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1. Treatments for intracranial hypertension in acute brain-injured patients: grading, timing, and association with outcome. Data from the SYNAPSE-ICU study

Author

Robba, Chiara, Graziano, Francesca, Guglielmi, Angelo, Rebora, Paola, Galimberti, Stefania, Taccone, Fabio S, Citerio, Giuseppe, Walter Videtta, Gustavo Domeniconi, María Estrella Giménez, Mariela Fumale, Edgar Daniel Amundarain, Matias Casanova, Michael Reade, Elizabeth Hallt, David Pearson, Ian Seppelt, Raimund Helbok, Valery Davidovich, Geert Meyfroidt, Ilaria Alice Crippa, Liese Mebis, Patrick Biston, Stijn Van De Velde, Glorieux Denis, Pedro Kurtz, Samia Yasin Wayhs, Mypinder Sekhon, Donald Griesdale, Andrea Rigamonti, José Miguel Montes, Rodrigo Pérez-Araos, Jorge H Mejia-Mantilla, Andrés Gempeler, Ray Mendoza, Natasa Kovac, Hedgar Berty Gutiérrez, Vera Spatenkova, Marek Fencl, Roman Gal, Ondrej Hrdy, Kamil Vrbica, Josef Skola, Eva Provaznikova, Jakub Kletecka, Pavel Lavicka, Piergiorgio Bresil, Marianne Levin, Josefine Thomsen, Thomas Egmose Larsen, Henrik Westy Hoffmeyer, Morten Olskjaer Holm, Jesper Borg Andersen, Birgitte Majholm, Margit Smitt, Heidi Shil Eddelien, Manuel Jibaja, Freddy Maldonado, María Fernanda García, Karim Asehnoune, Bertrand Pons, Gérard Audibert, Manon Lucca, Guillaume Besch, Pierluigi Banco, Raphael Cinotti, Hervé Q Uintard, Benjamin Soyer, Anais Caillard, Clement Gakuba, Romain Sonneville, Stefan Wolf, Kristina Fuest, Lea Albrecht, Sarah Grotheer, Sandro M Krieg, Stefan J Schaller, Charikleia Vrettou, Eftychia Kontoudaki, Anna Efthymiou, Elena Palli, Demosthenes Makris, Chrysi Diakaki, Christina Iasonidou, Aikaterini Dimoula, Georgios Koukoulitsios, George Kyriazopoulos, Nikolas Pantelas, Syragoula Tsikriki, Electra Eleni Stamou, Achileas Giannopoulos, Eleni Mouloudi, Ping Shum Hoi, Yan Chan Cheuk, Hewa Kandamby Darshana, Krisztián Tánczos, Gabor Nardai, Zoltan Szentkereszty, Harsh Sapra, Deepak Gupta, Kaveri Sharma, Saurabh Anand, Ankur Luthra, Summit Bloria, Rajeev Chauhan, Nidhi Panda, Ahmad Ozair, Bram Kilapong, Anass Alsudani, Giuseppe Citerio, Alessandra Soragni, Alessandro Motta, Andrea Marudi, Elisabetta Bertellini, Anselmo Caricato, Camilla Gelormini, Eleonora Ioannoni, Eleonora Stival, Serena Silva, Federico Pozzi, Iole Brunetti, Andrea Cortegiani, Edoardo Picetti, Federico Villa, Italo Calamai, Maria Chiara Casadio, Maria Concetta Quartarone, Marzia Grandis, Federico Magni, Silvia Del Bianco, Claudia Bonetti, Virginia Buldini, Aimone Giugni, Simone Maria Zerbi, Marco Carbonara, Antonella Cotoia, Antonio Izzi, Olegs Sabelnikovs, Muhammed Elhadi, Hazem Ahmed, Silvio A Ñamendys Silva, Gilberto Adrian Gasca López, Gentle S Shrestha, Shirish Maskey, Tamanna Bajracharya, Khadka Nilam, Prakash Kafle, Laleet Rajbanshi, Yam Bahadur Roka, Olufemi Idowu, Khan Muhammad Mukhtar, Juan Luis Pinedo Portilla, Klaudyna Kojder, Irene Aragao, Ricardo Freitas, Marco Simoes, Dario Batista, Cecília Pacheco, Fátima Assunção, Luís Lencastre, Pedro Cavaleiro, Mohamed Abdelaty, Alex Gritsan, Sergey Khomiakov Sergey, Dovbysh Nikolay, Yaseen Arabi, Primoz Gradisek, Petra Forjan, Mara Škoti, Suada Filekovic Ribaric, Nataša Milivojevic, Sergeja Kozar, Rafael Badenes, Aaron Blandino Ortiz, Mikel Celaya Lopez, Laura Galarza, Luisa Corral, Africa Lores, Ricard Soley, Laura Pariente, Pablo López Ojeda, Maria Dolores Arias Verdu, Luis Javier Yuste Dominguez, Maria Isabel Gonzalez Perez, Mireia Anglada, Patricia Duque, Ainhoa Serrano, Berta Monleon, Vanessa Blazquez, Mauro Oddo, Samia Abed Maillard, Paola Morelli, John-Paul Miroz, Eva Favre, Walid Sellami, Massimo Lamperti, Jamil Dibu, Richard Sivities, Angelos Kolias, Chris Thompson, Christopher Hawthorne, Justin Roberts, Lara Prisco, Roger Lightfoot, Josè I Suarez, Luci Rivera-Lara, Susanne Muehlschlegel, Juan Padilla, Sanjeev Sivakumar, Daiwai Olson, Robba, C, Graziano, F, Guglielmi, A, Rebora, P, Galimberti, S, Taccone, F, Citerio, G, Robba, Chiara, Graziano, Francesca, Guglielmi, Angelo, Rebora, Paola, Galimberti, Stefania, Taccone, Fabio S, Citerio, Giuseppe, and Walter Videtta, Gustavo Domeniconi, María Estrella Giménez, Mariela Fumale, Edgar Daniel Amundarain, Matias Casanova, Michael Reade, Elizabeth Hallt, David Pearson, Ian Seppelt, Raimund Helbok, Valery Davidovich, Geert Meyfroidt, Ilaria Alice Crippa, Liese Mebis, Patrick Biston, Stijn Van De Velde, Glorieux Denis, Pedro Kurtz, Samia Yasin Wayhs, Mypinder Sekhon, Donald Griesdale, Andrea Rigamonti, José Miguel Montes, Rodrigo Pérez-Araos, Jorge H Mejia-Mantilla, Andrés Gempeler, Ray Mendoza, Natasa Kovac, Hedgar Berty Gutiérrez, Vera Spatenkova, Marek Fencl, Roman Gal, Ondrej Hrdy, Kamil Vrbica, Josef Skola, Eva Provaznikova, Jakub Kletecka, Pavel Lavicka, Vera Spatenkova, Piergiorgio Bresil, Marianne Levin, Piergiorgio Bresil, Josefine Thomsen, Thomas Egmose Larsen, Henrik Westy Hoffmeyer, Morten Olskjaer Holm, Jesper Borg Andersen, Birgitte Majholm, Margit Smitt, Heidi Shil Eddelien, Manuel Jibaja, Freddy Maldonado, María Fernanda García, Karim Asehnoune, Bertrand Pons, Gérard Audibert, Manon Lucca, Guillaume Besch, Pierluigi Banco, Karim Asehnoune, Raphael Cinotti, Hervé Q Uintard, Benjamin Soyer, Anais Caillard, Clement Gakuba, Romain Sonneville, Stefan Wolf, Kristina Fuest, Lea Albrecht, Sarah Grotheer, Sandro M Krieg, Stefan J Schaller, Charikleia Vrettou, Eftychia Kontoudaki, Anna Efthymiou, Elena Palli, Demosthenes Makris, Chrysi Diakaki, Christina Iasonidou, Aikaterini Dimoula, Georgios Koukoulitsios, George Kyriazopoulos, Nikolas Pantelas, Syragoula Tsikriki, Electra Eleni Stamou, Charikleia Vrettou, Achileas Giannopoulos, Eleni Mouloudi, Ping Shum Hoi, Yan Chan Cheuk, Hewa Kandamby Darshana, Krisztián Tánczos, Gabor Nardai, Zoltan Szentkereszty, Harsh Sapra, Deepak Gupta, Kaveri Sharma, Saurabh Anand, Ankur Luthra, Summit Bloria, Rajeev Chauhan, Nidhi Panda, Ahmad Ozair, Bram Kilapong, Anass Alsudani, Giuseppe Citerio, Alessandra Soragni, Alessandro Motta, Andrea Marudi, Elisabetta Bertellini, Anselmo Caricato, Camilla Gelormini, Eleonora Ioannoni, Eleonora Stival, Serena Silva, Federico Pozzi, Iole Brunetti, Andrea Cortegiani, Edoardo Picetti, Federico Villa, Italo Calamai, Maria Chiara Casadio, Maria Concetta Quartarone, Marzia Grandis, Federico Magni, Silvia Del Bianco, Claudia Bonetti, Virginia Buldini, Aimone Giugni, Simone Maria Zerbi, Marco Carbonara, Antonella Cotoia, Antonio Izzi, Olegs Sabelnikovs, Muhammed Elhadi, Hazem Ahmed, Silvio A Ñamendys Silva, Gilberto Adrian Gasca López, Gentle S Shrestha, Shirish Maskey, Tamanna Bajracharya, Khadka Nilam, Prakash Kafle, Laleet Rajbanshi, Yam Bahadur Roka, Olufemi Idowu, Khan Muhammad Mukhtar, Juan Luis Pinedo Portilla, Klaudyna Kojder, Irene Aragao, Ricardo Freitas, Marco Simoes, Dario Batista, Cecília Pacheco, Fátima Assunção, Luís Lencastre, Pedro Cavaleiro, Mohamed Abdelaty, Alex Gritsan, Sergey Khomiakov Sergey, Dovbysh Nikolay, Yaseen Arabi, Primoz Gradisek, Petra Forjan, Mara Škoti, Suada Filekovic Ribaric, Primoz Gradisek, Nataša Milivojevic, Sergeja Kozar, Rafael Badenes, Aaron Blandino Ortiz, Mikel Celaya Lopez, Laura Galarza, Luisa Corral, Africa Lores, Ricard Soley, Laura Pariente, Pablo López Ojeda, Maria Dolores Arias Verdu, Luis Javier Yuste Dominguez, Maria Isabel Gonzalez Perez, Mireia Anglada, Patricia Duque, Ainhoa Serrano, Berta Monleon, Vanessa Blazquez, Mauro Oddo, Samia Abed Maillard, Paola Morelli, John-Paul Miroz, Eva Favre, Walid Sellami, Massimo Lamperti, Jamil Dibu, Richard Sivities, Angelos Kolias, Chris Thompson, Christopher Hawthorne, Justin Roberts, Lara Prisco, Roger Lightfoot, Josè I Suarez, Luci Rivera-Lara, Susanne Muehlschlegel, Juan Padilla, Sanjeev Sivakumar, Daiwai Olson

