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54. Role of HLA extended haplotypes in unrelated bone marrow transplantation

Author

La Nasa, G., Vacca, A., Pizzati, A., Ledda, A., Arras, M., Locatelli, Franco, Carcassi, C., Mulargia, M., Piras, E., Floris, R., Mantovani, D., Contu, L., Locatelli F. (ORCID:0000-0002-7976-3654), La Nasa, G., Vacca, A., Pizzati, A., Ledda, A., Arras, M., Locatelli, Franco, Carcassi, C., Mulargia, M., Piras, E., Floris, R., Mantovani, D., Contu, L., and Locatelli F. (ORCID:0000-0002-7976-3654)

Abstract

N/A

Published
1997

56. Thyroid and Celiac Disease: Clinical, Serological, and Echographic Study.

Author

Velluzi, F., Caradonna, A., Boy, M. F., Pinna, M. A., Cabula, R., Lai, M. A., Piras, E., Corda, G., Mossa, P., Atzeni, F., Loviselli, A., Usai, P., and Mariotti, S.

Subjects
THYROID diseases, AUTOIMMUNITY, PATIENTS, CELIAC disease, PALPATION, ULTRASONIC imaging
Abstract

Objective: We sought to reevaluate the prevalence of thyroid dysfunction and thyroid autoimmunity in 47 patients with celiac disease; 91 healthy subjects were studied as controls. Both patients and controls were from Sardinia, Italy. Methods: Diagnosis of celiac disease was made on the basis of clinical history, presence of positive antigliadin IgA (AGA-A) and IgG (AGA-G) antibodies, antireticulin antibodies (ARA), antiendomysium antibodies (EMA), and was confirmed by jejunal biopsy. HLA class II typing for DQB1 and DQA1 alleles was performed in 36/47 celiac patients. Thyroid was evaluated by palpation and echography; serum free thyroid hormones (FT4, FT3), thyrotropic hormone (TSH), and antithyroid peroxidase autoantibodies (anti-TPO) were assayed by radioimmunoassays. Results: The prevalence of anti-TPO was higher in celiac patients (29.7 %) than in healthy controls (9.6%) (p < 0.001) and thyroid echography frequently displayed (42.5%) a hypoechogenic pattern. Five anti-TPO-positive celiac patients were hypothyroid (two overt, three subclinical). A higher but not significantly different prevalence of anti-TPO (3/7 = 42.8%) was found in celiac patients displaying the DQBI*0502 genotype, when compared with the remaining patients (8/29 = 27.6%). Conclusions: An elevated prevalence of clinical and subclinical autoimmune thyroid autoimmunity was found in Sardinian celiac patients, especially in those displaying the DQBI*0502 genotype; this finding could be related to a particular genetic background of the Sardinian population. [ABSTRACT FROM AUTHOR]

Published
1998

59. ALLOGENEIC STEM CELL TRANSPLANTATION IN PATIENTS OLDER THAN 60 YEARS: A REGISTRY STUDY OF THE TRANSPLANT ACTIVITY FROM 2000 TO 2017 ON BEHALF OF THE GRUPPO ITALIANO TRAPIANTO DI MIDOLLO OSSEO (GITMO)

Author

Malagola, M., Polverelli, N., Martino, M., Rubini, V., Stanghellini, M. T. Lupo, Patriarca, F., Fanin, R., Bruno, B., Giaccone, L., Faraci, D. G., Grillo, G., Bramanti, S., Castagna, L., Bernasconi, P., Colombo, A. A., Gobbi, M., Nicoli, P., Natale, A., Santarone, S., Terruzzi, E., Olivieri, A., Scortechini, I., Chiusolo, P., Metafuni, E., Carella, A. M., Merla, E., Casini, M., Cavattoni, I., Arpinati, M., Nozzoli, C., Cutini, I., Mazza, P., Mazzone, A., Bassi, S., Onida, F., Saporiti, G., Canale, F. A., Vacca, A., Piras, E., Galieni, P., Falcioni, S., Luppi, M., Debbia, G., Iori, P. A., Ursula La Rocca, Pavone, V., Mele, A., Skert, C., Carobolante, F., Carluccio, P., Borghero, C., Elice, F., Proia, A., Fanelli, F., Selleri, C., Sacchi, N., Mammoliti, S., Oldani, E., Ciceri, F., Russo, D., and Bonifazi, F.

63. Human Mesenchymal stromal cells expressing a CNS-targeting receptor can be administrated intra nasally and cure expersimental autoimmune enchphlomyelitis

Author

Fransson, Moa, Piras, E, Wang, H, Burman, Joachim, Duprez, I, Harris, R, LeBlanc, K, Brittebo, Eva, Loskog, Angelica, Fransson, Moa, Piras, E, Wang, H, Burman, Joachim, Duprez, I, Harris, R, LeBlanc, K, Brittebo, Eva, and Loskog, Angelica

Abstract

Mesenchymal stromal cells (MSCs) are a heterogeneous population of stromal cells residing in most connective tissues and have the capacity to suppress effector cells of the immune system. In experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis, systemic treatments with both murine and human MSCs have proven beneficial because of their capacity to suppress overt immune reactions. However, systemic administration of such cells may cause problems with infectious disease and low numbers of cells that reach the inflamed tissue. We hypothesized that MSCs can be accumulated and retained in the CNS using gene transfer of a CNS-targeting device and intranasal cell delivery. In the current investigation, MSCs were engineered to express a myelin oligodendrocyte glycoprotein (MOG)-specific receptor using lentiviral vectors. Genetically engineered MSCs retained their suppressive capacity in vitro and successfully targeted the brain upon both intraperitoneal and intranasal delivery. Engineered MSCs cured mice from disease symptoms and these mice were resistant to further EAE challenge. Encephalitic T cells isolated from cured mice displayed an anergic profile while peripheral T cells were still responsive to stimuli. Further, MSC treatment reduced the level of inflammatory cytokines in the brain and implyed reduced damage to axons. In conclusion, MSCs can be genetically engineered to target CNS and efficiently suppress encephalomyelitis in an active EAE model upon intranasal delivery.

