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1. One-year survival and Quality of Life of first wave COVID-19 invasively ventilated patients in Lombardy, Italy

Author

Lorini, L, Labanca, R, Bugada, D, Cazzaniga, S, D'Amico, F, Grazioli, L, Marmiere, M, Novelli, L, Pozzi, M, Rona, R, Giani, M, Bellin, V, Lucchini, A, Raimondi, F, Rocchi, M, Salvioni, M, Foti, G, Landoni, G, Andreossi, M, Annoni, A, Azzolini, M, Baiardo Redaelli, M, Belletti, A, Belmonte, G, Benigni, A, Benini, A, Bonfanti, P, Borghi, G, Butovska, L, Cadone Ughi, E, Calabria, M, Celona, S, Ciceri, F, Consalvo, L, Farina, A, Ferlicca, D, Finazzi, S, Fominskiy, E, Grieco, S, Guzzo, F, Landini, S, Lo-Catelli, S, Lorini, A, Lorini, G, Magri, F, Manildo, E, Nava, C, Ortalda, A, Palumbo, D, Real, G, Rezoagli, E, Ripa, C, Saracino, M, Sosio, S, Trocchia, R, Villa, M, Zangrillo, A, Lorini L. F., Labanca R., Bugada D., Cazzaniga S., D'Amico F., Grazioli L., Marmiere M., Novelli L., Pozzi M., Rona R., Giani M., Bellin V., Lucchini A., Raimondi F., Rocchi M., Salvioni M. T., Foti G., Landoni G., Andreossi M., Annoni A., Azzolini M. L., Baiardo Redaelli M., Belletti A., Belmonte G., Benigni A., Benini A., Bonfanti P., Borghi G., Butovska L., Cadone Ughi E., Calabria M., Celona S., Ciceri F., Consalvo L., Farina A., Ferlicca D., Finazzi S., Fominskiy E. V., Grieco S., Guzzo F., Landini S., Lo-Catelli S., Lorini A., Lorini G., Magri F., Manildo E., Nava C., Ortalda A., Palumbo D., Real G., Rezoagli E., Ripa C., Saracino M., Sosio S., Trocchia R., Villa M., Zangrillo A., Lorini, L, Labanca, R, Bugada, D, Cazzaniga, S, D'Amico, F, Grazioli, L, Marmiere, M, Novelli, L, Pozzi, M, Rona, R, Giani, M, Bellin, V, Lucchini, A, Raimondi, F, Rocchi, M, Salvioni, M, Foti, G, Landoni, G, Andreossi, M, Annoni, A, Azzolini, M, Baiardo Redaelli, M, Belletti, A, Belmonte, G, Benigni, A, Benini, A, Bonfanti, P, Borghi, G, Butovska, L, Cadone Ughi, E, Calabria, M, Celona, S, Ciceri, F, Consalvo, L, Farina, A, Ferlicca, D, Finazzi, S, Fominskiy, E, Grieco, S, Guzzo, F, Landini, S, Lo-Catelli, S, Lorini, A, Lorini, G, Magri, F, Manildo, E, Nava, C, Ortalda, A, Palumbo, D, Real, G, Rezoagli, E, Ripa, C, Saracino, M, Sosio, S, Trocchia, R, Villa, M, Zangrillo, A, Lorini L. F., Labanca R., Bugada D., Cazzaniga S., D'Amico F., Grazioli L., Marmiere M., Novelli L., Pozzi M., Rona R., Giani M., Bellin V., Lucchini A., Raimondi F., Rocchi M., Salvioni M. T., Foti G., Landoni G., Andreossi M., Annoni A., Azzolini M. L., Baiardo Redaelli M., Belletti A., Belmonte G., Benigni A., Benini A., Bonfanti P., Borghi G., Butovska L., Cadone Ughi E., Calabria M., Celona S., Ciceri F., Consalvo L., Farina A., Ferlicca D., Finazzi S., Fominskiy E. V., Grieco S., Guzzo F., Landini S., Lo-Catelli S., Lorini A., Lorini G., Magri F., Manildo E., Nava C., Ortalda A., Palumbo D., Real G., Rezoagli E., Ripa C., Saracino M., Sosio S., Trocchia R., Villa M., and Zangrillo A.

Abstract

BACKGROUND: Lombardy was the epicenter of the first coronavirus disease 2019 (COVID-19) outbreak in western countries. The outbreak began in February 2020 and rapidly disseminated throughout the region. ICU beds were vastly insufficient and clinical knowledge of disease was poor at that time. Unfortunately, data on long-term mortality, morbidity, and Quality of Life are scarce and controversial. The aim of this study was to evaluate 1-year survival, Quality of Life, and functional recovery in patients with COVID-19 admitted to Intensive Care Units. METHODS: All COVID-19 patients invasively ventilated and successfully discharged from 3 important academic hospitals in Lombardy were evaluated. Evaluations were performed by qualified medical staff and monitoring over time was performed by telephone call. Functional, cognitive, and psychological outcomes were explored using validated questionnaires. Selected patients were offered a follow-up chest computed tomography (CT) scan. RESULTS: Four hundred twenty-seven patients were invasively ventilated and 268 (63%) were successfully discharged. Out of these 268 patients, 266 (99%) were alive at one year with no patient loss during follow-up. Very severe or severe dyspnea was reported by 7% of patients, while most patients (84%) did not experience dyspnea at rest. A small proportion of patients (17%) reported severe anxiety/depression. Good Quality of Life was reported by 64% of survivors. In patients complaining of dyspnea on exertion, fibrotic-like changes were observed at chest CT scans in 32/37 (86%) and 7/11 (63%) patients who underwent CT at 3 months and 1 year, respectively. CONCLUSIONS: COVID-19 patients discharged from the hospital after invasive ventilation had excellent one-year survival and good overall recovery and Quality of Life.

Published
2024

4. Residual lung damage following ARDS in COVID-19 ICU survivors

Author

Compagnone N., Palumbo D., Cremona G., Vitali G., De Lorenzo R., Calvi M. R., Del Prete A., Baiardo Redaelli M., Calamara S., Belletti A., Steidler S., Conte C., Zangrillo A., De Cobelli F., Rovere-Querini P., Monti G., Castellani J., Cilla M., Cinel E., Di Tomasso N., Falbo E., Faustini C., Fedrizzi M., Ferrante M., Fresilli S., Landoni G., Magnaghi C., Maimeri N., Martinenghi S., Moizo E., Mucci M., Velati M., Compagnone, N., Palumbo, D., Cremona, G., Vitali, G., De Lorenzo, R., Calvi, M. R., Del Prete, A., Baiardo Redaelli, M., Calamara, S., Belletti, A., Steidler, S., Conte, C., Zangrillo, A., De Cobelli, F., Rovere-Querini, P., Monti, G., Castellani, J., Cilla, M., Cinel, E., Di Tomasso, N., Falbo, E., Faustini, C., Fedrizzi, M., Ferrante, M., Fresilli, S., Landoni, G., Magnaghi, C., Maimeri, N., Martinenghi, S., Moizo, E., Mucci, M., and Velati, M.

Subjects
Adult, Male, ARDS, chest CT scan, medicine.medical_treatment, critically ill patients, pulmonary function tests, Pulmonary function testing, COVID‐19, Interquartile range, DLCO, Intensive care, follow-up, Medicine, Humans, Survivors, Lung, Research Articles, Tidal volume, intensive care, follow‐up, Mechanical ventilation, Respiratory Distress Syndrome, pulmonary fibrosis, business.industry, SARS-CoV-2, COVID-19, General Medicine, respiratory system, acute respiratory distress syndrome, Middle Aged, medicine.disease, respiratory tract diseases, Intensive Care Units, Anesthesiology and Pain Medicine, medicine.anatomical_structure, Anesthesia, business, Research Article
Abstract

Background Coronavirus disease 2019 acute respiratory distress syndrome (COVID‐19 ARDS) is a disease that often requires invasive ventilation. Little is known about COVID‐19 ARDS sequelae. We assessed the mid‐term lung status of COVID‐19 survivors and investigated factors associated with pulmonary sequelae. Methods All adult COVID‐19 patients admitted to the intensive care unit from 25th February to 27th April 2020 were included. Lung function was evaluated through chest CT scan and pulmonary function tests (PFT). Logistic regression was used to identify predictors of persisting lung alterations. Results Forty‐nine patients (75%) completed lung assessment. Chest CT scan was performed after a median (interquartile range) time of 97 (89–105) days, whilst PFT after 142 (133–160) days. The median age was 58 (52–65) years and most patients were male (90%). The median duration of mechanical ventilation was 11 (6–16) days. Median tidal volume/ideal body weight (TV/IBW) was 6.8 (5.71–7.67) ml/Kg. 59% and 63% of patients showed radiological and functional lung sequelae, respectively. The diffusion capacity of carbon monoxide (DLCO) was reduced by 59%, with a median per cent of predicted DLCO of 72.1 (57.9–93.9) %. Mean TV/IBW during invasive ventilation emerged as an independent predictor of persistent CT scan abnormalities, whilst the duration of mechanical ventilation was an independent predictor of both CT and PFT abnormalities. The extension of lung involvement at hospital admission (evaluated through Radiographic Assessment of Lung Edema, RALE score) independently predicted the risk of persistent alterations in PFTs. Conclusions Both the extent of lung parenchymal involvement and mechanical ventilation protocols predict morphological and functional lung abnormalities months after COVID‐19.

Published
2022

5. [Dexamethasone in COVID-19: does one drug fit all?]

Author

Zangrillo, A, Landoni, G, Monti, G, Yavorovskiy, A G, Baiardo Redaelli, M, Zangrillo, A, Landoni, G, Monti, G, Yavorovskiy, A G, and Baiardo Redaelli, M

Subjects
SARS-CoV-2, Humans, COVID-19, Dexamethasone
Published
2022

8. Post-anaesthesia pulmonary complications after use of muscle relaxants (POPULAR): a multicentre, prospective observational study