Subjects
Subarachnoid haemorrhage, Traumatic brain injury, Intracranial pressure, Therapy intensity level, Critical Care and Intensive Care Medicine, Intracranial haemorrhage
Abstract

Purpose: Uncertainties remain about the safety and efficacy of therapies for managing intracranial hypertension in acute brain injured (ABI) patients. This study aims to describe the therapeutical approaches used in ABI, with/without intracranial pressure (ICP) monitoring, among different pathologies and across different countries, and their association with sixmonths mortality and neurological outcome. Methods: A preplanned subanalysis of the SYNAPSE-ICU study, a multicentre, prospective, international, observational cohort study, describing the ICP treatment, graded according to Therapy Intensity Level (TIL) scale, in patients with ABI during the first week of intensive care unit (ICU) admission. Results: 2320 patients were included in the analysis. The median age was 55 (I-III quartiles = 39-69) years, and 800 (34.5%) were female. During the first week from ICU admission, no-basic TIL was used in 382 (16.5%) patients, mild-moderate in 1643 (70.8%), and extreme in 295 cases (eTIL, 12.7%). Patients who received eTIL were younger (median age 49 (I-III quartiles = 35-62) vs 56 (40-69) years, p

Published
2023

2. Key Factors Associated With Pulmonary Sequelae in the Follow-Up of Critically Ill COVID-19 Patients

Author

Jessica González, Jordi de Batlle, Iván D. Benítez, Gerard Torres, Sally Santisteve, Adriano D.S. Targa, Clara Gort-Paniello, Anna Moncusí-Moix, Maria Aguilà, Fatty Seck, Adrián Ceccato, Ricard Ferrer, Anna Motos, Jordi Riera, Laia Fernández, Rosario Menéndez, José Ángel Lorente, Oscar Peñuelas, Dario Garcia-Gasulla, Yhivian Peñasco, Pilar Ricart, Elena Abril Palomares, Luciano Aguilera, Alejandro Rodríguez, Maria Victoria Boado Varela, Belén Beteré, Juan Carlos Pozo-Laderas, Jordi Solé-Violan, Inmaculada Salvador-Adell, Mariana Andrea Novo, José Barberán, Rosario Amaya Villar, José Garnacho-Montero, José M. Gómez, Aaron Blandino Ortiz, Luis Tamayo Lomas, Alejandro Úbeda, Mercedes Catalán-González, Angel Sánchez-Miralles, Ignacio Martínez Varela, Ruth Noemí Jorge García, Nieves Franco, Víctor D. Gumucio-Sanguino, Elena Bustamante-Munguira, Luis Jorge Valdivia, Jesús Caballero, Elena Gallego, Covadonga Rodríguez, Álvaro Castellanos-Ortega, Josep Trenado, Judith Marin-Corral, Guillermo M. Albaiceta, Maria del Carmen de la Torre, Ana Loza-Vázquez, Pablo Vidal, Jose M. Añón, Cristina Carbajales Pérez, Victor Sagredo, Nieves Carbonell, Lorenzo Socias, Carme Barberà, Angel Estella, Emili Diaz, David de Gonzalo-Calvo, Antoni Torres, Ferran Barbé, María Aguilar Cabello, Victoria Alcaraz-Serrano, Cesar Aldecoa, Cynthia Alegre, Ángela Algaba Calderón, Sergio Álvarez, Antonio Álvarez Ruiz, Ruth Andrea, Maria de Alba Aparicio, Marta Arrieta, J. Ignacio Ayestarán, Joan Ramon Badia, Mariona Badía, Orville Báez Pravia, Ana Balan Mariño, Begoña Balsera, Laura Barbena, Enric Barbeta, Tommaso Bardi, Patricia Barral Segade, Marta Barroso, José Ángel Berezo García, Jesus Bermejo, Judit Bigas, Rafael Blancas, María Luisa Blasco Cortés, María Bodi Saera, Neus Bofill, María Teresa Bouza Vieiro, Leticia Bueno, Juan Bustamante-Munguira, Cecilia del Busto Martínez, David Campi Hermoso, Sandra Campos Fernández, Iosune Cano, Joan Canseco, Pablo Cardinal Fernández, Laura Carrión García, Sulamita Carvalho, Manuel Castellà, Andrea Castellví, Pedro Castro, María José Centelles-Serrano, Ramon Cicuendez Ávila, Catia Cillóniz, Luisa Clar, Cristina Climent, Jordi Codina, Pamela Conde, Sofía Contreras, Raul de Frutos Parra, Raul de Pablo Sánchez, Diego De Mendoza, Yolanda Díaz, María Digna Rivas Vilas, Cristina Dólera Moreno, Irene Dot, Pedro Enríquez Giraudo, Inés Esmorís Arijón, Teresa Farre Monjo, Javier Fernández, Carlos Ferrando, Albert Figueras, Lorena Forcelledo Espina, Enric Franquesa, Àngels Furro, Albert Gabarrus, Cristóbal Galbán, Felipe García, Beatriz García, Emilio García Prieto, Carlos García Redruello, Amaia García Sagastume, Maria Luisa Gascón Castillo, Gemma Gomà, Vanesa Gómez Casal, Silvia Gómez, Carmen Gómez Gonzalez, Federico Gordo, Maria Pilar Gracia, María José Gutierrez Fernández, Alba Herraiz, Rubén Herrán-Monge, Mercedes Ibarz, Silvia Iglesias, Maria Teresa Janer, Gabriel Jiménez, Mar Juan Díaz, Karsa Kiarostami, Juan I. Lazo Álvarez, Miguel León, Alexandre López-Gavín, Desiree Macias Guerrero, Nuria Mamolar Herrera, Rafael Mañez Mendiluce, Cecilia L. Mantellini, Gregorio Marco Naya, Iris Marco Barcos, Pilar Marcos, Enrique Marmol Peis, Marta Martín Cuadrado, María Cruz Martin Delgado, Paula Martín Vicente, María Martínez, Carmen Eulalia Martínez Fernández, Maria Dolores Martínez Juan, Basilisa Martínez Palacios, Juan Fernando Masa Jimenez, Joan Ramon Masclans, Emilio Maseda, Eva María Menor Fernández, Priscila Metora Banderas, Olga Minguez, Mar Miralbés, Josman Monclou, Juan Carlos Montejo-González, Neus Montserrat, María Mora Aznar, Dulce Morales, Sara Guadalupe Moreno Cano, David Mosquera Rodríguez, Rosana Muñoz-Bermúdez, José María Nicolás, Ramon Nogue Bou, Rafaela Nogueras Salinas, Marta Ocón, Ana Ortega, Sergio Ossa, Pablo Pagliarani, Francisco Parrilla, José Pedregosa-Díaz, Leire Pérez Bastida, Purificación Pérez, Felipe Pérez-García, Gloria Pérez Planelles, Eva Pérez Rubio, David Pestaña Laguna, Javier Prados, Andrés Pujol, Núria Ramon Coll, Gloria Renedo Sanchez-Giron, Ferran Roche-Campo, Laura Rodriguez, Felipe Rodríguez de Castro, Silvia Rodríguez, Covadonga Rodríguez Ruiz, Jorge Rubio, Alberto Rubio López, Ángela Leonor Ruiz-García, Miriam Ruiz Miralles, Pablo Ryan Murúa, Eva Saborido Paz, Ana Salazar Degracia, Miguel Sanchez, Ana Sánchez, Susana Sancho Chinesta, Bitor Santacoloma, Maria Teresa Sariñena, Marta Segura Pensado, Lidia Serra, Mireia Serra-Fortuny, Ainhoa Serrano Lázaro, Lluís Servià, Laura Soliva, Carla Speziale, Adrián Tormos, Mateu Torres, Celia Tranque-Liberal, Sandra Trefler, Javier Trujillano, Rafaela Vaca, Estela Val, Luis Valdivia Ruiz, Montserrat Vallverdú, Maria Van der Hofstadt Martin-Montalvo, Sabela Vara Adrio, Nil Vázquez, Javier Vengoechea, Clara Vilà-Vilardel, Judit Vilanova, Tatiana Villada Warrington, Hua Yang, Minlan Yang, and Ana Zapatero

Subjects
Pulmonary and Respiratory Medicine
Published
2023

3. Abstract P6-10-09: Mutational landscape of breast cancer patients in ROME trial: preliminary results

Author

Andrea Botticelli, Simone Scagnoli, Pierfranco Conte, Chiara Cremolini, Paolo Antonio Ascierto, Federico Cappuzzo, Massimo Aglietta, Federica Mazzuca, Ettore Capoluongo, Giovanni Blandino, Umberto Malapelle, Marianna Nuti, Giulia D’Amati, Bruna Cerbelli, Giancarlo Pruneri, Mauro Biffoni, Giuseppe Giannini, Francesco Cognetti, Giuseppe Curigliano, and Paolo Marchetti