64. Engineered T regulatory cells target CNS and suppress active EAE upon intra nasal delivery

Author

Fransson, Moa, Piras, E, Wang, H, Burman, Joachim, Harris, R, Brittebo, Eva, Loskog, Angelica, Fransson, Moa, Piras, E, Wang, H, Burman, Joachim, Harris, R, Brittebo, Eva, and Loskog, Angelica

Abstract

Multiple sclerosis (MS) is an autoimmune disorder of the central nervous system (CNS). In the murine experimental autoimmune encephalomyelitis (EAE) model of MS, T regulatory (Treg) cell therapy has proven beneficial. However, systemic administration of such cells may immunologically compromise the recipient and promote infections due to general immunosuppression. We hypothesized that Tregs can be equipped with a CNS-targeting receptor and be delivered intra-nasally to avoid systemic exposure. In the current investigation, CD4+ T cells were modified with a lentiviral vector system to express a myelin oligodendrocyte (MOG)-targeting receptor in trans with the FoxP3 gene that drives Treg differentiation. The genetically engineered Tregs demonstrated suppressive capacity in vitro and were then tested in the EAE model. Engineered Tregs localized to the brain and suppressed ongoing encephalomyelitis in vivo. Cured mice were rechallenged with an EAE-inducing inoculum but remained healthy. Cytokine profile of the brain reveled lower levels of effector cytokines in TregCAR treated mice and acordingly, reduced axonal damage was seen in these mice. In conclusion, CNS-specific Tregs were able to localize to the CNS and efficiently cure mice with ongoing EAE.

65. CAR/FoxP3-engineered T regulatory cells target the CNS and suppress EAE upon intranasal delivery

Author

Fransson Moa, Piras Elena, Burman Joachim, Nilsson Berith, Essand Magnus, Lu BinFeng, Harris Robert A, Magnusson Peetra U, Brittebo Eva, and Loskog Angelica SI

Subjects
MS, redirected cells, T regulatory cells, EAE, FoxP3, Myelin oligodendrocyte glycoprotein (MOG), Neurology. Diseases of the nervous system, RC346-429
Abstract

Abstract Background Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS). In the murine experimental autoimmune encephalomyelitis (EAE) model of MS, T regulatory (Treg) cell therapy has proved to be beneficial, but generation of stable CNS-targeting Tregs needs further development. Here, we propose gene engineering to achieve CNS-targeting Tregs from naïve CD4 cells and demonstrate their efficacy in the EAE model. Methods CD4+ T cells were modified utilizing a lentiviral vector system to express a chimeric antigen receptor (CAR) targeting myelin oligodendrocyte glycoprotein (MOG) in trans with the murine FoxP3 gene that drives Treg differentiation. The cells were evaluated in vitro for suppressive capacity and in C57BL/6 mice to treat EAE. Cells were administered by intranasal (i.n.) cell delivery. Results The engineered Tregs demonstrated suppressive capacity in vitro and could efficiently access various regions in the brain via i.n cell delivery. Clinical score 3 EAE mice were treated and the engineered Tregs suppressed ongoing encephalomyelitis as demonstrated by reduced disease symptoms as well as decreased IL-12 and IFNgamma mRNAs in brain tissue. Immunohistochemical markers for myelination (MBP) and reactive astrogliosis (GFAP) confirmed recovery in mice treated with engineered Tregs compared to controls. Symptom-free mice were rechallenged with a second EAE-inducing inoculum but remained healthy, demonstrating the sustained effect of engineered Tregs. Conclusion CNS-targeting Tregs delivered i.n. localized to the CNS and efficiently suppressed ongoing inflammation leading to diminished disease symptoms.

Published
2012
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66. Ethical issues of unrelated hematopoietic stem cell transplantation in adult thalassemia patients

Author

Piras Eugenia, Vacca Adriana, d'Aloja Ernesto, La Nasa Giorgio, Caocci Giovanni, Pintor Michela, Demontis Roberto, and Pisu Salvatore

Subjects
Medical philosophy. Medical ethics, R723-726
Abstract

Abstract Background Beta thalassemia major is a severe inherited form of hemolytic anemia that results from ineffective erythropoiesis. Allogenic hematopoietic stem cell transplantation (HSCT) remains the only potentially curative therapy. Unfortunately, the subgroup of adult thalassemia patients with hepatomegaly, portal fibrosis and a history of irregular iron chelation have an elevated risk for transplantation-related mortality that is currently estimated to be about 29 percent. Discussion Thalassemia patients may be faced with a difficult choice: they can either continue conventional transfusion and iron chelation therapy or accept the high mortality risk of HSCT in the hope of obtaining complete recovery. Throughout the decision making process, every effort should be made to sustain and enhance autonomous choice. The concept of conscious consent becomes particularly important. The patient must be made fully aware of the favourable and adverse outcomes of HSCT. Although it is the physician's duty to illustrate the possibility of completely restoring health, considerable emphasis should be put on the adverse effects of the procedure. The physician also needs to decide whether the patient is eligible for HSCT according to the "rule of descending order". The patient must be given full details on self-care and fundamental lifestyle changes and be fully aware that he/she will be partly responsible for the outcome. Summary Only if all the aforesaid conditions are satisfied can it be considered reasonable to propose unrelated HSCT as a potential cure for high risk thalassemia patients.