Author

Kirmeier, E, Eriksson, L, Lewald, H, Jonsson Fagerlund, M, Hoeft, A, Hollmann, M, Meistelman, C, Hunter, J, Ulm, K, Blobner, M, Abad Gurumeta, A, Abernethy, C, Abigail, P, Achaibar, K, Adam, E, Afshari, A, Agudelo Montoya, M, Akgun, F, Aletti, G, Alkis, N, Allan, K, Allan, A, Allaouchiche, B, Allcock, C, Almasy, E, Amey, I, Amigoni, M, Andersen, E, Andersson, P, Anipchenko, N, Antunes, P, Armstrong, E, Aslam, T, Aslin, B, Assuncao, J, Ausserer, J, Avvai, M, Awad, N, Ayas Montero, B, Ayuso, M, Azevedo, P, Badarau, V, Badescu, R, Baiardo Redaelli, M, Baird, C, Baird, Y, Baker, T, Balaji, P, Balan, C, Balandin, A, Balescu-Arion, C, Baliuliene, V, Baltasar Isabel, J, Baluch, S, Bandrabur, D, Bankewitz, C, Barber, K, Barbera, F, Barcraft-Barnes, H, Barletti, V, Barnett, G, Baron, K, Barros, A, Barsan, V, Bartlett, P, Batistaki, C, Baumgarten, G, Baytas, V, Beauchamp, N, Becerra Cayetano, I, Bell, S, Bellandi, M, Belletti, A, Belmonte Cuenca, J, Benitez-Cano, A, Beretta, L, Berger, M, Bergmann, N, Bergmark, K, Bermudez Lopez, M, Bernotaite, M, Beurskens, C, Bidd, H, Bifulco, F, Bignami, E, Bilic, A, Bilskiene, D, Bischoff, P, Bishop, L, Bjonness, T, Blaylock, H, Blethyn, K, Blincoe, T, Blokhin, I, Blunt, N, Boer, C, Bois, G, Bonicolini, E, Booth, J, Borecka-Kedzierska, M, Borstnar, K, Borys, M, Boselli, E, Bouvet, L, Bouwman, A, Bowen, L, Bowrey, S, Boxall, L, Bozic, T, Bradley, T, Branco, T, Brazzi, L, Brazzoni, M, Brear, T, Brogly, N, Brohi, F, Broms, J, Bubliauskas, A, Bucolo, G, Buerkle, H, Buggy, D, Buhre, W, Bukauskas, T, Butturini, F, Byttner, A, Cabrera Diaz, I, Calderon, A, Calhau, R, Callejo, A, Cammu, G, Campesato, M, Can, O, Candeias, M, Cantor, A, Carise, E, Carmona, C, Carreteiro, J, Carrieri, C, Carter, A, Casal, M, Casanova, I, Cascella, M, Casero, L, Casiraghi, G, Castelo-Branco, L, Castro Arranz, C, Cernea, D, Cervantes, J, Chandler, B, Charnock, R, Chatzimicali, A, Chinery, E, Chishti, A, Chondhury, P, Christie, E, Christodoudiles, G, Ciardo, S, Cimpeanu, L, Cindea, I, Cinnella, G, Clark, S, Clayton, M, Cocu, S, Collyer, T, Colvin, C, Cope, S, Copeta, F, Copotoiu, S, Correia de Barros, F, Corso, R, Cortegiani, A, Costa, G, Cowton, A, Cox, N, Craig, J, Cricca, V, Cronin, J, Cunha, M, Cuomo, A, Curley, K, Czuczwar, M, Dabrowska, D, Damster, S, Danguy des Deserts, M, Daniliuc, A, Danninger, T, Darwish, I, Dascalu, C, Davies, K, Davies, S, De Boer, H, De Flaviis, A, De Selincourt, G, Deana, C, Debaene, B, Debreceni, G, Dedhia, J, Delgado Garcia, I, Della Rocca, G, Delroy-Buelles, L, Desai, T, Dhillon, P, Di Giacinto, I, Di Mauro, P, Diaz Gomez, T, Dimitrovski, A, Dinic, V, Dirzu, D, Divander, M, Dolinar, J, Domingues, S, Doolan, J, Downes, C, Dragoescu, N, Droc, G, Dum, E, Dumitrescu, A, Duncan, L, Dzurnakova, P, Eberl, S, Edwards, J, Edwards, M, Ekelund, K, Ekengren, P, Elghouty, E, Ellerkmann, R, Ellis, H, Elme, A, Ernst, T, Errando, C, Estenes, S, Ewaldsson, C, Farid, N, Featherstone, J, Febres, D, Fedorov, S, Feggeler, J, Feijten, P, Fellmann, T, Fernandez Candil, J, Fernandez Castineira, A, Fernandez Castineira, J, Fernando, A, Ferrando, C, Ferreira, L, Ferreira, P, Feyling, A, Filipescu, D, Fleischer, A, Floris, L, Foerster, U, Fox, B, Franke, U, Frasca, D, Frey, C, Frost, V, Fullin, G, Fumagalli, J, Furneval, J, Fusari, M, Gallacher, S, Galushka, S, Gambale, G, Gambino, I, Garcia-Perez, M, Garg, S, Garlak, J, Gavranovic, Z, Gavrilov, R, Gaynor, L, Gecaj Gashi, A, Georghiou, M, Gerjevic, B, Gferer, G, Giarratano, A, Gibson, A, Gievski, V, Giles, J, Gillberg, L, Gilowska, K, Gilsanz Rodriguez, F, Gioia, A, Giovannoni, C, Girotra, V, Gkinas, D, Gkiokas, G, Godoroja, D, Goebel, U, Goel, V, Gonzalez, M, Goranovic, T, Gornik-Wlaszczuk, E, Gosavi, S, Gottfridsson, P, Gottschalk, A, Granell, M, Granstrom, A, Grassetto, A, Greenwood, A, Grigoras, I, Grintescu, I, Gritsan, A, Gritsan, G, Grynyuk, A, Guadagnin, G, Guarnieri, M, Guclu, C, Guerrero Diez, M, Gunenc, F, Gunther, U, Gupta, P, Guttenthaler, V, Hack, Y, Hafisayena, A, Hagau, N, Haldar, J, Hales, D, Hanci, V, Hanna-Jumma, S, Harazim, H, Harlet, P, Harper, D, Harris, B, Harvey, O, Hashimi, M, Hawkins, L, Hayes, C, Heaton, J, Heier, T, Helliwell, L, Hemmes, S, Henderson, K, Hermanides, J, Hermanns, H, Herrera Hueso, B, Hestenes, S, Hettiarachchi, R, Highgate, J, Hodgson, K, Hoelbling, D, Holland, J, Horhota, L, Hormis, A, Hribar, R, Hua, A, Humphreys, S, Humphries, R, Humplikova, S, Hunt, J, Husnain, A, Hussein, A, Hyams, B, Iannuccelli, F, Ilette, K, Ilyas, C, Inan, T, India, I, Ionitav, V, Irwin, F, Jain, V, Janez, B, Jankovic, R, Jenkins, S, Jenko, M, Jimenez, R, Jimenez Gomez, B, Joachim, S, Joelsson-Alm, E, John, J, Jonikaite, L, Jovic, M, Jungwirth, B, Junke, E, Kabakov, B, Kadaoui, S, Kanski, A, Karadag, S, Karbonskiene, A, Karjagin, J, Kasnik, D, Katanolli, F, Katsika, E, Kaufmann, K, Keane, H, Kelly, M, Kent, M, Keraitiene, G, Khudhur, A, Khuenl-Brady, K, Kidd, L, King, S, Kirchgassner, K, Klancir, T, Klucniks, A, Knotzer, J, Knowlden, P, Koers, L, Kompan, J, Koneti, K, Kooij, F, Koolen, E, Koopman - van Gemert, A, Kopp, K, Korfiotis, D, Korolkov, O, Kosinova, M, Kostenberger, M, Kotzinger, O, Kovacevic, M, Kranke, P, Kranke, E, Kraus, C, Kraus, S, Kubitzek, C, Kucharski, R, Kucukguclu, S, Kudrashou, A, Kumar, V, Kummen, L, Kunit, C, Kushakovsky, V, Kuvaki, B, Kuzmanovska, B, Kyttari, A, Landoni, G, Lau, G, Lazarev, K, Legett, S, Legrottaglie, A, Leonardi, S, Leong, M, Lercher, H, Leuvrey, M, Leva, B, Levstek, M, Limb, J, Lindholm, E, Linton, F, Liperi, C, Lipski, F, Lirk, P, Lisi, A, Liskova, K, Lluch Oltra, A, Loganathan, V, Lombardi, S, Lopez, E, Lopez Rodriguez, M, Lorenzini, L, Lowicka, M, Lugovoy, A, Luippold, M, Lumb, A, Macas, A, Macgregor, M, Machado, H, Maciariello, M, Madeira, I, Maitan, S, Majewski, J, Maldini, B, Malewski, G, Manfredini, L, Manner, O, Marchand, B, Marcu, A, Margalef, J, Margarson, M, Marinheiro, L, Markic, A, Markovic Bozic, J, Marrazzo, F, Martin, J, Martin Ayuso, M, Martinez, E, Martino, E, Martinson, V, Marusic-Gaser, K, Mascarenhas, C, Mathis, C, Matsota, P, Mavrommati, E, Mazul Sunko, B, Mccourt, K, Mcgill, N, Mckee, R, Meco, B, Meier, S, Melbourne, S, Melbybrathen, G, Meli, A, Melia, A, Melotti, R, Menga, M, Mercer, P, Merotra, S, Mescolini, S, Metterlein, T, Michalov, M, Michlig, S, Midgley, S, Milic, M, Milojevic, M, Minana, A, Minto, G, Mirabella, L, Mirea, L, Mittelstadt, L, Moeglen, A, Moise, A, Mokini, Z, Molin, A, Molto, L, Monea, M, Montalto, F, Montgomery, J, Montgomery, C, Montillo, G, Moore, S, Moore, F, Moreira, Z, Moreno, T, Moreno, R, Moret, E, Moreton, S, Morgan, M, Moro Velasco, C, Morri, D, Moull, A, Moura, F, Mraz, P, Mrozek, K, Mukhtar, K, Muniyappa, S, Murray, H, Murthy, B, Mushambi, M, Nadolski, M, Nardelli, P, Nardin, G, Navarro Perez, R, Naveiro, A, Negri, M, Nesek Adam, V, Neskovic, V, Neuwersch, S, Neves, M, Nguyen, B, Ni Eochagain, A, Nicholas, C, Nightingale, J, Norrie, K, Novak-Jankovic, V, Novakova, A, Novillo, M, Numan, S, Oduro-Dominah, L, Oldner, A, Oliveira, I, Ologoiu, D, Oloktsidou, I, O'Reilly, R, Orlando, A, Ovezov, A, Ozbilgin, S, Paal, P, Padin Barreiro, L, Palugniok, R, Papaioannou, A, Papapostolou, K, Paranthaman, P, Pardey Bracho, G, Parente, S, Parfeni, A, Pasin, L, Passey, S, Pastor, E, Patch, S, Patil, A, Paunescu, M, Pehboeck, D, Pereira, M, Pereira, C, Perez Caballero, P, Perez Garcia, A, Perez Soto, A, Perez Tejero, G, Perez-Cerda, F, Pesenti, A, Petta, R, Philippe, S, Pickering, D, Pico Veloso, J, Pina, P, Pinho-Oliveira, V, Pinol, S, Pinto, R, Pistidda, L, Pitterle, M, Piwowarczyk, P, Plotnikova, O, Pohl, H, Poldermann, J, Polkovicova, L, Pompei, L, Popescu, M, Popovic, R, Pota, V, Potocnik, M, Potrec, B, Potter, A, Pramod, N, Prchalova, M, Preckel, B, Pugh, R, Pulletz, M, Radoeshki, A, Rafi, A, Ragazzi, R, Raineri Santi, M, Rajamanickam, T, Rajput, Z, Ramachandran, R, Ramasamy, R, Ramessur, S, Rao, R, Rasmussen, A, Rato, A, Razaque, U, Real Navacerrada, M, Reavley, C, Reid, J, Reschreiter, H, Rial, E, Ribas Carrasco, P, Ribeiro, S, Rich, N, Richardson, L, Rimaitis, K, Rimaitis, M, Ringvold, E, Ripke, F, Ristescu, I, Ritchie, K, Rodenas, F, Rodrigues, P, Rogers, E, Rogerson, D, Romagnoli, S, Romero, E, Rondovic, G, Rose, B, Roth, W, Rotter, M, Rousseau, G, Rudjord, A, Rueffert, H, Rundgren, M, Rupprecht, K, Rushton, A, Russotto, V, Rypulak, E, Ryszka, M, Sa, J, Sa Couto, P, Saby, S, Sagic, J, Saleh, O, Sales, G, Sanchez Sanchez, Y, Sanghera, S, Sanli Karip, C, Santiveri Papiol, F, Santos, S, Sarno, S, Saul, D, Saunders, D, Savic, N, Scalco, L, Scanlon, D, Schaller, S, Schax, C, Scheffer, G, Schening, A, Schiavone, V, Schmidt-Ehrenberg, F, Schmidt-Mutter, C, Schonberg, C, Schopflin, C, Schreiber, J, Schultz, M, Schurig, M, Scott, C, Sebestian, S, Sehgal, S, Sem, V, Semenas, E, Serafini, E, Serchan, P, Shields, M, Shobha, R, Shosholcheva, M, Siamansour, T, Siddaiah, N, Siddiqi, K, Sinclair, R, Singh, P, Singh, R, Sinha, A, Skinner, A, Smee, E, Smekalova, O, Smith, N, Smith, T, Smitz, C, Smole, D, Sojcic, N, Soler Pedrola, M, Somanath, S, Sonksen, J, Sorella, M, Sormus, A, Soro, M, Soto, C, Spada, A, Spadaro, S, Spaeth, J, Sparr, H, Spielmann, A, Spindler-Vesel, A, Stamelos, M, Stancombe L, L, Stanculescu, A, Standl, T, Standley, T, Stanek, O, Stanisavljevic, S, Starczewska, M, Stauble, C, Steen, J, Stefan, O, Stell, E, Stera, C, Stevens, M, Stoerckel, M, Stosic, B, Stourac, P, Stroumpoulis, K, Struck, R, Suarez de la Rica, A, Sultanpori, A, Sundara Rajan, R, Suying, O, Svensen, C, Swan, L, Syrogianni, P, Sysiak, J, Szederjesi, J, Taddei, S, Tan Hao, E, Tanou, V, Tarabova, K, Tardaguila Sancho, P, Tarroso, M, Tartaglione, M, Taylor, E, Tbaily, L, Telford, R, Terenzoni, M, Theodoraki, K, Thornley, H, Tiganiuc, L, Toim, H, Tomescu, D, Tommasino, C, Toni, J, Toninelli, A, Toretti, I, Townley, S, Trepenaitis, D, Trethowan, B, Tsaousi, G, Tsiftsi, A, Tudor, A, Turan, G, Turhan, S, Unic-Stojanovic, D, Unterbuchner, C, Unzueta, C, Uranjek, J, Ursic, T, Vaida, S, Valldeperas Ferrer, S, Valldeperas Hernandez, M, Valsamidis, D, Van Beek, R, Van dasselaer, N, Van Der Beek, T, Van Duivenvoorde, Y, van Klei, W, Van Poorter, F, Van Zaane, B, Van Zundert, T, Van Zyl, R, Vargas Munoz, A, Varsani, N, Vasconcelos, P, Vassilakis, G, Vecchiatini, T, Vecera, L, Vercauteren, M, Verdouw, B, Verheyen, V, Verri, M, Vicari Sottosanti, L, Vico, M, Vidal Mitjans, P, Vilardi, A, Vissicchio, D, Vitale, G, Vitkovic, B, Vizcaychipi, M, Voicu, A, Voje, M, Volfova, I, Volta, C, Von Lutterotti, T, von Tiesenhausen, A, Vrecic-Slabe, S, Vukcevic, D, Vukovic, R, Vullo, P, Wade, A, Wallberg, H, Wallden, J, Wallner, J, Walther Sturesson, L, Watson, D, Weber, S, Wegiel Leskiewiq, A, Weller, D, Wensing, C, Werkmann, M, Westberg, H, Wikstrom, E, Williams, B, Wilson, R, Wirth, S, Wittmann, M, Wood, L, Wright, S, Zachoval, C, Zambon, M, Zampieri, S, Zampone, S, Zangrillo, A, Zani, G, Zavackiene, A, Zieglerder, R, Zonneveldt, H, Zsisku, L, Zucker, T, Zukowski, M, Zuleika, M, Zupaneie, D, Kirmeier E., Eriksson L. I., Lewald H., Jonsson Fagerlund M., Hoeft A., Hollmann M., Meistelman C., Hunter J. M., Ulm K., Blobner M., Abad Gurumeta A., Abernethy C., Abigail P., Achaibar K., Adam E., Afshari A., Agudelo Montoya M. E., Akgun F. N., Aletti G., Alkis N., Allan K., Allan A., Allaouchiche B., Allcock C., Almasy E., Amey I., Amigoni M., Andersen E., Andersson P., Anipchenko N., Antunes P., Armstrong E., Aslam T. N., Aslin B., Assuncao J. P., Ausserer J., Avvai M., Awad N., Ayas Montero B., Ayuso M., Azevedo P., Badarau V., Badescu R., Baiardo Redaelli M., Baird C., Baird Y., Baker T., Balaji P., Balan C., Balandin A., Balescu-Arion C., Baliuliene V., Baltasar Isabel J., Baluch S. N., Bandrabur D., Bankewitz C., Barber K., Barbera F., Barcraft-Barnes H., Barletti V., Barnett G., Baron K., Barros A., Barsan V., Bartlett P., Batistaki C., Baumgarten G., Baytas V., Beauchamp N., Becerra Cayetano I. A., Bell S., Bellandi M., Belletti A., Belmonte Cuenca J., Benitez-Cano A., Beretta L., Berger M., Bergmann N., Bergmark K., Bermudez Lopez M., Bernotaite M., Beurskens C., Bidd H., Bifulco F., Bignami E., Bilic A., Bilskiene D., Bischoff P., Bishop L., Bjonness T., Blaylock H., Blethyn K., Blincoe T., Blokhin I., Blunt N., Boer C., Bois G., Bonicolini E., Booth J., Borecka-Kedzierska M., Borstnar K., Borys M., Boselli E., Bouvet L., Bouwman A., Bowen L., Bowrey S., Boxall L., Bozic T., Bradley T., Branco T., Brazzi L., Brazzoni M., Brear T., Brogly N., Brohi F., Broms J., Bubliauskas A., Bucolo G. E., Buerkle H., Buggy D., Buhre W., Bukauskas T., Butturini F., Byttner A., Cabrera Diaz I., Calderon A., Calhau R., Callejo A., Cammu G., Campesato M., Can O. S., Candeias M., Cantor A., Carise E., Carmona C., Carreteiro J., Carrieri C., Carter A., Casal M., Casanova I., Cascella M., Casero L. M., Casiraghi G. M., Castelo-Branco L., Castro Arranz C., Cernea D. D., Cervantes J., Chandler B., Charnock R., Chatzimicali A., Chinery E., Chishti A., Chondhury P., Christie E., Christodoudiles G., Ciardo S., Cimpeanu L., Cindea I., Cinnella G., Clark S., Clayton M., Cocu S., Collyer T., Colvin C., Cope S., Copeta F., Copotoiu S. -M., Correia de Barros F., Corso R. M., Cortegiani A., Costa G., Cowton A., Cox N., Craig J., Cricca V., Cronin J., Cunha M., Cuomo A., Curley K., Czuczwar M., Dabrowska D., Damster S., Danguy des Deserts M., Daniliuc A., Danninger T., Darwish I., Dascalu C., Davies K., Davies S., De Boer H., De Flaviis A., De Selincourt G., Deana C., Debaene B., Debreceni G., Dedhia J., Delgado Garcia I., Della Rocca G., Delroy-Buelles L., Desai T., Dhillon P., Di Giacinto I., Di Mauro P., Diaz Gomez T. V., Dimitrovski A., Dinic V., Dirzu D. -S., Divander M. B., Dolinar J., Domingues S., Doolan J., Downes C., Dragoescu N. A., Droc G., Dum E., Dumitrescu A., Duncan L., Dzurnakova P., Eberl S., Edwards J., Edwards M., Ekelund K., Ekengren P., Elghouty E., Ellerkmann R., Ellis H., Elme A., Ernst T., Errando C. L., Estenes S., Ewaldsson C., Farid N., Featherstone J., Febres D., Fedorov S., Feggeler J., Feijten P., Fellmann T., Fernandez Candil J., Fernandez Castineira A., Fernandez Castineira J., Fernando A., Ferrando C., Ferreira L., Ferreira P., Feyling A., Filipescu D., Fleischer A., Floris L., Foerster U., Fox B., Franke U., Frasca D., Frey C., Frost V., Fullin G., Fumagalli J., Furneval J., Fusari M., Gallacher S., Galushka S., Gambale G., Gambino I., Garcia-Perez M. L., Garg S., Garlak J., Gavranovic Z., Gavrilov R., Gaynor L., Gecaj Gashi A., Georghiou M., Gerjevic B., Gferer G., Giarratano A., Gibson A., Gievski V., Giles J., Gillberg L., Gilowska K., Gilsanz Rodriguez F., Gioia A., Giovannoni C., Girotra V., Gkinas D., Gkiokas G., Godoroja D., Goebel U., Goel V., Gonzalez M., Goranovic T., Gornik-Wlaszczuk E., Gosavi S., Gottfridsson P., Gottschalk A., Granell M., Granstrom A., Grassetto A., Greenwood A., Grigoras I., Grintescu I., Gritsan A., Gritsan G., Grynyuk A., Guadagnin G. M., Guarnieri M., Guclu C., Guerrero Diez M., Gunenc F., Gunther U., Gupta P., Guttenthaler V., Hack Y., Hafisayena A., Hagau N., Haldar J., Hales D., Hanci V., Hanna-Jumma S., Harazim H., Harlet P., Harper D., Harris B., Harvey O., Hashimi M., Hawkins L., Hayes C., Heaton J., Heier T., Helliwell L., Hemmes S., Henderson K., Hermanides J., Hermanns H., Herrera Hueso B., Hestenes S., Hettiarachchi R., Highgate J., Hodgson K., Hoelbling D., Holland J., Horhota L., Hormis A., Hribar R., Hua A., Humphreys S., Humphries R., Humplikova S., Hunt J., Husnain A., Hussein A., Hyams B., Iannuccelli F., Ilette K., Ilyas C., Inan T., India I., Ionitav V., Irwin F., Jain V., Janez B., Jankovic R., Jenkins S., Jenko M., Jimenez R., Jimenez Gomez B., Joachim S., Joelsson-Alm E., John J., Jonikaite L., Jovic M., Jungwirth B., Junke E., Kabakov B., Kadaoui S. -D., Kanski A., Karadag S., Karbonskiene A., Karjagin J., Kasnik D., Katanolli F., Katsika E., Kaufmann K., Keane H., Kelly M., Kent M., Keraitiene G., Khudhur A., Khuenl-Brady K., Kidd L., King S., Kirchgassner K., Klancir T., Klucniks A., Knotzer J., Knowlden P., Koers L., Kompan J., Koneti K. K., Kooij F., Koolen E., Koopman - van Gemert A. W. M. M., Kopp K., Korfiotis D., Korolkov O., Kosinova M., Kostenberger M., Kotzinger O., Kovacevic M., Kranke P., Kranke E., Kraus C., Kraus S., Kubitzek C., Kucharski R., Kucukguclu S., Kudrashou A., Kumar V., Kummen L., Kunit C., Kushakovsky V., Kuvaki B., Kuzmanovska B., Kyttari A., Landoni G., Lau G., Lazarev K., Legett S., Legrottaglie A. M., Leonardi S., Leong M., Lercher H., Leuvrey M., Leva B., Levstek M., Limb J., Lindholm E., Linton F., Liperi C., Lipski F., Lirk P., Lisi A., Liskova K., Lluch Oltra A., Loganathan V., Lombardi S., Lopez E., Lopez Rodriguez M., Lorenzini L., Lowicka M., Lugovoy A., Luippold M., Lumb A., Macas A., Macgregor M., Machado H., Maciariello M., Madeira I., Maitan S., Majewski J., Maldini B., Malewski G., Manfredini L., Manner O., Marchand B., Marcu A., Margalef J., Margarson M., Marinheiro L., Markic A., Markovic Bozic J., Marrazzo F., Martin J., Martin Ayuso M., Martinez E., Martino E. A., Martinson V., Marusic-Gaser K., Mascarenhas C., Mathis C., Matsota P., Mavrommati E., Mazul Sunko B., McCourt K., McGill N., McKee R., Meco B. C., Meier S., Melbourne S., Melbybrathen G., Meli A., Melia A., Melotti R. M., Menga M. R., Mercer P., Merotra S., Mescolini S., Metterlein T., Michalov M., Michlig S., Midgley S., Milic M., Milojevic M., Minana A., Minto G., Mirabella L., Mirea L., Mittelstadt L., Moeglen A., Moise A., Mokini Z., Molin A., Molto L., Monea M. C., Montalto F., Montgomery J., Montgomery C., Montillo G., Moore S., Moore F., Moreira Z., Moreno T., Moreno R., Moret E., Moreton S., Morgan M., Moro Velasco C., Morri D., Moull A., Moura F., Mraz P., Mrozek K., Mukhtar K., Muniyappa S., Murray H., Murthy B. V., Mushambi M., Nadolski M., Nardelli P., Nardin G., Navarro Perez R., Naveiro A., Negri M., Nesek Adam V., Neskovic V., Neuwersch S., Neves M., Nguyen B., Ni Eochagain A., Nicholas C., Nightingale J., Norrie K., Novak-Jankovic V., Novakova A., Novillo M., Numan S., Oduro-Dominah L., Oldner A., Oliveira I., Ologoiu D., Oloktsidou I., O'Reilly R., Orlando A., Ovezov A., Ozbilgin S., Paal P., Padin Barreiro L., Palugniok R., Papaioannou A., Papapostolou K., Paranthaman P., Pardey Bracho G., Parente S., Parfeni A., Pasin L., Passey S., Pastor E., Patch S., Patil A., Paunescu M. -A., Pehboeck D., Pereira M., Pereira C., Perez Caballero P., Perez Garcia A., Perez Soto A., Perez Tejero G., Perez-Cerda F., Pesenti A., Petta R., Philippe S., Pickering D., Pico Veloso J., Pina P., Pinho-Oliveira V., Pinol S., Pinto R., Pistidda L., Pitterle M., Piwowarczyk P., Plotnikova O., Pohl H., Poldermann J., Polkovicova L., Pompei L., Popescu M., Popovic R., Pota V., Potocnik M., Potrec B., Potter A., Pramod N., Prchalova M., Preckel B., Pugh R., Pulletz M., Radoeshki A., Rafi A., Ragazzi R., Raineri Santi M., Rajamanickam T., Rajput Z., Ramachandran R., Ramasamy R., Ramessur S., Rao R., Rasmussen A., Rato A., Razaque U., Real Navacerrada M. I., Reavley C., Reid J., Reschreiter H., Rial E., Ribas Carrasco P., Ribeiro S., Rich N., Richardson L., Rimaitis K., Rimaitis M., Ringvold E. -M., Ripke F., Ristescu I., Ritchie K., Rodenas F., Rodrigues P., Rogers E., Rogerson D., Romagnoli S., Romero E., Rondovic G., Rose B. O., Roth W., Rotter M. -T., Rousseau G., Rudjord A., Rueffert H., Rundgren M., Rupprecht K., Rushton A., Russotto V., Rypulak E., Ryszka M., Sa J., Sa Couto P., Saby S., Sagic J., Saleh O., Sales G., Sanchez Sanchez Y., Sanghera S., Sanli Karip C., Santiveri Papiol F. J., Santos S., Sarno S., Saul D., Saunders D., Savic N., Scalco L., Scanlon D., Schaller S., Schax C., Scheffer G. J., Schening A., Schiavone V., Schmidt-Ehrenberg F., Schmidt-Mutter C., Schonberg C., Schopflin C., Schreiber J. -U., Schultz M., Schurig M., Scott C., Sebestian S., Sehgal S., Sem V., Semenas E., Serafini E., Serchan P., Shields M., Shobha R., Shosholcheva M., Siamansour T., Siddaiah N., Siddiqi K., Sinclair R., Singh P., Singh R., Sinha A., Skinner A., Smee E., Smekalova O., Smith N., Smith T., Smitz C., Smole D., Sojcic N., Soler Pedrola M., Somanath S., Sonksen J., Sorella M. C., Sormus A., Soro M., Soto C., Spada A., Spadaro S., Spaeth J., Sparr H., Spielmann A., Spindler-Vesel A., Stamelos M., Stancombe L L., Stanculescu A., Standl T., Standley T., Stanek O., Stanisavljevic S., Starczewska M., Stauble C., Steen J., Stefan O. M., Stell E., Stera C., Stevens M., Stoerckel M., Stosic B., Stourac P., Stroumpoulis K., Struck R., Suarez de la Rica A., Sultanpori A., Sundara Rajan R., Suying O., Svensen C., Swan L., Syrogianni P., Sysiak J., Szederjesi J., Taddei S., Tan Hao E., Tanou V., Tarabova K., Tardaguila Sancho P., Tarroso M., Tartaglione M., Taylor E., Tbaily L., Telford R., Terenzoni M., Theodoraki K., Thornley H., Tiganiuc L., Toim H., Tomescu D., Tommasino C., Toni J., Toninelli A., Toretti I., Townley S., Trepenaitis D., Trethowan B., Tsaousi G., Tsiftsi A., Tudor A., Turan G., Turhan S. C., Unic-Stojanovic D., Unterbuchner C., Unzueta C., Uranjek J., Ursic T., Vaida S., Valldeperas Ferrer S., Valldeperas Hernandez M. I., Valsamidis D., Van Beek R., Van dasselaer N., Van Der Beek T., Van Duivenvoorde Y., van Klei W. A., Van Poorter F., Van Zaane B., Van Zundert T., Van Zyl R., Vargas Munoz A. M., Varsani N., Vasconcelos P., Vassilakis G., Vecchiatini T., Vecera L., Vercauteren M., Verdouw B., Verheyen V., Verri M., Vicari Sottosanti L. G., Vico M., Vidal Mitjans P., Vilardi A., Vissicchio D., Vitale G., Vitkovic B., Vizcaychipi M. P., Voicu A., Voje M., Volfova I., Volta C. A., Von Lutterotti T., von Tiesenhausen A., Vrecic-Slabe S., Vukcevic D., Vukovic R., Vullo P. A., Wade A., Wallberg H., Wallden J., Wallner J., Walther Sturesson L., Watson D., Weber S., Wegiel Leskiewiq A., Weller D., Wensing C., Werkmann M., Westberg H., Wikstrom E., Williams B., Wilson R., Wirth S., Wittmann M., Wood L., Wright S., Zachoval C., Zambon M., Zampieri S., Zampone S., Zangrillo A., Zani G., Zavackiene A., Zieglerder R., Zonneveldt H., Zsisku L., Zucker T. -P., Zukowski M., Zuleika M., Zupaneie D., Kirmeier, E, Eriksson, L, Lewald, H, Jonsson Fagerlund, M, Hoeft, A, Hollmann, M, Meistelman, C, Hunter, J, Ulm, K, Blobner, M, Abad Gurumeta, A, Abernethy, C, Abigail, P, Achaibar, K, Adam, E, Afshari, A, Agudelo Montoya, M, Akgun, F, Aletti, G, Alkis, N, Allan, K, Allan, A, Allaouchiche, B, Allcock, C, Almasy, E, Amey, I, Amigoni, M, Andersen, E, Andersson, P, Anipchenko, N, Antunes, P, Armstrong, E, Aslam, T, Aslin, B, Assuncao, J, Ausserer, J, Avvai, M, Awad, N, Ayas Montero, B, Ayuso, M, Azevedo, P, Badarau, V, Badescu, R, Baiardo Redaelli, M, Baird, C, Baird, Y, Baker, T, Balaji, P, Balan, C, Balandin, A, Balescu-Arion, C, Baliuliene, V, Baltasar Isabel, J, Baluch, S, Bandrabur, D, Bankewitz, C, Barber, K, Barbera, F, Barcraft-Barnes, H, Barletti, V, Barnett, G, Baron, K, Barros, A, Barsan, V, Bartlett, P, Batistaki, C, Baumgarten, G, Baytas, V, Beauchamp, N, Becerra Cayetano, I, Bell, S, Bellandi, M, Belletti, A, Belmonte Cuenca, J, Benitez-Cano, A, Beretta, L, Berger, M, Bergmann, N, Bergmark, K, Bermudez Lopez, M, Bernotaite, M, Beurskens, C, Bidd, H, Bifulco, F, Bignami, E, Bilic, A, Bilskiene, D, Bischoff, P, Bishop, L, Bjonness, T, Blaylock, H, Blethyn, K, Blincoe, T, Blokhin, I, Blunt, N, Boer, C, Bois, G, Bonicolini, E, Booth, J, Borecka-Kedzierska, M, Borstnar, K, Borys, M, Boselli, E, Bouvet, L, Bouwman, A, Bowen, L, Bowrey, S, Boxall, L, Bozic, T, Bradley, T, Branco, T, Brazzi, L, Brazzoni, M, Brear, T, Brogly, N, Brohi, F, Broms, J, Bubliauskas, A, Bucolo, G, Buerkle, H, Buggy, D, Buhre, W, Bukauskas, T, Butturini, F, Byttner, A, Cabrera Diaz, I, Calderon, A, Calhau, R, Callejo, A, Cammu, G, Campesato, M, Can, O, Candeias, M, Cantor, A, Carise, E, Carmona, C, Carreteiro, J, Carrieri, C, Carter, A, Casal, M, Casanova, I, Cascella, M, Casero, L, Casiraghi, G, Castelo-Branco, L, Castro Arranz, C, Cernea, D, Cervantes, J, Chandler, B, Charnock, R, Chatzimicali, A, Chinery, E, Chishti, A, Chondhury, P, Christie, E, Christodoudiles, G, Ciardo, S, Cimpeanu, L, Cindea, I, Cinnella, G, Clark, S, Clayton, M, Cocu, S, Collyer, T, Colvin, C, Cope, S, Copeta, F, Copotoiu, S, Correia de Barros, F, Corso, R, Cortegiani, A, Costa, G, Cowton, A, Cox, N, Craig, J, Cricca, V, Cronin, J, Cunha, M, Cuomo, A, Curley, K, Czuczwar, M, Dabrowska, D, Damster, S, Danguy des Deserts, M, Daniliuc, A, Danninger, T, Darwish, I, Dascalu, C, Davies, K, Davies, S, De Boer, H, De Flaviis, A, De Selincourt, G, Deana, C, Debaene, B, Debreceni, G, Dedhia, J, Delgado Garcia, I, Della Rocca, G, Delroy-Buelles, L, Desai, T, Dhillon, P, Di Giacinto, I, Di Mauro, P, Diaz Gomez, T, Dimitrovski, A, Dinic, V, Dirzu, D, Divander, M, Dolinar, J, Domingues, S, Doolan, J, Downes, C, Dragoescu, N, Droc, G, Dum, E, Dumitrescu, A, Duncan, L, Dzurnakova, P, Eberl, S, Edwards, J, Edwards, M, Ekelund, K, Ekengren, P, Elghouty, E, Ellerkmann, R, Ellis, H, Elme, A, Ernst, T, Errando, C, Estenes, S, Ewaldsson, C, Farid, N, Featherstone, J, Febres, D, Fedorov, S, Feggeler, J, Feijten, P, Fellmann, T, Fernandez Candil, J, Fernandez Castineira, A, Fernandez Castineira, J, Fernando, A, Ferrando, C, Ferreira, L, Ferreira, P, Feyling, A, Filipescu, D, Fleischer, A, Floris, L, Foerster, U, Fox, B, Franke, U, Frasca, D, Frey, C, Frost, V, Fullin, G, Fumagalli, J, Furneval, J, Fusari, M, Gallacher, S, Galushka, S, Gambale, G, Gambino, I, Garcia-Perez, M, Garg, S, Garlak, J, Gavranovic, Z, Gavrilov, R, Gaynor, L, Gecaj Gashi, A, Georghiou, M, Gerjevic, B, Gferer, G, Giarratano, A, Gibson, A, Gievski, V, Giles, J, Gillberg, L, Gilowska, K, Gilsanz Rodriguez, F, Gioia, A, Giovannoni, C, Girotra, V, Gkinas, D, Gkiokas, G, Godoroja, D, Goebel, U, Goel, V, Gonzalez, M, Goranovic, T, Gornik-Wlaszczuk, E, Gosavi, S, Gottfridsson, P, Gottschalk, A, Granell, M, Granstrom, A, Grassetto, A, Greenwood, A, Grigoras, I, Grintescu, I, Gritsan, A, Gritsan, G, Grynyuk, A, Guadagnin, G, Guarnieri, M, Guclu, C, Guerrero Diez, M, Gunenc, F, Gunther, U, Gupta, P, Guttenthaler, V, Hack, Y, Hafisayena, A, Hagau, N, Haldar, J, Hales, D, Hanci, V, Hanna-Jumma, S, Harazim, H, Harlet, P, Harper, D, Harris, B, Harvey, O, Hashimi, M, Hawkins, L, Hayes, C, Heaton, J, Heier, T, Helliwell, L, Hemmes, S, Henderson, K, Hermanides, J, Hermanns, H, Herrera Hueso, B, Hestenes, S, Hettiarachchi, R, Highgate, J, Hodgson, K, Hoelbling, D, Holland, J, Horhota, L, Hormis, A, Hribar, R, Hua, A, Humphreys, S, Humphries, R, Humplikova, S, Hunt, J, Husnain, A, Hussein, A, Hyams, B, Iannuccelli, F, Ilette, K, Ilyas, C, Inan, T, India, I, Ionitav, V, Irwin, F, Jain, V, Janez, B, Jankovic, 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V., Mushambi M., Nadolski M., Nardelli P., Nardin G., Navarro Perez R., Naveiro A., Negri M., Nesek Adam V., Neskovic V., Neuwersch S., Neves M., Nguyen B., Ni Eochagain A., Nicholas C., Nightingale J., Norrie K., Novak-Jankovic V., Novakova A., Novillo M., Numan S., Oduro-Dominah L., Oldner A., Oliveira I., Ologoiu D., Oloktsidou I., O'Reilly R., Orlando A., Ovezov A., Ozbilgin S., Paal P., Padin Barreiro L., Palugniok R., Papaioannou A., Papapostolou K., Paranthaman P., Pardey Bracho G., Parente S., Parfeni A., Pasin L., Passey S., Pastor E., Patch S., Patil A., Paunescu M. -A., Pehboeck D., Pereira M., Pereira C., Perez Caballero P., Perez Garcia A., Perez Soto A., Perez Tejero G., Perez-Cerda F., Pesenti A., Petta R., Philippe S., Pickering D., Pico Veloso J., Pina P., Pinho-Oliveira V., Pinol S., Pinto R., Pistidda L., Pitterle M., Piwowarczyk P., Plotnikova O., Pohl H., Poldermann J., Polkovicova L., Pompei L., Popescu M., Popovic R., Pota V., Potocnik M., Potrec B., Potter A., Pramod N., Prchalova M., Preckel B., Pugh R., Pulletz M., Radoeshki A., Rafi A., Ragazzi R., Raineri Santi M., Rajamanickam T., Rajput Z., Ramachandran R., Ramasamy R., Ramessur S., Rao R., Rasmussen A., Rato A., Razaque U., Real Navacerrada M. 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M., Stell E., Stera C., Stevens M., Stoerckel M., Stosic B., Stourac P., Stroumpoulis K., Struck R., Suarez de la Rica A., Sultanpori A., Sundara Rajan R., Suying O., Svensen C., Swan L., Syrogianni P., Sysiak J., Szederjesi J., Taddei S., Tan Hao E., Tanou V., Tarabova K., Tardaguila Sancho P., Tarroso M., Tartaglione M., Taylor E., Tbaily L., Telford R., Terenzoni M., Theodoraki K., Thornley H., Tiganiuc L., Toim H., Tomescu D., Tommasino C., Toni J., Toninelli A., Toretti I., Townley S., Trepenaitis D., Trethowan B., Tsaousi G., Tsiftsi A., Tudor A., Turan G., Turhan S. C., Unic-Stojanovic D., Unterbuchner C., Unzueta C., Uranjek J., Ursic T., Vaida S., Valldeperas Ferrer S., Valldeperas Hernandez M. I., Valsamidis D., Van Beek R., Van dasselaer N., Van Der Beek T., Van Duivenvoorde Y., van Klei W. A., Van Poorter F., Van Zaane B., Van Zundert T., Van Zyl R., Vargas Munoz A. M., Varsani N., Vasconcelos P., Vassilakis G., Vecchiatini T., Vecera L., Vercauteren M., Verdouw B., Verheyen V., Verri M., Vicari Sottosanti L. G., Vico M., Vidal Mitjans P., Vilardi A., Vissicchio D., Vitale G., Vitkovic B., Vizcaychipi M. P., Voicu A., Voje M., Volfova I., Volta C. A., Von Lutterotti T., von Tiesenhausen A., Vrecic-Slabe S., Vukcevic D., Vukovic R., Vullo P. A., Wade A., Wallberg H., Wallden J., Wallner J., Walther Sturesson L., Watson D., Weber S., Wegiel Leskiewiq A., Weller D., Wensing C., Werkmann M., Westberg H., Wikstrom E., Williams B., Wilson R., Wirth S., Wittmann M., Wood L., Wright S., Zachoval C., Zambon M., Zampieri S., Zampone S., Zangrillo A., Zani G., Zavackiene A., Zieglerder R., Zonneveldt H., Zsisku L., Zucker T. -P., Zukowski M., Zuleika M., and Zupaneie D.