Subjects
Cancer Research, Oncology
Abstract

BACKGROUND: The Rome Trial is a randomized phase II trial (NCT04591431). The aim is to evaluate efficacy and safety of a tailored treatment (TT) compared to standard of care (SoC) in patients with solid tumors. Here we report the preliminary results of the molecular alterations, microsatellite status (MS) and tumor mutational burden (TMB) in metastatic breast cancer (mBC) cohort. METHODS: MBC patients who received at least 1 and no more than 2 systemic treatments were enrolled. Tissue samples were collected within 6 months from the screening. Centralized Next Generation Sequencing (NGS) was performed on both tissue and liquid biopsy. Molecular alterations were evaluated by the Molecular Tumor Board (MTB) using COSMIC, ClinVar, OncoKB and VarSome datasets. Genes with at least 10% frequency of mutation, MS and TMB are reported. RESULTS: From Oct 2020 to June 2022, 980 pts with solid tumors were enrolled. Complete screening mutational data are available for sixty-two pts from the mBC cohort (63% HR+/HER2-, 35% triple negative, 2% HR-/HER2+). NGS was available both on tissue and liquid biopsy in 48 (77%) pts, 14 had only liquid biopsy available due to tissue test failure. 328 genes resulted altered with a median of 7 alteration per pts (0-31). Some pathways were frequently altered: PIK3CA/AKT/MTOR (60%), TP53 (60%), Cell cycle/cycline (35%), FGF/FGFR (26%), BRCA1/2 (17%). The most frequent altered genes were: TP53 (61%), PIK3CA (50%), ESR1 (27%), CCND1 (27%), FGF19 (24%), FGF3 (24%), FGF4 (22%), MYC (22%), FGFR1 (21%), PTEN (21%), EMSY (16%), RB1 (14%), RAD21 (14%), TET2 (13%), BRCA2 (11%), GATA3 (11%), KRAS (10%). No pts with MSI status were reported. Eight (13%) had a high TMB (>10) and the overall median TMB was 5.5 (0-24). Median TMB was similar in tissue and liquid samples (5 and 5.3 mut/mb, p= 0.8). Actionable mutations were detected in 34 pts (54%). Twenty-eight (45%) pts were assigned to a specific TT after the MTB discussion: ipatasertib (16), pemigatinib (5), ipilimumab plus nivolumab (4), lapatinib plus trastuzumab, TDM1 and everolimus (1). MTB requested a germline test for 6 pts: 4 were confirmed (66%; 2 BRCA, 1 PALB2, 1 BRIP1). CONCLUSIONS: The extensive NGS analysis performed in the ROME trial shown that several pathways are commonly mutated in mBC, with target drug potentially available. About 15% of pts had a high TMB but MSI is confirmed as a rare event in breast cancer. Germline mutations have been identified in patients with no prior indication for germline testing. Citation Format: Andrea Botticelli, Simone Scagnoli, Pierfranco Conte, Chiara Cremolini, Paolo Antonio Ascierto, Federico Cappuzzo, Massimo Aglietta, Federica Mazzuca, Ettore Capoluongo, Giovanni Blandino, Umberto Malapelle, Marianna Nuti, Giulia D’Amati, Bruna Cerbelli, Giancarlo Pruneri, Mauro Biffoni, Giuseppe Giannini, Francesco Cognetti, Giuseppe Curigliano, Paolo Marchetti. Mutational landscape of breast cancer patients in ROME trial: preliminary results [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-10-09.

Published
2023

5. Millimeter Wave and Free-space-optics for Future Dual-connectivity 6DOF Mobile Multi-user VR Streaming

Author

Jacob Chakareski, Mahmudur Khan, Tanguy Ropitault, and Steve Blandino

Subjects
Computer Networks and Communications, Hardware and Architecture
Abstract

Dual-connectivity streaming is a key enabler of next-generation six Degrees Of Freedom (6DOF) Virtual Reality (VR) scene immersion. Indeed, using conventional sub-6 GHz WiFi only allows to reliably stream a low-quality baseline representation of the VR content, while emerging high-frequency communication technologies allow to stream in parallel a high-quality user viewport-specific enhancement representation that synergistically integrates with the baseline representation to deliver high-quality VR immersion. We investigate holistically as part of an entire future VR streaming system two such candidate emerging technologies, Free Space Optics (FSO) and millimeter-Wave (mmWave), that benefit from a large available spectrum to deliver unprecedented data rates. We analytically characterize the key components of the envisioned dual-connectivity 6DOF VR streaming system that integrates in addition edge computing and scalable 360° video tiling, and we formulate an optimization problem to maximize the immersion fidelity delivered by the system, given the WiFi and mmWave/FSO link rates, and the computing capabilities of the edge server and the users’ VR headsets. This optimization problem is mixed integer programming of high complexity and we formulate a geometric programming framework to compute the optimal solution at low complexity. We carry out simulation experiments to assess the performance of the proposed system using actual 6DOF navigation traces from multiple mobile VR users that we collected. Our results demonstrate that our system considerably advances the traditional state of the art and enables streaming of 8K-120 frames-per-second (fps) 6DOF content at high fidelity.

Published
2023

6. Valorisation of the invasive alga Rugulopteryx okamurae through the production of monomeric sugars

Author

Cristina Agabo-García, Luis I. Romero-García, Carlos J. Álvarez-Gallego, and Ana Blandino

Subjects
General Medicine, Applied Microbiology and Biotechnology, Biotechnology
Abstract

Abstract Rugulopteryx okamurae is an invasive brown alga causing severe environmental and economic problems on the western Mediterranean coasts. Thus, in addition to the difficulties caused to the fishing and tourism sectors, there is a need to manage its accumulation on the beaches. This work aims to valorise this waste by using it as raw material for producing monosaccharides through a two-stage sequential process. These sugars could be used for different fermentative processes to obtain high-value-added bioproducts. In this work, biological pretreatment of the previously conditioned seaweed with the fungus Aspergillus awamori in solid-state fermentation (SSF), followed by enzymatic hydrolysis with a commercial enzyme cocktail, was performed. The effect of the extension of the biological pretreatment (2, 5, 8 and 12 days) on the subsequent release of total reducing sugars (TRS) in the enzymatic hydrolysis stage was studied. To analyse this effect, experimental data of TRS produced along the hydrolysis were fitted to simple first-order kinetics. Also, the secretion of cellulase and alginate lyase by the fungus, along with the biological pretreatment, was determined. The results suggest that 5 days of biological pretreatment of the macroalgae with A. awamori followed by enzymatic saccharification for 24 h with Cellic CTec2® (112 FP units/g of dry biomass) are the best conditions tested, allowing the production of around 240 g of TRS per kg of dried biomass. The main sugars obtained were glucose (95.8 %) and mannitol (1.5 %), followed by galactose (1 %), arabinose (0.9 %) and fucose (0.5 %). Key points • Five-day SSF by A. awamori was the best condition to pretreat R. okamurae. • Five-day SSF was optimal for alginate lyase production (1.63 ±0.011 IU/g biomass). • A maximum yield of 239 mg TRS/g biomass was obtained (with 95.8 % glucose). Graphical Abstract

Published
2023

7. Linac-based stereotactic salvage reirradiation for intraprostatic prostate cancer recurrence: toxicity and outcomes

Author

Salvatore Cozzi, Sebastiano Finocchi Ghersi, Lilia Bardoscia, Masoumeh Najafi, Gladys Blandino, Emanuele Alì, Matteo Augugliaro, Federica Vigo, Maria Paola Ruggieri, Raffaele Cardano, Lucia Giaccherini, Federico Iori, Andrea Botti, Valeria Trojani, Patrizia Ciammella, and Cinzia Iotti

Subjects
Oncology, Radiology, Nuclear Medicine and imaging
Abstract

Background The rates of local failure after curative radiotherapy for prostate cancer (PC) remain high despite more accurate locoregional treatments available, with one third of patients experiencing biochemical failure and clinical relapse occurring in 30–47% of cases. Today, androgen deprivation therapy (ADT) is the treatment of choice in this setting, but with not negligible toxicity and low effects on local disease. Therefore, the treatment of intraprostatic PC recurrence represents a challenge for radiation oncologists. Prostate reirradiation (Re-I) might be a therapeutic possibility. We present our series of patients treated with salvage stereotactic Re‑I for intraprostatic recurrence of PC after radical radiotherapy, with the aim of evaluating feasibility and safety of linac-based prostate Re‑I. Materials and methods We retrospectively evaluated toxicities and outcomes of patients who underwent salvage reirradiation using volumetric modulated arc therapy (VMAT) for intraprostatic PC recurrence. Inclusion criteria were age ≥ 18 years, histologically proven diagnosis of PC, salvage Re‑I for intraprostatic recurrence after primary radiotherapy for PC with curative intent, concurrent/adjuvant ADT with stereotactic body radiation therapy (SBRT) allowed, performance status ECOG 0–2, restaging choline/PSMA-PET/TC and prostate MRI after biochemical recurrence, and signed informed consent. Results From January 2019 to April 2022, 20 patients were recruited. Median follow-up was 26.7 months (range 7–50). After SBRT, no patients were lost at follow-up and all are still alive. One- and 2‑year progression free survival (PFS) was 100% and 81.5%, respectively, while 2‑year biochemical progression-free survival (bFFS) was 88.9%. Four patients (20%) experienced locoregional lymph node progression and were treated with a further course of SBRT. Prostate reirradiation allowed the ADT start to be postponed for 12–39 months. Re‑I was well tolerated by all patients and none discontinued the treatment. No cases of ≥ G3 genitourinary (GU) or gastrointestinal (GI) toxicity were reported. Seven (35%) and 2 (10%) patients experienced acute G1 and G2 GU toxicity, respectively. Late GU toxicity was recorded in 10 (50%) patients, including 8 (40%) G1 and 2 (10%) G2. ADT-related side effects were found in 7 patients (hot flashes and asthenia). Conclusion Linac-based SBRT is a safe technique for performing Re‑I for intraprostatic recurrence after primary curative radiotherapy for PC. Future prospective, randomized studies are desirable to better understand the effectiveness of reirradiation and the still open questions in this field.