Published
2011
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67. Infected pancreatic necrosis: outcomes and clinical predictors of mortality. A post hoc analysis of the MANCTRA-1 international study

Author

Podda, Mauro, Pellino, Gianluca, Di Saverio, Salomone, Coccolini, Federico, Pacella, Daniela, Cioffi, Stefano Piero Bernardo, Virdis, Francesco, Balla, Andrea, Ielpo, Benedetto, Pata, Francesco, Poillucci, Gaetano, Ortenzi, Monica, Damaskos, Dimitrios, De Simone, Belinda, Sartelli, Massimo, Leppaniemi, Ari, Jayant, Kumar, Catena, Fausto, Giuliani, Antonio, Di Martino, Marcello, Pisanu, Adolfo, Chiara Gerardi, Stavros Gourgiotis, Cristiana Riboni, Alessio Giordano, Luca Ferrario, Vanni Agnoletti, Yoram Kruger, Damian Mole, Ferdinando Agresta, Mikel Prieto Calvo, Michael Wilson, Fiammetta Soggiu, Alaa Hamdan, Carlos Augusto Gomes, Gustavo Fraga, Argyrios Ioannidis, Zaza Demetrashvili, Saaz Sahani, Lovenish Bains, Almu'atasim Khamees, Hazim Ababneh, Osama Aljaiuossi, Samuel Pimentel, Ikhwan Sani Mohamad, Ahmad Ramzi Yusoff, Narcis Octavian Zarnescu, Valentin Calu, Andrey Litvin, Dusan Lesko, Ahmed Elmehrath, Mohamedraed Elshami, Martin de Santibañes, Justin Gundara, Kamel Alawadhi, Rashid Lui, Alexander Julianov, Sergio Ralon, Ibrahim-Umar Garzali, Gustavo M Machain, Ibabe Villalabeitia, Darwin Artidoro Quispe-Cruz, Abigail Cheska C Orantia, Maciej Walędziak, Tiago Correia de Sá, Syed Muhammad Ali, Bojan Kovacevic, Colin Noel, Haidar M Abdalah, Ali Kchaou, Arda Isik, Luca Ansaloni, Walter Biffl, Mario Guerrieri, Alberto Sartori, Manuel Abradelo, Giuseppe Nigri, Nicola Di Lorenzo, Andrea Mingoli, Massimo Chiarugi, Juliana Di Menno Stavron, Oscar Mazza, José Ignacio Valenzuela, Diana Alejandra Pantoja Pachajoa, Fernando Andrés Alvarez, Julian Ezequiel Liaño, Joan Tefay, Abdulrahman Alshaikh, Layla Hasan, Felipe Couto Gomes, Thiago R A Calderan, Elcio S Hirano, Dragomir Dardanov, Azize Saroglu, Boyko Atanasov, Nikolay Belev, Nikola Kovachev, Shannon Melissa Chan, Hon-Ting Lok, Diego Salcedo, Diana Robayo, María Alejandra Triviño, Jan Manak, Jorann de Araujo, Ananya Sethi, Ahmed Awad, Merihan Elbadawy, Ahmed Farid, Asmaa Hanafy, Ahmed Nafea, Ghozy Sherief, Abbas Salah Alzhraa, Wafaa Abdelsalam, Sameh Emile, Ahmed Elfallal, Hossam Elfeki, Hosam Elghadban, Ashraf Shoma, Mohamed Shetiwy, Mohamed Elbahnasawy, Salem Mohamed, Emad Fawzi Hamed, Usama Ahmed Khalil, Elie Chouillard, Andrew Gumbs, Andrea Police, Andrea Mabilia, Kakhi Khutsishvili, Anano Tvaladze, Orestis Ioannidis, Elissavet Anestiadou, Lydia Loutzidou, Konstantinis Konstantinidis, Sofia Konstantinidou, Dimitrios Manatakis, Vasileios Acheimastos, Nikolaos Tasis, Nikolaos Michalopoulos, Panagiotis Kokoropoulos, Maria Papadoliopoulou, Maria Sotiropoulou, Stylianos Kapiris, Panagiotis Metaxas, Ioannis Tsouknidas, Despoina Kefili, George Petrakis, Eirini Synekidou, Konstantinos Dakis, Eirini Alexandridou, Aristeidis Papadopoulos, Christos Chouliaras, Odysseas Mouzakis, Francesk Mulita, Ioannis Maroulis, Michail Vailas, Tania Triantafyllou, Dimitrios Theodorou, Eftychios Lostoridis, Eleni-Aikaterini Nagorni, Paraskevi Tourountzi, Efstratia Baili, Alexandros Charalabopoulos, Theodore Liakakos, Dimitrios Schizas, Alexandros Kozadinos, Athanasios Syllaios, Nikolaos Machairas, Stylianos Kykalos, Paraskevas Stamopoulos, Spiros Delis, Christos Farazi-Chongouki, Evangelos Kalaitzakis, Miltiadis Giannarakis, Konstantinos Lasithiotakis, Giorgia Petra, Amit Gupta, Noushif Medappil, Vijayanand Muthukrishnan, Jubin Kamar, Pawan Lal, Rajendra Agarwal, Matteo Magnoli, Paolo Aonzo, Alberto Serventi, Pierpaolo Di Lascio, Margherita Pinto, Carlo Bergamini, Andrea Bottari, Laura Fortuna, Jacopo Martellucci, Atea Cicako, Claudio Miglietta, Mario Morino, Daniele Delogu, Andrea Picchetto, Marco Assenza, Giancarlo D'Ambrosio, Giulio Argenio, Mariano Fortunato Armellino, Giovanna Ioia, Savino Occhionorelli, Dario Andreotti, Lacavalla Domenico, Davide Luppi, Massimiliano Casadei, Luca Di Donato, Farshad Manoochehri, Tiziana Rita Lucia Marchese, William Sergi, Roberto Manca, Raimondo Murgia, Enrico Piras, Lorenzo Conti, Simone Gianazza, Andrea Rizzi, Edoardo Segalini, Marco Monti, Elena Iiritano, Nicolò Maria Mariani, Enrico De Nicola, Giovanna Scifo, Giusto Pignata, Jacopo Andreuccetti, Francesco Fleres, Guglielmo Clarizia, Alessandro Spolini, Alan Biloslavo, Paola Germani, Manuela Mastronardi, Selene Bogoni, Silvia Palmisano, Nicolo' De Manzini, Marco Vito Marino, Gennaro Martines, Giuseppe Trigiante, Elpiniki Lagouvardou, Gabriele Anania, Cristina Bombardini, Dario Oppici, Tiziana Pilia, Valentina Murzi, Emanuela Gessa, Umberto Bracale, Maria Michela Di Nuzzo, Roberto Peltrini, Francesco Salvetti, Jacopo Viganò, Gabriele Sganga, Valentina Bianchi, Pietro Fransvea, Tommaso Fontana, Giuliano Sarro, Vincenza Paola Dinuzzi, Luca Scaravilli, Mario Virgilio Papa, Elio Jovine, Giulia Ciabatti, Laura Mastrangelo, Matteo Rottoli, Claudio Ricci, Iris Shari Russo, Alberto Aiolfi, Davide Bona, Francesca Lombardo, Pasquale Cianci, Mariagrazia Sederino, Roberto Bini, Osvaldo Chiara, Stefano