Abstract

Background: Results from retrospective studies suggest that use of neuromuscular blocking agents during general anaesthesia might be linked to postoperative pulmonary complications. We therefore aimed to assess whether the use of neuromuscular blocking agents is associated with postoperative pulmonary complications. Methods: We did a multicentre, prospective observational cohort study. Patients were recruited from 211 hospitals in 28 European countries. We included patients (aged ≥18 years) who received general anaesthesia for any in-hospital procedure except cardiac surgery. Patient characteristics, surgical and anaesthetic details, and chart review at discharge were prospectively collected over 2 weeks. Additionally, each patient underwent postoperative physical examination within 3 days of surgery to check for adverse pulmonary events. The study outcome was the incidence of postoperative pulmonary complications from the end of surgery up to postoperative day 28. Logistic regression analyses were adjusted for surgical factors and patients' preoperative physical status, providing adjusted odds ratios (ORadj) and adjusted absolute risk reduction (ARRadj). This study is registered with ClinicalTrials.gov, number NCT01865513. Findings: Between June 16, 2014, and April 29, 2015, data from 22 803 patients were collected. The use of neuromuscular blocking agents was associated with an increased incidence of postoperative pulmonary complications in patients who had undergone general anaesthesia (1658 [7·6%] of 21 694); ORadj 1·86, 95% CI 1·53–2·26; ARRadj −4·4%, 95% CI −5·5 to −3·2). Only 2·3% of high-risk surgical patients and those with adverse respiratory profiles were anaesthetised without neuromuscular blocking agents. The use of neuromuscular monitoring (ORadj 1·31, 95% CI 1·15–1·49; ARRadj −2·6%, 95% CI −3·9 to −1·4) and the administration of reversal agents (1·23, 1·07–1·41; −1·9%, −3·2 to −0·7) were not associated with a decreased risk of postoperative pulmonary

Published
2019

11. Awake Fiberoptic Intubation Protocols in the Operating Room for Anticipated Difficult Airway: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Author

Cabrini, L., Baiardo Redaelli, M., Ball, L., Filippini, M., Fominskiy, E., Pintaudi, M., Putzu, A., Votta, C. D., Sorbello, M., Antonelli, Massimo, Landoni, G., Pelosi, P., Zangrillo, A., Antonelli M. (ORCID:0000-0003-3007-1670), Cabrini, L., Baiardo Redaelli, M., Ball, L., Filippini, M., Fominskiy, E., Pintaudi, M., Putzu, A., Votta, C. D., Sorbello, M., Antonelli, Massimo, Landoni, G., Pelosi, P., Zangrillo, A., and Antonelli M. (ORCID:0000-0003-3007-1670)

Abstract

Awake fiberoptic intubation is one of the recommended strategies for surgical patients with anticipated difficult airway, especially when concurrent difficult ventilation is expected. We performed the first systematic review of randomized controlled trials assessing different protocols for awake fiberoptic intubation in anticipated difficult airway, including studies investigating elective awake fiberoptic intubation for scheduled surgery; randomized controlled trials comparing different methods for performing awake fiberoptic intubation; and adult patients with anticipated difficult airway. We excluded studies in the nonoperating theater settings, randomized controlled trials comparing awake fiberoptic intubation with other techniques, and studies based on simulation. Primary outcomes were success rate and death; secondary outcomes were major adverse events. Thirty-seven randomized controlled trials evaluating 2045 patients and 4 areas were identified: premedication, local anesthesia, sedation, and ancillary techniques to facilitate awake fiberoptic intubation. Quality of evidence was moderate-low and based on small-sampled randomized controlled trials. Overall, 12 of 2045 intubation failures (0.59%) and 7 of 2045 severe adverse events (0.34%) occurred, with no permanent consequences or death. All evaluated methods to achieve local anesthesia performed similarly well. No differences were observed in success rate with different sedatives. Dexmedetomidine resulted in fewer desaturation episodes compared to propofol and opioids with or without midazolam (relative risk, 0.51 [95% CI, 0.28-0.95]; P = .03); occurrence of desaturation was similar with remifentanil versus propofol, while incidence of apnoea was lower with sevoflurane versus propofol (relative risk, 0.43 [95% CI, 0.22-0.81]; P = .01). A high degree of efficacy and safety was observed with minimal differences among different protocols; dexmedetomidine might offer a better safety profile compared to other sed

Published
2019

13. Interventions affecting mortality in critically ill and perioperative patients: A systematic review of contemporary trials

Author

Baiardo Redaelli, M, Landoni, G, Di Sanzo, S, Frassoni, S, Sartini, C, Cabrini, L, Monti, G, Scandroglio, M, Zangrillo, A, Bellomo, R, Baiardo Redaelli, M, Landoni, G, Di Sanzo, S, Frassoni, S, Sartini, C, Cabrini, L, Monti, G, Scandroglio, M, Zangrillo, A, and Bellomo, R

Abstract

Purpose Confounders in randomized controlled trials (RCTs) reporting significant effects on mortality in critically ill patients using non-surgical techniques have not been systematically explored. We aimed to identify factors unrelated to the reported intervention that might have affected the findings and robustness of such trials. Methods We searched Pubmed/MEDLINE for all RCTs on any non-surgical interventions reporting an effect on unadjusted mortality in critically ill patients between 1/1/2000 and 1/12/2015. We assessed: the number needed to treat/harm (NNT or NNH), sample size, trial design (blinded/unblinded, single or multinational, single or multicenter (sRCT or mRCT)), intention to treat (ITT) analysis, and countries of origin. Results Almost half of RCTs were sRCTs. Median sample size was small, and 1/3 were not analyzed according to ITT principle. Lack of ITT analysis was associated with greater effect size (p = 0.0028). Harm was more likely in mRCTs (p = 0.002) and/or in blinded RCTs (p = 0.003). Blinded RCTs had double sample size (p = 0.007) and an increased NNT/NNH (p = 0.002). Finally, mRCTs had higher NNT (p = 0.005) and NNH (p = 0.02), and harm was only detected in studies from Western countries (p = 0.007). Conclusions These observations imply that major systematic biases exist and affect trial findings irrespective of the intervention being studied.

Published
2017

14. Cardiac protection with phosphocreatine: a meta-analysis

Author

Fominskiy, Evgeny, primary, Lomivorotov, V, additional, Nepomniashchikh, V, additional, Likhvantsev, V, additional, Ma, J, additional, Lembo, R, additional, Baiardo Redaelli, M, additional, Abubakirov, M, additional, Perovsky, P, additional, Zangrillo, A, additional, and Landoni, G, additional

Published
2016
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16. One-Year Multidisciplinary Follow-Up of Patients With COVID-19 Requiring Invasive Mechanical Ventilation

Author

Marco Ripa, Alberto Zangrillo, Beatrice Righetti, Francesco De Cobelli, Pasquale Nardelli, Alessandro Ortalda, Maria Rosa Calvi, Giovanni Borghi, Evgeny Fominskiy, Filippo D'Amico, Alessandro Belletti, Moreno Tresoldi, Marco Saracino, Margherita Rocchi, Francesca Guzzo, Diego Palumbo, Giovanni Landoni, Marilena Marmiere, Lorenzo Dagna, Martina Baiardo Redaelli, Zangrillo, A., Belletti, A., Palumbo, D., Calvi, M. R., Guzzo, F., Fominskiy, E. V., Ortalda, A., Nardelli, P., Ripa, M., Baiardo Redaelli, M., Borghi, G., Landoni, G., D'Amico, F., Marmiere, M., Righetti, B., Rocchi, M., Saracino, M., Tresoldi, M., Dagna, L., and De Cobelli, F.

Subjects
Adult, ARDS, medicine.medical_specialty, post-intensive care syndrome, Activities of daily living, Adolescent, medicine.medical_treatment, intensive care unit, law.invention, coronavirus disease 2019, Quality of life, law, Activities of Daily Living, medicine, Humans, Depression (differential diagnoses), Mechanical ventilation, pulmonary fibrosis, SARS-CoV-2, business.industry, COVID-19, acute respiratory distress syndrome, medicine.disease, Respiration, Artificial, Intensive care unit, Intensive Care Units, Anesthesiology and Pain Medicine, quality of life, Emergency medicine, Anxiety, Observational study, Original Article, lung recovery, medicine.symptom, Cardiology and Cardiovascular Medicine, business, Follow-Up Studies
Abstract

Objective Patients with COVID-19 frequently develop acute respiratory distress syndrome (ARDS) requiring intensive care unit (ICU) admission. Data on long-term survival of these patients are lacking. We investigated 1-year survival, quality of life and functional recovery of COVID-19 ARDS patients requiring invasive mechanical ventilation Design Prospective observational study Setting Tertiary-care university hospital Participants All COVID-19 ARDS patients receiving invasive mechanical ventilation and discharged alive from hospital Interventions Patients were contacted by phone after 1-year. Functional, cognitive, and psychological outcomes were explored through a questionnaire and assessed using validated scales. Patients were offered the possibility to undergo a follow-up chest CT scan. Measurements and Main Results The study included all adult (age ≥ 18 years) patients with COVID-19-related ARDS admitted to an ICU of our institution between February 25th, 2020 - April 27th, 2020), who received at least one day of invasive mechanical ventilation (IMV). Of 116 patients who received IMV, 61 (52.6%) survived to hospital discharge. These survivors were assessed one year after discharge and 56 completed a battery of tests of cognition, activities of daily living and interaction with family members. They had overall good functional recovery, with >80% reporting good recovery and no difficulties in usual activities. A total of 52 (93%) of patients had no dyspnea at rest. Severe anxiety/depression was reported by five (8.9%) of patients. Comparing 2-months and 1-year data, we observed the most significant improvements in the areas of working status and exertional dyspnea. One-year Chest CT scans were available for 36 patients: fibrotic-like changes were present in four patients. Conclusions All patients who survived the acute phase of the COVID-19 disease and were discharged from the hospital were alive at the 1-year follow up and the vast majority of them had good overall recovery and quality of life. Study Registration ClinicalTrials.gov NCT04318366

Published
2022

17. Prevalence, Characteristics, Risk Factors, and Outcomes of Invasively Ventilated COVID-19 Patients with Acute Kidney Injury and Renal Replacement Therapy

Author

Elena Moizo, Stefano Turi, Corrado Campochiaro, Alberto Zangrillo, Cristina Mattioli, Pasquale Nardelli, Paolo Silvani, Martina Crivellari, Giovanni Landoni, Marianna Sartorelli, Maria Grazia Calabrò, Fabio Ciceri, Francesco Giuseppe Nisi, Maria Luisa Azzolini, Giovanni Borghi, Marina Pieri, Antonio Dell'Acqua, Fabrizio Monaco, Martina Baiardo Redaelli, Caterina Conte, Alessandro Belletti, Ary Serpa Neto, Gabriele Valsecchi, Piera Angelillo, Evgeny Fominskiy, Cristina Barberio, Milena Mucci, Luigi Beretta, Rinaldo Bellomo, Anna Mara Scandroglio, Alfredo Ravizza, Stefano Tentori, Lorenzo Dagna, Giacomo Monti, Intensive Care Medicine, Fominskiy, E. V., Scandroglio, A. M., Monti, G., Calabro, M. G., Landoni, G., Dell'Acqua, A., Beretta, L., Moizo, E., Ravizza, A., Monaco, F., Campochiaro, C., Pieri, M., Azzolini, M. L., Borghi, G., Crivellari, M., Conte, C., Mattioli, C., Silvani, P., Mucci, M., Turi, S., Tentori, S., Baiardo Redaelli, M., Sartorelli, M., Angelillo, P., Belletti, A., Nardelli, P., Nisi, F. G., Valsecchi, G., Barberio, C., Ciceri, F., Serpa Neto, A., Dagna, L., Bellomo, R., and Zangrillo, A.

