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4. Acute cholecystitis management in high-risk, critically ill, and unfit-for-surgery patients: the Italian Society of Emergency Surgery and Trauma (SICUT) guidelines

Author

Coccolini, Federico, Cucinotta, Eugenio, Mingoli, Andrea, Zago, Mauro, Altieri, Gaia, Biloslavo, Alan, Caronna, Roberto, Cengeli, Ismail, Cicuttin, Enrico, Cirocchi, Roberto, Cobuccio, Luigi, Costa, Gianluca, Cozza, Valerio, Cremonini, Camilla, Del Vecchio, Giovanni, Dinatale, Giuseppe, Fico, Valeria, Galatioto, Christian, Kuriara, Hayato, Lacavalla, Domenico, La Greca, Antonio, Larghi, Alberto, Mariani, Diego, Mirco, Paolo, Occhionorelli, Savino, Parini, Dario, Polistina, Francesco, Rimbas, Mihai, Sapienza, Paolo, Tartaglia, Dario, Tropeano, Giuseppe, Venezia, Piero, Venezia, Dario Francesco, Zaghi, Claudia, and Chiarugi, Massimo

Published
2024
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6. Strategies to prevent blood loss and reduce transfusion in emergency general surgery, WSES-AAST consensus paper

Author

Federico Coccolini, Aryeh Shander, Marco Ceresoli, Ernest Moore, Brian Tian, Dario Parini, Massimo Sartelli, Boris Sakakushev, Krstina Doklestich, Fikri Abu-Zidan, Tal Horer, Vishal Shelat, Timothy Hardcastle, Elena Bignami, Andrew Kirkpatrick, Dieter Weber, Igor Kryvoruchko, Ari Leppaniemi, Edward Tan, Boris Kessel, Arda Isik, Camilla Cremonini, Francesco Forfori, Lorenzo Ghiadoni, Massimo Chiarugi, Chad Ball, Pablo Ottolino, Andreas Hecker, Diego Mariani, Ettore Melai, Manu Malbrain, Vanessa Agostini, Mauro Podda, Edoardo Picetti, Yoram Kluger, Sandro Rizoli, Andrey Litvin, Ron Maier, Solomon Gurmu Beka, Belinda De Simone, Miklosh Bala, Aleix Martinez Perez, Carlos Ordonez, Zenon Bodnaruk, Yunfeng Cui, Augusto Perez Calatayud, Nicola de Angelis, Francesco Amico, Emmanouil Pikoulis, Dimitris Damaskos, Raul Coimbra, Mircea Chirica, Walter L. Biffl, and Fausto Catena

Subjects
Blood management, Mortality, Morbidity, Policy, Management, Jehovah’s witnesses, Surgery, RD1-811, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Abstract Emergency general surgeons often provide care to severely ill patients requiring surgical interventions and intensive support. One of the primary drivers of morbidity and mortality is perioperative bleeding. In general, when addressing life threatening haemorrhage, blood transfusion can become an essential part of overall resuscitation. However, under all circumstances, indications for blood transfusion must be accurately evaluated. When patients decline blood transfusions, regardless of the reason, surgeons should aim to provide optimal care and respect and accommodate each patient’s values and target the best outcome possible given the patient’s desires and his/her clinical condition. The aim of this position paper was to perform a review of the existing literature and to provide comprehensive recommendations on organizational, surgical, anaesthetic, and haemostatic strategies that can be used to provide optimal peri-operative blood management, reduce, or avoid blood transfusions and ultimately improve patient outcomes.

Published
2024
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7. Strategies to prevent blood loss and reduce transfusion in emergency general surgery, WSES-AAST consensus paper

Author

Coccolini, Federico, Shander, Aryeh, Ceresoli, Marco, Moore, Ernest, Tian, Brian, Parini, Dario, Sartelli, Massimo, Sakakushev, Boris, Doklestich, Krstina, Abu-Zidan, Fikri, Horer, Tal, Shelat, Vishal, Hardcastle, Timothy, Bignami, Elena, Kirkpatrick, Andrew, Weber, Dieter, Kryvoruchko, Igor, Leppaniemi, Ari, Tan, Edward, Kessel, Boris, Isik, Arda, Cremonini, Camilla, Forfori, Francesco, Ghiadoni, Lorenzo, Chiarugi, Massimo, Ball, Chad, Ottolino, Pablo, Hecker, Andreas, Mariani, Diego, Melai, Ettore, Malbrain, Manu, Agostini, Vanessa, Podda, Mauro, Picetti, Edoardo, Kluger, Yoram, Rizoli, Sandro, Litvin, Andrey, Maier, Ron, Beka, Solomon Gurmu, De Simone, Belinda, Bala, Miklosh, Perez, Aleix Martinez, Ordonez, Carlos, Bodnaruk, Zenon, Cui, Yunfeng, Calatayud, Augusto Perez, de Angelis, Nicola, Amico, Francesco, Pikoulis, Emmanouil, Damaskos, Dimitris, Coimbra, Raul, Chirica, Mircea, Biffl, Walter L., and Catena, Fausto

Published
2024
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9. FADS1/2 control lipid metabolism and ferroptosis susceptibility in triple-negative breast cancer

Author

Nicla Lorito, Angela Subbiani, Alfredo Smiriglia, Marina Bacci, Francesca Bonechi, Laura Tronci, Elisabetta Romano, Alessia Corrado, Dario Livio Longo, Marta Iozzo, Luigi Ippolito, Giuseppina Comito, Elisa Giannoni, Icro Meattini, Alexandra Avgustinova, Paola Chiarugi, Angela Bachi, and Andrea Morandi

Subjects
Ferroptosis, Lipid Metabolism, Polyunsaturated Fatty Acids, Desaturases, Lipid Droplets, Medicine (General), R5-920, Genetics, QH426-470
Abstract

Abstract Triple-negative breast cancer (TNBC) has limited therapeutic options, is highly metastatic and characterized by early recurrence. Lipid metabolism is generally deregulated in TNBC and might reveal vulnerabilities to be targeted or used as biomarkers with clinical value. Ferroptosis is a type of cell death caused by iron-dependent lipid peroxidation which is facilitated by the presence of polyunsaturated fatty acids (PUFA). Here we identify fatty acid desaturases 1 and 2 (FADS1/2), which are responsible for PUFA biosynthesis, to be highly expressed in a subset of TNBC with a poorer prognosis. Lipidomic analysis, coupled with functional metabolic assays, showed that FADS1/2 high-expressing TNBC are susceptible to ferroptosis-inducing agents and that targeting FADS1/2 by both genetic interference and pharmacological approach renders those tumors ferroptosis-resistant while unbalancing PUFA/MUFA ratio by the supplementation of exogenous PUFA sensitizes resistant tumors to ferroptosis induction. Last, inhibiting lipid droplet (LD) formation and turnover suppresses the buffering capacity of LD and potentiates iron-dependent cell death. These findings have been validated in vitro and in vivo in mouse- and human-derived clinically relevant models and in a retrospective cohort of TNBC patients.

Published
2024
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11. Long-Term Treatment Over 52 Weeks with Monthly Fremanezumab in Drug-Resistant Migraine: A Prospective Multicenter Cohort Study

Author

Caponnetto, Valeria, Russo, Antonio, Silvestro, Marcello, Tessitore, Alessandro, De Icco, Roberto, Vaghi, Gloria, Sances, Grazia, Tassorelli, Cristina, Baraldi, Carlo, Castro, Flavia Lo, Guerzoni, Simona, Prudenzano, Maria Pia, Fallacara, Adriana, Gentile, Martino, Ornello, Raffaele, Onofri, Agnese, Burgalassi, Andrea, Chiarugi, Alberto, De Cesaris, Francesco, Granato, Antonio, Casalena, Alfonsina, De Tommaso, Marina, Mampreso, Edoardo, Merlo, Paola, Coppola, Gianluca, Battistini, Stefania, Rebecchi, Valentina, Rainero, Innocenzo, Sepe, Federica Nicoletta, Dalla Volta, Giorgio, Sacco, Simona, Geppetti, Pierangelo, and Iannone, Luigi Francesco

Published
2023
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13. Anatomy and Classification of Pelvic Trauma

Author

Jacopo Giuliani, Riccardo Guelfi, Camilla Cremonini, Dario Tartaglia, Giuseppe Zocco, Massimo Chiarugi, and Federico Coccolini

Subjects
Pelvic Fracture, Blunt Trauma, Hemodynamic Status, Bleeding, Vascular Injuries, Diseases of the circulatory (Cardiovascular) system, RC666-701, Surgery, RD1-811
Abstract

Pelvic fracture is one of the most complex injuries in trauma treatment. Bleeding continues to be one of the primary causes of death from pelvic fracture, and the severity of bleeding is not necessarily correlated with the fracture pattern. The priorities in managing pelvic fractures include controlling bleeding. Historically, classification systems only consider the anatomical fracture pattern, which does not correlate with the outcomes. The World Society of Emergency Surgery (WSES) classification considers both the pelvic fracture pattern and the hemodynamic condition of the patient. Vascular injuries caused by pelvic fractures are potentially lethal because they often manifest as non-compressible multifocal venous bleeding (80–85% of pelvic bleeding) and less frequently as arterial bleeding (15–20% of pelvic bleeding). The presence of vascular injury and open pelvic fractures are independent factors contributing to mortality. Another fundamental factor in the management of pelvic vascular trauma is time [1]. In this context, the assessment of potentially significant vascular injury and timely hemorrhage control should be the highest priorities in the acute management of these injuries. Classification of pelvic injuries that considers both the fracture pattern and the hemodynamic status of the patient, such as the WSES classification, appears to have greater utility in clinical practice compared to the diffused anatomical classification.