Cioffi, Stefano Cantafio, Guido Coretti, Edelweiss Licitra, Grazia Savino, Sergio Grimaldi, Raffaele Porfidia, Elisabetta Moggia, Mauro Garino, Chiara Marafante, Antonio Pesce, Nicolò Fabbri, Carlo Vittorio Feo, Ester Marra, Marina Troian, Davide Drigo, Carlo Nagliati, Andrea Muratore, Riccardo Danna, Alessandra Murgese, Michele Crespi, Claudio Guerci, Alice Frontali, Luca Ferrari, Francesco Favi, Erika Picariello, Alessia Rampini, Fabrizio D'Acapito, Giorgio Ercolani, Leonardo Solaini, Francesco Palmieri, Matteo Calì, Francesco Ferrara, Irnerio Angelo Muttillo, Edoardo Maria Muttillo, Biagio Picardi, Raffaele Galleano, Ali Badran, Omar Ghazouani, Maurizio Cervellera, Gaetano Campanella, Gennaro Papa, Annamaria Di Bella, Gennaro Perrone, Gabriele Luciano Petracca, Concetta Prioriello, Mario Giuffrida, Federico Cozzani, Matteo Rossini, Marco Inama, Giovanni Butturini, Gianluigi Moretto, Luca Morelli, Giulio Candio, Simone Guadagni, Enrico Cicuttin, Camilla Cremonini, Dario Tartaglia, Valerio Genovese, Nicola Cillara, Alessandro Cannavera, Antonello Deserra, Arcangelo Picciariello, Vincenzo Papagni, Leonardo Vincenti, Giulia Bagaglini, Giuseppe Sica, Pierfrancesco Lapolla, Gioia Brachini, Dario Bono, Antonella Nicotera, Marcello Zago, Fabrizio Sammartano, Laura Benuzzi, Marco Stella, Stefano Rossi, Alessandra Cerioli, Caterina Puccioni, Stefano Olmi, Carolina Rubicondo, Matteo Uccelli, Anna Guida, Pasquale Lepiane, Diego Sasia, Giorgio Giraudo, Sara Salomone, Elena Belloni, Alessandra Cossa, Francesco Lancellotti, Roberto Caronna, Piero Chirletti, Paolina Saullo, Raffaele Troiano, Felice Mucilli, Mirko Barone, Massimo Ippoliti, Michele Grande, Bruno Sensi, Leandro Siragusa, Andrea Santini, Isidoro Di Carlo, Massimiliano Veroux, Rossella Gioco, Gastone Veroux, Giuseppe Currò, Michele Ammendola, Iman Komaei, Giuseppe Navarra, Valeria Tonini, Lodovico Sartarelli, Marco Ceresoli, Stefano Perrone, Linda Roccamatisi, Paolo Millo, Riccardo Brachet Contul, Elisa Ponte, Matteo Zuin, Giuseppe Portale, Alice Sabrina Tonello, Geri Fratini, Matteo Bianchini, Bruno Perotti, Emanuele Doria, Elia Giuseppe Lunghi, Diego Visconti, Khayry Al-Shami, Sajeda Awadi, Mohammad Musallam Khalil Buwaitel, Mo'taz Fawzat Naief Naffa', Ahmad Samhouri, Hatem Sawalha, Mohd Firdaus Che Ani, Ida Nadiah Ahmed Fathil, Jih Huei, Jose-Luis Beristain-Hernandez, Alejandro Garcia-Meza, Rafael Sepulveda-Rdriguez, Edgard Efren Lozada Hernández, Camilo Levi Acuña Pinzón, Jefferson Nieves Condoy, Francisco C Becerra García, Mohammad Sadik, Bushra Kadir, Jalpa Devi, Nandlal Seerani, Zainab, Mohammad Sohail-Asghar, Ameer Afzal, Ali Akbar, Helmut Segovia Lohse, Herald Segovia Lohse, Zamiara Solange Leon Cabrera, Gaby Susana Yamamoto Seto, José Ríos Chiuyari, Jorge Ordemar, Martha Rodríguez, Abigail Cheska C Orantia-Carlos, Margie Antionette Quitoy, Andrzej Kwiatkowski, Maciej Mawlichanów, Mónica Rocha, Carlos Soares, Alexandru Rares Stoian, Andreea Diana Draghici, Valentin Titus Grigorean, Raluca Bievel Radulescu, Radu Virgil Costea, Eugenia Claudia Zarnescu, Mikhail Kurtenkov, George Gendrikson, Volovich Alla-Angelina, Tsurbanova Arina, Ayrat Kaldarov, Mahir Gachabayov, Abakar Abdullaev, Milica Milentijevic, Milovan Karamarkovic, Arpád Panyko, Jozef Radonak, Marek Soltes, Laura Álvarez Morán, Haydée Calvo García, Pilar Suárez Vega, Sergio Estevez, Fabio Ausania, Jordi Farguell, Carolina González-Abós, Santiago Sánchez-Cabús, Belén Martín, Víctor Molina, Luis Oms, Lucas Ilzarbe, Eva Pont Feijóo, Elena Sofia Perra, Noel Rojas-Bonet, Rafael Penalba-Palmí, Susana Pérez-Bru, Jaume Tur-Martínez, Andrea Álvarez-Torrado, Marta Domingo-Gonzalez, Javier Tejedor-Tejada, Yaiza García Del Alamo, Fernando Mendoza-Moreno, Francisca García-Moreno-Nisa, Belén Matías-García, Manuel Durán, Rafael Calleja-Lozano, José Manuel Perez de Villar, Luis Sánchez-Guillén, Iban Caravaca, Daniel Triguero-Cánovas, Antonio Carlos Maya Aparicio, Blas Durán Meléndez, Andrea Masiá Palacios, Aitor Landaluce-Olavarria, Mario De Francisco, Begoña Estraviz-Mateos, Felipe Alconchel, Tatiana Nicolás-López, Pablo Ramírez, Virginia Duran Muñoz-Cruzado, Felipe Parej Ciuró, Eduardo Perea Del Pozo, Sergio Olivares Pizarro, Vicente Herrera Cabrera, Jose Muros Bayo, Hytham K S Hamid, Raffaello Roesel, Alessandra Cristaudi, Kinan Abbas, Iyad Ali, Ahmed Tlili, Hüseyin Bayhan, Mehmet Akif Türkoğlu, Mustafa Yener Uzunoglu, Ibrahim Fethi Azamat, Nail Omarov, Derya Salim Uymaz, Fatih Altintoprak, Emrah Akin, Necattin First, Koray Das, Nazmi Ozer, Ahmet Seker, Yasin Kara, Mehmet Abdussamet Bozkurt, Ali Kocataş, Semra Demirli Atici, Murat Akalin, Bulent Calik, Elif Colak, Yuksel Altinel, Serhat Meric, Yunus Emre Aktimur, Victoria Hudson, Jean-Luc Duval, Mansoor Khan, Ahmed Saad, Mandeep Kaur, Alison Bradley, Katherine Fox, Ivan Tomasi, Daniel Beasley, Alekhya Kotta Prasanti, Pinky Kotecha, Husam Ebied, Michaela Paul, Hemant Sheth, Ioannis Gerogiannis, Mohannad Gaber, Zara Sheikh, Shatadru Seth, Maria Kunitsyna, Cosimo Alex Leo, Vittoria Bellato, Noman Zafar, Amr Elserafy, Giles Bond-Smith, Giovanni Tebala, Pawan Mathur, Izza