Subjects
Male, medicine.medical_specialty, Continuous Renal Replacement Therapy, Coronavirus disease 2019 (COVID-19), medicine.medical_treatment, 030232 urology & nephrology, Hospital mortality, 030204 cardiovascular system & hematology, urologic and male genital diseases, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Prevalence, medicine, Humans, Hospital Mortality, Renal replacement therapy, Stage (cooking), Aged, Ventilators, Mechanical, Coronavirus disease 2019, SARS-CoV-2, business.industry, urogenital system, Acute kidney injury, COVID-19, Hematology, General Medicine, Middle Aged, Tertiary care hospital, medicine.disease, Respiration, Artificial, Methods observational, female genital diseases and pregnancy complications, Coronavirus, Critical care, Treatment Outcome, Nephrology, Emergency medicine, Female, business, Research Article, Healthcare system
Abstract

Background: There is no information on acute kidney injury (AKI) and continuous renal replacement therapy (CRRT) among invasively ventilated coronavirus disease 2019 (COVID-19) patients in Western healthcare systems. Objective: To study the prevalence, characteristics, risk factors and outcome of AKI and CRRT among invasively ventilated COVID-19 patients. Methods: Observational study in a tertiary care hospital in Milan, Italy. Results: Among 99 patients, 72 (75.0%) developed AKI and 17 (17.7%) received CRRT. Most of the patients developed stage 1 AKI (33 [45.8%]), while 15 (20.8%) developed stage 2 AKI and 24 (33.4%) a stage 3 AKI. Patients who developed AKI or needed CRRT at latest follow-up were older, and among CRRT treated patients a greater proportion had preexisting CKD. Hospital mortality was 38.9% for AKI and 52.9% for CRRT patients. Conclusions: Among invasively ventilated COVID-19 patients, AKI is very common and CRRT use is common. Both carry a high risk of in-hospital mortality.

Published
2021

18. 'Neuromonitoring as an alternative to awake intubation in uncooperative patients at risk for cervical spine injury'

Author

Alberto Zangrillo, Martina Baiardo Redaelli, Luca Cabrini, Cabrini, L., Baiardo Redaelli, M., and Zangrillo, A.

Subjects
business.industry, medicine.medical_treatment, MEDLINE, Cervical Cord, Cervical cord, General Medicine, Cervical spine injury, Neck Injuries, medicine.anatomical_structure, Anesthesiology and Pain Medicine, Anesthesia, Cervical Vertebrae, Intubation, Intratracheal, Intubation, Medicine, Humans, business, Cervical vertebrae, Awake intubation
Published
2020

19. Tracheal intubation in patients at risk for cervical spinal cord injury: A systematic review

Author

Alberto Zangrillo, Ottavia Pallanch, Valentina Paola Plumari, Paolo Pelosi, Laura Pasin, Lorenzo Ball, Martina Baiardo Redaelli, Alessandro Putzu, Carmine D. Votta, Evgeny Fominskiy, Martina Filippini, Margherita Pintaudi, Giovanni Landoni, Luca Cabrini, Cabrini, L., Baiardo Redaelli, M., Filippini, M., Fominskiy, E., Pasin, L., Pintaudi, M., Plumari, V. P., Putzu, A., Votta, C. D., Pallanch, O., Ball, L., Landoni, G., Pelosi, P., Zangrillo, A., University of Zurich, and Cabrini, Luca

Subjects
medicine.medical_treatment, Laryngoscopy, 610 Medicine & health, 11171 Cardiocentro Ticino, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, 030202 anesthesiology, law, medicine, Intubation, Risk factor, Spinal cord injury, medicine.diagnostic_test, business.industry, Tracheal intubation, Postoperative complication, 030208 emergency & critical care medicine, General Medicine, medicine.disease, Anesthesiology and Pain Medicine, Meta-analysis, Anesthesia, 2703 Anesthesiology and Pain Medicine, business
Abstract

Background Tracheal intubation in patients at risk for secondary spinal cord injury is potentially difficult and risky. Objectives To compare tracheal intubation techniques in adult patients at risk for secondary cervical spinal cord injury undergoing surgery. Primary outcome was first-attempt failure rate. Secondary outcomes were time to successful intubation and procedure complications. Design Systematic review and meta-analysis of randomized controlled trials (RCTs) with trial sequential analysis (TSA). Data sources Databases searched up to July 2019. Eligibility Randomized controlled trials comparing different intubation techniques. Results We included 18 trials enrolling 1972 patients. Four studies used the "awake" approach, but no study compared awake versus non-awake techniques. In remaining 14 RCTs, intubation was performed under general anesthesia. First-attempt failure rate was similar when comparing direct laryngoscopy or fiberoptic bronchoscopy versus other techniques. A better first-attempt failure rate was found with videolaryngoscopy and when pooling all the fiberoptic techniques together. All these results appeared not significant at TSA, suggesting inconclusive evidence. Intubating lighted stylet allowed faster intubation. Postoperative neurological complications were 0.34% (no significant difference among techniques). No life-threatening adverse event was reported; mild local complications were common (19.5%). The certainty of evidence was low to very low mainly due to high imprecision and indirectness. Conclusions Videolaryngoscopy and fiberoptic-assisted techniques might be associated with higher first-attempt failure rate over controls. However, low to very low certainty of evidence does not allow firm conclusions on the best tracheal intubation in patients at risk for cervical spinal cord injury.

Published
2020

20. The effect of a rapid molecular blood test on the use of antibiotics for nosocomial sepsis: a randomized clinical trial

Author

Ana Paula de Paula Rosa Passetti, Stephanie Itala Rizk, Maria Renata Gomes Franco, Flavia Rossi, Juliano Pinheiro de Almeida, Cecilia Eugênia Charbel, Helio Hehl Caiaffa Filho, Rinaldo Focaccia Siciliano, Cristhieni Rodrigues, Tania Mara Varejão Strabelli, Luciane de Carvalho Sarahyba da Silva, Ludhmila Abrahão Hajjar, Rafael Alves Franco, Daniel De Backer, David Everson Uip, Giovanni Landoni, Martina Baiardo Redaelli, Julia Tizue Fukushima, Rogério Zeigler, Rodrigues, C., Siciliano, R. F., Filho, H. C., Charbel, C. E., De Carvalho Sarahyba Da Silva, L., Baiardo Redaelli, M., De Paula Rosa Passetti, A. P., Franco, M. R. G., Rossi, F., Zeigler, R., De Backer, D., Franco, R. A., De Almeida, J. P., Rizk, S. I., Fukushima, J. T., Landoni, G., Uip, D. E., Hajjar, L. A., and Strabelli, T. M. V.

Subjects
medicine.medical_specialty, medicine.drug_class, Antibiotics, Critical Care and Intensive Care Medicine, Blood culture, law.invention, Sepsis, 03 medical and health sciences, Nosocomial infection, 0302 clinical medicine, Randomized controlled trial, law, Intensive care, Internal medicine, medicine, Clinical endpoint, Blood test, Intention-to-treat analysis, medicine.diagnostic_test, business.industry, Research, lcsh:Medical emergencies. Critical care. Intensive care. First aid, Généralités, 030208 emergency & critical care medicine, lcsh:RC86-88.9, Antibiotic therapy, medicine.disease, Rapid molecular test, Critical care, 030228 respiratory system, business
Abstract

Background: Appropriate use of antimicrobials is essential to improve outcomes in sepsis. The aim of this study was to determine whether the use of a rapid molecular blood test - SeptiFast (SF) reduces the antibiotic consumption through early de-escalation in patients with nosocomial sepsis compared with conventional blood cultures (BCs). Methods: This was a prospective, randomized, superiority, controlled trial conducted at Sao Paulo Heart Institute in the period October 2012-May 2016. Adult patients admitted to the hospital for at least 48 h with a diagnosis of nosocomial sepsis underwent microorganism identification by both SF test and BCs. Patients randomized into the intervention group received antibiotic therapy adjustment according to the results of SF. Patients randomized into the control group received standard antibiotic adjustment according to the results of BCs. The primary endpoint was antimicrobial consumption during the first 14 days after randomization. Results: A total of 200 patients were included (100 in each group). The intention to treat analysis found no significant differences in median antibiotic consumption. In the subgroup of patients with positive SF and blood cultures (19 and 25 respectively), we found a statistically significant reduction in the median antimicrobial consumption which was 1429 (1071-2000) days of therapy (DOT)/1000 patients-day in the intervention group and 1889 (1357-2563) DOT/1000 patients-day in the control group (p = 0.017), in the median time of antimicrobial de-escalation (8 versus 54 h - p < 0.001), in the duration of antimicrobial therapy (p = 0.039) and in anti-gram-positive antimicrobial costs (p = 0.002). Microorganism identification was possible in 24.5% of patients (45/184) by SF and 21.2% (39/184) by BC (p = 0.45). Conclusion: This randomized clinical trial showed that the use of a rapid molecular-based pathogen identification test does not reduce the median antibiotic consumption in nosocomial sepsis. However, in patients with positive microbiological tests, the use of SeptiFast reduced antimicrobial consumption through early de-escalation compared to conventional blood cultures. These results were driven by a reduction in the consumption of antimicrobials used for Gram-positive bacteria. Trial registration: The trial was registered at ClinicalTrials.gov (NCT 01450358) on 12th October 2011, SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2019

21. How to obtain severe hypoglycemia without causing brain or cardiac damage

Author

Yamume Tshomba, Fabio Ciceri, Lorenzo Dagna, Alberto Zangrillo, Paolo Navalesi, Martina Baiardo Redaelli, Vanesa Gregorc, Giovanni Landoni, Baiardo Redaelli, M., Zangrillo, A., Gregorc, V., Ciceri, F., Dagna, L., Tshomba, Y., Navalesi, P., and Landoni, G.

Subjects
0301 basic medicine, Blood Glucose, Heart Diseases, medicine.medical_treatment, Apoptosis, Brain damage, Hypoglycemia, Bioinformatics, Oxidative Phosphorylation, 03 medical and health sciences, 0302 clinical medicine, Extracorporeal Membrane Oxygenation, Neoplasms, Extracorporeal membrane oxygenation, Medicine, Animals, Humans, Glycolysis, business.industry, Cancer, Brain, General Medicine, Models, Theoretical, medicine.disease, Mitochondria, Perfusion, 030104 developmental biology, Carotid Arteries, Glucose, Brain Injuries, Cancer cell, Patient Safety, medicine.symptom, business, Energy source, 030217 neurology & neurosurgery
Abstract

Cancer is the second cause of death worldwide, but current therapies are often insufficient or linked with toxicity. Initial evidence in scientific literature seems to support the role of non-pharmacological strategies, including hypoglycemia, in cancer treatment. The biological rationale for hypoglycemia-based treatment of cancer resides in the evidence that cancer cells predominantly utilize glucose as an energy source; notably, cancer cells seem to have damaged glycolysis regulation and few, defective mitochondria showing impaired oxidative phosphorylation. Preliminary data arising from both preclinical and human studies support the role of hypoglycemia in inducing apoptosis on cancer cells. In this paper, we describe how to induce and maintain severe hypoglycemia without causing damage to either the brain or the heart. Our hypothesis is that ExtraCorporeal Membrane Oxygenation (ECMO) and selective glucose perfusion of the carotid vessels are able to maintain severe hypoglycemia without causing cardiac or brain damage. This will allow physicians to study the effect of severe hypoglycemia on cancer cell apoptosis in vivo.

Published
2019

22. The Fragility Index in peri-operative randomised trials that reported significant mortality effects in adults

Author

F. Corrao, Alberto Zangrillo, Chiara Sartini, R. Cuffaro, Rinaldo Bellomo, Rosalba Lembo, Giovanni Landoni, M Baiardo Redaelli, L. Bertaggia, Bertaggia, L., Baiardo Redaelli, M., Lembo, R., Sartini, C., Cuffaro, R., Corrao, F., Zangrillo, A., Landoni, G., and Bellomo, R.

Subjects
Adult, medicine.medical_specialty, Critical Care, Psychological intervention, MEDLINE, Perioperative Care, law.invention, 03 medical and health sciences, 0302 clinical medicine, Fragility, Randomized controlled trial, 030202 anesthesiology, law, Internal medicine, Anesthesiology, Statistical significance, medicine, Humans, 030212 general & internal medicine, Mortality, Randomized Controlled Trials as Topic, business.industry, fragility Index, peri-operative, Perioperative, anaesthesia, mortality, Exact test, Anesthesiology and Pain Medicine, business, randomised controlled trial
Abstract

More than one million peri-operative patients die each year. Thus, small improvements in peri-operative care may save thousands of lives. However, clinicians need confidence in the robustness of trial findings. The Fragility Index may complement frequentist analysis and provide quantitative assessment of robustness. We searched MEDLINE for peri-operative critical care randomised controlled trials that reported a statistically significant difference in mortality. We identified 46 trials with 37,347 participants. The median (IQR [range]) Fragility Index was 2 (1–3 [0–49]). Eleven trials had a Fragility Index of zero (changing from the Chi-square test to Fisher's exact test removed significance) and seven trials had a Fragility Index of 1. Only 23/46 trials had a Fragility Index greater than the number of patients lost to follow-up. There was a strong positive correlation between the Fragility Index and: the number of participants, R 2 =0.97, p&nbsp

Published
2019

23. Post-anaesthesia pulmonary complications after use of muscle relaxants (POPULAR): a multicentre, prospective observational study