Published
2024
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14. More early bleeds associated with high baseline direct oral anticoagulant levels in atrial fibrillation: the MAS study

Author

Testa, Sophie, Dellanoce, Claudia, Paoletti, Oriana, Morandini, Rossella, Tala, Maurizio, Ciampa, Antonio, Gaeta, Martina, Chiarugi, Paolo, Casini, Monica, Guerri, Valentina, Santoro, Rita Carlotta, Iannaccaro, Piergiorgio, Iannone, Angela Maria, Campagna, Maddalena, De Candia, Erica, Alberelli, Maria Adele, Basso, Maria, De Cristofaro, Raimondo, Di Gennaro, Leonardo, Ferretti, Antonietta, Sorrentino, Silvia, Pignatelli, Pasquale, Menichelli, Danilo, Pastori, Daniele, Saliola, Mirella, Faioni, Elena Maria, Avarello, Ilaria, Razzari, Cristina, Chistolini, Antonio, Aprile, Simona Michela, Santoro, Cristina, Serrao, Alessandra, Esteban, Maria del Pilar, Ricca, Sergio, Marietta, Marco, Arletti, Laura, Coluccio, Valeria, Debbia, Giulia, Grisolia, Deborah, Serra, Domizio, Orselli, Alberto, Pescarollo, Alessandra, Verna, Sandra, Di Gregorio, Patrizia, Cassetti, Giuseppina, Molteni, Mauro, Monelli, Mauro, Paparo, Carmelo, Resani, Guido, Di Gregorio, Nicoletta, Grassi, Davide, Lodigiani, Corrado, Banfi, Elena, Ferrazzi, Paola, Librè, Luca, Pacetti, Veronica, Sacco, Clara, Bucciarelli, Paolo, Martinelli, Ida, Abbattista, Maria, Artoni, Andrea, Capecchi, Marco, Gianniello, Francesca, Scimeca, Barbara, Turrini, Anna, Moretta, Francesca, Parise, Giorgio, Zeccardo, Ciro, Fregoni, Vittorio, Balboni, Massimo, Leggio, Federico, Poli, Daniela, Ria, Luigi, Spagnolo, Marina, Dirienzo, Giovanni, Dirienzo, Lavinia, Fuzio, Diana, Donadini, Marco Paolo, Squizzato, Alessandro, Ageno, Walter, Colombo, Giovanna, Galliazzo, Silvia, Gallo, Andrea, Tamborini Permunian, Eleonora, Virano, Alexandra, Falanga, Anna, Barcella, Luca, Gamba, Sara, Lerede, Teresa, Maggioni, Anna, Russo, Laura, Schieppati, Francesca, Zunino, Federica, Barillari, Giovanni, Bertone, Antonella, Poz, Alessandra, Venturelli, Ugo, Serricchio, Giuseppina, Brevi, Francesca, Palareti, Gualtiero, Legnani, Cristina, Cini, Michela, Antonucci, Emilia, Tripodi, Armando, and Tosetto, Alberto

Published
2024
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16. Validation of the Italian version of the Cluster Headache Impact Questionnaire (CHIQ)

Author

Onofri, Agnese, Iannone, Luigi Francesco, Granato, Antonio, Garascia, Gabriele, Bartole, Luca, Manganotti, Paolo, Vollono, Catello, Romozzi, Marina, Sottani, Costanza, Calabresi, Paolo, Tassorelli, Cristina, Sances, Grazia, Allena, Marta, De Icco, Roberto, De Cesaris, Francesco, Burgalassi, Andrea, Chiarugi, Alberto, Baraldi, Carlo, Guerzoni, Simona, Prudenzano, Maria Pia, Fallacara, Adriana, Albanese, Maria, Rainero, Innocenzo, Coppola, Gianluca, Casalena, Alfonsina, Mampreso, Edoardo, Pistoia, Francesca, Sarchielli, Paola, Morson, Marisa, Sacco, Simona, Geppetti, Pierangelo, and Ornello, Raffaele

Published
2023
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17. Cesena guidelines: WSES consensus statement on laparoscopic-first approach to general surgery emergencies and abdominal trauma

Author

Giacomo Sermonesi, Brian W. C. A. Tian, Carlo Vallicelli, Fikri M. Abu‑Zidan, Dimitris Damaskos, Michael Denis Kelly, Ari Leppäniemi, Joseph M. Galante, Edward Tan, Andrew W. Kirkpatrick, Vladimir Khokha, Oreste Marco Romeo, Mircea Chirica, Manos Pikoulis, Andrey Litvin, Vishal Girishchandra Shelat, Boris Sakakushev, Imtiaz Wani, Ibrahima Sall, Paola Fugazzola, Enrico Cicuttin, Adriana Toro, Francesco Amico, Francesca Dal Mas, Belinda De Simone, Michael Sugrue, Luigi Bonavina, Giampiero Campanelli, Paolo Carcoforo, Lorenzo Cobianchi, Federico Coccolini, Massimo Chiarugi, Isidoro Di Carlo, Salomone Di Saverio, Mauro Podda, Michele Pisano, Massimo Sartelli, Mario Testini, Andreas Fette, Sandro Rizoli, Edoardo Picetti, Dieter Weber, Rifat Latifi, Yoram Kluger, Zsolt Janos Balogh, Walter Biffl, Hans Jeekel, Ian Civil, Andreas Hecker, Luca Ansaloni, Francesca Bravi, Vanni Agnoletti, Solomon Gurmu Beka, Ernest Eugene Moore, and Fausto Catena

Subjects
Laparoscopy, Laparoscopic approach, Minimally invasive surgery/approach, Emergency general surgery, Acute care surgery, Trauma surgery hemodynamic stability, Surgery, RD1-811, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Abstract Background Laparoscopy is widely adopted across nearly all surgical subspecialties in the elective setting. Initially finding indication in minor abdominal emergencies, it has gradually become the standard approach in the majority of elective general surgery procedures. Despite many technological advances and increasing acceptance, the laparoscopic approach remains underutilized in emergency general surgery and in abdominal trauma. Emergency laparotomy continues to carry a high morbidity and mortality. In recent years, there has been a growing interest from emergency and trauma surgeons in adopting minimally invasive surgery approaches in the acute surgical setting. The present position paper, supported by the World Society of Emergency Surgery (WSES), aims to provide a review of the literature to reach a consensus on the indications and benefits of a laparoscopic-first approach in patients requiring emergency abdominal surgery for general surgery emergencies or abdominal trauma. Methods This position paper was developed according to the WSES methodology. A steering committee performed the literature review and drafted the position paper. An international panel of 54 experts then critically revised the manuscript and discussed it in detail, to develop a consensus on a position statement. Results A total of 323 studies (systematic review and meta-analysis, randomized clinical trial, retrospective comparative cohort studies, case series) have been selected from an initial pool of 7409 studies. Evidence demonstrates several benefits of the laparoscopic approach in stable patients undergoing emergency abdominal surgery for general surgical emergencies or abdominal trauma. The selection of a stable patient seems to be of paramount importance for a safe adoption of a laparoscopic approach. In hemodynamically stable patients, the laparoscopic approach was found to be safe, feasible and effective as a therapeutic tool or helpful to identify further management steps and needs, resulting in improved outcomes, regardless of conversion. Appropriate patient selection, surgeon experience and rigorous minimally invasive surgical training, remain crucial factors to increase the adoption of laparoscopy in emergency general surgery and abdominal trauma. Conclusions The WSES expert panel suggests laparoscopy as the first approach for stable patients undergoing emergency abdominal surgery for general surgery emergencies and abdominal trauma.