Abid, Nnaemeka Chidumije, Pardip Sandhar, Syed Osama Zohaib Ullah, Tamara Lezama, Muhammad Hassan Anwaar, Conor Magee, Salma Ahmed, Brooke Davies, Jeyakumar Apollos, Kieran McCormack, Hasham Choudhary, Triantafyllos Doulias, Tamsin Morrison, Anna Palepa, Fernando Bonilla Cal, Lianet Sánchez, Fabiana Domínguez, Ibrahim Al-Raimi, Haneen Alshargabi, Abdullah Meead, Serge Chooklin, Serhii Chuklin, Andriy Bilyak, Institut Català de la Salut, [Podda M] Emergency Surgery Unit, Department of Surgical Science, Policlinico Universitario 'D. Casula', Azienda Ospedaliero-Universitaria di Cagliari, University of Cagliari, Cagliari, Italy. [Pellino G] Department of Advanced Medical and Surgical Sciences, Università degli Studi della Campania 'Luigi Vanvitelli', Naples, Italy. Unitat de Cirurgia de Còlon i Recte, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Di Saverio S] Department of Surgery, 'Madonna del Soccorso' Hospital, San Benedetto del Tronto, Italy. [Coccolini F] General, Emergency and Trauma Surgery Unit, Pisa University Hospital, Pisa, Italy. [Pacella D] Department of Public Health, University of Naples Federico II, Naples, Italy. [Cioffi SPB] Trauma and Acute Care Surgery Unit, 'Niguarda Ca Granda' Hospital, Milan, Italy, Vall d'Hebron Barcelona Hospital Campus, Podda, Mauro, Pellino, Gianluca, Di Saverio, Salomone, Coccolini, Federico, Pacella, Daniela, Cioffi, Stefano Piero Bernardo, Virdis, Francesco, Balla, Andrea, Ielpo, Benedetto, Pata, Francesco, Poillucci, Gaetano, Ortenzi, Monica, Damaskos, Dimitrio, De Simone, Belinda, Sartelli, Massimo, Leppaniemi, Ari, Jayant, Kumar, Catena, Fausto, Giuliani, Antonio, Di Martino, Marcello, Pisanu, Adolfo, Chiara Gerardi, Stavros Gourgiotis, Cristiana Riboni, Alessio Giordano, Luca Ferrario, Vanni Agnoletti, Yoram Kruger, Damian Mole, Ferdinando Agresta, Mikel Prieto Calvo, Michael Wilson, Fiammetta Soggiu, Alaa Hamdan, Carlos Augusto Gomes, Gustavo Fraga, Argyrios Ioannidis, Zaza Demetrashvili, Saaz Sahani, Lovenish Bains, Almu'atasim Khamees, Hazim Ababneh, Osama Aljaiuossi, Samuel Pimentel, Ikhwan Sani Mohamad, Ahmad Ramzi Yusoff, Narcis Octavian Zarnescu, Valentin Calu, Andrey Litvin, Dusan Lesko, Ahmed Elmehrath, Mohamedraed Elshami, Martin de Santibañes, Justin Gundara, Kamel Alawadhi, Rashid Lui, Alexander Julianov, Sergio Ralon, Ibrahim-Umar Garzali, Gustavo M Machain, Ibabe Villalabeitia, Darwin Artidoro Quispe-Cruz, Abigail Cheska C Orantia, Maciej Walędziak, Tiago Correia de Sá, Syed Muhammad Ali, Bojan Kovacevic, Colin Noel, Haidar M Abdalah, Ali Kchaou, Arda Isik, Luca Ansaloni, Walter Biffl, Mario Guerrieri, Alberto Sartori, Manuel Abradelo, Giuseppe Nigri, Nicola Di Lorenzo, Andrea Mingoli, Massimo Chiarugi, Juliana Di Menno Stavron, Oscar Mazza, José Ignacio Valenzuela, Diana Alejandra Pantoja Pachajoa, Fernando Andrés Alvarez, Julian Ezequiel Liaño, Joan Tefay, Abdulrahman Alshaikh, Layla Hasan, Felipe Couto Gomes, Thiago R A Calderan, Elcio S Hirano, Dragomir Dardanov, Alexander Julianov, Azize Saroglu, Boyko Atanasov, Nikolay Belev, Nikola Kovachev, Shannon Melissa Chan, Hon-Ting Lok, Diego Salcedo, Diana Robayo, María Alejandra Triviño, Jan Manak, Saaz Sahani, Jorann de Araujo, Ananya Sethi, Ahmed Awad, Merihan Elbadawy, Ahmed Farid, Asmaa Hanafy, Ahmed Nafea, Ghozy Sherief, Abbas Salah Alzhraa, Wafaa Abdelsalam, Sameh Emile, Ahmed Elfallal, Hossam Elfeki, Hosam Elghadban, Ashraf Shoma, Mohamed Shetiwy, Mohamed Elbahnasawy, Salem Mohamed, Emad Fawzi Hamed, Usama Ahmed Khalil, Elie Chouillard, Andrew Gumbs, Andrea Police, Andrea Mabilia, Kakhi Khutsishvili, Anano Tvaladze, Orestis Ioannidis, Elissavet Anestiadou, Lydia Loutzidou, Konstantinis Konstantinidis, Sofia Konstantinidou, Dimitrios Manatakis, Vasileios Acheimastos, Nikolaos Tasis, Nikolaos Michalopoulos, Panagiotis Kokoropoulos, Maria Papadoliopoulou, Maria Sotiropoulou, Stylianos Kapiris, Panagiotis Metaxas, Ioannis Tsouknidas, Despoina Kefili, George Petrakis, Eirini Synekidou, Konstantinos Dakis, Eirini Alexandridou, Aristeidis Papadopoulos, Christos Chouliaras, Odysseas Mouzakis, Francesk Mulita, Ioannis Maroulis, Michail Vailas, Tania 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Subjects
Infected pancreatic necrosi, Digestive System Diseases::Pancreatic Diseases::Pancreatitis::Pancreatitis, Acute Necrotizing [DISEASES], Infected pancreatic necrosis, Pàncrees - Infecció, 3126 Surgery, anesthesiology, intensive care, radiology, enfermedades del sistema digestivo::enfermedades pancreáticas::pancreatitis::pancreatitis aguda necrotizante [ENFERMEDADES], técnicas de investigación::métodos epidemiológicos::estadística como asunto::probabilidad::riesgo::factores de riesgo [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Acute pancreatitis, infecciones bacterianas y micosis::infección::infecciones intraabdominales [ENFERMEDADES], Pancreatitis, International study, Organ failure, Surgery, Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Mortality, Acute pancreatiti, Pàncrees - Necrosi, Bacterial Infections and Mycoses::Infection::Intraabdominal Infections [DISEASES]
Abstract