Author

Kirmeier E. a, Eriksson L. I. c, Lewald H. a, Jonsson Fagerlund, M. c Hoeft, A. f Hollmann, M. g Meistelman, C. e Hunter, J. M. d Ulm, K. b Blobner, M. aEmail Author, Abad Gurumeta, A. Abernethy, C. Abigail, P. Achaibar, K. Adam, E. Afshari, Agudelo Montoya, M. E. Akgün, F. N. Aletti, G. Alkış, N. Allan, K. Allan, A. Allaouchiche, B. Allcock, C. Almasy, E. Amey, I. Amigoni, M. Andersen, E. Andersson, P. Anipchenko, N. Antunes, P. Armstrong, E. Aslam, T. N. Aslin, B. Assunção, J. P. Ausserer, J. Avvai, M. Awad, Ayas Montero, B. Ayuso, M. Azevedo, P. Badarau, V. Badescu, Baiardo Redaelli, M. Baird, C. Baird, Y. Baker, T. Balaji, P. Bălan, C. Balandin, A. Balescu-Arion, C. Baliuliene, Baltasar Isabel, J. Baluch, S. N. Bandrabur, D. Bankewitz, C. Barber, K. Barbera, F. Barcraft-Barnes, H. Barletti, V. Barnett, G. Baron, K. Barros, A. Barsan, V. Bartlett, P. Batistaki, C. Baumgarten, G. Baytas, V. Beauchamp, Becerra Cayetano, I. A. Bell, S. Bellandi, M. Belletti, Belmonte Cuenca, J. Benitez-Cano, A. Beretta, L. Berger, M. Bergmann, N. Bergmark, Bermudez Lopez, M. Bernotaite, M. Beurskens, C. Bidd, H. Bifulco, F. Bignami, E. Bilic, A. Bilskiene, D. Bischoff, P. Bishop, L. Bjonness, T. Blaylock, H. Blethyn, K. Blincoe, T. Blokhin, I. Blunt, N. Boer, C. Bois, G. Bonicolini, E. Booth, J. Borecka-Kedzierska, M. Borstnar, K. Borys, M. Boselli, E. Bouvet, L. Bouwman, A. Bowen, L. Bowrey, S. Boxall, L. Božić, T. Bradley, T. Branco, T. Brazzi, L. Brazzoni, M. Brear, T. Brogly, N. Brohi, F. Broms, J. Bubliauskas, A. Bucolo, G. E. Buerkle, H. Buggy, D. Buhre, W. Bukauskas, T. Butturini, F. Byttner, Cabrera Díaz, I. Calderon, A. Calhau, R. Callejo, A. Cammu, G. Campesato, M. Can, Ö. S. Candeias, M. Cantor, A. Carise, E. Carmona, C. Carreteiro, J. Carrieri, C. Carter, A. Casal, M. Casanova, I. Cascella, M. Casero, L. M. Casiraghi, G. M. Castelo-Branco, Castro Arranz, C. Cernea, D. D. Cervantes, J. Chandler, B. Charnock, R. Chatzimicali, A. Chinery, E. Chishti, A. Chondhury, P. Christie, E. Christodoudiles, G. Ciardo, S. Cimpeanu, L. Cindea, I. Cinnella, G. Clark, S. Clayton, M. Cocu, S. Collyer, T. Colvin, C. Cope, S. Copeta, F. Copotoiu, S. -M., Correia de Barros, F. Corso, R. M. Cortegiani, A. Costa, G. Cowton, A. Cox, N. Craig, J. Cricca, V. Cronin, J. Cunha, M. Cuomo, A. Curley, K. Czuczwar, M. Dabrowska, D. Damster, Danguy des Déserts, M. Daniliuc, A. Danninger, T. Darwish, I. Dascalu, C. Davies, K. Davies, De Boer, De Flaviis, De Selincourt, G. Deana, C. Debaene, B. Debreceni, G. Dedhia, Delgado Garcia, Della Rocca, G. Delroy-Buelles, L. Desai, T. Dhillon, Di Giacinto, Di Mauro, Diaz Gomez, T. V. Dimitrovski, A. Dinic, V. Dîrzu, D. -S., Divander M. B., Dolinar J., Domingues S., Doolan J., Downes C., Dragoescu N. A., Droc G., Dum E., Dumitrescu A., Duncan L., Dzurňáková P., Eberl S., Edwards J., Edwards M., Ekelund K., Ekengren P., Elghouty E., Ellerkmann R., Ellis H., Elme A., Ernst T., Errando C. L., Estenes S., Ewaldsson C., Farid N., Featherstone J., Febres D., Fedorov S., Feggeler J., Feijten P., Fellmann T., Fernandez Candil, Fernandez Castineira, Fernández Castineira, J. Fernando, A. Ferrando, C. Ferreira, L. Ferreira, P. Feyling, A. Filipescu, D. Fleischer, A. Floris, L. Foerster, U. Fox, B. Franke, U. Frasca, D. Frey, C. Frost, V. Fullin, G. Fumagalli, J. Furneval, J. Fusari, M. Gallacher, S. Galushka, S. Gambale, G. Gambino, I. Garcia-Perez, M. L. Garg, S. Garlak, J. Gavranovic, Z. Gavrilov, R. Gaynor, Gecaj Gashi, A. Georghiou, M. Gerjevic, B. Gferer, G. Giarratano, A. Gibson, A. Gievski, V. Giles, J. Gillberg, L. Gilowska, Gilsanz Rodriguez, F. Gioia, A. Giovannoni, C. Girotra, V. Gkinas, D. Gkiokas, G. Godoroja, D. Goebel, U. Goel, V. Gonzalez, M. Goranovic, T. Gornik-Wlaszczuk, E. Gosavi, S. Gottfridsson, P. Gottschalk, A. Granell, M. Granstrom, A. Grassetto, A. Greenwood, A. Grigoras, I. Grintescu, I. Gritsan, A. Gritsan, G. Grynyuk, A. Guadagnin, G. M. Guarnieri, M. Güçlü, Guerrero Diez, M. Gunenc, F. Günther, U. Gupta, P. Guttenthaler, V. Hack, Y. Hafisayena, A. Hagau, N. Haldar, J. Hales, D. Hancı, V. Hanna-Jumma, S. Harazim, H. Harlet, P. Harper, D. Harris, B. Harvey, O. Hashimi, M. Hawkins, L. Hayes, C. Heaton, J. Heier, T. Helliwell, L. Hemmes, S. Henderson, K. Hermanides, J. Hermanns, Herrera Hueso, B. Hestenes, S. Hettiarachchi, R. Highgate, J. Hodgson, K. Hoelbling, D. Holland, J. Horhota, L. Hormis, A. Hribar, R. Hua, A. Humphreys, S. Humphries, R. Humpliková, S. Hunt, J. Husnain, A. Hussein, A. Hyams, B. Iannuccelli, F. Ilette, K. Ilyas, C. Inan, T. India, I. Ionițăv, V. Irwin, F. Jain, V. Janez, B. Jankovic, R. Jenkins, S. Jenko, M. Jimenez, Jiménez Gomez, B. Joachim, S. Joelsson-Alm, E. John, J. Jonikaite, L. Jovic, M. Jungwirth, B. Junke, E. Kabakov, B. Kadaoui, S. -D., Kanski A., Karadag S., Karbonskiene A., Karjagin J., Kasnik D., Katanolli F., Katsika E., Kaufmann K., Keane H., Kelly M., Kent M., Keraitiene G., Khudhur A., Khuenl-Brady K., Kidd L., King S., Kirchgäßner K., Klancir T., Klucniks A., Knotzer J., Knowlden P., Koers L., Kompan J., Koneti K. K., Kooij F., Koolen E., Koopman - van Gemert, A. W. M. M. Kopp, K. Korfiotis, D. Korolkov, O. Kosinová, M. Köstenberger, M. Kotzinger, O. Kovačević, M. Kranke, P. Kranke, E. Kraus, C. Kraus, S. Kubitzek, C. Kucharski, R. Kucukguclu, S. Kudrashou, A. Kumar, V. Kummen, L. Kunit, C. Kushakovsky, V. Kuvaki, B. Kuzmanovska, B. Kyttari, A. Landoni, G. Lau, G. Lazarev, K. Legett, S. Legrottaglie, A. M. Leonardi, S. Leong, M. Lercher, H. Leuvrey, M. Leva, B. Levstek, M. Limb, J. Lindholm, E. Linton, F. Liperi, C. Lipski, F. Lirk, P. Lisi, A. Lišková, Lluch Oltra, A. Loganathan, V. Lombardi, S. Lopez, Lopez Rodríguez, M. Lorenzini, L. Lowicka, M. Lugovoy, A. Luippold, M. Lumb, A. Macas, A. 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Ricardo, Callejo, Angel, Cammu, Guy, Campesato, Manuela, Can, Özlem S, Candeias, Margarida, Cantor, Andreea, Carise, Elsa, Carmona, Cristina, Carreteiro, Joana, Carrieri, Cosima, Carter, Anna, Casal, Manuela, Casanova, Irene, Cascella, Marco, Casero, Luis M., Casiraghi, Guiseppina Maria, Castelo-Branco, Laila, Castro Arranz, Carlo, Cernea, Daniela Denisa, Cervantes, Jesoporiol, Chandler, Ben, Charnock, Robert, Chatzimicali, Aikaterini, Chinery, Elane, Chishti, Ahmed, Chondhury, Priyakam, Christie, Emily, Christodoudiles, George, Ciardo, Stefano, Cimpeanu, Luminata, Cindea, Iulia, Cinnella, Gilda, Clark, Sebastian, Clayton, Matthew, Cocu, Simona, Collyer, Thoma, Colvin, Carie, Cope, Sean, Copeta, Filomena, Copotoiu, Sanda-Maria, Correia de Barros, Filinto, Corso, Ruggero Massimo, Cortegiani, Andrea, Costa, Gabriela, Cowton, Amanda, Cox, Nicola, Craig, Jame, Cricca, Valentina, Cronin, John, Cunha, Mariana, Cuomo, Arturo, Curley, Katherine, Czuczwar, Mirosław, Dabrowska, Domenika, Damster, Sabrine, Danguy des Déserts, Marc, Daniliuc, Aura, Danninger, Thoma, Darwish, Imad, Dascalu, Corina, Davies, Kirsty, Davies, Simon, De Boer, Han, De Flaviis, Adelisa, De Selincourt, Gabrielle, Deana, Cristian, Debaene, Bertrand, Debreceni, Gabor, Dedhia, Jatin, Delgado Garcia, Isabel, Della Rocca, Giorgio, Delroy-Buelles, Llana, Desai, Tejal, Dhillon, Parveen, Di Giacinto, Ida, Di Mauro, Piero, Diaz Gomez, Tamara V., Dimitrovski, Aleksandar, Dinic, Vesna, Dîrzu, Dan-Sebastian, Divander, Mona Britt, Dolinar, Janez, Domingues, Susana, Doolan, Jame, Downes, Charlotte, Dragoescu, Nicoleta Alice, Droc, Gabriela, Dum, Elisabeth, Dumitrescu, Alexandra, Duncan, Louise, Dzurňáková, Paul, Eberl, Susanne, Edwards, Jayne, Edwards, Mark, Ekelund, Kim, Ekengren, Patrik, Elghouty, Eyad, Ellerkmann, Richard, Ellis, Helen, Elme, Andrea, Ernst, Thoma, Errando, Carlos Lui, Estenes, Simao, Ewaldsson, Calli, Farid, Nahla, Featherstone, Jame, Febres, Daniela, Fedorov, Sergey, Feggeler, Johanna, Feijten, Prisca, Fellmann, Tobia, Fernandez Candil, Juan, Fernandez Castineira, Ana, Fernández Castineira, Juan, Fernando, Aruna, Ferrando, Carlo, Ferreira, Leonia, Ferreira, Patrick, Feyling, Ander, Filipescu, Daniela, Fleischer, Andrea, Floris, Leda, Foerster, Ur, Fox, Benjamin, Franke, Uwe, Frasca, Deni, Frey, Christian, Frost, Victoria, Fullin, Giorgio, Fumagalli, Jacopo, Furneval, Julie, Fusari, Maurizio, Gallacher, Stuart, Galushka, Svetlana, Gambale, Giorgio, Gambino, Irene, Garcia-Perez, Maria Luisa, Garg, Sanjeev, Garlak, Justyna, Gavranovic, Zeljka, Gavrilov, Roman, Gaynor, Lame, Gecaj Gashi, Agreta, Georghiou, Maria, Gerjevic, Bozena, Gferer, Gudrun, Giarratano, Antonino, Gibson, Andy, Gievski, Vanja, Giles, Julian, Gillberg, Lar, Gilowska, Katarzyna, Gilsanz Rodriguez, Fernando, Gioia, Antonio, Giovannoni, Cecilia, Girotra, Vandana, Gkinas, Dimitrio, Gkiokas, George, Godoroja, Daniela, Goebel, Ulrich, Goel, Vandana, Gonzalez, Matilde, Goranovic, Tatjana, Gornik-Wlaszczuk, Ewa, Gosavi, Smita, Gottfridsson, peter, Gottschalk, André, Granell, Manuel, Granstrom, Anna, Grassetto, Alberto, Greenwood, Anna, Grigoras, Ioana, Grintescu, Ioana, Gritsan, Alexey, Gritsan, Galina, Grynyuk, Andriy, Guadagnin, Giovanni Maria, Guarnieri, Marcello, Güçlü, Çiğdem, Guerrero Diez, Maria, Gunenc, Ferim, Günther, Ulf, Gupta, Pawan, Guttenthaler, Vera, Hack, Yvonne, Hafisayena, Ade, Hagau, Natalia, Haldar, Jagannath, Hales, Dawn, Hancı, Volkan, Hanna-Jumma, Sameer, Harazim, Hana, Harlet, Pierre, Harper, Daniel, Harris, Benjamin, Harvey, Orla, Hashimi, Medita, Hawkins, Lesley, Hayes, Conrad, Heaton, Jame, Heier, Tom, Helliwell, Laurence, Hemmes, Sabrine, Henderson, Kate, Hermanides, Jeroen, Hermanns, Henning, Herrera Hueso, Berta, Hestenes, Siv, Hettiarachchi, Roshane, Highgate, Judith, Hodgson, Keith, Hoelbling, Daniel, Holland, Jonathan, Horhota, Lucian, Hormis, Anil, Hribar, Renata, Hua, Alina, Humphreys, Sally, Humphries, Ryan, Humpliková, Simona, Hunt, Janez, Husnain, Ali, Hussein, Ahmed, Hyams, Benjamin, Iannuccelli, Fabrizio, Ilette, Katie, Ilyas, Carl, Inan, Turgay, India, Immaculada, Ionițăv, Victor, Irwin, Foo, Jain, Vipul, Janez, Benedikt, Jankovic, Radmilo, Jenkins, Sarah, Jenko, Matej, Jimenez, Raquel, Jiménez Gomez, Bárbara, Joachim, Sugganthi, Joelsson-Alm, Eva, John, John, Jonikaite, Lina, Jovic, Miomir, Jungwirth, Bettina, Junke, Etienne, Kabakov, Bory, Kadaoui, Salah-Din, Kanski, Andrzej, Karadag, Süheyla, Karbonskiene, Aurika, Karjagin, Juri, Kasnik, Darja, Katanolli, Fato, Katsika, Eleni, Kaufmann, Kai, Keane, Helen, Kelly, Martin, Kent, Melanie, Keraitiene, Grazina, Khudhur, Ahmed, Khuenl-Brady, Karin, Kidd, Laurie, King, Siobhan, Kirchgäßner, Katharina, Klancir, Tino, Klucniks, Andri, Knotzer, Johann, Knowlden, Peter, Koers, Lena, Kompan, Janez, Koneti, Kiran K, Kooij, Fabian, Koolen, Eric, Koopman - van Gemert, Anna Wilhelmina Margaretha Maria, Kopp, Kristen, Korfiotis, Dimitrio, Korolkov, Oleg, Kosinová, Martina, Köstenberger, Marku, Kotzinger, Oskar, Kovačević, Marko, Kranke, Peter, Kranke, Eva, Kraus, Christiane, Kraus, Stephanie, Kubitzek, Christiane, Kucharski, Rafal, Kucukguclu, Semih, Kudrashou, Allaksandr, Kumar, Vinayak, Kummen, Live, Kunit, Cornelia, Kushakovsky, Vlad, Kuvaki, Bahar, Kuzmanovska, Biljana, Kyttari, Aikaterina, Landoni, Giovanni, Lau, Gary, Lazarev, Konstantin, Legett, Samantha, Legrottaglie, Anna Maria, Leonardi, Silvia, Leong, Maria, Lercher, Helene, Leuvrey, Matthieu, Leva, Brigitte, Levstek, Meta, Limb, Jame, Lindholm, Espen, Linton, Fiona, Liperi, Corradero, Lipski, Fabian, Lirk, Philipp, Lisi, Alberto, Lišková, Katarina, Lluch Oltra, Aitana, Loganathan, Vinothan, Lombardi, Stefania, Lopez, Eloisa, Lopez Rodríguez, Maria, Lorenzini, Laura, Lowicka, Malgorzata, Lugovoy, Alexander, Luippold, Madeleine, Lumb, Andrew, Macas, Andriu, Macgregor, Mark, Machado, Humberto, Maciariello, Maria, Madeira, Isabel, Maitan, Stefan, Majewski, Jacek, Maldini, Branka, Malewski, Georgia, Manfredini, Livia, Männer, Olja, Marchand, Bahareh, Marcu, Alexandra, Margalef, Jordi, Margarson, Michael, Marinheiro, Lucia, Markic, Ana, Markovic Bozic, Jasmina, Marrazzo, Francesco, Martin, Jane, Martin Ayuso, Maria, Martinez, Esteher, Martino, Enrico Antonio, Martinson, Victoria, Marusic-Gaser, Katarina, Mascarenhas, Catia, Mathis, Cindy, Matsota, Paraskevi, Mavrommati, Eleni, Mazul Sunko, Branka, McCourt, Killian, McGill, Neil, McKee, Raymond, Meço, Başak Ceyda, Meier, Sonja, Melbourne, Susan, Melbybråthen, Grethe, Meli, Andrea, Melia, Aiden, Melotti, Rita Maria, Menga, Maria Rosaria, Mercer, Pauline, Merotra, Susan, Mescolini, Silvia, Metterlein, Thoma, Michalov, Martin, Michlig, Sam, Midgley, Susan, Milić, Morena, Milojevic, Milan, Miñana, Amanda, Minto, Gary, Mirabella, Lucia, Mirea, Liliana, Mittelstädt, Ludger, Moeglen, Aude, Moise, Alida, Mokini, Zhirajr, Molin, Anna, Moltó, Lui, Monea, Maria Concetta, Montalto, Francesca, Montgomery, Jane, Montgomery, Claire, Montillo, Gerardo, Moore, Sally, Moore, Faye, Moreira, Zelia, Moreno, Tania, Moreno, Ricardo, Moret, Enrique, Moreton, Sarah, Morgan, Marianne, Moro Velasco, Concepción, Morri, Davide, Moull, Alice, Moura, Fernando, Mráz, Peter, Mrozek, Katarzyna, Mukhtar, Karim, Muniyappa, Sudeshkumar, Murray, Heather, Murthy, Burra VS, Mushambi, Mary, Nadolski, Maria, Nardelli, Pasquale, Nardin, Giordano, Navarro Pérez, Rosalía, Naveiro, Andrea, Negri, Manuela, Nesek Adam, Visnja, Neskovic, Vojislava, Neuwersch, Stefan, Neves, Miriam, Nguyen, Bavinh, Ní Eochagáin, Aisling, Nicholas, Caroline, Nightingale, Jeremy, Norrie, Kylie, Novak-Jankovic, Vesna, Novakova, Andrea, Novillo, Marta, Numan, Sandra, Oduro-Dominah, Louise, Oldner, Ander, Oliveira, Isabel, Ologoiu, Daniela, Oloktsidou, Irini, O'Reilly, Rosalind, Orlando, Alessandro, Ovezov, Alexey, Ozbilgin, Sule, Paal, Peter, Padin Barreiro, Lidia, Palugniok, Ryszard, Papaioannou, Alexandra, Papapostolou, Konstantino, Paranthaman, Prabhakar, Pardey Bracho, Gilda, Parente, Suzana, Parfeni, Alexandru, Pasin, Laura, Passey, Samuel, Pastor, Ernesto, Patch, Sarah, Patil, Andan, Paunescu, Marilena-Alina, Pehboeck, Daniel, Pereira, Manuela, Pereira, Carla, Perez Caballero, Paula, Pérez García, Aníbal, Pérez Soto, Antonia, Perez Tejero, Gisela, Perez-Cerda, Francisco, Pesenti, Antonio, Petta, Rocco, Philippe, Simon, Pickering, David, Pico Veloso, Jandro, Pina, Pedro, Pinho-Oliveira, Vítor, Pinol, Santiago, Pinto, Rita, Pistidda, Laura, Pitterle, Manuela, Piwowarczyk, Paweł, Plotnikova, Olga, Pohl, Holger, Poldermann, Jorinde, Polkovicová, Lucia, Pompei, Livia, Popescu, Mihai, Popović, Radmila, Pota, Vincenzo, Potocnik, Miriam, Potręć, Beata, Potter, Alison, Pramod, Nalwaya, Prchalova, Martina, Preckel, Benedikt, Pugh, Richard, Pulletz, Mark, Radoeshki, Aleksandar, Rafi, Amir, Ragazzi, Riccardo, Raineri Santi, Maurizio, Rajamanickam, Tamiselvan, Rajput, Zahra, Ramachandran, Rajeskar, Ramasamy, Radhika, Ramessur, Suneil, Rao, Roshan, Rasmussen, Ander, Rato, André, Razaque, Usman, Real Navacerrada, M. Isabel, Reavley, Caroline, Reid, Jame, Reschreiter, Henrik, Rial, Erick, Ribas Carrasco, Patricia, Ribeiro, Sandy, Rich, Nathalie, Richardson, Lydia, Rimaitis, Kestuti, Rimaitis, Mariu, Ringvold, Else-Marie, Ripke, Fabian, Ristescu, Irina, Ritchie, Keith, Ródenas, Frederic, Rodrigues, Patrícia, Rogers, Emma, Rogerson, David, Romagnoli, Stefano, Romero, Esther, Rondovic, Goran, Rose, Bernd Oliver, Roth, Winfried, Rotter, Marie-Therese, Rousseau, Guy, Rudjord, Ander, Rueffert, Henrik, Rundgren, Malin, Rupprecht, Korbinian, Rushton, Andrew, Russotto, Vincenzo, Rypulak, Elżbieta, Ryszka, Maciej, Sà, Jacinta, Sà Couto, Paula, Saby, Sandrine, Sagic, Jelena, Saleh, Omar, Sales, Gabriele, Sánchez Sánchez, Yván, Sanghera, Sumayer, Şanli Karip, Ceren, Santiveri Papiol, Francisco Javier, Santos, Sofia, Sarno, Stephen, Saul, Daniel, Saunders, David, Savic, Nenad, Scalco, Loïc, Scanlon, Deborah, Schaller, Stefan, Schax, Christoph, Scheffer, Gert Jan, Schening, Anna, Schiavone, Vincenzo, Schmidt-Ehrenberg, Florian, Schmidt-Mutter, Catherine, Schönberg, Christina, Schopflin, Christian, Schreiber, Jan-Uwe, Schultz, Marcu, Schurig, Marlen, Scott, Carmen, Sebestian, Siby, Sehgal, Selena, Sem, Victoria, Semenas, Egidiju, Serafini, Elena, Serchan, Pashalitsa, Shields, Martin, Shobha, Ramakrishnan, Shosholcheva, Mirjana, Siamansour, Tanja, Siddaiah, Narendra, Siddiqi, Khalid, Sinclair, Rhona, Singh, Permendra, Singh, Rajendra, Sinha, Aneeta, Sinha, Ashok, Skinner, Amanda, Smee, Elizabeth, Smekalova, Olga, Smith, Neil, Smith, Thoma, Smitz, Carine, Smole, Daniel, Sojčić, Nataša, Soler Pedrola, Maria, Somanath, Sameer, Sonksen, Julian, Sorella, Maria Christina, Sörmus, Alar, Soro, Marina, Soto, Carmen, Spada, Anna, Spadaro, Savino, Spaeth, Johanne, Sparr, Harald, Spielmann, Annika, Spindler-Vesel, Alenka, Stamelos, Matthaio, Stancombe L, Liucia, Stanculescu, Andreea, Standl, Thoma, Standley, Tom, Stanek, Ondrej, Stanisavljević, Snežana, Starczewska, Malgorzata, Stäuble, Christiane, Steen, Julie, Stefan, Oana Maria, Stell, Elizabeth, Stera, Caterina, Stevens, Marku, Stoerckel, Marlène, Stošić, Biljana, Stourac, Petr, Stroumpoulis, Konstantino, Struck, Rafael, Suarez de la Rica, Alejandro, Sultanpori, Altaf, Sundara Rajan, Rajinikanth, Suying, Ong, Svensen, Christer, Swan, Louise, Syrogianni, Paulina, Sysiak, Justyna, Szederjesi, Jano, Taddei, Stefania, Tan Hao, Ern, Tanou, Virginia, Tarabová, Katarina, Tardaguila Sancho, Paula, Tarroso, Maria, Tartaglione, Marco, Taylor, Emma, Tbaily, Lee, Telford, Richard, Terenzoni, Massimo, Theodoraki, Kassiani, Thornley, Helen, Tiganiuc, Liviu, Toim, Hardo, Tomescu, Dana, Tommasino, Concezione, Toni, Jessica, Toninelli, Arturo, Toretti, Ilaria, Townley, Stephen, Trepenaitis, Dariu, Trethowan, Brian, Tsaousi, Georgia, Tsiftsi, Aikaterini, Tudor, Adrada, Turan, Güldem, Turhan, Sanem Çakar, Unic-Stojanovic, Dragana, Unterbuchner, Christoph, Unzueta, Carmen, Uranjek, Jasna, Ursic, Tomaz, Vaida, Simona, Valldeperas Ferrer, Silvia, Valldeperas Hernandez, Maria Inmaculada, Valsamidis, Dimitri, Van Beek, Rienk, Van dasselaer, Nick, Van Der Beek, Tim, Van Duivenvoorde, Yoni, van Klei, Wilton A., Van Poorter, Fran, Van Zaane, Ba, Van Zundert, Tom, Van Zyl, Rebekka, Vargas Munoz, Ana Milena, Varsani, Nimu, Vasconcelos, Pedro, Vassilakis, Georgio, Vecchiatini, Tommaso, Vecera, Lubomir, Vercauteren, Marcel, Verdouw, Ba, Verheyen, Veerle, Verri, Marco, Vicari Sottosanti, Luigi Giancarlo, Vico, Manuel, Vidal Mitjans, Patricia, Vilardi, Anna, Vissicchio, Daniela, Vitale, Giovanni, Vitković, Bibiana, Vizcaychipi, Marcela Paola, Voicu, Alexandra, Voje, Minca, Volfová, Ivana, Volta, Carlo Alberto, Von Lutterotti, Theresa, von Tiesenhausen, Anna, Vrecic-Slabe, Simona, Vukcevic, Dejan, Vukovic, Rade, Vullo, P. Agostina, Wade, Andrew, Wallberg, Hanna, Wallden, Jakob, Wallner, Johann, Walther Sturesson, Louise, Watson, Davina, Weber, Stefan, Wegiel Leskiewiq, Anna, Weller, Debbie, Wensing, Carine, Werkmann, Marku, Westberg, Henrik, Wikström, Erik, Williams, Benedict, Wilson, Robin, Wirth, Steffen, Wittmann, Maria, Wood, Laura, Wright, Stella, Zachoval, Christian, Zambon, Massimo, Zampieri, Silvia, Zampone, Salvatore, Zangrillo, Alberto, Zani, Gianluca, Zavackiene, Asta, Zieglerder, Raphael, Zonneveldt, Harry, Zsisku, Lajo, Zucker, Tom-Philipp, Żukowski, Maciej, Zuleika, Mehrun, and Zupanĕiĕ, Darja