Published
2023
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18. Thrombotic events associated with low baseline direct oral anticoagulant levels in atrial fibrillation: the MAS study

Author

Testa, Sophie, Dellanoce, Claudia, Paoletti, Oriana, Morandini, Rossella, Tala, Maurizio, Ciampa, Antonio, Gaeta, Martina, Chiarugi, Paolo, Casini, Monica, Guerri, Valentina, Santoro, Rita Carlotta, Iannaccaro, Piergiorgio, Iannone, Angela Maria, Campagna, Maddalena, De Candia, Erica, Alberelli, Maria Adele, Basso, Maria, De Cristofaro, Raimondo, Di Gennaro, Leonardo, Ferretti, Antonietta, Sorrentino, Silvia, Pignatelli, Pasquale, Menichelli, Danilo, Pastori, Daniele, Saliola, Mirella, Faioni, Elena Maria, Avarello, Ilaria, Razzari, Cristina, Chistolini, Antonio, Aprile, Simona Michela, Santoro, Cristina, Serrao, Alessandra, Esteban, Maria del Pilar, Ricca, Sergio, Marietta, Marco, Arletti, Laura, Coluccio, Valeria, Debbia, Giulia, Grisolia, Deborah, Serra, Domizio, Orselli, Alberto, Pescarollo, Alessandra, Verna, Sandra, Di Gregorio, Patrizia, Cassetti, Giuseppina, Molteni, Mauro, Monelli, Mauro, Paparo, Carmelo, Resani, Guido, Di Gregorio, Nicoletta, Grassi, Davide, Lodigiani, Corrado, Banfi, Elena, Ferrazzi, Paola, Librè, Luca, Pacetti, Veronica, Sacco, Clara, Bucciarelli, Paolo, Martinelli, Ida, Abbattista, Maria, Artoni, Andrea, Capecchi, Marco, Gianniello, Francesca, Scimeca, Barbara, Turrini, Anna, Moretta, Francesca, Parise, Giorgio, Zeccardo, Ciro, Fregoni, Vittorio, Balboni, Massimo, Leggio, Federico, Poli, Daniela, Ria, Luigi, Spagnolo, Marina, Dirienzo, Giovanni, Dirienzo, Lavinia, Fuzio, Diana, Donadini, Marco Paolo, Squizzato, Alessandro, Ageno, Walter, Colombo, Giovanna, Galliazzo, Silvia, Gallo, Andrea, Permunian, Eleonora Tamborini, Virano, Alexandra, Falanga, Anna, Barcella, Luca, Gamba, Sara, Lerede, Teresa, Maggioni, Anna, Russo, Laura, Schieppati, Francesca, Zunino, Federica, Barillari, Giovanni, Bertone, Antonella, Poz, Alessandra, Venturelli, Ugo, Serricchio, Giuseppina, Brevi, Francesca, Palareti, Gualtiero, Legnani, Cristina, Cini, Michela, Antonucci, Emilia, Tripodi, Armando, and Tosetto, Alberto

Published
2024
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19. Cesena guidelines: WSES consensus statement on laparoscopic-first approach to general surgery emergencies and abdominal trauma

Author

Sermonesi, Giacomo, Tian, Brian W. C. A., Vallicelli, Carlo, Abu‑Zidan, Fikri M., Damaskos, Dimitris, Kelly, Michael Denis, Leppäniemi, Ari, Galante, Joseph M., Tan, Edward, Kirkpatrick, Andrew W., Khokha, Vladimir, Romeo, Oreste Marco, Chirica, Mircea, Pikoulis, Manos, Litvin, Andrey, Shelat, Vishal Girishchandra, Sakakushev, Boris, Wani, Imtiaz, Sall, Ibrahima, Fugazzola, Paola, Cicuttin, Enrico, Toro, Adriana, Amico, Francesco, Mas, Francesca Dal, De Simone, Belinda, Sugrue, Michael, Bonavina, Luigi, Campanelli, Giampiero, Carcoforo, Paolo, Cobianchi, Lorenzo, Coccolini, Federico, Chiarugi, Massimo, Di Carlo, Isidoro, Di Saverio, Salomone, Podda, Mauro, Pisano, Michele, Sartelli, Massimo, Testini, Mario, Fette, Andreas, Rizoli, Sandro, Picetti, Edoardo, Weber, Dieter, Latifi, Rifat, Kluger, Yoram, Balogh, Zsolt Janos, Biffl, Walter, Jeekel, Hans, Civil, Ian, Hecker, Andreas, Ansaloni, Luca, Bravi, Francesca, Agnoletti, Vanni, Beka, Solomon Gurmu, Moore, Ernest Eugene, and Catena, Fausto

Published
2023
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20. Correction: ECLAPTE: Effective Closure of LAParoTomy in Emergency—2023 World Society of Emergency Surgery guidelines for the closure of laparotomy in emergency settings

Author

Frassini, Simone, Cobianchi, Lorenzo, Fugazzola, Paola, Biffl, Walter L., Coccolini, Federico, Damaskos, Dimitrios, Moore, Ernest E., Kluger, Yoram, Ceresoli, Marco, Coimbra, Raul, Davies, Justin, Kirkpatrick, Andrew, Di Carlo, Isidoro, Hardcastle, Timothy C., Isik, Arda, Chiarugi, Massimo, Gurusamy, Kurinchi, Maier, Ronald V., Segovia Lohse, Helmut A., Jeekel, Hans, Boermeester, Marja A., Abu-Zidan, Fikri, Inaba, Kenji, Weber, Dieter G., Augustin, Goran, Bonavina, Luigi, Velmahos, George, Sartelli, Massimo, Di Saverio, Salomone, Ten Broek, Richard P. G., Granieri, Stefano, Dal Mas, Francesca, Farè, Camilla Nikita, Peverada, Jacopo, Zanghì, Simone, Viganò, Jacopo, Tomasoni, Matteo, Dominioni, Tommaso, Cicuttin, Enrico, Hecker, Andreas, Tebala, Giovanni D., Galante, Joseph M., Wani, Imtiaz, Khokha, Vladimir, Sugrue, Michael, Scalea, Thomas M., Tan, Edward, Malangoni, Mark A., Pararas, Nikolaos, Podda, Mauro, De Simone, Belinda, Ivatury, Rao, Cui, Yunfeng, Kashuk, Jeffry, Peitzman, Andrew, Kim, Fernando, Pikoulis, Emmanouil, Sganga, Gabriele, Chiara, Osvaldo, Kelly, Michael D., Marzi, Ingo, Picetti, Edoardo, Agnoletti, Vanni, De’Angelis, Nicola, Campanelli, Giampiero, de Moya, Marc, Litvin, Andrey, Martínez-Pérez, Aleix, Sall, Ibrahima, Rizoli, Sandro, Tomadze, Gia, Sakakushev, Boris, Stahel, Philip F., Civil, Ian, Shelat, Vishal, Costa, David, Chichom-Mefire, Alain, Latifi, Rifat, Chirica, Mircea, Amico, Francesco, Pardhan, Amyn, Seenarain, Vidya, Boyapati, Nikitha, Hatz, Basil, Ackermann, Travis, Abeyasundara, Sandun, Fenton, Linda, Plani, Frank, Sarvepalli, Rohit, Rouhbakhshfar, Omid, Caleo, Pamela, Ho-Ching Yau, Victor, Clement, Kristenne, Christou, Erasmia, Castillo, Ana María González, Gosal, Preet K. S., Balasubramaniam, Sunder, Hsu, Jeremy, Banphawatanarak, Kamon, Pisano, Michele, Toro, Adriana, Michele, Altomare, Cioffi, Stefano P. B., Spota, Andrea, Catena, Fausto, and Ansaloni, Luca

Published
2023
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21. 2023 WSES guidelines for the prevention, detection, and management of iatrogenic urinary tract injuries (IUTIs) during emergency digestive surgery

Author

de’Angelis, Nicola, Schena, Carlo Alberto, Marchegiani, Francesco, Reitano, Elisa, De Simone, Belinda, Wong, Geoffrey Yuet Mun, Martínez-Pérez, Aleix, Abu-Zidan, Fikri M., Agnoletti, Vanni, Aisoni, Filippo, Ammendola, Michele, Ansaloni, Luca, Bala, Miklosh, Biffl, Walter, Ceccarelli, Graziano, Ceresoli, Marco, Chiara, Osvaldo, Chiarugi, Massimo, Cimbanassi, Stefania, Coccolini, Federico, Coimbra, Raul, Di Saverio, Salomone, Diana, Michele, Dioguardi Burgio, Marco, Fraga, Gustavo, Gavriilidis, Paschalis, Gurrado, Angela, Inchingolo, Riccardo, Ingels, Alexandre, Ivatury, Rao, Kashuk, Jeffry L., Khan, Jim, Kirkpatrick, Andrew W., Kim, Fernando J., Kluger, Yoram, Lakkis, Zaher, Leppäniemi, Ari, Maier, Ronald V., Memeo, Riccardo, Moore, Ernest E., Ordoñez, Carlos A., Peitzman, Andrew B., Pellino, Gianluca, Picetti, Edoardo, Pikoulis, Manos, Pisano, Michele, Podda, Mauro, Romeo, Oreste, Rosa, Fausto, Tan, Edward, Ten Broek, Richard P., Testini, Mario, Tian Wei Cheng, Brian Anthony, Weber, Dieter, Sacco, Emilio, Sartelli, Massimo, Tonsi, Alfredo, Dal Moro, Fabrizio, and Catena, Fausto

Published
2023
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22. ECLAPTE: Effective Closure of LAParoTomy in Emergency—2023 World Society of Emergency Surgery guidelines for the closure of laparotomy in emergency settings