The identification of high-risk patients in the early stages of infected pancreatic necrosis (IPN) is critical, because it could help the clinicians to adopt more effective management strategies. We conducted a post hoc analysis of the MANCTRA-1 international study to assess the association between clinical risk factors and mortality among adult patients with IPN. Univariable and multivariable logistic regression models were used to identify prognostic factors of mortality. We identified 247 consecutive patients with IPN hospitalised between January 2019 and December 2020. History of uncontrolled arterial hypertension (p = 0.032; 95% CI 1.135–15.882; aOR 4.245), qSOFA (p = 0.005; 95% CI 1.359–5.879; aOR 2.828), renal failure (p = 0.022; 95% CI 1.138–5.442; aOR 2.489), and haemodynamic failure (p = 0.018; 95% CI 1.184–5.978; aOR 2.661), were identified as independent predictors of mortality in IPN patients. Cholangitis (p = 0.003; 95% CI 1.598–9.930; aOR 3.983), abdominal compartment syndrome (p = 0.032; 95% CI 1.090–6.967; aOR 2.735), and gastrointestinal/intra-abdominal bleeding (p = 0.009; 95% CI 1.286–5.712; aOR 2.710) were independently associated with the risk of mortality. Upfront open surgical necrosectomy was strongly associated with the risk of mortality (p p = 0.018; 95% CI 0.138–0.834; aOR 0.339) and enteral nutrition (p = 0.003; 95% CI 0.143–0.716; aOR 0.320) were found as protective factors. Organ failure, acute cholangitis, and upfront open surgical necrosectomy were the most significant predictors of mortality. Our study confirmed that, even in a subgroup of particularly ill patients such as those with IPN, upfront open surgery should be avoided as much as possible. Study protocol registered in ClinicalTrials.Gov (I.D. Number NCT04747990). Graphical abstract