Subjects
Pulmonary and Respiratory Medicine, pulmonary complications, muscle relaxants, Post-anaesthesia complications, Neuromuscular Blockade, pulmonary complication, muscle relaxant, neuromuscular block, postoperative pulmonary complication, business.industry, Retrospective cohort study, post-operative pulmonary complications, Neuromuscular monitoring, Neuromuscular Blocking Agents, Sugammadex, NO, Anaesthesia, 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, Anesthesia, Medicine, General anaesthesia, Neuromuscular Agents, 030212 general & internal medicine, MED/41 - ANESTESIOLOGIA, Prospective cohort study, business, medicine.drug
Abstract

Background: Results from retrospective studies suggest that use of neuromuscular blocking agents during general anaesthesia might be linked to postoperative pulmonary complications. We therefore aimed to assess whether the use of neuromuscular blocking agents is associated with postoperative pulmonary complications. Methods: We did a multicentre, prospective observational cohort study. Patients were recruited from 211 hospitals in 28 European countries. We included patients (aged ≥18 years) who received general anaesthesia for any in-hospital procedure except cardiac surgery. Patient characteristics, surgical and anaesthetic details, and chart review at discharge were prospectively collected over 2 weeks. Additionally, each patient underwent postoperative physical examination within 3 days of surgery to check for adverse pulmonary events. The study outcome was the incidence of postoperative pulmonary complications from the end of surgery up to postoperative day 28. Logistic regression analyses were adjusted for surgical factors and patients' preoperative physical status, providing adjusted odds ratios (ORadj) and adjusted absolute risk reduction (ARRadj). This study is registered with ClinicalTrials.gov, number NCT01865513. Findings: Between June 16, 2014, and April 29, 2015, data from 22 803 patients were collected. The use of neuromuscular blocking agents was associated with an increased incidence of postoperative pulmonary complications in patients who had undergone general anaesthesia (1658 [7·6%] of 21 694); ORadj 1·86, 95% CI 1·53–2·26; ARRadj −4·4%, 95% CI −5·5 to −3·2). Only 2·3% of high-risk surgical patients and those with adverse respiratory profiles were anaesthetised without neuromuscular blocking agents. The use of neuromuscular monitoring (ORadj 1·31, 95% CI 1·15–1·49; ARRadj −2·6%, 95% CI −3·9 to −1·4) and the administration of reversal agents (1·23, 1·07–1·41; −1·9%, −3·2 to −0·7) were not associated with a decreased risk of postoperative pulmonary complications. Neither the choice of sugammadex instead of neostigmine for reversal (ORadj 1·03, 95% CI 0·85–1·25; ARRadj −0·3%, 95% CI −2·4 to 1·5) nor extubation at a train-of-four ratio of 0·9 or more (1·03, 0·82–1·31; −0·4%, −3·5 to 2·2) was associated with better pulmonary outcomes. Interpretation: We showed that the use of neuromuscular blocking drugs in general anaesthesia is associated with an increased risk of postoperative pulmonary complications. Anaesthetists must balance the potential benefits of neuromuscular blockade against the increased risk of postoperative pulmonary complications. Funding: European Society of Anaesthesiology.

Published
2019

24. Randomized Evidence for Reduction of Perioperative Mortality: An Updated Consensus Process

Author

Caetano Nigro Neto, Luigi Verniero, Marta Mucchetti, Massimiliano Paltenghi, Gordana Gazivoda, Fabrizio Monaco, Nicola Latronico, Alberto Zangrillo, Antonella Vezzani, Vladimir V. Lomivorotov, Paolo Mura, Rosetta Lobreglio, Laura Ruggeri, Francesco Santini, Rosalba Lembo, Rinaldo Bellomo, Marco Ganzaroli, Eugenio Garofalo, Adele Conte, Daniele Marianello, Gabriele Finco, Andrea Székely, Mario Musu, Desiderio Piras, Valentina Tarzia, Evgeny Fominskiy, Giovanni Landoni, Ludhmila Abrahão Hajjar, Claudio Riefolo, Marco Comis, Martina Baiardo Redaelli, Gianluca Paternoster, Antonio Pisano, Laura Pasin, Massimiliano Conte, Gabriele Alvaro, Giuseppe Buscaglia, Erika Dal Checco, Giovanni De Vuono, Vadim Pasyuga, Giovanni Pala, Maria Luisa Azzolini, Alessandro Belletti, Agostino Roasio, Francesco Corradi, Alberto Castella, Landoni, Giovanni, Pisano, A, Lomivorotov, V, Alvaro, G, Hajjar, L, Paternoster, G, Nigro Neto, C, Latronico, N, Fominskiy, E, Pasin, L, Finco, G, Lobreglio, R, Azzolini, Ml, Buscaglia, G, Castella, A, Comis, M, Conte, A, Conte, M, Corradi, F, Checco, Ed, De Vuono, G, Ganzaroli, M, Garofalo, E, Gazivoda, G, Lembo, R, Marianello, D, Baiardo Redaelli, M, Monaco, F, Tarzia, V, Mucchetti, M, Belletti, A, Mura, P, Musu, M, Pala, G, Paltenghi, M, Pasyuga, V, Piras, D, Riefolo, C, Roasio, A, Ruggeri, L, Santini, F, Székely, A, Verniero, L, Vezzani, A, Zangrillo, Alberto, and Bellomo, R.

Subjects
medicine.medical_specialty, Consensus, perioperative care, Selective decontamination, anesthesia, consensus, intensive care, mortality, Congresses as Topic, Humans, Perioperative Care, Postoperative Complications, Randomized Controlled Trials as Topic, Cardiology and Cardiovascular Medicine, Anesthesiology and Pain Medicine, Psychological intervention, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, 030202 anesthesiology, Intensive care, medicine, Intensive care medicine, Glycemic, business.industry, Perioperative, Levosimendan, Surgical procedures, business, Tranexamic acid, medicine.drug
Abstract

Objective Of the 230 million patients undergoing major surgical procedures every year, more than 1 million will die within 30 days. Thus, any nonsurgical interventions that help reduce perioperative mortality might save thousands of lives. The authors have updated a previous consensus process to identify all the nonsurgical interventions, supported by randomized evidence, that may help reduce perioperative mortality. Design and Setting A web-based international consensus conference. Participants The study comprised 500 clinicians from 61 countries. Interventions A systematic literature search was performed to identify published literature about nonsurgical interventions, supported by randomized evidence, showing a statistically significant impact on mortality. A consensus conference of experts discussed eligible papers. The interventions identified by the conference then were submitted to colleagues worldwide through a web-based survey. Measurements and Main Results The authors identified 11 interventions contributing to increased survival (perioperative hemodynamic optimization, neuraxial anesthesia, noninvasive ventilation, tranexamic acid, selective decontamination of the gastrointestinal tract, insulin for tight glycemic control, preoperative intra-aortic balloon pump, leuko-depleted red blood cells transfusion, levosimendan, volatile agents, and remote ischemic preconditioning) and 2 interventions showing increased mortality (beta-blocker therapy and aprotinin). Interventions then were voted on by participating clinicians. Percentages of agreement among clinicians in different countries differed significantly for 6 interventions, and a variable gap between evidence and clinical practice was noted. Conclusions The authors identified 13 nonsurgical interventions that may decrease or increase perioperative mortality, with variable agreement by clinicians. Such interventions may be optimal candidates for investigation in high-quality trials and discussion in international guidelines to reduce perioperative mortality.

Published
2017

25. Interventions affecting mortality in critically ill and perioperative patients: A systematic review of contemporary trials

Author

Giacomo Monti, Luca Cabrini, Alberto Zangrillo, Rinaldo Bellomo, Mara Scandroglio, Chiara Sartini, Samuele Frassoni, Giovanni Landoni, Stefania Di Sanzo, Martina Baiardo Redaelli, Baiardo Redaelli, Martina, Landoni, Giovanni, Di Sanzo, Stefania, Frassoni, Samuele, Sartini, Chiara, Cabrini, Luca, Monti, Giacomo, Scandroglio, Mara, Zangrillo, Alberto, Bellomo, Rinaldo, Baiardo Redaelli, M, Landoni, G, Di Sanzo, S, Frassoni, S, Sartini, C, Cabrini, L, Monti, G, Scandroglio, M, Zangrillo, A, and Bellomo, R

Subjects
medicine.medical_specialty, Critical Care, Critical Illness, MEDLINE, Psychological intervention, Anesthesia, Critically ill, Intensive care, Mortality, Perioperative, Randomized clinical trials, RCT, Review, Trials, Critical Care and Intensive Care Medicine, Trial, law.invention, 03 medical and health sciences, 0302 clinical medicine, Bias, Randomized controlled trial, law, Bia, Internal medicine, medicine, Humans, 030212 general & internal medicine, Perioperative Period, Intensive care medicine, Randomized Controlled Trials as Topic, Intention-to-treat analysis, business.industry, Confounding, 030208 emergency & critical care medicine, 030228 respiratory system, Sample size determination, Critical illness, Number needed to treat, Critical Illne, Randomized clinical trial, business, Human
Abstract

Purpose Confounders in randomized controlled trials (RCTs) reporting significant effects on mortality in critically ill patients using non-surgical techniques have not been systematically explored. We aimed to identify factors unrelated to the reported intervention that might have affected the findings and robustness of such trials. Methods We searched Pubmed/MEDLINE for all RCTs on any non-surgical interventions reporting an effect on unadjusted mortality in critically ill patients between 1/1/2000 and 1/12/2015. We assessed: the number needed to treat/harm (NNT or NNH), sample size, trial design (blinded/unblinded, single or multinational, single or multicenter (sRCT or mRCT)), intention to treat (ITT) analysis, and countries of origin. Results Almost half of RCTs were sRCTs. Median sample size was small, and 1/3 were not analyzed according to ITT principle. Lack of ITT analysis was associated with greater effect size (p = 0.0028). Harm was more likely in mRCTs (p = 0.002) and/or in blinded RCTs (p = 0.003). Blinded RCTs had double sample size (p = 0.007) and an increased NNT/NNH (p = 0.002). Finally, mRCTs had higher NNT (p = 0.005) and NNH (p = 0.02), and harm was only detected in studies from Western countries (p = 0.007). Conclusions These observations imply that major systematic biases exist and affect trial findings irrespective of the intervention being studied.

Published
2017

26. Remote Ischemic Preconditioning and Cardiac Surgery

Author

Derek Hausenloy, Kai Zacharowski, Nana-Maria Wagner, Patrick Meybohm, Derek Yellon, Giovanni LANDONI, Landoni, Giovanni, Baiardo Redaelli, M, and Votta, Cd

Subjects
Male, medicine.medical_specialty, business.industry, MEDLINE, General Medicine, 030204 cardiovascular system & hematology, Cardiac surgery, 03 medical and health sciences, 0302 clinical medicine, Text mining, Postoperative Complications, Anesthesia, Internal medicine, Cardiology, medicine, Ischemic preconditioning, Humans, Female, 030212 general & internal medicine, Coronary Artery Bypass, Cardiac Surgical Procedures, business, Ischemic Preconditioning
Published
2016

27. Volatile Agents in Medical and Surgical Intensive Care Units: A Meta-Analysis of Randomized Clinical Trials

Author

Giovanni Landoni, Carmine D. Votta, Anna Mara Scandroglio, Mattia Bellandi, Alberto Zangrillo, Laura Pasin, Giovanni Borghi, Martina Baiardo Redaelli, Luca Cabrini, Landoni, Giovanni, Pasin, L, Cabrini, L, Scandroglio, Am, Baiardo Redaelli, M, Votta, Cd, Bellandi, M, Borghi, G, and Zangrillo, Alberto

Subjects
medicine.medical_specialty, Critical Care, Sedation, critically ill, anesthesia, intensive care, mechanical ventilation, sedation, volatile agents, Airway Extubation, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Intensive care, medicine, Humans, 030212 general & internal medicine, Intensive care medicine, Randomized Controlled Trials as Topic, business.industry, 030208 emergency & critical care medicine, Intensive care unit, Clinical trial, Intensive Care Units, Anesthesiology and Pain Medicine, Strictly standardized mean difference, Meta-analysis, Anesthetics, Inhalation, medicine.symptom, Cardiology and Cardiovascular Medicine, business
Abstract

OBJECTIVE:To comprehensively assess published randomized peer-reviewed studies related to volatile agents used for sedation in intensive care unit (ICU) settings, with the hypothesis that volatile agents could reduce time to extubation in adult patients.DESIGN:Systematic review and meta-analysis of randomized trials.SETTING:Intensive care units.PARTICIPANTS:Critically ill patients.INTERVENTIONS:None.MEASUREMENTS AND MAIN RESULTS:The BioMedCentral, PubMed, Embase, and Cochrane Central Register databases of clinical trials were searched systematically for studies on volatile agents used in the ICU setting. Articles were assessed by trained investigators, and divergences were resolved by consensus. Inclusion criteria included random allocation to treatment (volatile agents versus any intravenous comparator, with no restriction on dose or time of administration) in patients requiring mechanical ventilation in the ICU. Twelve studies with 934 patients were included in the meta-analysis. The use of halogenated agents reduced the time to extubation (standardized mean difference = -0.78 [-1.01 to -0.55] hours; p for effect

Published
2016

28. Worldwide Opinion on Multicenter Randomized Interventions Showing Mortality Reduction in Critically Ill Patients: A Democracy-Based Medicine Approach

Author

Fabio Guarracino, Gordana Gazivoda, Fabrizio Monaco, Rosetta Lobreglio, Francesco Santini, Alberto Zangrillo, Valery V. Likhvantsev, Vladimir V. Lomivorotov, Martina Baiardo Redaelli, Jan Kunstýř, Luca Cabrini, Laura Pasin, Gabriele Alvaro, Giovanni Borghi, Rinaldo Bellomo, Nazar Bukamal, Laura Ruggeri, Massimo Zambon, Luca Lucchetta, Massimiliano Conte, Rosalba Lembo, Antonio Pisano, Alberto Castella, Simona Silvetti, Giovanni Landoni, Marta Mucchetti, Ludhmila Abrahão Hajjar, Gianluca Paternoster, Miomir Jovic, Giovanni De Vuono, Giovanni Pala, Massimiliano Greco, Jun Ma, Andrea Montisci, Gabriele Finco, Vadim Pasyuga, Marina Pieri, Marco Comis, Pisano, A, Landoni, Giovanni, Lomivorotov, V, Comis, M, Gazivoda, G, Conte, M, Hajjar, L, Finco, G, Jovic, M, Mucchetti, M, Kunstýř, J, Paternoster, G, Likhvantsev, V, Ruggeri, L, Ma, J, Alvaro, G, Bukamal, N, Borghi, G, Pasyuga, V, Cabrini, L, Greco, M, Guarracino, F, Lembo, R, Lobreglio, R, Monaco, F, Montisci, A, Pala, G, Pasin, L, Pieri, M, Santini, F, Silvetti, S, Zambon, M, Baiardo Redaelli, M, Castella, A, De Vuono, G, Lucchetta, L, Zangrillo, Alberto, and Bellomo, R.

Subjects
medicine.medical_specialty, Internationality, Critical Care, consensus conference, media_common.quotation_subject, critically ill, Critical Illness, Placebo-controlled study, MEDLINE, Psychological intervention, 030204 cardiovascular system & hematology, anesthesia, survival, law.invention, 03 medical and health sciences, intensive care, mortality, 0302 clinical medicine, Randomized controlled trial, law, Intensive care, Voting, Physicians, medicine, Humans, Multicenter Studies as Topic, 030212 general & internal medicine, Hospital Mortality, Intensive care medicine, media_common, Randomized Controlled Trials as Topic, Evidence-Based Medicine, business.industry, Evidence-based medicine, Systematic review, Anesthesiology and Pain Medicine, Family medicine, business, Cardiology and Cardiovascular Medicine
Abstract

Objectives Democracy-based medicine is a combination of evidence-based medicine (systematic review), expert assessment, and worldwide voting by physicians to express their opinions and self-reported practice via the Internet. The authors applied democracy-based medicine to key trials in critical care medicine. Design and Setting A systematic review of literature followed by web-based voting on findings of a consensus conference. Participants A total of 555 clinicians from 61 countries. Interventions The authors performed a systematic literature review (via searching MEDLINE/PubMed, Scopus, and Embase) and selected all multicenter randomized clinical trials in critical care that reported a significant effect on survival and were endorsed by expert clinicians. Then they solicited voting and self-reported practice on such evidence via an interactive Internet questionnaire. Relationships among trial sample size, design, and respondents’ agreement were investigated. The gap between agreement and use/avoidance and the influence of country origin on physicians’ approach to interventions also were investigated. Measurements and Main Results According to 24 multicenter randomized controlled trials, 15 interventions affecting mortality were identified. Wide variabilities in both the level of agreement and reported practice among different interventions and countries were found. Moreover, agreement and reported practice often did not coincide. Finally, a positive correlation among agreement, trial sample size, and number of included centers was found. On the contrary, trial design did not influence clinicians’ agreement. Conclusions Physicians’ clinical practice and agreement with the literature vary among different interventions and countries. The role of these interventions in affecting survival should be further investigated to reduce both the gap between evidence and clinical practice and transnational differences.

Published
2016

29. Impact and Feasibility of Mechanical Ventilation at a Surgical Center in Sierra Leone: Experience From EMERGENCY's Hospital in Goderich.

Author

Spagnolello O, Cole RD, Unisa J, Vandi H, Macarthy M, Gatti S, Cormio M, Portella G, and Baiardo Redaelli M

Subjects
Humans, Sierra Leone, Retrospective Studies, Female, Male, Adult, Adolescent, Young Adult, Middle Aged, Child, Critical Illness therapy, Emergency Service, Hospital statistics & numerical data, Emergency Service, Hospital organization & administration, Respiration, Artificial statistics & numerical data, Intensive Care Units organization & administration, Feasibility Studies
Abstract

Objectives: Despite the large burden of critically ill patients in developing countries, mechanical ventilation (MV) is scarce in these low-resource settings. In the absence of data, issues like costs and lack of training are often felt to outweigh the benefits of potential MV implementation in such places. We aimed to investigate the impact and feasibility of MV in a surgical ICU in West Africa., Design: This is a 7-month retrospective observational study (from October 25, 2022, to May 25, 2023), covering all patients consecutively admitted to ICU., Setting: The NGO EMERGENCY's hospital in Goderich, Freetown, Sierra Leone. The hospital is a referral center for acute care surgery., Patients: Critical patients admitted to the hospital's ICU., Interventions: Following brief, practical training of the nursing staff, one basic mechanical ventilator was installed at the hospital's ICU, under the supervision of two intensivists. Only patients with a body weight of over 15 kg and who met the "extreme criteria" for MV received this life-saving therapy., Measurements and Main Results: Of the 195 files of patients admitted to ICU during the study period, 162 were analyzed. The median age was 16 (interquartile range 7-27) and 48.1% of the population were under 14 years. The most common cause of admission was trauma (58.6%), followed by acute abdomen (33.3%), caustic soda ingestion (6.2%), and burns (1.9%). Of the overall population, 26 patients (16%) underwent MV (88.5% trauma cases vs. 11.5% acute abdomen). Median time on MV was 24 hours (12-64). The mortality rate in the MV group was 30.8% (8/26), while in the overall study population, it was 11.7% (19/162). One potentially life-threatening event of tube obstruction was handled appropriately., Conclusions: This study strongly supports the implementation of MV in low-resource settings. In our experience, the consistent benefit of reduced mortality among critical patients largely outweighs the associated challenges., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Published
2024
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30. Amino acids and the kidney; friends or foes?