Author

Frassini, Simone, Cobianchi, Lorenzo, Fugazzola, Paola, Biffl, Walter L., Coccolini, Federico, Damaskos, Dimitrios, Moore, Ernest E., Kluger, Yoram, Ceresoli, Marco, Coimbra, Raul, Davies, Justin, Kirkpatrick, Andrew, Di Carlo, Isidoro, Hardcastle, Timothy C., Isik, Arda, Chiarugi, Massimo, Gurusamy, Kurinchi, Maier, Ronald V., Segovia Lohse, Helmut A., Jeekel, Hans, Boermeester, Marja A., Abu-Zidan, Fikri, Inaba, Kenji, Weber, Dieter G., Augustin, Goran, Bonavina, Luigi, Velmahos, George, Sartelli, Massimo, Di Saverio, Salomone, Ten Broek, Richard P. G., Granieri, Stefano, Dal Mas, Francesca, Farè, Camilla Nikita, Peverada, Jacopo, Zanghì, Simone, Viganò, Jacopo, Tomasoni, Matteo, Dominioni, Tommaso, Cicuttin, Enrico, Hecker, Andreas, Tebala, Giovanni D., Galante, Joseph M., Wani, Imtiaz, Khokha, Vladimir, Sugrue, Michael, Scalea, Thomas M., Tan, Edward, Malangoni, Mark A., Pararas, Nikolaos, Podda, Mauro, De Simone, Belinda, Ivatury, Rao, Cui, Yunfeng, Kashuk, Jeffry, Peitzman, Andrew, Kim, Fernando, Pikoulis, Emmanouil, Sganga, Gabriele, Chiara, Osvaldo, Kelly, Michael D., Marzi, Ingo, Picetti, Edoardo, Agnoletti, Vanni, De’Angelis, Nicola, Campanelli, Giampiero, de Moya, Marc, Litvin, Andrey, Martínez-Pérez, Aleix, Sall, Ibrahima, Rizoli, Sandro, Tomadze, Gia, Sakakushev, Boris, Stahel, Philip F., Civil, Ian, Shelat, Vishal, Costa, David, Chichom-Mefire, Alain, Latifi, Rifat, Chirica, Mircea, Amico, Francesco, Pardhan, Amyn, Seenarain, Vidya, Boyapati, Nikitha, Hatz, Basil, Ackermann, Travis, Abeyasundara, Sandun, Fenton, Linda, Plani, Frank, Sarvepalli, Rohit, Rouhbakhshfar, Omid, Caleo, Pamela, Ho-Ching Yau, Victor, Clement, Kristenne, Christou, Erasmia, Castillo, Ana María González, Gosal, Preet K. S., Balasubramaniam, Sunder, Hsu, Jeremy, Banphawatanarak, Kamon, Pisano, Michele, Adriana, Toro, Michele, Altomare, Cioffi, Stefano P. B., Spota, Andrea, Catena, Fausto, and Ansaloni, Luca

Published
2023
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23. Source control in emergency general surgery: WSES, GAIS, SIS-E, SIS-A guidelines

Author

Coccolini, Federico, Sartelli, Massimo, Sawyer, Robert, Rasa, Kemal, Viaggi, Bruno, Abu-Zidan, Fikri, Soreide, Kjetil, Hardcastle, Timothy, Gupta, Deepak, Bendinelli, Cino, Ceresoli, Marco, Shelat, Vishal G., Broek, Richard ten, Baiocchi, Gian Luca, Moore, Ernest E., Sall, Ibrahima, Podda, Mauro, Bonavina, Luigi, Kryvoruchko, Igor A., Stahel, Philip, Inaba, Kenji, Montravers, Philippe, Sakakushev, Boris, Sganga, Gabriele, Ballestracci, Paolo, Malbrain, Manu L. N. G., Vincent, Jean-Louis, Pikoulis, Manos, Beka, Solomon Gurmu, Doklestic, Krstina, Chiarugi, Massimo, Falcone, Marco, Bignami, Elena, Reva, Viktor, Demetrashvili, Zaza, Di Saverio, Salomone, Tolonen, Matti, Navsaria, Pradeep, Bala, Miklosh, Balogh, Zsolt, Litvin, Andrey, Hecker, Andreas, Wani, Imtiaz, Fette, Andreas, De Simone, Belinda, Ivatury, Rao, Picetti, Edoardo, Khokha, Vladimir, Tan, Edward, Ball, Chad, Tascini, Carlo, Cui, Yunfeng, Coimbra, Raul, Kelly, Michael, Martino, Costanza, Agnoletti, Vanni, Boermeester, Marja A., De’Angelis, Nicola, Chirica, Mircea, Biffl, Walt L., Ansaloni, Luca, Kluger, Yoram, Catena, Fausto, and Kirkpatrick, Andrew W.

Published
2023
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25. The unrestricted global effort to complete the COOL trial

Author

Kirkpatrick, Andrew W., Coccolini, Federico, Tolonen, Matti, Minor, Samuel, Catena, Fausto, Gois, Jr., Emanuel, Doig, Christopher J., Hill, Michael D., Ansaloni, Luca, Chiarugi, Massimo, Tartaglia, Dario, Ioannidis, Orestis, Sugrue, Michael, Colak, Elif, Hameed, S. Morad, Lampela, Hanna, Agnoletti, Vanni, McKee, Jessica L., Garraway, Naisan, Sartelli, Massimo, Ball, Chad G., Parry, Neil G., Voght, Kelly, Julien, Lisa, Kroeker, Jenna, Roberts, Derek J., Faris, Peter, Tiruta, Corina, Moore, Ernest E., Ammons, Lee Anne, Anestiadou, Elissavet, Bendinelli, Cino, Bouliaris, Konstantinos, Carroll, Rosemarry, Ceresoli, Marco, Favi, Francesco, Gurrado, Angela, Rezende-Neto, Joao, Isik, Arda, Cremonini, Camilla, Strambi, Silivia, Koukoulis, Georgios, Testini, Mario, Trpcic, Sandy, Pasculli, Alessandro, Picariello, Erika, Abu-Zidan, Fikri, Adeyeye, Ademola, Augustin, Goran, Alconchel, Felipe, Altinel, Yuksel, Hernandez Amin, Luz Adriana, Aranda-Narváez, José Manuel, Baraket, Oussama, Biffl, Walter L., Baiocchi, Gian Luca, Bonavina, Luigi, Brisinda, Giuseppe, Cardinali, Luca, Celotti, Andrea, Chaouch, Mohamed, Chiarello, Maria, Costa, Gianluca, de’Angelis, Nicola, De Manzini, Nicolo, Delibegovic, Samir, Di Saverio, Salomone, De Simone, Belinda, Dubuisson, Vincent, Fransvea, Pietro, Garulli, Gianluca, Giordano, Alessio, Gomes, Carlos, Hayati, Firdaus, Huang, Jinjian, Ibrahim, Aini Fahriza, Huei, Tan Jih, Jailani, Ruhi Fadzlyana, Khan, Mansoor, Luna, Alfonso Palmieri, Malbrain, Manu L. N. G., Marwah, Sanjay, McBeth, Paul, Mihailescu, Andrei, Morello, Alessia, Mulita, Francesk, Murzi, Valentina, Mohammad, Ahmad Tarmizi, Parmar, Simran, Pak, Ajay, Wong, Michael Pak-Kai, Pantalone, Desire, Podda, Mauro, Puccioni, Caterina, Rasa, Kemal, Ren, Jianan, Roscio, Francesco, Gonzalez-Sanchez, Antonio, Sganga, Gabriele, Scheiterle, Maximilian, Slavchev, Mihail, Smirnov, Dmitry, Tosi, Lorenzo, Trivedi, Anand, Vega, Jaime Andres Gonzalez, Waledziak, Maciej, Xenaki, Sofia, Winter, Desmond, Wu, Xiuwen, Zakaria, Andee Dzulkarnean, and Zakaria, Zaidi

Published
2023
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27. Rimegepant as an acute treatment in a refractory migraine patient non-responder to two anti-CGRP monoclonal antibodies and triptans: Case report and pharmacological considerations

Author

Andrea Burgalassi, Giulia Vigani, Alberto Boccalini, Francesco De Cesaris, Guido Mannaioni, Alberto Chiarugi, Pierangelo Geppetti, and Luigi Francesco Iannone

Subjects
Therapeutics. Pharmacology, RM1-950, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Background: Small molecule receptor antagonists (gepants), or monoclonal antibodies (mAbs) against calcitonin gene-related peptide (CGRP) have recently become available for migraine prophylaxis and/or acute treatment. Considering their shared mechanisms of action, if the failure to an anti-CGRP(R) mAbs preclude the effectiveness of gepants or vice versa is still unknown. Herein, we report the first case of a patient with refractory migraine responsive to the acute use of rimegepant that previously failed two different anti-CGRP(R) mAbs and with no response to other acute treatments. Finally, we performed a literature review on the use of gepants in patients that failed other anti-CGRP and/or triptans. Case: A 56-year-old female with a long history of chronic migraine without aura, fulfilling the EHF definition for a diagnosis of refractory migraine. Overall, the patient treated five not-consecutive migraine attacks. All of them were treated according to the predefined criteria. The mean (±SD) NRS before rimegepant assumption was 7.8 ± 0.9, all attacks cause at least severe impairment at onset, and no rescue medications were used. Pain free at 2 hours was achieved in three out of five attacks (60.0%), with no recurrence of migraine in the following 24 hours. The patient reported also a sustained benefit the day after the drug assumption. The response pain free was achieved after a mean time of 13.3 ± 4.5 minutes considering only attacks successfully treated (three out of five attacks). No adverse events were reported. Conclusions: In conclusion, rimegepant for acute treatment may be a viable option in patients with partial or no response to triptans that failed preventive treatments targeting the CGRP pathway, regardless to ligand or receptor. The failure of anti-CGRP(R) mAbs does not necessarily preclude the use of gepants (acute and/or preventive), but further studies are urgently needed to provide evidence on the efficacy of these treatments in managing drug-resistant migraine and to identify novel treatments for patients.