Published
2023

8. Comparative outcomes of extracorporeal membrane oxygenation for COVID-19 delivered in experienced European centres during successive SARS-CoV-2 variant outbreaks (ECMO-SURGES): an international, multicentre, retrospective cohort study

Author

Matthieu Schmidt, David Hajage, Micha Landoll, Benjamin Pequignot, Elise Langouet, Matthieu Amalric, Armand Mekontso-Dessap, Luis Chiscano-Camon, Katy Surman, Dylan Finnerty, Patricia Santa-Teresa, Antonio Arcadipane, Pablo Millán, Roberto Roncon-Albuquerque, Aaron Blandino-Ortiz, Pablo Blanco-Schweizer, Pilar Ricart, Ricardo Gimeno-Costa, Carlos Luis Albacete, Philip Fortuna, Peter Schellongowski, Dieter Dauwe, Hadrien Winiszewski, Antoine Kimmoun, Bruno Levy, Greet Hermans, Giacomo Grasselli, Guillaume Lebreton, Christophe Guervilly, Gennaro Martucci, Christian Karagiannidis, Jordi Riera, Alain Combes, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de cardiologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre d'investigation clinique Paris Est [CHU Pitié Salpêtrière] (CIC Paris-Est), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Pharmacoépidémiologie et évaluation des soins [iPLesp] (PEPITES), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Sorbonne Université (SU), Universität Witten Herdecke, Rheinisch-Westfälische Technische Hochschule Aachen University (RWTH), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), CHU Marseille, IMRB - 'Biomechanics and Respiratory Apparatus' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Henri Mondor, Groupe de recherche clinique CARMAS (Cardiovascular and Respiratory Manifestations of Acute lung injury and Sepsis) (CARMAS), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-CHU Henri Mondor [Créteil], Vall d'Hebron University Hospital [Barcelona], Royal Papworth Hospital [Cambridge, UK] (RPH), Hospital General Universitario 'Gregorio Marañón' [Madrid], Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione (ISMETT), Universidad Loyola Andalucía = Loyola University Andalucía, Hospital de São João [Porto], Hospital Universitario Ramón y Cajal [Madrid], Universidad de Alcalá - University of Alcalá (UAH), Rio Hortega University Hospital (Hospital Universitario Río Hortega) [Valladolid, Spain] (RHUH), Germans Trias i Pujol University Hospital [Badalona, Barcelona, Spain] (GTPUH), Hospital Universitari i Politècnic La Fe = University and Polytechnic Hospital La Fe, Hospital Clínico Universitario Virgen de la Arrixaca = University Hospital Virgen de la Arrixaca [Murcia], Centro Hospitalar de Lisboa Central E.P.E, Medizinische Universität Wien = Medical University of Vienna, University Hospitals Leuven [Leuven], Service d'anesthésie et soins intensifs [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( UR 3920) (PCVP / CARDIO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), and Vall d’Hebron Research Institute (VHIR)

Subjects
Pulmonary and Respiratory Medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases
Abstract

International audience

Published
2023

9. In-hospital and 6-month outcomes in patients with COVID-19 supported with extracorporeal membrane oxygenation (EuroECMO-COVID): a multicentre, prospective observational study

Author

Roberto Lorusso, Maria Elena De Piero, Silvia Mariani, Michele Di Mauro, Thierry Folliguet, Fabio Silvio Taccone, Luigi Camporota, Justyna Swol, Dominik Wiedemann, Mirko Belliato, Lars Mikael Broman, Alain Vuylsteke, Yigal Kassif, Anna Mara Scandroglio, Vito Fanelli, Philippe Gaudard, Stephane Ledot, Julian Barker, Udo Boeken, Sven Maier, Alexander Kersten, Bart Meyns, Matteo Pozzi, Finn M Pedersen, Peter Schellongowski, Kaan Kirali, Nicholas Barrett, Jordi Riera, Thomas Mueller, Jan Belohlavek, Valeria Lo Coco, Iwan C C Van der Horst, Bas C T Van Bussel, Ronny M Schnabel, Thijs Delnoij, Gil Bolotin, Luca Lorini, Martin O Schmiady, David Schibilsky, Mariusz Kowalewski, Luis F Pinto, Pedro E Silva, Igor Kornilov, Aaron Blandino Ortiz, Leen Vercaemst, Simon Finney, Peter P Roeleveld, Matteo Di Nardo, Felix Hennig, Marta Velia Antonini, Mark Davidson, Tim J Jones, Thomas Staudinger, Peter Mair, Juliane Kilo, Christoph Krapf, Kathrin Erbert, Andreas Peer, Nikolaos Bonaros, Florian Kotheletner, Niklas Krenner Mag, Liana Shestakova, Greet Hermans, Dieter Dauwe, Philippe Meersseman, Bernard Stockman, Leda Nobile, Olivier Lhereux, Alexandre Nrasseurs, Jacques Creuter, Daniel De Backer, Simone Giglioli, Gregoire Michiels, Pierre Foulon, Matthias Raes, Inez Rodrigus, Matthias Allegaert, Philippe Jorens, Gerd Debeucklare, Michael Piagnerelli, Patrick Biston, Harlinde Peperstraete, Komeel Vandewiele, Olivier Germay, Dimitri Vandeweghe, Sven Havrin, Marc Bourgeois, Marc-Gilbert Lagny, Genette Alois, Nathalie Lavios, Benoit Misset, Romain Courcelle, Philippe J Timmermans, Alaaddin Yilmaz, Michiel Vantomout, Jerone Lehaen, Ame Jassen, Herbert Guterman, Maarten Strauven, Piet Lormans, Bruno Verhamme, catherine Vandewaeter, Frederik Bonte, Dominique Vionne, Martin Balik, Jan Blàha, Michal Lips, Michal Othal, Filip Bursa, Radim Spacek, Steffen Christensen, Vibeke Jorgensen, Marc Sorensen, Soren A Madsen, Severin Puss, Aleksandr Beljantsev, gabriel Saiydoun, Antonio Fiore, Pascal Colson, Florian Bazalgette, Xavier Capdevila, Sebastien Kollen, Laurent Muller, Jean-Francois Obadia, Pierre-Yves Dubien, Lucrezia Ajrhourh, Pierre G Guinot, Jonathan Zarka, Patricia Besserve, Maximilian V Malfertheiner, Esther Dreier, Birgit Heinze, Payam Akhyari, Artur Lichtenberg, Hug Aubin, Alexander Assman, Diyar Saeed, Holger Thiele, Matthias Baumgaertel, Jan D Schmitto, Natanov Ruslan, Axel Haverich, Matthias Thielmann, Thorsten Brenner, Arjang Ruhpawar, Christoph Benk, Martin Czerny, Dawid L Staudacher, Fridhelm Beyersdorf, Johannes Kalbhenn, Philipp Henn, Aron-Frederik Popov, Torje Iuliu, Ralf Muellenbach, Christian Reyher, Caroline Rolfes, Gosta Lotz, Michael Sonntagbauer, Helen Winkels, Julia Fichte, Robert Stohr, Sebastian Kalverkamp, Christian Karagiannidis, Simone Schafer, Alexei Svetlitchny, Hans-Bernd Hopf, Dominik Jarczak, Heinirich Groesdonk, Magdalena Rommer, Jan Hirsch, Christian Kaehny, Dimitros Soufleris, Georgios Gavriilidis, Kostantinos Pontikis, Magdalini Kyriakopoulou, Anna Kyriakoudi, Serena O'Brien, Ian Conrick-Martin, Edmund Carton, Maged Makhoul, Josef Ben-Ari, Amir Hadash, Alexander Kogan, Reut Kassif Lerner, Anas Abu-Shakra, Moshe Matan, Ahmad Balawona, Erez Kachel, Roman Altshuler, Ori Galante, Lior Fuchs, Yaniv Almog, Yaron S Ishay, Yael Lichter, Amir Gal-oz, Uri Carmi, Asaph Nini, Arie Soroksky, Hagi Dekel, Ziv Rozman, Emad Tayem, Eduard Ilgiyaev, Yuval Hochman, daniel Miltau, Avigal Rapoport, Arieh Eden, Dmitry Kompanietz, Michael Yousif, Miri Golos, Lorenzo Grazioli, Davide Ghitti, Antonio Loforte, Daniela Di Luca, Massimo Baiocchi, Davide Pacini, Antioco Cappai, Paolo Meani, Michele Mondino, Claudio F Russo, Marco Ranucci, Dario Fina, Marco Cotza, Andrea Ballotta, Giovanni Landoni, Pasquale Nardelli, Eygeny V Fominski, Luca Brazzi, Giorgia Montrucchio, Gabriele Sales, Umberto Simonetti, Sergio Livigni, Daniela Silengo, Giulia Arena, Stefania S Sovatzis, Antonella Degani, Mariachiara Riccardi, Elisa Milanesi, Giuseppe Raffa, Gennaro Martucci, Antonio Arcadipane, Giovanna Panarello, Giovanni Chiarini, Sergio Cattaneo, Carmine Puglia, Stefano Benussi, Giuseppe Foti, Marco Giani, Michela Bombino, Maria Cristina Costa, Roberto Rona, Leonello Avalli, Abele Donati, Roberto Carozza, Francesco Gasparri, Andrea Carsetti, Marco Picichè, Anna Marinello, Vinicio Danzi, Anita Zanin, Ignazio Condello, Flavio Fiore, Marco Moscarelli, Giuseppe Nasso, Giuseppe Speziale, Luca Sandrelli, Andrea Montalto, Francesco Musumeci, Alessandro Circelli, Emanuele Russo, Vanni Agnoletti, Ruggero Rociola, Aldo D Milano, Emanuele Pilato, Giuseppe Comentale, Andrea Montisci, Francesco Alessandri, Antonella Tosi, Francesco Pugliese, Giovanni Giordano, Simone Carelli, Domenico L Grieco, Antonio M Dell'Anna, Massimo Antonelli, Enrico Ramoni, Josè Zulueta, Mauro Del Giglio, Sebastiano Petracca, Pietro Bertini, Fabio Guarracino, Luigi De Simone, Paolo M Angeletti, Francesco Forfori, Francesco Taraschi, Veronica N Quintiliani, Robertas Samalavicius, Agne Jankuviene, Nadezda Scupakova, Karolis Urbonas, Juozas Kapturauskas, Gro Soerensen, Piotr Suwalski, Luis Linhares Santos, Ana Marques, Marisa Miranda, Sonia Teixeira, Andrea Salgueiro, Filipe Pereira, Michail Ketskalo, Sergey Tsarenko, Alexandra Shilova, Ivan Afukov, Konstantin Popugaev, Sergei Minin, Daniil Shelukhin, Olga Malceva, Moroz Gleb, Alexander Skopets, Roman Kornelyuk, Alexandr Kulikov, Vadim Okhrimchuk, Alexandr Turchaninov, Maxim Petrushin, Anastasia Sheck, Akhmed Mekulov, Svetlana Ciryateva, Dmitry Urusov, Vojka Gorjup, Alenka Golicnik, Tomaz Goslar, Ricard Ferrer, Maria Martinez-Martinez, Eduard Argudo, Neiser Palmer, Raul De Pablo Sanchez, Lucas Juan Higuera, Lucas Arnau Blasco, Josè A Marquez, Fabrizio Sbraga, Mari Paz Fuset, Pablo Ruiz De Gopegui, Luis M Claraco, Josè A De Ayala, Maranta Peiro, Pilar Ricart, Sergio Martinez, Fernando Chavez, Marc Fabra, elena Sandoval, David Toapanta, Albert Carraminana, Adrian Tellez, Jeysson Ososio, Pablo Milan, Jorge Rodriguez, Garcia Andoni, Carola Gutierrez, Enrique Perez de la Sota, Andrea Eixeres-Esteve, Maria Teresa Garcia-Maellas, Judit Gutierrez-Gutierrez, Rafael Arboleda-Salazar, Patricia Santa Teresa, Alexis Jaspe, Alberto Garrido, Galo Castaneda, Sara Alcantara, Nuria Martinez, Marina Perez, Hector Villanueva, Anxela Vidal Gonzalez, Juan Paez, Arnoldo Santon, Cesar Perez, Marta Lopez, Maria Isabel Rubio Lopez, Antonio Gordillo, Jose Naranjo-Izurieta, Javier Munoz, Immaculada Alcalde, Fernando Onieva, Ricardo Gimeno Costa, Francisco Perez, Isabel Madrid, Monica Gordon, Carlos L Albacete Moreno, Daniel Perez, Nayara Lopez, Domingo Martinenz, Pablo Blanco-Schweizer, Cristina Diez, David Perez, Ana Prieto, Gloria Renedo, Elena Bustamante, Ramon Cicuendez, Rafael Citores, Victoria Boado, Katherine Garcia, Roberto Voces, Monica Domezain, Jose Maria Nunez Martinez, Raimundo Vicente, David Martin, Antonio Andreu, Vanesa Gomez Casal, Ignacio Chico, Eva Maria Menor, Sabela Vara, Jose Gamacho, Helen Perez-Chomon, Francisco Javier Gonzales, Irene Barrero, Luis Martin-Villen, Esperanza Fernandez, Maria Mendoza, Joaquin Navarro, Joaquin Colomina Climent, Alfredo Gonzales-Perez, Guillermo Muniz-Albaceita, Laura Amado, Raquel Rodriguez, Emilio Ruiz, Maria Eiras, Edgars Grins, Rosen Magnus, Mikael Kanetoft, Marcus Eidevald, Pia Watson, Paul R Vogt, Peter Steiger, Tobias Aigner, Alberto Weber, Jurg Grunefelder, Martin Kunz, Martin Grapow, Thierry Aymard, Diana Reser, Gianluca Agus, Jolanda Consiglio, Matthias Haenggi, Jenni Hansjoerg, Manuela Iten, Thomas Doeble, Urs Zenklusen, Xavier Bechtold, Giovanni Faedda, Manuel Iafrate, Amanda Rohjer, Layla Bergamaschi, Jos Maessen, Dinis Reis Miranda, H Endeman, D Gommers, C Meuwese, Jacinta Maas, MJ Van Gijlswijk, RN Van Berg, Dario Candura, Marcel Van der Linden, Merijin Kant, JJ Van der Heijden, Eric Scholten, Nicole Van Belle-van Haren, WK Lagrand, Alexander P Vlaar, Syste De Jong, Basar Cander, Murat Sargin, Murat Ugur, Mehmet A Kaygin, Kathleen Daly, Nicola Agnew, Laura Head, Laura Kelly, Gunawardena Anoma, Clare Russell, Verna Aquino, Ian Scott, Lucy Flemming, Stuart Gillon, Olivia Moore, Elton Gelandt, George Auzinger, Sameer Patel, Robert Loveridge, MUMC+: MA Cardiothoracale Chirurgie (3), CTC, RS: Carim - V04 Surgical intervention, University of Zurich, and Lorusso, Roberto