Published
2023

68. coMpliAnce with evideNce-based cliniCal guidelines in the managemenT of acute biliaRy pancreAtitis): The MANCTRA-1 international audit

Author

Mauro Podda, Daniela Pacella, Gianluca Pellino, Federico Coccolini, Alessio Giordano, Salomone Di Saverio, Francesco Pata, Benedetto Ielpo, Francesco Virdis, Dimitrios Damaskos, Belinda De Simone, Ferdinando Agresta, Massimo Sartelli, Ari Leppaniemi, Cristiana Riboni, Vanni Agnoletti, Damian Mole, Yoram Kluger, Fausto Catena, Adolfo Pisanu, Chiara Gerardi, Salomone di Saverio, Dimitris Damaskos, Stavros Gourgiotis, Gaetano Poillucci, Kumar Jayant, Luca Ferrario, Mikel Prieto Calvo, Michael Wilson, Fiammetta Soggiu, Alaa Hamdan, Carlos Augusto Gomes, Gustavo Fraga, Argyrios Ioannidis, Zaza Demetrashvili, Saaz Sahani, Lovenish Bains, Almu'atasim Khamees, Hazim Ababneh, Osama Aljaiuossi, Samuel Pimentel, Ikhwan Sani Mohamad, Ahmad Ramzi Yusoff, Narcis Octavian Zarnescu, Valentin Calu, Andrey Litvin, Dusan Lesko, Ahmed Elmehrath, Mohamedraed Elshami, Martin de Santibañes, Justin Gundara, Kamel Alawadhi, Rashid Lui, Alexander Julianov, Sergio Ralon, Ibrahim-Umar Garzali, Gustavo M. Machain, Darwin Artidoro Quispe-Cruz, Abigail Cheska C. Orantia, Maciej Walędziak, Tiago Correia de Sá, Syed Muhammad Ali, Bojan Kovacevic, Colin Noel, Haidar M. Abdalah, Ali Kchaou, Arda Isik, Luca Ansaloni, Walter Biffl, Mario Guerrieri, Alberto Sartori, Manuel Abradelo, Giuseppe Nigri, Nicola Di Lorenzo, Andrea Mingoli, Massimo Chiarugi, Juliana Di Menno Stavron, Oscar Mazza, José Ignacio Valenzuela, Diana Alejandra Pantoja Pachajoa, Fernando Andrés Alvarez, Julian Ezequiel Liaño, Joan Tefay, Abdulrahman Alshaikh, Layla Hasan, Felipe Couto Gomes, Gustavo P. Fraga, Thiago R.A. Calderan, Elcio S. Hirano, Dragomir Dardanov, Azize Saroglu, Boyko Atanasov, Nikolay Belev, Nikola Kovachev, Shannon Melissa Chan, Hon-Ting Lok, Diego Salcedo, Diana Robayo, María Alejandra Triviño, Jan Manak, Jorann de Araujo, Ananya Sethi, Ahmed Awad, Merihan Elbadawy, Ahmed Farid, Asmaa Hanafy, Ahmed Nafea, null Sherief-Ghozy, Alzhraa Salah – Abbas, Wafaa Abdelsalam, Sameh Emile, Ahmed Elfallal, Hossam Elfeki, Hosam Elghadban, Ashraf Shoma, Mohamed Shetiwy, Mohamed Elbahnasawy, Salem- Mohamed, Emad Fawzi Hamed, Usama Ahmed Khalil, Elie Chouillard, Andrew Gumbs, Andréa Police, Andrea Mabilia, Kakhi Khutsishvili, Anano Tvaladze, Orestis Ioannidis, Elissavet Anestiadou, Lydia Loutzidou, Konstantinis Konstantinidis, Sofia Konstantinidou, Dimitrios Manatakis, Vasileios Acheimastos, Nikolaos Tasis, Nikolaos Michalopoulos, Panagiotis Kokoropoulos, Maria Papadoliopoulou, Maria Sotiropoulou, Stylianos Kapiris, Panagiotis Metaxas, Ioannis Tsouknidas, Despoina Kefili, George Petrakis, Konstantinos Dakis, Eirini Alexandridou, Eirini Synekidou, Kostas Dakis, Aristeidis Papadopoulos, Christos Chouliaras, Odysseas Mouzakis, Francesk Mulita, Ioannis Maroulis, Michail Vailas, Tania Triantafyllou, Dimitrios Theodorou, Eftychios Lostoridis, Eleni-Aikaterini Nagorni, Paraskevi Tourountzi, Efstratia Baili, Alexandros Charalabopoulos, Theodore Liakakos, Dimitrios Schizas, Alexandros Kozadinos, Athanasios Syllaios, Nikolaos Machairas, Stylianos Kykalos, Paraskevas Stamopoulos, Spiros Delis, Christos Farazi-Chongouki, Evangelos Kalaitzakis, Miltiadis Giannarakis, Konstantinos Lasithiotakis, Giorgia Petra, Amit Gupta, Noushif Medappil, Vijayanand Muthukrishnan, Jubin Kamar, Pawan Lal, Rajendra Agarwal, Matteo Magnoli, Paolo Aonzo, Alberto Serventi, Antonio Giuliani, Pierpaolo Di Lascio, Margherita Pinto, Carlo Bergamini, Andrea Bottari, Laura Fortuna, Jacopo Martellucci, Atea Cicako, Claudio Miglietta, Mario Morino, Daniele Delogu, Andrea Picchetto, Marco Assenza, Giancarlo D'Ambrosio, Giulio Argenio, Mariano Fortunato Armellino, Giovanna Ioia, Savino Occhionorelli, Dario Andreotti, Lacavalla Domenico, Davide Luppi, Massimiliano Casadei, Luca Di Donato, Farshad Manoochehri, Tiziana Rita Lucia Marchese, William Sergi, Roberto Manca, Raimondo Murgia, Enrico Piras, Lorenzo Conti, Simone Gianazza, Andrea Rizzi, Edoardo Segalini, Marco Monti, Elena Iiritano, Nicolò Maria Mariani, Enrico De Nicola, Giovanna Scifo, Giusto Pignata, Jacopo Andreuccetti, Francesco Fleres, Guglielmo Clarizia, Alessandro Spolini, Alan Biloslavo, Paola Germani, Manuela Mastronardi, Selene Bogoni, Silvia Palmisano, Nicolo’ De Manzini, Marco Vito Marino, Gennaro Martines, Giuseppe Trigiante, Elpiniki Lagouvardou, Gabriele Anania, Cristina Bombardini, Dario Oppici, Tiziana Pilia, Valentina Murzi, Emanuela Gessa, Umberto Bracale, Maria Michela Di Nuzzo, Roberto Peltrini, Francesco Salvetti, Jacopo Viganò, Gabriele Sganga, Valentina Bianchi, Pietro Fransvea, Tommaso Fontana, Giuliano Sarro, Vincenza Paola Dinuzzi, Luca Scaravilli, Mario Virgilio Papa, Elio Jovine, Giulia Ciabatti, Laura Mastrangelo, Matteo