Published
2024
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28. The mitochondriogenic but not the immunosuppressant effects of mTOR inhibitors prompt neuroprotection and delay disease evolution in a mouse model of progressive multiple sclerosis

Author

Daniela Buonvicino, Sara Pratesi, Giuseppe Ranieri, Alessandra Pistolesi, Daniele Guasti, and Alberto Chiarugi

Subjects
Progressive EAE, Dexamethasone, Fingolimod, Rapamycin, Mitochondria, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Introduction: Purportedly, the progression of multiple sclerosis (MS) occurs when neurodegenerative processes due to derangement of axonal bioenergetics take over the autoimmune response. However, a clear picture of the causative interrelationship between autoimmunity and axonal mitochondrial dysfunction in progressive MS (PMS) pathogenesis waits to be provided. Methods: In the present study, by adopting the NOD mouse model of PMS, we compared the pharmacological effects of the immunosuppressants dexamethasone and fingolimod with those of mTOR inhibitors rapamycin and everolimus that, in addition to immunosuppression, also regulate mitochondrial functioning. Female Non-Obese Diabetic (NOD) mice were immunized with MOG35–55 and treated with drugs to evaluate functional, immune and mitochondrial parameters during disease evolution. Results: We found that dexamethasone and fingolimod did not affect the pattern of progression as well as survival. Conversely, mTOR inhibitors rapamycin and everolimus delayed disease progression and robustly extended survival of immunized mice. The same effects were obtained when treatment was delayed by 30 days after immunization. Remarkably, dexamethasone and fingolimod prompted the same degree of immunosuppression of rapamycin within both spleen and spinal cord of mice. However, only rapamycin prompted mitochondriogenesis by increasing mitochondrial content, and expression of several mitochondrial respiratory complex subunits, thereby preventing mtDNA reduction in the spinal cords of immunized mice. These pharmacodynamic effects were not reproduced in healthy NOD mice, suggesting a disease context-dependent pharmacodynamic effect. Discussion: Data corroborate the key role of mitochondriogenesis to treatment of MS progression, and for the first time disclose the translational potential of mTOR inhibitors in PMS therapy.

Published
2024
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29. 2023 WSES guidelines for the prevention, detection, and management of iatrogenic urinary tract injuries (IUTIs) during emergency digestive surgery

Author

Nicola de’Angelis, Carlo Alberto Schena, Francesco Marchegiani, Elisa Reitano, Belinda De Simone, Geoffrey Yuet Mun Wong, Aleix Martínez-Pérez, Fikri M. Abu-Zidan, Vanni Agnoletti, Filippo Aisoni, Michele Ammendola, Luca Ansaloni, Miklosh Bala, Walter Biffl, Graziano Ceccarelli, Marco Ceresoli, Osvaldo Chiara, Massimo Chiarugi, Stefania Cimbanassi, Federico Coccolini, Raul Coimbra, Salomone Di Saverio, Michele Diana, Marco Dioguardi Burgio, Gustavo Fraga, Paschalis Gavriilidis, Angela Gurrado, Riccardo Inchingolo, Alexandre Ingels, Rao Ivatury, Jeffry L. Kashuk, Jim Khan, Andrew W. Kirkpatrick, Fernando J. Kim, Yoram Kluger, Zaher Lakkis, Ari Leppäniemi, Ronald V. Maier, Riccardo Memeo, Ernest E. Moore, Carlos A. Ordoñez, Andrew B. Peitzman, Gianluca Pellino, Edoardo Picetti, Manos Pikoulis, Michele Pisano, Mauro Podda, Oreste Romeo, Fausto Rosa, Edward Tan, Richard P. Ten Broek, Mario Testini, Brian Anthony Tian Wei Cheng, Dieter Weber, Emilio Sacco, Massimo Sartelli, Alfredo Tonsi, Fabrizio Dal Moro, and Fausto Catena

Subjects
Iatrogenic urinary tract injury, Ureteral injury, Bladder injury, Urinary injury prevention, Urinary injury diagnosis, Urinary injury management, Surgery, RD1-811, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Abstract Iatrogenic urinary tract injury (IUTI) is a severe complication of emergency digestive surgery. It can lead to increased postoperative morbidity and mortality and have a long-term impact on the quality of life. The reported incidence of IUTIs varies greatly among the studies, ranging from 0.3 to 1.5%. Given the high volume of emergency digestive surgery performed worldwide, there is a need for well-defined and effective strategies to prevent and manage IUTIs. Currently, there is a lack of consensus regarding the prevention, detection, and management of IUTIs in the emergency setting. The present guidelines, promoted by the World Society of Emergency Surgery (WSES), were developed following a systematic review of the literature and an international expert panel discussion. The primary aim of these WSES guidelines is to provide evidence-based recommendations to support clinicians and surgeons in the prevention, detection, and management of IUTIs during emergency digestive surgery. The following key aspects were considered: (1) effectiveness of preventive interventions for IUTIs during emergency digestive surgery; (2) intra-operative detection of IUTIs and appropriate management strategies; (3) postoperative detection of IUTIs and appropriate management strategies and timing; and (4) effectiveness of antibiotic therapy (including type and duration) in case of IUTIs.

Published
2023
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30. ECLAPTE: Effective Closure of LAParoTomy in Emergency—2023 World Society of Emergency Surgery guidelines for the closure of laparotomy in emergency settings

Author

Simone Frassini, Lorenzo Cobianchi, Paola Fugazzola, Walter L. Biffl, Federico Coccolini, Dimitrios Damaskos, Ernest E. Moore, Yoram Kluger, Marco Ceresoli, Raul Coimbra, Justin Davies, Andrew Kirkpatrick, Isidoro Di Carlo, Timothy C. Hardcastle, Arda Isik, Massimo Chiarugi, Kurinchi Gurusamy, Ronald V. Maier, Helmut A. Segovia Lohse, Hans Jeekel, Marja A. Boermeester, Fikri Abu-Zidan, Kenji Inaba, Dieter G. Weber, Goran Augustin, Luigi Bonavina, George Velmahos, Massimo Sartelli, Salomone Di Saverio, Richard P. G. Ten Broek, Stefano Granieri, Francesca Dal Mas, Camilla Nikita Farè, Jacopo Peverada, Simone Zanghì, Jacopo Viganò, Matteo Tomasoni, Tommaso Dominioni, Enrico Cicuttin, Andreas Hecker, Giovanni D. Tebala, Joseph M. Galante, Imtiaz Wani, Vladimir Khokha, Michael Sugrue, Thomas M. Scalea, Edward Tan, Mark A. Malangoni, Nikolaos Pararas, Mauro Podda, Belinda De Simone, Rao Ivatury, Yunfeng Cui, Jeffry Kashuk, Andrew Peitzman, Fernando Kim, Emmanouil Pikoulis, Gabriele Sganga, Osvaldo Chiara, Michael D. Kelly, Ingo Marzi, Edoardo Picetti, Vanni Agnoletti, Nicola De’Angelis, Giampiero Campanelli, Marc de Moya, Andrey Litvin, Aleix Martínez-Pérez, Ibrahima Sall, Sandro Rizoli, Gia Tomadze, Boris Sakakushev, Philip F. Stahel, Ian Civil, Vishal Shelat, David Costa, Alain Chichom-Mefire, Rifat Latifi, Mircea Chirica, Francesco Amico, Amyn Pardhan, Vidya Seenarain, Nikitha Boyapati, Basil Hatz, Travis Ackermann, Sandun Abeyasundara, Linda Fenton, Frank Plani, Rohit Sarvepalli, Omid Rouhbakhshfar, Pamela Caleo, Victor Ho-Ching Yau, Kristenne Clement, Erasmia Christou, Ana María González Castillo, Preet K. S. Gosal, Sunder Balasubramaniam, Jeremy Hsu, Kamon Banphawatanarak, Michele Pisano, Toro Adriana, Altomare Michele, Stefano P. B. Cioffi, Andrea Spota, Fausto Catena, and Luca Ansaloni

Subjects
Laparotomy closure, Midline incision, Emergency, Abdominal wall incision, Closure technique, Incisional hernia, Surgery, RD1-811, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Abstract Laparotomy incisions provide easy and rapid access to the peritoneal cavity in case of emergency surgery. Incisional hernia (IH) is a late manifestation of the failure of abdominal wall closure and represents frequent complication of any abdominal incision: IHs can cause pain and discomfort to the patients but also clinical serious sequelae like bowel obstruction, incarceration, strangulation, and necessity of reoperation. Previous guidelines and indications in the literature consider elective settings and evidence about laparotomy closure in emergency settings is lacking. This paper aims to present the World Society of Emergency Surgery (WSES) project called ECLAPTE (Effective Closure of LAParoTomy in Emergency): the final manuscript includes guidelines on the closure of emergency laparotomy.