Subjects
Pulmonary and Respiratory Medicine, 2740 Pulmonary and Respiratory Medicine, 610 Medicine & health, 10023 Institute of Intensive Care Medicine
Abstract

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has been widely used in patients with COVID-19, but uncertainty remains about the determinants of in-hospital mortality and data on post-discharge outcomes are scarce. The aims of this study were to investigate the variables associated with in-hospital outcomes in patients who received ECMO during the first wave of COVID-19 and to describe the status of patients 6 months after ECMO initiation.METHODS: EuroECMO-COVID is a prospective, multicentre, observational study developed by the European Extracorporeal Life Support Organization. This study was based on data from patients aged 16 years or older who received ECMO support for refractory COVID-19 during the first wave of the pandemic-from March 1 to Sept 13, 2020-at 133 centres in 21 countries. In-hospital mortality and mortality 6 months after ECMO initiation were the primary outcomes. Mixed-Cox proportional hazards models were used to investigate associations between patient and management-related variables (eg, patient demographics, comorbidities, pre-ECMO status, and ECMO characteristics and complications) and in-hospital deaths. Survival status at 6 months was established through patient contact or institutional charts review. This study is registered with ClinicalTrials.gov, NCT04366921, and is ongoing.FINDINGS: Between March 1 and Sept 13, 2020, 1215 patients (942 [78%] men and 267 [22%] women; median age 53 years [IQR 46-60]) were included in the study. Median ECMO duration was 15 days (IQR 8-27). 602 (50%) of 1215 patients died in hospital, and 852 (74%) patients had at least one complication. Multiorgan failure was the leading cause of death (192 [36%] of 528 patients who died with available data). In mixed-Cox analyses, age of 60 years or older, use of inotropes and vasopressors before ECMO initiation, chronic renal failure, and time from intubation to ECMO initiation of 4 days or more were associated with higher in-hospital mortality. 613 patients did not die in hospital, and 547 (95%) of 577 patients for whom data were available were alive at 6 months. 102 (24%) of 431 patients had returned to full-time work at 6 months, and 57 (13%) of 428 patients had returned to part-time work. At 6 months, respiratory rehabilitation was required in 88 (17%) of 522 patients with available data, and the most common residual symptoms included dyspnoea (185 [35%] of 523 patients) and cardiac (52 [10%] of 514 patients) or neurocognitive (66 [13%] of 512 patients) symptoms.INTERPRETATION: Patient's age, timing of cannulation (FUNDING: None.

Published
2023

12. Modulating Long Term Memory at Late-Encoding Phase: An rTMS Study

Author

Luca Cuffaro, Tommaso Piccoli, Giuseppe Giglia, Fabio Aleo, Pierangelo Sardo, Giuseppe Ferraro, Filippo Brighina, Massimo Gangitano, Giuditta Gambino, Valeria Blandino, Giglia, G, Gambino, G, Cuffaro, L, Aleo, F, Sardo, P, Ferraro, G, Blandino, V, Brighina, F, Gangitano, M, Piccoli, T, Giglia Giuseppe, Gambino Giuditta, Cuffaro Luca, Aleo Fabio, Sardo Pierangelo, Ferraro Giuseppe, Blandino Valeria, Brighina Filippo, Gangitano Massimo, and Piccoli T

Subjects
Memory, Long-Term, Explicit memory, Long term memory, Phase (waves), Prefrontal Cortex, Stimulation, DLPFC, Settore BIO/09 - Fisiologia, Dorsolateral Prefrontal Cortex, Encoding (memory), rTMS, Reaction Time, medicine, Humans, Radiology, Nuclear Medicine and imaging, Radiological and Ultrasound Technology, business.industry, Long-term memory, Neurophysiology, Transcranial Magnetic Stimulation, Dorsolateral prefrontal cortex, medicine.anatomical_structure, Neurology, Settore MED/26 - Neurologia, Neurology (clinical), Implicit memory, Anatomy, business, Neuroscience, psychological phenomena and processes
Abstract

Despite a huge effort of the scientific community, the functioning of Long-Term Memory (LTM) processes is still debated and far from being elucidated. Functional and neurophysiological data point to an involvement of Dorsolateral Prefrontal Cortex (DLPFC) in both encoding and retrieval phases. However, the recently proposed Explicit/Implicit Memory Encoding and Retrieval (EIMER) model proposes that LTM at the encoding phase consists of anatomically and chronologically different sub-phases. On this basis, we aimed to investigate the role of right DLPFC during a late-encoding phase by means of low-frequency rTMS. Thirty right-handed healthy subjects were divided into three experimental groups. Inhibitory rTMS was applied over right-DLPFC immediately after the encoding phase (Late-Encoding Group) or before recognition phase (Pre-Recognition Group), 24 h after, of an LTM task. Both groups also received sham stimulation during the non-target phase, while the third group (Sham Group) received only sham stimulation in both phases. The Late-Encoding Group collected a lower number of correct responses compared with Sham Group (p = 0.00), while Pre-Retrieval Group increased accuracy as compared to the Sham Group (p = 0.0). rTMS-inhibition of the right DLPFC seems able to interfere with LTM memory performances when delivered at a late stage of the encoding phase, with opposite effects at the pre-retrieval phase.