Author

Baiardo Redaelli M, Landoni G, Monti G, and Bellomo R

Abstract

Purpose of Review: Acute kidney injury (AKI) is common in hospitalized patients and is independently associated with morbidity and mortality. Moreover, AKI increases the risk of chronic kidney disease, which is a major healthcare problem. Currently, no single therapy has been proven to be effective in preventing AKI. The role of amino acids in the context of kidney function and AKI prevention has been controversial and most of the evidence is available from nutritional studies. However, knowledge of amino acids in recruiting renal functional reserve and their potential role to protect renal function under stress has recently expanded., Recent Findings: The nephroprotective effects of amino acids were first postulated in 1973. Recently, this strategy gained renewed interest and has been more extensively studied, reintroducing their use in clinical situations characterized by a high incidence of AKI. Intravenous amino acids administration for kidney protection is now supported by a large multinational randomized double-blind controlled trial in cardiac surgery and by experimental and observational data. All such data support the rationale for a biologically and clinically important nephroprotective effect., Summary: The infusion of amino acids was recently found to reduce the incidence of AKI in cardiac surgery patients and surgical patients. This strategy for the protection of renal function is supported by a multicenter, international, double-blind randomized trial, with a huge potential for additional application in several clinical fields. Several mechanisms of action support the robustness of these findings and are summarized in this manuscript., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Published
2024
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31. A Randomized Trial of Intravenous Amino Acids for Kidney Protection.

Author

Landoni G, Monaco F, Ti LK, Baiardo Redaelli M, Bradic N, Comis M, Kotani Y, Brambillasca C, Garofalo E, Scandroglio AM, Viscido C, Paternoster G, Franco A, Porta S, Ferrod F, Calabrò MG, Pisano A, Vendramin I, Barucco G, Federici F, Severi L, Belletti A, Cortegiani A, Bruni A, Galbiati C, Covino A, Baryshnikova E, Giardina G, Venditto M, Kroeller D, Nakhnoukh C, Mantovani L, Silvetti S, Licheri M, Guarracino F, Lobreglio R, Di Prima AL, Fresilli S, Labanca R, Mucchetti M, Lembo R, Losiggio R, Bove T, Ranucci M, Fominskiy E, Longhini F, Zangrillo A, and Bellomo R

Subjects
Aged, Female, Humans, Male, Middle Aged, Creatinine blood, Double-Blind Method, Infusions, Intravenous, Kidney drug effects, Renal Replacement Therapy, Acute Kidney Injury diagnosis, Acute Kidney Injury epidemiology, Acute Kidney Injury etiology, Acute Kidney Injury prevention & control, Amino Acids administration & dosage, Amino Acids adverse effects, Cardiac Surgical Procedures adverse effects, Cardiopulmonary Bypass adverse effects, Postoperative Complications diagnosis, Postoperative Complications epidemiology, Postoperative Complications etiology, Postoperative Complications prevention & control
Abstract

Background: Acute kidney injury (AKI) is a serious and common complication of cardiac surgery, for which reduced kidney perfusion is a key contributing factor. Intravenous amino acids increase kidney perfusion and recruit renal functional reserve. However, the efficacy of amino acids in reducing the occurrence of AKI after cardiac surgery is uncertain., Methods: In a multinational, double-blind trial, we randomly assigned adult patients who were scheduled to undergo cardiac surgery with cardiopulmonary bypass to receive an intravenous infusion of either a balanced mixture of amino acids, at a dose of 2 g per kilogram of ideal body weight per day, or placebo (Ringer's solution) for up to 3 days. The primary outcome was the occurrence of AKI, defined according to the Kidney Disease: Improving Global Outcomes creatinine criteria. Secondary outcomes included the severity of AKI, the use and duration of kidney-replacement therapy, and all-cause 30-day mortality., Results: We recruited 3511 patients at 22 centers in three countries and assigned 1759 patients to the amino acid group and 1752 to the placebo group. AKI occurred in 474 patients (26.9%) in the amino acid group and in 555 (31.7%) in the placebo group (relative risk, 0.85; 95% confidence interval [CI], 0.77 to 0.94; P = 0.002). Stage 3 AKI occurred in 29 patients (1.6%) and 52 patients (3.0%), respectively (relative risk, 0.56; 95% CI, 0.35 to 0.87). Kidney-replacement therapy was used in 24 patients (1.4%) in the amino acid group and in 33 patients (1.9%) in the placebo group. There were no substantial differences between the two groups in other secondary outcomes or in adverse events., Conclusions: Among adult patients undergoing cardiac surgery, infusion of amino acids reduced the occurrence of AKI. (Funded by the Italian Ministry of Health; PROTECTION ClinicalTrials.gov number, NCT03709264.)., (Copyright © 2024 Massachusetts Medical Society.)

Published
2024
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32. Management of severe tetanus in Afghanistan: lessons from the field.

Author

Spagnolello O, Aryan AK, Ahmadzai M, Dost A, Boosti AG, Ceccarelli G, Portella G, and Baiardo Redaelli M

Subjects
Humans, Male, Afghanistan, Child, Respiration, Artificial, Magnesium Sulfate therapeutic use, Magnesium Sulfate administration & dosage, Intensive Care Units, Tetanus drug therapy
Abstract

Introduction: Tetanus is a rather rare disease in the Western countries thanks to widespread vaccination programs and the availability of prophylactics for patients with tetanus-prone injuries. The few cases that do occur are promptly managed in intensive care units (ICUs). However, tetanus is not so rare in developing countries, where access to a suitable level of care is limited. An unstable political situation can be a significant factor influencing patient outcomes., Case Report: A ten-year-old boy presented at the EMERGENCY hospital in Lashkar-Gah (southern Afghanistan) with generalized tetanus after falling off his bicycle. In response to his rapidly deteriorating general conditions - respiratory failure and hemodynamic instability - the patient was urgently transferred by ambulance to the ICU at the EMERGENCY hospital in Kabul (northern Afghanistan). The patient was placed on mechanical ventilation while receiving intravenous sedation and pharmacologic paralysis for almost four weeks. A prolonged infusion of a high dose of magnesium sulphate and labetalol was also given to counteract autonomic dysfunction. Multiple complications related to the long stay in the ICU were observed and promptly addressed. During this period, several mass casualties took place in Kabul, which stretched the hospital's surge capacity. The patient was discharged and accompanied back to Lashkar-Gah three months after his admission to the hospital., Conclusion: This case report shows some of the many difficulties that arise when managing a patient with severe tetanus in a war zone where resources are limited., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2024 Ornella Spagnolello, Ahmad K Aryan, Muhebullah Ahmadzai, Arezo Dost, Abdul G Boosti, Giancarlo Ceccarelli, Gina Portella, Martina Baiardo Redaelli.)

Published
2024
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34. Interventions reducing mortality in COVID-19 patients: a systematic review of randomized evidence.

Author

Maimeri N, Marmiere M, Losiggio R, Nardelli P, Baiardo Redaelli M, Fresilli S, D'Amico F, Zangrillo A, Hajjar LA, and Landoni G

Subjects
Humans, Hospitalization, COVID-19 Drug Treatment, Adrenal Cortex Hormones therapeutic use, Immunologic Factors therapeutic use, Anti-Infective Agents therapeutic use, Hospital Mortality, SARS-CoV-2, COVID-19 mortality, COVID-19 therapy, Randomized Controlled Trials as Topic
Abstract

Introduction: COVID-19 pandemic changed the way medical research is published, possibly forever. As the need for rapidity led to the rise of preprint servers, the undeniable drop in the overall quality of scientific publications requires an in-depth review of all available evidence. The present manuscript aims to identify and summarize all treatments which have been reported to reduce mortality in randomized trials in hospitalized COVID-19 patients., Evidence Acquisition: Independent investigators searched MEDLINE/PubMed, Scopus, and Embase databases to identify all randomized trials of any intervention influencing mortality in hospitalized COVID-19 patients up to August 18 th , 2022. Articles were selected only when they fulfilled all the following: randomized trial design; dealing with any kind of interventions in adult hospitalized COVID-19 patients; and statistically significant reduction in mortality., Evidence Synthesis: We identified 28 interventions (42 manuscripts) reducing mortality in hospitalized COVID-19 patients. About 60% of the studies (26/42) were multicentric, for a total of 1140 centers involved worldwide. Several of these studies were published in high-ranked, peer-reviewed journals. Interventions with randomized evidence of mortality reduction in hospitalized COVID-19 patients belonged to 5 domains: corticosteroids, immunomodulators, antimicrobials, supportive therapies, and other drugs., Conclusions: Many interventions have the potential to reduce mortality in COVID-19 hospitalized patients. The correct treatment of future pandemics relies on large, multicentric randomized clinical trials for further evaluation of these promising strategies.

Published
2024
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35. Antiandrogen agents in COVID-19: a meta-analysis of randomized trials.

Author

Kotani Y, Landoni G, Scquizzato T, Mohamed N, Baiardo Redaelli M, Sofia R, Fresilli S, Zangrillo A, and Azzolini ML

Subjects
Humans, COVID-19 mortality, Hospitalization, SARS-CoV-2, Respiration, Artificial, Androgen Antagonists therapeutic use, Randomized Controlled Trials as Topic, COVID-19 Drug Treatment
Abstract

Introduction: Antiandrogen therapy can reduce the expression of transmembrane protease 2, which is essential for severe acute respiratory syndrome coronavirus-2 to enter the host cells. Prior trials suggested the efficacy of antiandrogen agents in patients with COVID-19. We investigated whether antiandrogen agents reduce mortality compared to placebo or usual care., Evidence Acquisition: We searched for randomized controlled trials comparing antiandrogen agents with placebo or usual care alone in adults with COVID-19 in PubMed, EMBASE, the Cochrane Library, the reference lists of retrieved articles, and publications by manufacturers of antiandrogen agents. The primary outcome was mortality at the longest follow-up available. The secondary outcomes included clinical worsening, the need for invasive mechanical ventilation, admission to the intensive care unit, hospitalization, and thrombotic events. We registered this systematic review and meta-analysis in PROSPERO International Prospective Register of Systematic Reviews (CRD42022338099)., Evidence Synthesis: We included 13 randomized controlled trials enrolling 1934 COVID-19 patients. We found that antiandrogen agents reduced mortality at the longest follow-up available (91/1021 [8.9%] vs. 245/913 [27%]; risk ratio =0.40; 95% confidence interval, 0.25-0.65; P=0.0002; I 2 =54%). Antiandrogen therapy also reduced clinical worsening (127/1016 [13%] vs. 298/911 [33%]; risk ratio =0.44; 95% confidence interval, 0.27-0.71; P=0.0007; I 2 =70%) and hospitalization (97/160 [4.4%] vs. 24/165 [15%]; risk ratio =0.24; 95% confidence interval, 0.10-0.58; P=0.002; I 2 =44%). There was no significant difference in the other outcomes between the two treatment groups., Conclusions: Antiandrogen therapy reduced mortality and clinical worsening in adult patients with COVID-19.

Published
2024
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36. Two-year multidisciplinary follow-up of COVID-19 patients requiring invasive and noninvasive respiratory support.

Author

Tresoldi M, Zangrillo A, Belletti A, Ramirez GA, Bozzolo E, Guzzo F, Marinosci A, Fominskiy EV, DA Prat V, Marmiere M, Palumbo D, Del Prete L, D'Amico F, Bellino C, Morando D, Saracino M, Ortalda A, Castelli E, Rocchi M, Baiardo Redaelli M, Scotti R, DI Terlizzi G, Azzolini ML, Guaschino G, Avitabile E, Borghi G, Soddu D, Dagna L, Landoni G, and DE Cobelli F

Subjects
Humans, Follow-Up Studies, Quality of Life, Respiration, Artificial methods, COVID-19 complications, COVID-19 therapy, Noninvasive Ventilation methods
Abstract

Background: COVID-19 patients frequently develop respiratory failure requiring mechanical ventilation. Data on long-term survival of patients who had severe COVID-19 are insufficient. We assessed and compared two-year survival, CT imaging, quality of life, and functional recovery of COVID-19 ARDS patients requiring respiratory support with invasive (IMV) versus noninvasive ventilation (NIV)., Methods: Patients with COVID-19 pneumonia admitted up to May 28 th , 2020, who required IMV or NIV, and survived to hospital discharge were enrolled. Patients were contacted two years after discharge to assess vital status, functional, psychological, and cognitive outcomes using validated scales. Patients with persistent respiratory symptoms or high burden of residual lung damage at previous CT scan received a two-year chest CT scan., Results: Out of 61 IMV survivors, 98% were alive at two-year follow-up, and 52 completed the questionnaire. Out of 82 survivors receiving NIV only, 94% were alive at two years, and 47 completed the questionnaire. We found no major differences between invasively and noninvasively ventilated patients, with overall acceptable functional recovery. Among the 99 patients completing the questionnaire, 23 have more than moderate exertional dyspnea. Chest CT scans showed that 4 patients (all received IMV) had fibrotic-like changes., Conclusions: Patients who received mechanical ventilation due to COVID-19 and were discharged from hospital had a 96% survival rate at the two-year follow-up. There was no difference in overall recovery and quality of life between patients who did and did not require IMV, although respiratory morbidity remains high.

Published
2023
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37. Positive single-center randomized trials and subsequent multicenter randomized trials in critically ill patients: a systematic review.

Author

Kotani Y, Turi S, Ortalda A, Baiardo Redaelli M, Marchetti C, Landoni G, and Bellomo R

Subjects
Adult, Humans, Randomized Controlled Trials as Topic, Multicenter Studies as Topic, Critical Illness therapy
Abstract

Background: It is unclear how often survival benefits observed in single-center randomized controlled trials (sRCTs) involving critically ill patients are confirmed by subsequent multicenter randomized controlled trials (mRCTs). We aimed to perform a systemic literature review of sRCTs with a statistically significant mortality reduction and to evaluate whether subsequent mRCTs confirmed such reduction., Methods: We searched PubMed for sRCTs published in the New England Journal of Medicine, JAMA, or Lancet, from inception until December 31, 2016. We selected studies reporting a statistically significant mortality decrease using any intervention (drug, technique, or strategy) in adult critically ill patients. We then searched for subsequent mRCTs addressing the same research question tested by the sRCT. We compared the concordance of results between sRCTs and mRCTs when any mRCT was available. We registered this systematic review in the PROSPERO International Prospective Register of Systematic Reviews (CRD42023455362)., Results: We identified 19 sRCTs reporting a significant mortality reduction in adult critically ill patients. For 16 sRCTs, we identified at least one subsequent mRCT (24 trials in total), while the interventions from three sRCTs have not yet been addressed in a subsequent mRCT. Only one out of 16 sRCTs (6%) was followed by a mRCT replicating a significant mortality reduction; 14 (88%) were followed by mRCTs with no mortality difference. The positive finding of one sRCT (6%) on intensive glycemic control was contradicted by a subsequent mRCT showing a significant mortality increase. Of the 14 sRCTs referenced at least once in international guidelines, six (43%) have since been either removed or suggested against in the most recent versions of relevant guidelines., Conclusion: Mortality reduction shown by sRCTs is typically not replicated by mRCTs. The findings of sRCTs should be considered hypothesis-generating and should not contribute to guidelines., (© 2023. The Author(s).)

Published
2023
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38. High dose esomeprazole as an anti-inflammatory agent in sepsis: Protocol for a randomized controlled trial.

Author

Monti G, Konkayev A, Carta S, Bradic N, Bruni A, Kotani Y, Guarracino F, Redkin I, Biondi-Zoccai G, Benedetto U, D'Ascenzo F, Garofalo E, Baiardo Redaelli M, Brizzi G, Forfori F, Borghi G, Scapol S, Momesso E, Cuffaro R, Boffa N, Rauch S, D'Amico F, Montrucchio G, Pace MC, Galbiati C, Bosso S, Savelli F, Giardina G, Silvetti S, Tripodi VF, Labanca R, Lembo R, Marmiere M, Marzaroli M, Nakhnoukh C, Valsecchi D, Finco G, Agrò FE, Bove T, Corradi F, Longhini F, Landoni G, Bellomo R, and Zangrillo A

Abstract

Background: Sepsis is caused by dysregulated immune responses due to infection and still presents high mortality rate and limited efficacious therapies, apart from antibiotics. Recent evidence suggests that very high dose proton pump inhibitors might regulate major sepsis mediators' secretion by monocytes, which might attenuate excessive host reactions and improve clinical outcomes. This effect is obtained with doses which are approximately 50 times higher than prophylactic esomeprazole single daily administration and 17 times higher than the cumulative dose of a three day prophylaxis. We aim to perform a randomized trial to investigate if high dose esomeprazole reduces organ dysfunction in patients with sepsis or septic shock., Methods: This study, called PPI-SEPSIS, is a multicenter, randomized, double blind, placebo-controlled clinical trial on critically ill septic patients admitted to the emergency department or intensive care unit. A total of 300 patients will be randomized to receive high dose esomeprazole (80 mg bolus followed by 12 mg/h for 72 h and a second 80 mg bolus 12 h after the first one) or equivolume placebo (sodium chloride 0.9%), with 1:1 allocation. The primary endpoint of the study will be mean daily Sequential Organ Failure Assessment (SOFA) score over 10 days. Secondary outcomes will include antibiotic-free days, single organ failure severity, intensive care unit-free days at day 28, and mortality., Discussion: This trial aims to test the efficacy of high dose esomeprazole to reduce acute organ dysfunction in patients with septic shock., Trial Registration: This trial was registered on ClinicalTrials.gov with the trial identification NCT03452865 in March 2018., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Published
2023
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39. Continuous vs Intermittent Meropenem Administration in Critically Ill Patients With Sepsis: The MERCY Randomized Clinical Trial.

Author

Monti G, Bradic N, Marzaroli M, Konkayev A, Fominskiy E, Kotani Y, Likhvantsev VV, Momesso E, Nogtev P, Lobreglio R, Redkin I, Toffoletto F, Bruni A, Baiardo Redaelli M, D'Andrea N, Paternoster G, Scandroglio AM, Gallicchio F, Ballestra M, Calabrò MG, Cotoia A, Perone R, Cuffaro R, Montrucchio G, Pota V, Ananiadou S, Lembo R, Musu M, Rauch S, Galbiati C, Pinelli F, Pasin L, Guarracino F, Santarpino G, Agrò FE, Bove T, Corradi F, Forfori F, Longhini F, Cecconi M, Landoni G, Bellomo R, and Zangrillo A

Subjects
Humans, Female, Middle Aged, Male, Meropenem therapeutic use, Critical Illness therapy, Double-Blind Method, Anti-Bacterial Agents adverse effects, Anti-Bacterial Agents administration & dosage, Monobactams therapeutic use, Shock, Septic mortality, Sepsis complications, Hypersensitivity
Abstract

Importance: Meropenem is a widely prescribed β-lactam antibiotic. Meropenem exhibits maximum pharmacodynamic efficacy when given by continuous infusion to deliver constant drug levels above the minimal inhibitory concentration. Compared with intermittent administration, continuous administration of meropenem may improve clinical outcomes., Objective: To determine whether continuous administration of meropenem reduces a composite of mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria compared with intermittent administration in critically ill patients with sepsis., Design, Setting, and Participants: A double-blind, randomized clinical trial enrolling critically ill patients with sepsis or septic shock who had been prescribed meropenem by their treating clinicians at 31 intensive care units of 26 hospitals in 4 countries (Croatia, Italy, Kazakhstan, and Russia). Patients were enrolled between June 5, 2018, and August 9, 2022, and the final 90-day follow-up was completed in November 2022., Interventions: Patients were randomized to receive an equal dose of the antibiotic meropenem by either continuous administration (n = 303) or intermittent administration (n = 304)., Main Outcomes and Measures: The primary outcome was a composite of all-cause mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria at day 28. There were 4 secondary outcomes, including days alive and free from antibiotics at day 28, days alive and free from the intensive care unit at day 28, and all-cause mortality at day 90. Seizures, allergic reactions, and mortality were recorded as adverse events., Results: All 607 patients (mean age, 64 [SD, 15] years; 203 were women [33%]) were included in the measurement of the 28-day primary outcome and completed the 90-day mortality follow-up. The majority (369 patients, 61%) had septic shock. The median time from hospital admission to randomization was 9 days (IQR, 3-17 days) and the median duration of meropenem therapy was 11 days (IQR, 6-17 days). Only 1 crossover event was recorded. The primary outcome occurred in 142 patients (47%) in the continuous administration group and in 149 patients (49%) in the intermittent administration group (relative risk, 0.96 [95% CI, 0.81-1.13], P = .60). Of the 4 secondary outcomes, none was statistically significant. No adverse events of seizures or allergic reactions related to the study drug were reported. At 90 days, mortality was 42% both in the continuous administration group (127 of 303 patients) and in the intermittent administration group (127 of 304 patients)., Conclusions and Relevance: In critically ill patients with sepsis, compared with intermittent administration, the continuous administration of meropenem did not improve the composite outcome of mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria at day 28., Trial Registration: ClinicalTrials.gov Identifier: NCT03452839.

Published
2023
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40. Civilian war victims in Afghanistan: five-year report from the Kabul EMERGENCY NGO hospital.