Published
2023
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31. Source control in emergency general surgery: WSES, GAIS, SIS-E, SIS-A guidelines

Author

Federico Coccolini, Massimo Sartelli, Robert Sawyer, Kemal Rasa, Bruno Viaggi, Fikri Abu-Zidan, Kjetil Soreide, Timothy Hardcastle, Deepak Gupta, Cino Bendinelli, Marco Ceresoli, Vishal G. Shelat, Richard ten Broek, Gian Luca Baiocchi, Ernest E. Moore, Ibrahima Sall, Mauro Podda, Luigi Bonavina, Igor A. Kryvoruchko, Philip Stahel, Kenji Inaba, Philippe Montravers, Boris Sakakushev, Gabriele Sganga, Paolo Ballestracci, Manu L. N. G. Malbrain, Jean-Louis Vincent, Manos Pikoulis, Solomon Gurmu Beka, Krstina Doklestic, Massimo Chiarugi, Marco Falcone, Elena Bignami, Viktor Reva, Zaza Demetrashvili, Salomone Di Saverio, Matti Tolonen, Pradeep Navsaria, Miklosh Bala, Zsolt Balogh, Andrey Litvin, Andreas Hecker, Imtiaz Wani, Andreas Fette, Belinda De Simone, Rao Ivatury, Edoardo Picetti, Vladimir Khokha, Edward Tan, Chad Ball, Carlo Tascini, Yunfeng Cui, Raul Coimbra, Michael Kelly, Costanza Martino, Vanni Agnoletti, Marja A. Boermeester, Nicola De’Angelis, Mircea Chirica, Walt L. Biffl, Luca Ansaloni, Yoram Kluger, Fausto Catena, and Andrew W. Kirkpatrick

Subjects
Source control, Emergency, Infections, Abdominal, Surgery, Trauma, RD1-811, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Abstract Intra-abdominal infections (IAI) are among the most common global healthcare challenges and they are usually precipitated by disruption to the gastrointestinal (GI) tract. Their successful management typically requires intensive resource utilization, and despite the best therapies, morbidity and mortality remain high. One of the main issues required to appropriately treat IAI that differs from the other etiologies of sepsis is the frequent requirement to provide physical source control. Fortunately, dramatic advances have been made in this aspect of treatment. Historically, source control was left to surgeons only. With new technologies non-surgical less invasive interventional procedures have been introduced. Alternatively, in addition to formal surgery open abdomen techniques have long been proposed as aiding source control in severe intra-abdominal sepsis. It is ironic that while a lack or even delay regarding source control clearly associates with death, it is a concept that remains poorly described. For example, no conclusive definition of source control technique or even adequacy has been universally accepted. Practically, source control involves a complex definition encompassing several factors including the causative event, source of infection bacteria, local bacterial flora, patient condition, and his/her eventual comorbidities. With greater understanding of the systemic pathobiology of sepsis and the profound implications of the human microbiome, adequate source control is no longer only a surgical issue but one that requires a multidisciplinary, multimodality approach. Thus, while any breach in the GI tract must be controlled, source control should also attempt to control the generation and propagation of the systemic biomediators and dysbiotic influences on the microbiome that perpetuate multi-system organ failure and death. Given these increased complexities, the present paper represents the current opinions and recommendations for future research of the World Society of Emergency Surgery, of the Global Alliance for Infections in Surgery of Surgical Infection Society Europe and Surgical Infection Society America regarding the concepts and operational adequacy of source control in intra-abdominal infections.

Published
2023
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38. The unrestricted global effort to complete the COOL trial

Author

Andrew W. Kirkpatrick, Federico Coccolini, Matti Tolonen, Samuel Minor, Fausto Catena, Emanuel Gois, Christopher J. Doig, Michael D. Hill, Luca Ansaloni, Massimo Chiarugi, Dario Tartaglia, Orestis Ioannidis, Michael Sugrue, Elif Colak, S. Morad Hameed, Hanna Lampela, Vanni Agnoletti, Jessica L. McKee, Naisan Garraway, Massimo Sartelli, Chad G. Ball, Neil G. Parry, Kelly Voght, Lisa Julien, Jenna Kroeker, Derek J. Roberts, Peter Faris, Corina Tiruta, Ernest E. Moore, Lee Anne Ammons, Elissavet Anestiadou, Cino Bendinelli, Konstantinos Bouliaris, Rosemarry Carroll, Marco Ceresoli, Francesco Favi, Angela Gurrado, Joao Rezende-Neto, Arda Isik, Camilla Cremonini, Silivia Strambi, Georgios Koukoulis, Mario Testini, Sandy Trpcic, Alessandro Pasculli, Erika Picariello, Fikri Abu-Zidan, Ademola Adeyeye, Goran Augustin, Felipe Alconchel, Yuksel Altinel, Luz Adriana Hernandez Amin, José Manuel Aranda-Narváez, Oussama Baraket, Walter L. Biffl, Gian Luca Baiocchi, Luigi Bonavina, Giuseppe Brisinda, Luca Cardinali, Andrea Celotti, Mohamed Chaouch, Maria Chiarello, Gianluca Costa, Nicola de’Angelis, Nicolo De Manzini, Samir Delibegovic, Salomone Di Saverio, Belinda De Simone, Vincent Dubuisson, Pietro Fransvea, Gianluca Garulli, Alessio Giordano, Carlos Gomes, Firdaus Hayati, Jinjian Huang, Aini Fahriza Ibrahim, Tan Jih Huei, Ruhi Fadzlyana Jailani, Mansoor Khan, Alfonso Palmieri Luna, Manu L. N. G. Malbrain, Sanjay Marwah, Paul McBeth, Andrei Mihailescu, Alessia Morello, Francesk Mulita, Valentina Murzi, Ahmad Tarmizi Mohammad, Simran Parmar, Ajay Pak, Michael Pak-Kai Wong, Desire Pantalone, Mauro Podda, Caterina Puccioni, Kemal Rasa, Jianan Ren, Francesco Roscio, Antonio Gonzalez-Sanchez, Gabriele Sganga, Maximilian Scheiterle, Mihail Slavchev, Dmitry Smirnov, Lorenzo Tosi, Anand Trivedi, Jaime Andres Gonzalez Vega, Maciej Waledziak, Sofia Xenaki, Desmond Winter, Xiuwen Wu, Andee Dzulkarnean Zakaria, and Zaidi Zakaria

Subjects
Intraperitoneal sepsis, Septic shock, Peritonitis, Open abdomen, Multiple organ dysfunction, Laparotomy, Surgery, RD1-811, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Abstract Background Severe complicated intra-abdominal sepsis (SCIAS) has an increasing incidence with mortality rates over 80% in some settings. Mortality typically results from disruption of the gastrointestinal tract, progressive and self-perpetuating bio-mediator generation, systemic inflammation, and multiple organ failure. A further therapeutic option may be open abdomen (OA) management with negative peritoneal pressure therapy (NPPT) to remove inflammatory ascites and attenuate the systemic damage from SCIAS, although there are definite risks of leaving the abdomen open whenever it might possibly be closed. This potential therapeutic paradigm is the rationale being assessed in the Closed Or Open after Laparotomy (COOL trial) ( https://clinicaltrials.gov/ct2/show/NCT03163095 ). Initially, the COOL trial received Industry sponsorship; however, this funding mandated the use of a specific trademarked and expensive NPPT device in half of the patients allocated to the intervention (open) arm. In August 2022, the 3 M/Acelity Corporation without consultation but within the terms of the contract canceled the financial support of the trial. Although creating financial difficulty, there is now no restriction on specific NPPT devices and removing a cost-prohibitive intervention creates an opportunity to expand the COOL trial to a truly global basis. This document describes the evolution of the COOL trial, with a focus on future opportunities for global growth of the study. Methods The COOL trial is the largest prospective randomized controlled trial examining the random allocation of SCIAS patients intra-operatively to either formal closure of the fascia or the use of the OA with an application of an NPPT dressing. Patients are eligible if they have free uncontained intraperitoneal contamination and physiologic derangements exemplified by septic shock OR severely adverse predicted clinical outcomes. The primary outcome is intended to definitively inform global practice by conclusively evaluating 90-day survival. Initial recruitment has been lower than hoped but satisfactory, and the COOL steering committee and trial investigators intend with increased global support to continue enrollment until recruitment ensures a definitive answer. Discussion OA is mandated in many cases of SCIAS such as the risk of abdominal compartment syndrome associated with closure, or a planned second look as for example part of “damage control”; however, improved source control (locally and systemically) is the most uncertain indication for an OA. The COOL trial seeks to expand potential sites and proceed with the evaluation of NPPT agnostic to device, to properly examine the hypothesis that this treatment attenuates systemic damage and improves survival. This approach will not affect internal validity and should improve the external validity of any observed results of the intervention. Trial registration: National Institutes of Health ( https://clinicaltrials.gov/ct2/show/NCT03163095 ).