Published
2021

13. Cerebro-spinal fluid glucose and lactate concentrations changes in response to therapies in patIents with primary brain injury: the START-TRIP study

Author

Gouvêa Bogossian, Elisa, Taleb, Chahnez, Aspide, Raffaele, Badenes, Rafael, Battaglini, Denise, Bilotta, Federico, Blandino Ortiz, Aaron, Caricato, Anselmo, Castioni, Carlo Alberto, Citerio, Giuseppe, Ferraro, Gioconda, Martino, Costanza, Melchionda, Isabella, Montanaro, Federica, Monleon Lopez, Berta, Nato, Consolato Gianluca, Piagnerelli, Michael, Picetti, Edoardo, Robba, Chiara, Simonet, Olivier, Thooft, Aurelie, Taccone, Fabio Silvio, Gouvêa Bogossian, E, Taleb, C, Aspide, R, Badenes, R, Battaglini, D, Bilotta, F, Blandino Ortiz, A, Caricato, A, Castioni, C, Citerio, G, Ferraro, G, Martino, C, Melchionda, I, Montanaro, F, Monleon Lopez, B, Nato, C, Piagnerelli, M, Picetti, E, Robba, C, Simonet, O, Thooft, A, and Taccone, F

Subjects
Cerebrospinal fluid, Glucose, Traumatic brain injury, Intracranial pressure, Acute brain injury, Lactate, Subarachnoid hemorrhage, Intracerebral hemorrhage, Critical Care and Intensive Care Medicine
Abstract

Introduction Altered levels of cerebrospinal fluid (CSF) glucose and lactate concentrations are associated with poor outcomes in acute brain injury patients. However, no data on changes in such metabolites consequently to therapeutic interventions are available. The aim of the study was to assess CSF glucose-to-lactate ratio (CGLR) changes related to therapies aimed at reducing intracranial pressure (ICP). Methods A multicentric prospective cohort study was conducted in 12 intensive care units (ICUs) from September 2017 to March 2022. Adult (> 18 years) patients admitted after an acute brain injury were included if an external ventricular drain (EVD) for intracranial pressure (ICP) monitoring was inserted within 24 h of admission. During the first 48–72 h from admission, CGLR was measured before and 2 h after any intervention aiming to reduce ICP (“intervention”). Patients with normal ICP were also sampled at the same time points and served as the “control” group. Results A total of 219 patients were included. In the intervention group (n = 115, 53%), ICP significantly decreased and CPP increased. After 2 h from the intervention, CGLR rose in both the intervention and control groups, although the magnitude was higher in the intervention than in the control group (20.2% vs 1.6%; p = 0.001). In a linear regression model adjusted for several confounders, therapies to manage ICP were independently associated with changes in CGLR. There was a weak inverse correlation between changes in ICP and CGRL in the intervention group. Conclusions In this study, CGLR significantly changed over time, regardless of the study group. However, these effects were more significant in those patients receiving interventions to reduce ICP.

Published
2023

14. Artificial intelligence, machine learning and deep learning in musculoskeletal imaging: Current applications

Author

Tommaso D'Angelo, Danilo Caudo, Alfredo Blandino, Moritz H. Albrecht, Thomas J. Vogl, Leon D. Gruenewald, Michele Gaeta, Ibrahim Yel, Vitali Koch, Simon S. Martin, Lukas Lenga, Giuseppe Muscogiuri, Sandro Sironi, Silvio Mazziotti, and Christian Booz

Subjects
Machine Learning, Deep Learning, Artificial Intelligence, Image Processing, Computer-Assisted, Humans, Radiology, Nuclear Medicine and imaging, Musculoskeletal System
Abstract

Artificial intelligence is rapidly expanding in all technological fields. The medical field, and especially diagnostic imaging, has been showing the highest developmental potential. Artificial intelligence aims at human intelligence simulation through the management of complex problems. This review describes the technical background of artificial intelligence, machine learning, and deep learning. The first section illustrates the general potential of artificial intelligence applications in the context of request management, data acquisition, image reconstruction, archiving, and communication systems. In the second section, the prospective of dedicated tools for segmentation, lesion detection, automatic diagnosis, and classification of musculoskeletal disorders is discussed.

Published
2022

17. Work-related and non-work-related fatal road accidents: Assessment of psychoactive substance use in commuting

Author

Alberto Blandino, Stefano Tambuzzi, Rosy Cotroneo, Domenico Di Candia, Alessio Battistini, Gaia Giordano, Umberto Genovese, and Riccardo Zoja

Subjects
Occupational accident, autopsy, driving under the influence, toxicology, traffic accident, Issues, ethics and legal aspects, Settore MED/43 - Medicina Legale, Health Policy, Law
Abstract

Commuting road traffic collisions (RTCs) are one of the main causes of occupational death worldwide, including Italy. Among the prominent yet relatively understudied personal risk factors in the subpopulation of workers, there is the use of psychoactive substances. Since the phenomenon of driving under alcohol and drugs effects in the commuter sub-population has so far been poorly studied, we carried out a study by comparing results obtained from the analysis of commuters and non-commuters. The percentage of commuting RTCs victims was 10.4% out of all the RTCs. Commuter victims were mostly men, 51–60 years-old, motorcyclists (32.1%) or car drivers (28.6%), employees, deceased during Fridays and Saturdays, in the afternoon (35.7%) and in the evening (32.1%). It was possible to perform toxicological analyses in 60.7% of commuter cases: approximately 40% tested positive, always and only for ethanol (median Blood Alcohol Concentration, BAC, of about 1.03 g/L). Values above the legal limit were observed in 23.5% of the toxicological samples analyzed from commuter accidents. Our findings contribute to bridging the gap in knowledge in the area of RTCs and commuting and emphasize the importance of carrying out toxicological investigations, with possible repercussions on both insurance issues and public health strategies, which are relevant for analyzing the phenomenon structurally.

Published
2022

18. Social Interactions Increase Activation of Vasopressin-Responsive Neurons in the Dorsal Raphe

Author

T N, Patel, H O, Caiola, O G, Mallari, K L, Blandino, A R, Goldenthal, S M, Dymecki, and B D, Rood

Subjects
Dorsal Raphe Nucleus, Male, Neurons, Mice, Serotonin, Vasopressins, General Neuroscience, Social Interaction, Animals, Humans, Female
Abstract

Social interactions play an important role in our daily lives and can profoundly impact our health for better and worse. To better understand the neural circuitry underlying social behavior, we focused on neural circuits involving vasopressin neurons of the bed nucleus of the stria terminalis (BNST) and serotonin neurons of the dorsal raphe (DR). Previous research shows that BNST vasopressin neurons are activated in male mice by interaction with a female and that vasopressin indirectly excites serotonin neurons. In our studies, we tested the hypothesis that specific social interactions would also activate neurons in the DR, specifically vasopressin 1A receptor (Avpr1a)-expressing neurons, which may be direct targets of the BNST vasopressin neurons. Using in separate experiments immunohistochemistry and in situ hybridization, we found that male and female subjects exposed to a female conspecific show activation in the DR, and the activated neurons include populations of Avpr1a-expressing and other non-serotonergic, non-Avpr1a neurons in roughly equal numbers. Avpr1a neurons in the DR constitute a largely undocumented neuron population. Electrophysiological data suggest that most DR Avpr1a neurons behave like fast spiking interneurons found in other brain regions. Examination of RNAseq and in situ hybridization data suggests that there are glutamatergic, GABAergic, and serotonergic subtypes of Avpr1a neurons in the DR. Together our data support a model in which a subset of vasopressin-responsive interneurons in the DR may relay stimulus specific social signals from the forebrain BNST to the serotonergic DR system, which could help direct prosocial stimulus specific behavioral responses.

Published
2022

19. Neurological Pupil Index and Delayed Cerebral Ischemia after Subarachnoid Hemorrhage: A Retrospective Multicentric Study

Author

Elisa Gouvêa Bogossian, Aaron Blandino Ortiz, Valentina Esposito, Anselmo Caricato, Cassia Righy Shinotsuka, Berta Monléon Lopez, Giuseppina Giannì, Elisabetta Macchini, Raúl de Pablo Sanchez, Luca Pisapia, Ricardo Turon, Bruno Gonçalves, Rafael Badenes, Pedro Kurtz, and Fabio Silvio Taccone

Subjects
Neurology (clinical), Critical Care and Intensive Care Medicine
Published
2023

22. Apoptotic cell death in disease-Current understanding of the NCCD 2023

Author

Vitale, Ilio, Pietrocola, Federico, Guilbaud, Emma, Aaronson, Stuart A, Abrams, John M, Adam, Dieter, Agostini, Massimiliano, Agostinis, Patrizia, Alnemri, Emad S, Altucci, Lucia, Amelio, Ivano, Andrews, David W, Aqeilan, Rami I, Arama, Eli, Baehrecke, Eric H, Balachandran, Siddharth, Bano, Daniele, Barlev, Nickolai A, Bartek, Jiri, Bazan, Nicolas G, Becker, Christoph, Bernassola, Francesca, Bertrand, Mathieu JM, Bianchi, Marco E, Blagosklonny, Mikhail V, Blander, J Magarian, Blandino, Giovanni, Blomgren, Klas, Borner, Christoph, Bortner, Carl D, Bove, Pierluigi, Boya, Patricia, Brenner, Catherine, Broz, Petr, Brunner, Thomas, Damgaard, Rune Busk, Calin, George A, Campanella, Michelangelo, Candi, Eleonora, Carbone, Michele, Carmona-Gutierrez, Didac, Cecconi, Francesco, Chan, Francis K-M, Chen, Guo-Qiang, Chen, Quan, Chen, Youhai H, Cheng, Emily H, Chipuk, Jerry E, Cidlowski, John A, Ciechanover, Aaron, Ciliberto, Gennaro, Conrad, Marcus, Cubillos-Ruiz, Juan R, Czabotar, Peter E, D'Angiolella, Vincenzo, Daugaard, Mads, Dawson, Ted M, Dawson, Valina L, De Maria, Ruggero, De Strooper, Bart, Debatin, Klaus-Michael, Deberardinis, Ralph J, Degterev, Alexei, Del Sal, Giannino, Deshmukh, Mohanish, Di Virgilio, Francesco, Diederich, Marc, Dixon, Scott J, Dynlacht, Brian D, El-Deiry, Wafik S, Elrod, John W, Engeland, Kurt, Fimia, Gian Maria, Galassi, Claudia, Ganini, Carlo, Garcia-Saez, Ana J, Garg, Abhishek D, Garrido, Carmen, Gavathiotis, Evripidis, Gerlic, Motti, Ghosh, Sourav, Green, Douglas R, Greene, Lloyd A, Gronemeyer, Hinrich, Häcker, Georg, Hajnóczky, György, Hardwick, J Marie, Haupt, Ygal, He, Sudan, Heery, David M, Hengartner, Michael O, Hetz, Claudio, Hildeman, David A, Ichijo, Hidenori, Inoue, Satoshi, Jäättelä, Marja, Janic, Ana, Joseph, Bertrand, Jost, Philipp J, and Kanneganti, Thirumala-Devi

Subjects
Mammals, Biochemistry & Molecular Biology, Cell Death, Carcinogenesis, Liver Disease, 1.1 Normal biological development and functioning, Apoptosis, Biological Sciences, Medical and Health Sciences, Good Health and Well Being, Underpinning research, Caspases, Animals, Humans, Generic health relevance, Digestive Diseases
Abstract

Apoptosis is a form of regulated cell death (RCD) that involves proteases of the caspase family. Pharmacological and genetic strategies that experimentally inhibit or delay apoptosis in mammalian systems have elucidated the key contribution of this process not only to (post-)embryonic development and adult tissue homeostasis, but also to the etiology of multiple human disorders. Consistent with this notion, while defects in the molecular machinery for apoptotic cell death impair organismal development and promote oncogenesis, the unwarranted activation of apoptosis promotes cell loss and tissue damage in the context of various neurological, cardiovascular, renal, hepatic, infectious, neoplastic and inflammatory conditions. Here, the Nomenclature Committee on Cell Death (NCCD) gathered to critically summarize anabundant pre-clinical literature mechanistically linking the core apoptotic apparatus to organismal homeostasis in the context of disease.