Author

Spagnolello O, Gatti S, Shahir MAA, Afzali MF, Portella G, and Baiardo Redaelli M

Subjects
Humans, Male, Adolescent, Female, Afghanistan epidemiology, Retrospective Studies, Hospitals, Hospitalization, War-Related Injuries epidemiology, War-Related Injuries therapy
Abstract

Background: Afghanistan has been plagued by war for more than 30 years, but little is known about the civilian cost of such a long-lasting conflict. In particular, the incidence of war injuries among civilians has largely been under-reported. EMERGENCY NGO's Surgical Centre for War Victims has been operating in Kabul since 2001, providing care free of charge to anyone injured in war. The primary aim of our study is to describe the population of patients admitted to our hospital in Kabul., Methods: This is a 5-year retrospective analysis of all recorded hospital admissions at EMERGENCY NGO's hospital in Kabul, Afghanistan, from 1 January 2017 to 31 December 2021., Results: During the study period, 16,053 patients were admitted. Of these, 85.7% were male and 17.5% were under 14 years old. The proportion of male patients increased progressively with the age ranges (from 63.4 to 89.0%). Bullet wounds were the most frequent kind of injury (55.6%), followed by shell, stab and mine wounds (32.2%, 8.3% and 3.9% respectively). Only 5.8% of patients arrived at our hospital within the "golden hour" following injury. No significant reduction in the hospitalization trend was observed over the study period. The overall in-hospital mortality rate was 4.41%, which bore no correlation to the number of admissions., Conclusions: This study provides for the first time epidemiology of war-related injuries in a hospital located in a place of long-standing conflict., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Published
2023
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41. Gender-gap in randomized clinical trials reporting mortality in the perioperative setting and critical care: 20 years behind the scenes.

Author

Romero CS, Maimeri N, Bonaccorso A, Baiardo-Redaelli M, Lombardi G, Iwuchukwu OF, Ortalda A, Schmid B, Fleming M, and Landoni G

Abstract

Background: Women researchers might experience obstacles in academic environments and might be underrepresented in the authorship of articles published in peer-reviewed journals., Material and Methods: This is a cross-sectional analysis of female-led RCTs describing all interventions reducing mortality in critically ill and perioperative patients from 1981 to December 31, 2020. We searched PubMed/MEDLINE and EMBASE with the keywords RCTs and mortality. The gender of the first author was extracted and descriptive analysis was performed including the year of publication, impact factor, country of the first author, and methodological aspects., Results: We analyzed 340 RCTs, of which 42 (12%) were led by female researchers. The presence of women increased from 8% (14/172) until 2010 up to 17% (28/168) in 2010 and beyond. The United States, the United Kingdom, and Brazil were the main countries of origin of female researchers. Women authors conducted mainly single-center and single-nation studies as compared to male authors. The median impact factor of the target journal was 6 (3-27) in women vs. 7 (3-28) in men, with a p-value of 0.67; Critical Care Medicine , JAMA , and The New England Journal of Medicine were the most frequent target journals for both women and men., Conclusion: In the last 40 years, only one out of eight RCTs had a woman as the first author but the presence of women increased up to 17% by 2010 and beyond. The impact factor of publication target journals was high and not different between genders., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (©2023PublishedbyElsevierInc.)

Published
2023
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42. Outcomes of noninvasive ventilation as the ceiling of treatment in patients with COVID-19.

Author

Ramirez GA, Bozzolo EP, Gobbi A, Castelli E, Centurioni C, DI Meo M, Della Torre E, DI Scala F, Morgillo A, Marinosci A, Miglio M, Scarpellini P, Tassan Din C, Castiglioni B, Oltolini C, Ripa M, DI Terlizzi G, DA Prat V, Damanti S, Scotti R, DI Lucca G, Baiardo Redaelli M, Plumari VP, Moizo E, Carcó F, Silvani P, DE Cobelli F, Landoni G, and Tresoldi M

Subjects
Humans, Aged, Respiration, Artificial, Continuous Positive Airway Pressure, Noninvasive Ventilation adverse effects, COVID-19 therapy, Respiratory Insufficiency therapy
Abstract

Background: Non-invasive mechanical ventilation (NIV) is effective for symptom relief and respiratory support in patients with respiratory insufficiency, severe comorbidities and no indication to intubation. Experience with NIV as the ceiling of treatment in severely compromised novel coronavirus disease (COVID-19) patients is lacking., Methods: We evaluated 159 patients with COVID-19-related acute respiratory syndrome (ARDS), 38 of whom with NIV as the ceiling of treatment, admitted to an ordinary ward and treated with continuous positive airway pressure (CPAP) and respiratory physiotherapy. Treatment failure and death were correlated with clinical and laboratory parameters in the whole cohort and in patients with NIV as the ceiling of treatment., Results: Patients who had NIV as the ceiling of treatment were elderly, with a low BMI and a high burden of comorbidities, showed clinical and laboratory signs of multiorgan insufficiency on admission and of rapidly deteriorating vital signs during the first week of treatment. NIV failure occurred overall in 77 (48%) patients, and 27/38 patients with NIV as the ceiling of treatment died. Congestive heart failure, chronic benign hematological diseases and inability/refusal to receive respiratory physiotherapy were independently associated to NIV failure and mortality. Need for increased positive end-expiratory pressures and low platelets were associated with NIV failure. Death was associated to cerebrovascular disease, need for CPAP cycles longer than 12 h and, in the subgroup of patients with NIV as the ceiling of treatment, was heralded by vital sign deterioration within 48 h., Conclusions: NIV and physiotherapy are a viable treatment option for patients with severe COVID-19 and severe comorbidities.

Published
2022
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43. Intravenous amino acid therapy for kidney protection in cardiac surgery a protocol for a multi-centre randomized blinded placebo controlled clinical trial. The PROTECTION trial.

Author

Landoni G, Brambillasca C, Baiardo Redaelli M, Bradić N, Ti LK, Povšić-Čevra Z, Nepomniashchikh VA, Zoccai GB, D'Ascenzo F, Romagnoli E, Scandroglio AM, Ballotta A, Rondello N, Franco A, Massaro C, Viscido C, Calabrò MG, Garofalo E, Canichella F, Monaco F, Severi L, Pisano A, Barucco G, Venditto M, Federici F, Licheri M, Paternoster G, Trompeo A, Belletti A, Mantovani LF, Perone R, Dalessandro G, Kroeller D, Haxhiademi D, Galbiati C, Tripodi VF, Giardina G, Lembo R, Nakhnoukh C, Guarracino F, Longhini F, Bove T, Zangrillo A, Bellomo R, and Fominskiy E

Subjects
Adult, Amino Acids, Clinical Trials, Phase III as Topic, Crystalloid Solutions, Humans, Kidney, Multicenter Studies as Topic, Quality of Life, Randomized Controlled Trials as Topic, Acute Kidney Injury epidemiology, Acute Kidney Injury etiology, Acute Kidney Injury prevention & control, Cardiac Surgical Procedures
Abstract

Background: Postoperative acute kidney injury (AKI) is frequent in cardiac surgery patients. Its pathophysiology is complex and involves decreased renal perfusion. Preliminary clinical evidence in critically ill patients shows that amino acids infusion increases renal blood flow and may decrease the incidence and severity of AKI. We designed a study to evaluate the effectiveness of perioperative continuous infusion of amino acids in decreasing AKI., Methods: This is a phase III, multi-center, randomized, double-blind, placebo-controlled trial. Adults undergoing cardiac surgery with cardiopulmonary bypass (CPB) are included. Patients are randomly assigned to receive either continuous infusion of a balanced mixture of amino acids in a dose of 2 g/kg ideal body weight/day or placebo (balanced crystalloid solution) from the operating room up to start of renal replacement therapy (RRT), or ICU discharge, or 72 h after the first dose. The primary outcome is the incidence of AKI during hospital stay defined by KDIGO (Kidney Disease: Improving Global Outcomes). Secondary outcomes include the need for, and duration of, RRT, mechanical ventilation; ICU and hospital length of stay; all-cause mortality at ICU, hospital discharge, 30, 90, and 180 days after randomization; quality of life at 180 days. Data will be analyzed in 3500 patients on an intention-to-treat basis., Discussion: The trial is ongoing and currently recruiting. It will be one of the first randomized controlled studies to assess the relationship between amino acids use and kidney injury in cardiac surgery. If our hypothesis is confirmed, this practice could reduce morbidity in the studied population., Study Registration: This trial was registered on ClinicalTrials.gov with the trial identification NCT03709264 in October 2018., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Published
2022
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44. A novel evidence-based algorithm to predict thromboembolism in patients with COVID-19: preliminary data from a single-center cohort.

Author

Ramirez GA, Calvisi SL, DE Lorenzo R, DA Prat V, Borio G, Gallina G, Farolfi F, Cavallo L, Pascali M, Castellani J, Baccellieri D, Guzzo F, Baiardo Redaelli M, Azzolini ML, Alba AC, Zangrillo A, Bozzolo EP, Scotti R, DI Lucca G, Piemonti L, Rovere Querini P, D'Angelo A, and Tresoldi M

Subjects
Algorithms, Hemorrhage, Humans, Inflammation, Preliminary Data, SARS-CoV-2, COVID-19 complications, COVID-19 epidemiology, Thromboembolism epidemiology, Thromboembolism etiology, Thrombosis epidemiology, Thrombosis etiology
Abstract

Background: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-related disease (COVID-19) is an infectious disease characterized by systemic inflammation, which might enhance baseline thrombotic risk, especially in hospitalized patients. Little is, however, known about predictors of thrombotic complications in patients with COVID-19., Methods: We prospectively followed up 180 hospitalized COVID-19 patients. Demographics, clinical and laboratory features at presentation and past medical history were tested as predictors of the first thrombotic complication through multivariate Cox regression analysis and a categorical score generated based on the results., Results: Sixty-four thromboses were recorded in 54 patients, of whom seven with thrombosis on admission and 47 with thrombosis during hospitalization. Patients with thrombosis were mainly Caucasian and diabetic, had marked baseline signs of inflammation and organ damage, lower PaO2/FiO2 ratio, higher D-dimer levels and history of major hemorrhages. The latter three variables were independently associated to thrombotic complications and concurred to a 0-5 score, which accounted for 80% of the total sample variability. Patients with three or more points of the newly generated score were at higher risk for thrombotic complications (HR=4.9, P<0.001). Patients with thrombotic complications were more likely to be admitted to intensive care and/or to die (HR=1.9, P=0.036). Five of 180 patients were diagnosed with disseminated intravascular coagulation and three of them died. Eleven minor and no major bleeding events were observed., Conclusions: Patients with COVID-19 are at increased risk for thrombosis and might be stratified on admission based on lower Pao2/FiO2 ratio, higher D-dimer levels and history of major hemorrhages.

Published
2022
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45. One-Year Multidisciplinary Follow-Up of Patients With COVID-19 Requiring Invasive Mechanical Ventilation.

Author

Zangrillo A, Belletti A, Palumbo D, Calvi MR, Guzzo F, Fominskiy EV, Ortalda A, Nardelli P, Ripa M, Baiardo Redaelli M, Borghi G, Landoni G, D'Amico F, Marmiere M, Righetti B, Rocchi M, Saracino M, Tresoldi M, Dagna L, and De Cobelli F

Subjects
Activities of Daily Living, Adolescent, Adult, Follow-Up Studies, Humans, Intensive Care Units, Quality of Life, SARS-CoV-2, COVID-19 therapy, Respiration, Artificial
Abstract

Objectives: Patients with COVID-19 frequently develop acute respiratory distress syndrome (ARDS) requiring intensive care unit (ICU) admission. Data on long-term survival of these patients are lacking. The authors investigated 1-year survival, quality of life, and functional recovery of patients with COVID-19 ARDS requiring invasive mechanical ventilation., Design: Prospective observational study., Setting: Tertiary-care university hospital., Participants: All patients with COVID-19 ARDS receiving invasive mechanical ventilation and discharged alive from hospital., Interventions: Patients were contacted by phone after 1 year. Functional, cognitive, and psychological outcomes were explored through a questionnaire and assessed using validated scales. Patients were offered the possibility to undergo a follow-up chest computed tomography (CT) scan., Measurements and Main Results: The study included all adult (age ≥18 years) patients with COVID-19-related ARDS admitted to an ICU of the authors' institution between February 25, 2020, and April 27, 2020, who received at least 1 day of invasive mechanical ventilation (IMV). Of 116 patients who received IMV, 61 (52.6%) survived to hospital discharge. These survivors were assessed 1 year after discharge and 56 completed a battery of tests of cognition, activities of daily living, and interaction with family members. They had overall good functional recovery, with >80% reporting good recovery and no difficulties in usual activities. A total of 52 (93%) of patients had no dyspnea at rest. Severe anxiety/depression was reported by 5 (8.9%) patients. Comparing 2-month and 1-year data, the authors observed the most significant improvements in the areas of working status and exertional dyspnea. One-year chest CT scans were available for 36 patients; fibrotic-like changes were present in 4 patients., Conclusions: All patients who survived the acute phase of COVID-19 and were discharged from the hospital were alive at the 1-year follow up, and the vast majority of them had good overall recovery and quality of life., Competing Interests: Conflict of Interest None., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Published
2022
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47. Percutaneous tracheostomy in COVID-19 patients: a new apneic approach.

Author

Moizo E, Zangrillo A, Colombo S, Leggieri C, Mucci M, Beccaria P, Pasculli N, Borghi G, Plumari VP, La Bruna A, Dossi R, Baiardo Redaelli M, Tornaghi A, Lombardi G, Landoni G, Dell'Acqua A, Guzzo F, and Monti G

Subjects
Apnea etiology, Humans, Pandemics, Respiration, Artificial methods, COVID-19, Tracheostomy adverse effects, Tracheostomy methods
Abstract

Background: Percutaneous dilation tracheostomy is an aerosol-generating procedure carrying a documented infectious risk during respiratory virus pandemics. For this reason, during the COVID-19 outbreak, surgical tracheostomy was preferred to the percutaneous one, despite the technique related complications increased risk., Methods: We describe a new sequence for percutaneous dilation tracheostomy procedure that could be considered safe both for patients and healthcare personnel. A fiberscope was connected to a video unit to allow bronchoscopy. Guidewire positioning was performed as usual. While the established standard procedure continues with the creation of the stoma without any change in mechanical ventilation, we retracted the bronchoscope until immediately after the access valve in the mount tube, allowing normal ventilation. After 3 minutes of ventilation with 100% oxygen, mechanical ventilation was stopped without disconnecting the circuit. During apnea, the stoma was created by dilating the trachea and the tracheostomy cannula was inserted. Ventilation was then resumed. We evaluated the safeness of the procedure by recording any severe desaturation and by performing serological tests to all personnel., Results: Thirty-six patients (38%) of 96 underwent tracheostomy; 22 (23%) percutaneous dilation tracheostomies with the new approach were performed without any desaturation. All personnel (150 operators) were evaluated for serological testing: 9 (6%) had positive serology but none of them had participated in tracheostomy procedures., Conclusion: This newly described percutaneous dilation tracheostomy technique was not related to severe desaturation events and we did not observe any positive serological test in health workers who performed the tracheostomies., (Copyright © 2021 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.)

Published
2022
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48. Residual lung damage following ARDS in COVID-19 ICU survivors.

Author

Compagnone N, Palumbo D, Cremona G, Vitali G, De Lorenzo R, Calvi MR, Del Prete A, Baiardo Redaelli M, Calamarà S, Belletti A, Steidler S, Conte C, Zangrillo A, De Cobelli F, Rovere-Querini P, and Monti G

Subjects
Adult, Humans, Intensive Care Units, Lung diagnostic imaging, Male, Middle Aged, SARS-CoV-2, Survivors, COVID-19, Respiratory Distress Syndrome diagnostic imaging, Respiratory Distress Syndrome etiology
Abstract

Background: Coronavirus disease 2019 acute respiratory distress syndrome (COVID-19 ARDS) is a disease that often requires invasive ventilation. Little is known about COVID-19 ARDS sequelae. We assessed the mid-term lung status of COVID-19 survivors and investigated factors associated with pulmonary sequelae., Methods: All adult COVID-19 patients admitted to the intensive care unit from 25th February to 27th April 2020 were included. Lung function was evaluated through chest CT scan and pulmonary function tests (PFT). Logistic regression was used to identify predictors of persisting lung alterations., Results: Forty-nine patients (75%) completed lung assessment. Chest CT scan was performed after a median (interquartile range) time of 97 (89-105) days, whilst PFT after 142 (133-160) days. The median age was 58 (52-65) years and most patients were male (90%). The median duration of mechanical ventilation was 11 (6-16) days. Median tidal volume/ideal body weight (TV/IBW) was 6.8 (5.71-7.67) ml/Kg. 59% and 63% of patients showed radiological and functional lung sequelae, respectively. The diffusion capacity of carbon monoxide (DL CO ) was reduced by 59%, with a median per cent of predicted DL CO of 72.1 (57.9-93.9) %. Mean TV/IBW during invasive ventilation emerged as an independent predictor of persistent CT scan abnormalities, whilst the duration of mechanical ventilation was an independent predictor of both CT and PFT abnormalities. The extension of lung involvement at hospital admission (evaluated through Radiographic Assessment of Lung Edema, RALE score) independently predicted the risk of persistent alterations in PFTs., Conclusions: Both the extent of lung parenchymal involvement and mechanical ventilation protocols predict morphological and functional lung abnormalities months after COVID-19., (© 2021 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Published
2022
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49. COVID-19 second wave: appropriateness of admissions to the Emergency Department of a main metropolitan hospital in Milan.

Author

Bossi E, Gianfredi V, Odone A, Valsecchi D, Franchini S, Etteri M, Cornero G, Casiraghi GM, Maimeri N, Beccaria PF, Moizo E, Mucci M, Silvani P, Plumari VP, Borghi G, Pasculli N, La Bruna A, Baiardo Redaelli M, Dell'Acqua A, Azzolini ML, Guzzo F, Alba AC, Sordoni S, Tozzi M, Nisi FG, Fresilli S, Zangrillo A, and Signorelli C

Subjects
Emergency Service, Hospital, Hospitalization, Hospitals, Urban, Humans, Italy epidemiology, Pandemics, SARS-CoV-2, COVID-19
Abstract

Background: In Europe, Italy and Lombardy, in autumn 2020, there was a steep increase in reported cases due to the second epidemic wave of SARS-Cov-2 infection. We aimed to evaluate the appropriateness of COVID-19 patients' admissions to the ED of the San Raffaele Hospital., Methods: We compared data between the inter-wave period (IWP, from 1st to 30th September) and the second wave period (WP, 1st October to 15th November) focusing on the ED presentation, discharge priority colour code and outcomes., Results: Out of 977 admissions with a SARS-Cov-2 positive swab, 6% were in the IWP and 94% in the WP. Red, yellow and white code increased (these latter from 1.8% to 5.4%) as well as self-presented in yellow and white code. Discharges home increased from 1.8% to 5.4%, while hospitalizations decreased from 63% to 51%., Discussion: We found a rise in white codes (among self-presented patients), indicating inappropriateness of admissions. The increase in discharges suggests that several patients did not require hospitalization., Conclusions: The pandemic brought out the fundamental role of primary care to manage patients with low-intensity needs. The important increase in ED admissions of COVID-19 patients caused a reduction of NO-COVID-19 patients, with possible inadequate treatment.

Published
2021
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50. Early versus late tracheal intubation in COVID-19 patients: a "pros/cons" debate also considering heart-lung interactions.

Author

Cabrini L, Ghislanzoni L, Severgnini P, Landoni G, Baiardo Redaelli M, Franchi F, and Romagnoli S

Subjects
Humans, Intubation, Intratracheal, Lung, Pandemics, SARS-CoV-2, COVID-19
Abstract

The best timing of orotracheal intubation and invasive ventilation in COVID-19 patients with acute respiratory distress syndrome is unknown. The use of non-invasive ventilation, a life-saving technique in many medical conditions, is debated in patients with ARDS since prolonged NIV and delayed intubation may be harmful. Shortage of intensive care beds and ventilators during a respiratory pandemic can trigger a widespread use of early non-invasive ventilation in many hospitals but which is the best way to ventilate patients with severe bilateral pneumonia and severely increased spontaneous ventilation is controversial. Moreover, viral spreading to health-care workers and other hospitalized patients is an issue for any device used to administer oxygen. Even if protective mechanical ventilation is currently the gold standard for the management of acute respiratory distress syndrome, tracheal intubation is not without risks and is associated with delirium, hemodynamic instability, immobilization and post intensive care syndrome. Both invasive and non-invasive ventilation are associated with advantages and limitations that should be carefully considered when patients with COVID-19-ARDS need our attention. In the absence of strong evidence, in this review we highlight all the pro and con of these two different approaches.

Published
2021
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