Published
2023
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40. Paracetamol and ibuprofen combination for the management of acute mild-to-moderate pain in children: expert consensus using the Nominal Group Technique (NGT)

Author

Niccolò Parri, Davide Silvagni, Alberto Chiarugi, Elisabetta Cortis, Antonio D’Avino, Marcello Lanari, Paola Giovanna Marchisio, Cesare Vezzoli, Stefania Zampogna, and Annamaria Staiano

Subjects
Ibuprofen, Paracetamol, Fixed-dose, Pediatric, Children, Acute pain, Pediatrics, RJ1-570
Abstract

Abstract Background Acute pain is a common symptom in children of all ages, and is associated with a variety of conditions. Despite the availability of guidelines, pain often remains underestimated and undertreated. Paracetamol and ibuprofen are the most commonly used drugs for analgesia in Pediatrics. Multimodal pain management by using a combination of paracetamol and ibuprofen results in greater analgesia. Methods An investigation using the Nominal Group Technique was carried out between May and August 2022. Two open (non-anonymous) questionnaires were consecutively sent to a Board of ten clinicians to understand their opinions on the use of the oral paracetamol and ibuprofen association. Answers were examined in a final meeting where conclusions were drawn. Results The board achieved a final consensus on a better analgesic power of paracetamol and ibuprofen in fixed-dose combination as compared to monotherapy, without compromising safety. Strong consensus was reached on the opinion that the fixed-dose combination of paracetamol and ibuprofen may be a useful option in case of inefficacy of one or other drug as monotherapy, especially in case of headaches, odontalgia, earache, and musculoskeletal pain. The use of the fixed combination may be also considered suitable for postoperative pain management. Conclusions The use of the fixed-dose combination may represent advantage in terms of efficacy and safety, allowing a better control of the dose of both paracetamol and ibuprofen as monotherapy, thus minimizing the risk of incorrect dosage. However, the limited evidence available highlights the need for future well designed studies to better define the advantages of this formulation in the various therapeutic areas.

Published
2023
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41. Inhibition of MMPs supports amoeboid angiogenesis hampering VEGF-targeted therapies via MLC and ERK 1/2 signaling

Author

Anastasia Chillà, Cecilia Anceschi, Elena Frediani, Francesca Scavone, Tommaso Del Rosso, Giuseppe Pelagio, Antonio Tufaro, Giuseppe De Palma, Mario Del Rosso, Gabriella Fibbi, Paola Chiarugi, Anna Laurenzana, and Francesca Margheri

Subjects
Angiogenesis, Protease inhibitors, Amoeboid migration, VEGF, Endothelial cells, ECFCs, Medicine
Abstract

Abstract Background In the past decades studies on anti-tumoral drugs inhibiting matrix metalloproteinase (MMPs) were disappointing. Recently, we demonstrated that mature endothelial cells (ECs) and endothelial colony forming cells (ECFCs) can switch between invasion modes to cope with challenging environments, performing the “amoeboid angiogenesis” in the absence of proteases activity. Methods We first set out to investigate by ELISA if the inhibitors of the main protease family involved in angiogenesis were differently expressed during breast cancer progression. We used Marimastat, a broad-spectrum MMP inhibitor, as a means of inducing amoeboid characteristics and studied VEGF role in amoeboid angiogenesis. Thus, we performed invasion and capillary morphogenesis assay, morphological, cell signaling and in vivo mouse studies. Results Our data showed that TIMP1, TIMP2, alpha2-antiplasmin, PAI-1 and cystatin increase in breast cancer serum of patients with primary cancer and lymph node positive compared to healthy women. In vitro results revealed that the most high-powered protease inhibitors able to induce amoeboid invasion of ECFCs were TIMP1, 2 and 3. Surprisingly, Marimastat promotes ECFC invasion and tubular formation in vitro and in vivo, inducing amoeboid characteristics. We observed that the combination of Marimastat plus VEGF doesn’t boost neither cell invasion nor vessel formation capacity. Moreover, inhibition of VEGF activity with Bevacizumab in the presence of Marimastat confirmed that amoeboid angiogenesis is independent from the stimulus of the main vascular growth factor, VEGF. Conclusions We underline the importance to consider the amoeboid mechanism of endothelial and cancer cell invasion, probably responsible for the failure of synthetic metalloproteinase inhibitors as cancer therapy and tumor resistance to VEGF-targeted therapies, to set-up new drugs to be used in cancer therapy.

Published
2023
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43. Inappropriate Underdosing of Direct Oral Anticoagulants in Atrial Fibrillation Patients: Results from the START2-AF Registry

Author

Daniela Poli, Emilia Antonucci, Walter Ageno, Martina Berteotti, Anna Falanga, Vittorio Pengo, Paolo Chiarugi, Benilde Cosmi, Carmelo Paparo, Antonio Chistolini, Antonio Insana, Domenico Lione, Giuseppe Malcangi, Giuliana Martini, Lucilla Masciocco, Simona Pedrini, Eugenio Bucherini, Daniele Pastori, Pasquale Pignatelli, Andrea Toma, Sophie Testa, Gualtiero Palareti, and START AF Study Group

Subjects
non valvular atrial fibrillation, bleeding, DOAC, low dosage, stroke, Medicine
Abstract

Background: Direct oral anticoagulants (DOACs) are recommended for stroke prevention in non-valvular atrial fibrillation (NVAF) patients. We aimed to describe the prevalence of inappropriate DOACs dose prescription in the START2-AF Registry, the outcomes according to the appropriateness of the dosage, and the factors associated with inappropriate dose prescription. Methods: Patients’ demographics and clinical data were prospectively collected as electronic files in an anonymous form on the website of the START2-Registry; DOACs dosage was determined to be appropriate when prescribed according to the European Heart Rhythm Association Guidelines. Results: We included 5943 NVAF patients on DOACs; 2572 (46.3%) were female patients. The standard dose (SD) was prescribed to 56.9% of patients and the low dose (LD) was prescribed to 43.1% of patients; 38.9% of all NVAF patients received an inappropriate LD DOAC and 0.3% received inappropriate SD. Patients treated with LD DOAC had a significantly higher rate of all bleedings (RR 1.5; 95% CI 1.2–2.0), major bleedings (RR 1.8; 95% CI 1.3–1.7), and mortality (RR 2.8; 95% CI 1.9–4.1) with respect to patients treated with SD DOAC. No difference was found among patients treated with appropriate and inappropriate LD regarding bleeding, thrombotic, and mortality rates. Age, body weight Conclusions: Inappropriate LD DOACs in NVAF patients is not associated with a reduction in bleeding risk, nor with an increased thrombotic risk. Instead, it is associated with higher mortality rate, suggesting that, in clinical practice, underdosing is preferred for patients at particularly high risk for adverse events.

Published
2024
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44. Taste Masking of Dexketoprofen Trometamol Orally Disintegrating Granules by High-Shear Coating with Glyceryl Distearate

Author

Ilaria Chiarugi, Diletta Biagi, Paolo Nencioni, Francesca Maestrelli, Maurizio Valleri, and Paola Angela Mura

Subjects
high-shear coating, taste masking, orally disintegrating granules, glyceryl distearate, hot-melt coating, design of experiments, Pharmacy and materia medica, RS1-441
Abstract

Orally disintegrating granules (ODGs) are a pharmaceutical form commonly used for the administration of NSAIDs because of their easy assumption and fast dispersion. The development of ODGs is not easy for drugs like dexketoprofen trometamol (DXKT), which have a bitter and burning taste. In this work, high-shear coating (HSC) was used as an innovative technique for DKXT taste masking. This study focused on coating DXKT granules using the HSC technique with a low-melting lipid excipient, glyceryl distearate (GDS). The HSC technique allowed for the coating to be developed through the thermal rise resulting from the friction generated by the granules movement inside the equipment, causing the coating excipient to soften. The design of the experiment was used to find the best experimental coating conditions in order to gain effective taste masking by suitably reducing the amount of drug released in the oral cavity. The influence of the granule dimensions was also investigated. Coating effectiveness was evaluated using a simulated saliva dissolution test. It was found that low impeller speed (300 rpm) and a 20% coating excipient were effective in suitably reducing the drug dissolution rate and then in taste masking. The coated granules were characterized for their morphology and solid-state properties by SEM, BET, XRPD, DSC, and NIR analyses. A human taste panel test confirmed the masking of DXKT taste in the selected batch granules.

Published
2024
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45. The Burden of Thin Melanomas in Tuscany, Italy, 1985–2017: Age- and Sex-Specific Temporal Trends in Incidence and Mortality

Author

Gianfranco Manneschi, Adele Caldarella, Saverio Caini, Saverio Checchi, Teresa Intrieri, Alessandra Chiarugi, Paolo Nardini, and Giovanna Masala

Subjects
cutaneous melanoma, Breslow thickness, incidence, mortality, trend, Tuscany, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

A steady increase in the incidence and mortality burden correlated to thin melanomas (≤1 mm) has been reported in recent years in some international studies, but there is currently a paucity of data from the Mediterranean area. We aimed to describe the epidemiological characteristics of thin melanoma in Tuscany, Central Italy. A total of 6002 first cutaneous invasive melanomas occurring from 1985 to 2017 were selected for analysis; data were retrieved from the local population-based cancer registry. The standardized incidence rate was 15.0 per 100,000 in the population, higher among men than women (16.5 vs. 14.1). Incidence rates tended to increase over time across all age group-specific population strata, with annual percent changes moderately higher among men (+8.0%) than women (+6.9%), especially among the elderly. Among both sexes and in each age group, the trend toward increasing incidence rates was particularly strong for thin melanomas. Survival was better among women than men across all categories of thickness. Approximately 15% of deaths occurred among patients with thin lesions, with no major temporal changes in recent years. This study contributes to an improved understanding of melanoma epidemiology in Tuscany and underscores the need for primary prevention strategies tackling the growing burden of thin melanomas.