Published
2023

25. Covert Tracking to Visual Stimuli in Comatose Patients With Traumatic Brain Injury

Author

Ayham Alkhachroum, Gabriela Aklepi, Amin Sarafraz, Linda E Robayo, Brian M Manolovitz, Carolos F Blandino, Brian Arwari, Evie Sobczak, Danielle H Bass, Pardis Ghamasaee, Daniel Samano, Nina Massad, Mohan Kottapally, Amedeo Merenda, Salim Dib, Jonathan R Jagid, W. Dalton Dietrich, Tatjana Rundek, Kristine O'Phelan, Jan Claassen, and Mark F. Walker

Subjects
Neurology (clinical)
Published
2023

26. Mesenchymal stromal cell therapy for feline chronic gingivostomatitis: Long term experience

Author

Soltero-Rivera, Maria, Hart, Sterling, Blandino, Andrew, Vapniarsky, Natalia, and Arzi, Boaz

Subjects
General Veterinary
Abstract

IntroductionMesenchymal stromal cells (MSC) therapy has emerged as a potential treatment option for refractory FCGS. However, there is a lack of long-term data on the use of MSC therapy in cats. This study aimed to evaluate the long-term safety and efficacy of MSC therapy for FCGS and investigate potential factors associated with treatment outcomes.MethodsThis study was a retrospective evaluation of 38 client-owned cats with refractory FCGS who received MSC therapy. Medical records, histopathology, and the Stomatitis Activity Disease Index (SDAI) were reviewed. Correlations of the long-term follow-up success rates with SDAI and cell line type used were conducted. A client survey was also performed to assess side effect occurrence, quality-of-life following treatment, and overall treatment satisfaction.ResultsLong-term follow-up ranged from 2 to 9 years post-MSC treatment. The overall positive response rate to MSC treatment was 65.5%, with 58.6% of cats exhibiting permanent improvement or cure. Adverse effects occurring during or immediately after treatment were noted in 34.2% of cases, the majority being transient, self-resolving transfusion-like reactions. No long-term adverse events were noted. No significant correlation in outcome was detected between allogeneic and autologous MSC treatment (p = 0.871) or the severity of the SDAI at entry (p = 0.848) or exit (p = 0.166), or the delta SDAI between entry and exit (p = 0.178). The status 6 months (none to partial improvement vs. substantial improvement to resolution) post-therapy was a predictor of long-term response (value of p DiscussionThe results of this study support the use of both autologous and allogeneic MSC as an efficacious and safe therapeutic option for refractory FCGS.

Published
2023

27. Role of multiparametric magnetic resonance imaging and targeted biopsy in the detection of clinically significant prostate cancer in patients with abnormal digital rectal examination

Author

Gianluca Giannarini, Vincenzo Ficarra, Marta Rossanese, Alessandro Buttitta, Angela Alibrandi, Giuseppina Anastasi, Alfredo Blandino, Antonio Ieni, and Maurizio Martini

Abstract

Background Few studies examined the role of prostate MRI in patients with abnormal digital rectal examination (DRE) and/or PSA > 10 ng/ml. In a cohort of non-screened patients with abnormal DRE, we investigated the rate of avoidable prostate biopsies and potentially missed clinically significant prostate cancer (csPCa) with negative MRI, and the concordance between targeted biopsy (TBx) and systematic biopsy (SBx) in detecting csPCa with positive MRI.Methods We retrospectively examined 199 biopsy-naïve patients with abnormal DRE who underwent prostate MRI before transperineal biopsy. Prostate Imaging - Reporting And Data System (PI-RADS) v2.1 ≥ 3 category of the index lesion defined a positive MRI. Combined TBx/SBx and SBX alone was performed for positive and negative MRI, respectively. An International Society of Urogenital Pathology Grade Group ≥2 defined csPCa. We calculated csPCa detection rate of TBx, SBx and combined TBx/SBx. The Cohen kappa statistic was used to measure the concordance between TBx and SBx.Results Ninety-one (45.7%) csPCa cases were detected. MRI was positive in 153 (76.9%) patients. In the 46 patients with negative MRI, SBx detected 5 (10.9%) csPCa cases. Prostate biopsy could, thus, be avoided in 41/199 (20.6%) patients at the cost of missing 5/91 (5.5%) csPCa cases. The concordance between TBx and SBx in detecting csPCa with positive mpMRI was substantial (k 0.70). Specifically, 6/86 (6.9%) csPCa cases were detected with TBx, and 17/86 (19.7%) with SBx alone. Concordance was almost perfect (k 0.82) in patients with PSA > 10 ng/ml. Only 4/38 (10.5%) csPCa cases were missed by TBx, and only 1 (2.6%) csPCa case was identified by TBx alone.Conclusion MRI in patients with abnormal DRE could avoid roughly 21% of unnecessary biopsies at the cost of missing approximately 6% of csPCa cases. Moreover, MRI and TBx complemented SBx in detecting csPCa in the subgroup with PSA > 10 ng/ml.

Published
2023

29. Supplementary Figure 3 from PI3K Inhibitors Curtail MYC-Dependent Mutant p53 Gain-of-Function in Head and Neck Squamous Cell Carcinoma

Author

Giovanni Blandino, Giulia Fontemaggi, Sabrina Strano, Laurie Ailles, Silvio Bicciato, Paola Muti, Giuseppe Sanguineti, Giuseppe Spriano, Raul Pellini, Renato Covello, Anthony C. Nichols, Christina Karamboulas, Jalna Meens, Emilia Maria Cristina Mazza, Valentina Manciocco, Mahrou Vahabi, Chiara Turco, Andrea Sacconi, Sara Valsoni, Claudio Pulito, and Federica Ganci

Abstract

Supplementary Figure 3

Published
2023

30. Data from PI3K Inhibitors Curtail MYC-Dependent Mutant p53 Gain-of-Function in Head and Neck Squamous Cell Carcinoma

Author

Giovanni Blandino, Giulia Fontemaggi, Sabrina Strano, Laurie Ailles, Silvio Bicciato, Paola Muti, Giuseppe Sanguineti, Giuseppe Spriano, Raul Pellini, Renato Covello, Anthony C. Nichols, Christina Karamboulas, Jalna Meens, Emilia Maria Cristina Mazza, Valentina Manciocco, Mahrou Vahabi, Chiara Turco, Andrea Sacconi, Sara Valsoni, Claudio Pulito, and Federica Ganci

Abstract

Purpose:Mutation of TP53 gene is a hallmark of head and neck squamous cell carcinoma (HNSCC) not yet exploited therapeutically. TP53 mutation frequently leads to the synthesis of mutant p53 proteins with gain-of-function activity, associated with radioresistance and high incidence of local recurrences in HNSCC.Experimental Design:Mutant p53–associated functions were investigated through gene set enrichment analysis in the Cancer Genome Atlas cohort of HNSCC and in a panel of 22 HNSCC cell lines. Mutant p53–dependent transcripts were analyzed in HNSCC cell line Cal27, carrying mutant p53H193L; FaDu, carrying p53R248L; and Detroit 562, carrying p53R175H. Drugs impinging on mutant p53-MYC–dependent signature were identified interrogating Connectivity Map (https://clue.io) derived from the Library of Integrated Network–based Cellular Signatures (LINCS) database (http://lincs.hms.harvard.edu/) and analyzed in HNSCC cell lines and patient-derived xenografts (PDX) models.Results:We identified a signature of transcripts directly controlled by gain-of-function mutant p53 protein and prognostic in HNSCC, which is highly enriched of MYC targets. Specifically, both in PDX and cell lines of HNSCC treated with the PI3Kα-selective inhibitor BYL719 (alpelisib) the downregulation of mutant p53/MYC-dependent signature correlates with response to this compound. Mechanistically, mutant p53 favors the binding of MYC to its target promoters and enhances MYC protein stability. Treatment with BYL719 disrupts the interaction of MYC, mutant p53, and YAP proteins with MYC target promoters. Of note, depletion of MYC, mutant p53, or YAP potentiates the effectiveness of BYL719 treatment.Conclusions:Collectively, the blocking of this transcriptional network is an important determinant for the response to BYL719 in HNSCC.

