcl-XL is constantly expressed by lung cancer stem cells (LCSCs) and has a prominent role in regulating LCSC survival. Whereas chemotherapeutic agents were scarcely effective against LCSC, the small molecule Bcl-2/Bcl-XL inhibitor ABT-737, but not the selective Bcl-2 inhibitor ABT-199, induced LCSC death at nanomolar concentrations. Differently from gemcitabine, which preferentially eliminated proliferating LCSC, ABT-737 had an increased cytotoxic activity in vitro towards quiescent/slow-proliferating LCSC, which expressed high levels of Bcl-XL. In vivo, ABT-737 as a single agent was able to inhibit the growth of LCSC-derived xenografts and to reduce cancer stem cell content in treated tumors. Altogether, these results indicate that quiescent/slow-proliferating LCSC strongly depend on Bcl-XL for their survival and indicate Bcl-XL inhibition as a potential therapeutic avenue in NSCLC.

Published
2014

44. Elimination of quiescent/slow-proliferating cancer stem cells by Bcl-XL inhibition in non-small cell lung cancer

Author

Zeuner, A, Francescangeli, F, Contavalli, Paola, Zapparelli, G, Apuzzo, T, Eramo, A, Baiocchi, M, De Angelis, M. L, Biffoni, M, Sette, G, Todaro, M, Stassi, G, De Maria Marchiano, Ruggero, De Maria Marchiano, Ruggero (ORCID:0000-0003-2255-0583), Zeuner, A, Francescangeli, F, Contavalli, Paola, Zapparelli, G, Apuzzo, T, Eramo, A, Baiocchi, M, De Angelis, M. L, Biffoni, M, Sette, G, Todaro, M, Stassi, G, De Maria Marchiano, Ruggero, and De Maria Marchiano, Ruggero (ORCID:0000-0003-2255-0583)

Abstract

Lung cancer is the most common cause of cancer-related mortality worldwide, urging the discovery of novel molecular targets and therapeutic strategies. Stem cells have been recently isolated from non-small cell lung cancer (NSCLC), thus allowing the investigation of molecular pathways specifically active in the tumorigenic population. We have found that Bcl-XL is constantly expressed by lung cancer stem cells (LCSCs) and has a prominent role in regulating LCSC survival. Whereas chemotherapeutic agents were scarcely effective against LCSC, the small molecule Bcl-2/Bcl-XL inhibitor ABT-737, but not the selective Bcl-2 inhibitor ABT-199, induced LCSC death at nanomolar concentrations. Differently from gemcitabine, which preferentially eliminated proliferating LCSC, ABT-737 had an increased cytotoxic activity in vitro towards quiescent/slow-proliferating LCSC, which expressed high levels of Bcl-XL. In vivo, ABT-737 as a single agent was able to inhibit the growth of LCSC-derived xenografts and to reduce cancer stem cell content in treated tumors. Altogether, these results indicate that quiescent/slow-proliferating LCSC strongly depend on Bcl-XL for their survival and indicate Bcl-XL inhibition as a potential therapeutic avenue in NSCLC.

Published
2014

48. Aortic valve-sparing operation: is long-term durability satisfactory?

Author

Martin Suarez, Sofia, Davide Pacini, Di Marco, Luca, Botta, Luca, Baiocchi, M., Bracchetti, Giovanni, Francesco Dimitri Petridis, roberto di bartolomeo, S. Martin Suarez, D. Pacini, L. Di Marco, L. Botta, M. Baiocchi, G. Bracchetti, F.D. Petridi, and R. Di Bartolomeo

Published
2008

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