Published
2024
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46. Correction: ECLAPTE: Effective Closure of LAParoTomy in Emergency—2023 World Society of Emergency Surgery guidelines for the closure of laparotomy in emergency settings

Author

Simone Frassini, Lorenzo Cobianchi, Paola Fugazzola, Walter L. Biffl, Federico Coccolini, Dimitrios Damaskos, Ernest E. Moore, Yoram Kluger, Marco Ceresoli, Raul Coimbra, Justin Davies, Andrew Kirkpatrick, Isidoro Di Carlo, Timothy C. Hardcastle, Arda Isik, Massimo Chiarugi, Kurinchi Gurusamy, Ronald V. Maier, Helmut A. Segovia Lohse, Hans Jeekel, Marja A. Boermeester, Fikri Abu-Zidan, Kenji Inaba, Dieter G. Weber, Goran Augustin, Luigi Bonavina, George Velmahos, Massimo Sartelli, Salomone Di Saverio, Richard P. G. Ten Broek, Stefano Granieri, Francesca Dal Mas, Camilla Nikita Farè, Jacopo Peverada, Simone Zanghì, Jacopo Viganò, Matteo Tomasoni, Tommaso Dominioni, Enrico Cicuttin, Andreas Hecker, Giovanni D. Tebala, Joseph M. Galante, Imtiaz Wani, Vladimir Khokha, Michael Sugrue, Thomas M. Scalea, Edward Tan, Mark A. Malangoni, Nikolaos Pararas, Mauro Podda, Belinda De Simone, Rao Ivatury, Yunfeng Cui, Jeffry Kashuk, Andrew Peitzman, Fernando Kim, Emmanouil Pikoulis, Gabriele Sganga, Osvaldo Chiara, Michael D. Kelly, Ingo Marzi, Edoardo Picetti, Vanni Agnoletti, Nicola De’Angelis, Giampiero Campanelli, Marc de Moya, Andrey Litvin, Aleix Martínez-Pérez, Ibrahima Sall, Sandro Rizoli, Gia Tomadze, Boris Sakakushev, Philip F. Stahel, Ian Civil, Vishal Shelat, David Costa, Alain Chichom-Mefire, Rifat Latifi, Mircea Chirica, Francesco Amico, Amyn Pardhan, Vidya Seenarain, Nikitha Boyapati, Basil Hatz, Travis Ackermann, Sandun Abeyasundara, Linda Fenton, Frank Plani, Rohit Sarvepalli, Omid Rouhbakhshfar, Pamela Caleo, Victor Ho-Ching Yau, Kristenne Clement, Erasmia Christou, Ana María González Castillo, Preet K. S. Gosal, Sunder Balasubramaniam, Jeremy Hsu, Kamon Banphawatanarak, Michele Pisano, Adriana Toro, Altomare Michele, Stefano P. B. Cioffi, Andrea Spota, Fausto Catena, and Luca Ansaloni

Subjects
Surgery, RD1-811, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Published
2023
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47. Acute mesenteric ischemia: updated guidelines of the World Society of Emergency Surgery

Author

Miklosh Bala, Fausto Catena, Jeffry Kashuk, Belinda De Simone, Carlos Augusto Gomes, Dieter Weber, Massimo Sartelli, Federico Coccolini, Yoram Kluger, Fikri M. Abu-Zidan, Edoardo Picetti, Luca Ansaloni, Goran Augustin, Walter L. Biffl, Marco Ceresoli, Osvaldo Chiara, Massimo Chiarugi, Raul Coimbra, Yunfeng Cui, Dimitris Damaskos, Salomone Di Saverio, Joseph M. Galante, Vladimir Khokha, Andrew W. Kirkpatrick, Kenji Inaba, Ari Leppäniemi, Andrey Litvin, Andrew B. Peitzman, Vishal G. Shelat, Michael Sugrue, Matti Tolonen, Sandro Rizoli, Ibrahima Sall, Solomon G. Beka, Isidoro Di Carlo, Richard Ten Broek, Chirika Mircea, Giovanni Tebala, Michele Pisano, Harry van Goor, Ronald V. Maier, Hans Jeekel, Ian Civil, Andreas Hecker, Edward Tan, Kjetil Soreide, Matthew J. Lee, Imtiaz Wani, Luigi Bonavina, Mark A. Malangoni, Kaoru Koike, George C. Velmahos, Gustavo P. Fraga, Andreas Fette, Nicola de’Angelis, Zsolt J. Balogh, Thomas M. Scalea, Gabriele Sganga, Michael D. Kelly, Jim Khan, Philip F. Stahel, and Ernest E. Moore

Subjects
Mesenteric ischemia, Mesenteric arterial occlusion, Mesenteric artery stenting, Bowel ischemia, Guidelines, Recommendations, Surgery, RD1-811, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Abstract Acute mesenteric ischemia (AMI) is a group of diseases characterized by an interruption of the blood supply to varying portions of the intestine, leading to ischemia and secondary inflammatory changes. If untreated, this process may progress to life-threatening intestinal necrosis. The incidence is low, estimated at 0.09–0.2% of all acute surgical admissions, but increases with age. Although the entity is an uncommon cause of abdominal pain, diligence is required because if untreated, mortality remains in the range of 50%. Early diagnosis and timely surgical intervention are the cornerstones of modern treatment to reduce the high mortality associated with this entity. The advent of endovascular approaches in parallel with modern imaging techniques is evolving and provides new treatment options. Lastly, a focused multidisciplinary approach based on early diagnosis and individualized treatment is essential. Thus, we believe that updated guidelines from World Society of Emergency Surgery are warranted, in order to provide the most recent and practical recommendations for diagnosis and treatment of AMI.

Published
2022
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50. Postoperative pain management in non-traumatic emergency general surgery: WSES-GAIS-SIAARTI-AAST guidelines

Author

Federico Coccolini, Francesco Corradi, Massimo Sartelli, Raul Coimbra, Igor A. Kryvoruchko, Ari Leppaniemi, Krstina Doklestic, Elena Bignami, Giandomenico Biancofiore, Miklosh Bala, Ceresoli Marco, Dimitris Damaskos, Walt L. Biffl, Paola Fugazzola, Domenico Santonastaso, Vanni Agnoletti, Catia Sbarbaro, Mirco Nacoti, Timothy C. Hardcastle, Diego Mariani, Belinda De Simone, Matti Tolonen, Chad Ball, Mauro Podda, Isidoro Di Carlo, Salomone Di Saverio, Pradeep Navsaria, Luigi Bonavina, Fikri Abu-Zidan, Kjetil Soreide, Gustavo P. Fraga, Vanessa Henriques Carvalho, Sergio Faria Batista, Andreas Hecker, Alessandro Cucchetti, Giorgio Ercolani, Dario Tartaglia, Joseph M. Galante, Imtiaz Wani, Hayato Kurihara, Edward Tan, Andrey Litvin, Rita Maria Melotti, Gabriele Sganga, Tamara Zoro, Alessandro Isirdi, Nicola De’Angelis, Dieter G. Weber, Adrien M. Hodonou, Richard tenBroek, Dario Parini, Jim Khan, Giovanni Sbrana, Carlo Coniglio, Antonino Giarratano, Angelo Gratarola, Claudia Zaghi, Oreste Romeo, Michael Kelly, Francesco Forfori, Massimo Chiarugi, Ernest E. Moore, Fausto Catena, and Manu L. N. G. Malbrain

Subjects
Morbidity, Acute, Pain, Treatment, Emergency, Surgery, RD1-811, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Abstract Background Non-traumatic emergency general surgery involves a heterogeneous population that may present with several underlying diseases. Timeous emergency surgical treatment should be supplemented with high-quality perioperative care, ideally performed by multidisciplinary teams trained to identify and handle complex postoperative courses. Uncontrolled or poorly controlled acute postoperative pain may result in significant complications. While pain management after elective surgery has been standardized in perioperative pathways, the traditional perioperative treatment of patients undergoing emergency surgery is often a haphazard practice. The present recommended pain management guidelines are for pain management after non-traumatic emergency surgical intervention. It is meant to provide clinicians a list of indications to prescribe the optimal analgesics even in the absence of a multidisciplinary pain team. Material and methods An international expert panel discussed the different issues in subsequent rounds. Four international recognized scientific societies: World Society of Emergency Surgery (WSES), Global Alliance for Infection in Surgery (GAIS), Italian Society of Anesthesia, Analgesia Intensive Care (SIAARTI), and American Association for the Surgery of Trauma (AAST), endorsed the project and approved the final manuscript. Conclusion Dealing with acute postoperative pain in the emergency abdominal surgery setting is complex, requires special attention, and should be multidisciplinary. Several tools are available, and their combination is mandatory whenever is possible. Analgesic approach to the various situations and conditions should be patient based and tailored according to procedure, pathology, age, response, and available expertise. A better understanding of the patho-mechanisms of postoperative pain for short- and long-term outcomes is necessary to improve prophylactic and treatment strategies.

Published
2022
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