Published
2023

31. Supplementary Figure 1 from PI3K Inhibitors Curtail MYC-Dependent Mutant p53 Gain-of-Function in Head and Neck Squamous Cell Carcinoma

Author

Giovanni Blandino, Giulia Fontemaggi, Sabrina Strano, Laurie Ailles, Silvio Bicciato, Paola Muti, Giuseppe Sanguineti, Giuseppe Spriano, Raul Pellini, Renato Covello, Anthony C. Nichols, Christina Karamboulas, Jalna Meens, Emilia Maria Cristina Mazza, Valentina Manciocco, Mahrou Vahabi, Chiara Turco, Andrea Sacconi, Sara Valsoni, Claudio Pulito, and Federica Ganci

Abstract

Supplementary Figure 1

Published
2023

32. Supplementary Figure 7 from PI3K Inhibitors Curtail MYC-Dependent Mutant p53 Gain-of-Function in Head and Neck Squamous Cell Carcinoma

Author

Giovanni Blandino, Giulia Fontemaggi, Sabrina Strano, Laurie Ailles, Silvio Bicciato, Paola Muti, Giuseppe Sanguineti, Giuseppe Spriano, Raul Pellini, Renato Covello, Anthony C. Nichols, Christina Karamboulas, Jalna Meens, Emilia Maria Cristina Mazza, Valentina Manciocco, Mahrou Vahabi, Chiara Turco, Andrea Sacconi, Sara Valsoni, Claudio Pulito, and Federica Ganci

Abstract

Supplementary Figure 7

Published
2023

33. Data from Downregulation of microRNAs 145-3p and 145-5p Is a Long-term Predictor of Postmenopausal Breast Cancer Risk: The ORDET Prospective Study

Author

Giovanni Blandino, Yosef Yarden, Joseph Beyene, Sabrina Strano, Francesca Biagioni, Franco Berrino, Vittorio Krogh, Sabina Sieri, Federica Ganci, Noa Bossel Ben Moshe, Sara Donzelli, Ahmed Hossain, Andrea Sacconi, and Paola Muti

Abstract

Background: miRNAs have been implicated in the regulation of key metabolic, inflammatory, and malignant pathways; hence, they might be considered both predictors and players of cancer development.Methods: Using a case–control study design nested in the ORDET prospective cohort study, we addressed the possibility that specific mRNAs can serve as early predictors of breast cancer incidence in postmenopausal women. We compared leukocyte miRNA profiles of 133 incident postmenopausal breast cancer cases and profiles of 133 women who remained healthy over a follow-up period of 20 years.Results: The analysis identified 20 differentially expressed miRNAs, 15 of which were downregulated. Of the 20 miRNAs, miR145-5p and miR145-3p, each derived from another arm of the respective pre-miRNA, were consistently and significantly downregulated in all the databases that we surveyed. For example, analysis of more than 1,500 patients (the UK Metabric cohort) indicated that high abundance of miR145-3p and miR145-5p was associated with longer, and for miR145-3p also statistically significant, survival. The experimental data attributed different roles to the identified miRNAs: Although the 5p isoform was associated with invasion and metastasis, the other isoform seems related to cell proliferation.Conclusions: These observations and the prospective design of our study lend support to the hypothesis that downregulation of specific miRNAs constitutes an early event in cancer development. This finding might be used for breast cancer prevention.Impact: The identification of the miRNAs as long-term biomarkers of breast cancer may have an impact on breast cancer prevention and early detection. Cancer Epidemiol Biomarkers Prev; 23(11); 2471–81. ©2014 AACR.

Published
2023

34. Supplementary Figure 6 from PI3K Inhibitors Curtail MYC-Dependent Mutant p53 Gain-of-Function in Head and Neck Squamous Cell Carcinoma

Author

Giovanni Blandino, Giulia Fontemaggi, Sabrina Strano, Laurie Ailles, Silvio Bicciato, Paola Muti, Giuseppe Sanguineti, Giuseppe Spriano, Raul Pellini, Renato Covello, Anthony C. Nichols, Christina Karamboulas, Jalna Meens, Emilia Maria Cristina Mazza, Valentina Manciocco, Mahrou Vahabi, Chiara Turco, Andrea Sacconi, Sara Valsoni, Claudio Pulito, and Federica Ganci

Abstract

Supplementary Figure 6

Published
2023

36. Supplementary Figure 2 from PI3K Inhibitors Curtail MYC-Dependent Mutant p53 Gain-of-Function in Head and Neck Squamous Cell Carcinoma

Author

Giovanni Blandino, Giulia Fontemaggi, Sabrina Strano, Laurie Ailles, Silvio Bicciato, Paola Muti, Giuseppe Sanguineti, Giuseppe Spriano, Raul Pellini, Renato Covello, Anthony C. Nichols, Christina Karamboulas, Jalna Meens, Emilia Maria Cristina Mazza, Valentina Manciocco, Mahrou Vahabi, Chiara Turco, Andrea Sacconi, Sara Valsoni, Claudio Pulito, and Federica Ganci

Abstract

Supplementary Figure 2

Published
2023

37. Data from A Division of Labor between YAP and TAZ in Non–Small Cell Lung Cancer

Author

Moshe Oren, Eytan Ruppin, Giovanni Blandino, Yael Aylon, Saptaparna Mukherjee, Ido Azuri, Silvia Di Agostino, Sanju Sinha, Bareket Dassa, and Michal Shreberk-Shaked

Abstract

Lung cancer is the leading cause of cancer-related deaths worldwide. The paralogous transcriptional cofactors Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ, also called WWTR1), the main downstream effectors of the Hippo signal transduction pathway, are emerging as pivotal determinants of malignancy in lung cancer. Traditionally, studies have tended to consider YAP and TAZ as functionally redundant transcriptional cofactors with similar biological impact. However, there is growing evidence that each of them also possesses distinct attributes. Here we sought to systematically characterize the division of labor between YAP and TAZ in non–small cell lung cancer (NSCLC), the most common histological subtype of lung cancer. Representative NSCLC cell lines as well as patient-derived data showed that the two paralogs orchestrated nonoverlapping transcriptional programs in this cancer type. YAP preferentially regulated gene sets associated with cell division and cell-cycle progression, whereas TAZ preferentially regulated genes associated with extracellular matrix organization. Depletion of YAP resulted in growth arrest, whereas its overexpression promoted cell proliferation. Likewise, depletion of TAZ compromised cell migration, whereas its overexpression enhanced migration. The differential effects of YAP and TAZ on key cellular processes were also associated with differential response to anticancer therapies. Uncovering the different activities and downstream effects of YAP and TAZ may thus facilitate better stratification of patients with lung cancer for anticancer therapies.Significance:Thease findings show that oncogenic paralogs YAP and TAZ have distinct roles in NSCLC and are associated with differential response to anticancer drugs, knowledge that may assist lung cancer therapy decisions.

Published
2023

38. Supplementary Figure 4 from PI3K Inhibitors Curtail MYC-Dependent Mutant p53 Gain-of-Function in Head and Neck Squamous Cell Carcinoma

Author

Giovanni Blandino, Giulia Fontemaggi, Sabrina Strano, Laurie Ailles, Silvio Bicciato, Paola Muti, Giuseppe Sanguineti, Giuseppe Spriano, Raul Pellini, Renato Covello, Anthony C. Nichols, Christina Karamboulas, Jalna Meens, Emilia Maria Cristina Mazza, Valentina Manciocco, Mahrou Vahabi, Chiara Turco, Andrea Sacconi, Sara Valsoni, Claudio Pulito, and Federica Ganci

Abstract

Supplementary Figure 4

Published
2023

39. Supplementary Figure 5 from PI3K Inhibitors Curtail MYC-Dependent Mutant p53 Gain-of-Function in Head and Neck Squamous Cell Carcinoma

Author

Giovanni Blandino, Giulia Fontemaggi, Sabrina Strano, Laurie Ailles, Silvio Bicciato, Paola Muti, Giuseppe Sanguineti, Giuseppe Spriano, Raul Pellini, Renato Covello, Anthony C. Nichols, Christina Karamboulas, Jalna Meens, Emilia Maria Cristina Mazza, Valentina Manciocco, Mahrou Vahabi, Chiara Turco, Andrea Sacconi, Sara Valsoni, Claudio Pulito, and Federica Ganci

Abstract

Supplementary Figure 5

Published
2023

40. Table S2: List of YAP-differential and TAZ-differential drugs from A Division of Labor between YAP and TAZ in Non–Small Cell Lung Cancer

Author

Moshe Oren, Eytan Ruppin, Giovanni Blandino, Yael Aylon, Saptaparna Mukherjee, Ido Azuri, Silvia Di Agostino, Sanju Sinha, Bareket Dassa, and Michal Shreberk-Shaked

Abstract

List of 142 YAP-differential drugs and 38 TAZ-differential drugs in LUAD cells. Each row is a drug, and each column specifies additional information, including dose used in the screen, drug targets, indication, clinical phase and the p-value of the comparison.

Published
2023

42. Data Supplement from Downregulation of microRNAs 145-3p and 145-5p Is a Long-term Predictor of Postmenopausal Breast Cancer Risk: The ORDET Prospective Study

Author

Giovanni Blandino, Yosef Yarden, Joseph Beyene, Sabrina Strano, Francesca Biagioni, Franco Berrino, Vittorio Krogh, Sabina Sieri, Federica Ganci, Noa Bossel Ben Moshe, Sara Donzelli, Ahmed Hossain, Andrea Sacconi, and Paola Muti

Abstract

Supplementary Table 1 - miR-125a-5p expression across different databases; Supplementary Table 2 - miR-99b expression across different databases; Supplementary Table 3 - miR-199a-5p expression across different databases; Supplementary Table 4 - miR-199b-5p expression across different databases; Supplementary Table 5 - miR-892b expression across different databases; Supplementary Table 6 - miR-141 expression across different databases; Supplementary Table 7 - miR-582-5p expression across different databases; Supplementary Table 8 - miR-138 expression across different databases; Supplementary Table 9 - miR-181c* expression across different databases; Supplementary Table 10 - miR-28-3p expression across different databases; Supplementary Table 11 - miR-1288 expression across different databases; Supplementary Table 12 - miR-224 expression across different databases; Supplementary Table 13 - miR-520a-3p expression across different databases; Supplementary Table 14 - miR-223 expression across different databases; Supplementary Table 15 - miR-539 expression across different databases; Supplementary Table 16 - miR-542-5p expression across different databases; Supplementary Table 17 - miR-122* expression across different databases; Supplementary Table 18 - miR-920 expression across different databases.

Published
2023

46. Supplementary Table 1 from Reversible Dysfunction of Wild-Type p53 following Homeodomain-Interacting Protein Kinase-2 Knockdown

Author

Gabriella D'Orazi, David Givol, Giovanni Blandino, Ada Sacchi, Carlo Leonetti, Marco Scarsella, Daniel A. Notterman, Eytan Domany, Ninette Amariglio, Gideon Rechavi, Hilah Gal, Lavinia Nardinocchi, and Rosa Puca

Abstract

Supplementary Table 1 from Reversible Dysfunction of Wild-Type p53 following Homeodomain-Interacting Protein Kinase-2 Knockdown

Published
2023

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