Rottoli, Claudio Ricci, Iris Shari Russo, Alberto Aiolfi, Davide Bona, Francesca Lombardo, Pasquale Cianci, Roberto Bini, Osvaldo Chiara, Stefano Cioffi, Stefano Cantafio, Guido Coretti, Edelweiss Licitra, Grazia Savino, Sergio Grimaldi, Raffaele Porfidia, Elisabetta Moggia, Mauro Garino, Chiara Marafante, Antonio Pesce, Nicolò Fabbri, Carlo Vittorio Feo, Ester Marra, Marina Troian, Davide Drigo, Carlo Nagliati, Muratore Andrea, Riccardo Danna, Alessandra Murgese, Michele Crespi, Claudio Guerci, Alice Frontali, Luca Ferrari, Francesco Favi, Erika Picariello, Alessia Rampini, Fabrizio D'Acapito, Giorgio Ercolani, Leonardo Solaini, Francesco Palmieri, Matteo Calì, Francesco Ferrara, Irnerio Angelo Muttillo, Edoardo Maria Muttillo, Biagio Picardi, Raffaele Galleano, Ali Badran, Omar Ghazouani, Maurizio Cervellera, Gaetano Campanella, Gennaro Papa, Annamaria Di Bella, Gennaro Perrone, Gabriele Luciano Petracca, Concetta Prioriello, Mario Giuffrida, Federico Cozzani, Matteo Rossini, Marco Inama, Giovanni Butturini, Gianluigi Moretto, Luca Morelli, Giulio Di Candio, Simone Guadagni, Enrico Cicuttin, Camilla Cremonini, Dario Tartaglia, Valerio Genovese, Nicola Cillara, Alessandro Cannavera, Antonello Deserra, Arcangelo Picciariello, Vincenzo Papagni, Leonardo Vincenti, Giulia Bagaglini, Giuseppe Sica, Pierfrancesco Lapolla, Gioia Brachini, Dario Bono, Antonella Nicotera, Marcello Zago, Fabrizio Sammartano, Laura Benuzzi, Marco Stella, Stefano Rossi, Alessandra Cerioli, Caterina Puccioni, Stefano Olmi, Carolina Rubicondo, Matteo Uccelli, Andrea Balla, Anna Guida, Pasquale Lepiane, Diego Sasia, Giorgio Giraudo, Sara Salomone, Elena Belloni, Alessandra Cossa, Francesco Lancellotti, Roberto Caronna, Piero Chirletti, Paolina Saullo, Raffaele Troiano, Felice Mucilli, Mirko Barone, Massimo Ippoliti, Michele Grande, Bruno Sensi, Leandro Siragusa, Monica Ortenzi, Andrea Santini, Isidoro Di Carlo, Massimiliano Veroux, Rossella Gioco, Gastone Veroux, Giuseppe Currò, Michele Ammendola, Iman Komaei, Giuseppe Navarra, Valeria Tonini, Lodovico Sartarelli, Samuele Vaccari, Marco Ceresoli, Stefano Perrone, Linda Roccamatisi, Paolo Millo, Riccardo Brachet Contul, Elisa Ponte, Matteo Zuin, Giuseppe Portale, Alice Sabrina Tonello, Geri Fratini, Matteo Bianchini, Bruno Perotti, Emanuele Doria, Elia Giuseppe Lunghi, Diego Visconti, Khayry Al-Shami, Sajeda Awadi, Mohammad Musallam Khalil Buwaitel, Mo'taz Fawzat Naief Naffa', Ahmad Samhouri, Hatem Sawalha, Mohd Firdaus Che Ani, Ida Nadiah Ahmed Fathil, Jih Huei, Andee Dzulkarnaen Zakaria, Mohammad Zawawi Ya'acob, Jose-Luis Beristain-Hernandez, Alejandro Garcia-Meza, Rafael Sepulveda-Rdriguez, Edgard Efren Lozada Hernández, Camilo Levi Acuña Pinzón, Jefferson Nieves Condoy, Francisco C. Becerra García, Mohammad Sadik, null Jalpa, Bushra kadir, Jalpa Devi, Nandlal Seerani, null Zainab, Mohammad Sohail- Asghar, Ameer Afzal, Ali Akbar, Helmut Segovia Lohse, Herald Segovia Lohse, Zamiara Solange Leon Cabrera, Gaby Susana Yamamoto Seto, José Ríos Chiuyari, Jorge Ordemar, Martha Rodríguez, Abigail Cheska C. Orantia-Carlos, Margie Antionette Quitoy, Andrzej Kwiatkowski, Maciej Mawlichanów, Mónica Rocha, Carlos Soares, Alexandru Rares Stoian, Andreea Diana Draghici, Valentin Titus Grigorean, Raluca Bievel Radulescu, Radu Virgil Costea, Eugenia Claudia Zarnescu, Mikhail Kurtenkov, George Gendrikson, Volovich Alla-Angelina, Tsurbanova Arina, Ayrat Kaldarov, Mahir Gachabayov, Abakar Abdullaev, Milica Milentijevic, Milovan Karamarkovic, Arpád Panyko, Jozef Radonak, Marek Soltes, Laura Álvarez Morán, Haydée Calvo García, Pilar Suárez Vega, Sergio Estevez, Fabio Ausania, Jordi Farguell, Carolina González-Abós, Santiago Sánchez-Cabús, Belén Martín, Víctor Molina, Luis Oms, Lucas Ilzarbe, Eva Pont Feijóo, Elena Sofia Perra, Noel Rojas-Bonet, Rafael Penalba-Palmí, Susana Pérez-Bru, Jaume Tur-Martínez, Andrea Álvarez-Torrado, Marta Domingo-Gonzalez, Javier Tejedor-Tejada, Marcello Di Martino, Yaiza García del Alamo, Fernando Mendoza-Moreno, Francisca García-Moreno-Nisa, Belén Matías-García, Manuel Durán, Rafael Calleja-Lozano, José Manuel Perez de Villar, Luis Sánchez-Guillén, Iban Caravaca, Daniel Triguero-Cánovas, Antonio Carlos Maya Aparicio, Blas Durán Meléndez, Andrea Masiá Palacios, Aitor Landaluce-olavarria, Mario De Francisco, Begoña Estraviz-Mateos, Felipe Alconchel, Tatiana Nicolás-López, Pablo Ramírez, Virginia Duran Muñoz-Cruzado, Felipe Pareja Ciuró, Eduardo Perea del Pozo, Sergio Olivares Pizarro, Vicente Herrera Cabrera, Jose Muros Bayo, Hytham K.S. Hamid, Raffaello Roesel, Alessandra Cristaudi, Kinan Abbas, Iyad Ali, Ahmed Tlili, Hüseyin Bayhan, Mehmet Akif Türkoğlu, Mustafa Yener Uzunoglu, Ibrahim Fethi Azamat, Nail Omarov, Derya Salim Uymaz, Fatih Altintoprak, Emrah Akin, Necattin First, Koray Das, Nazmi Ozer, Ahmet Seker, Yasin Kara, Mehmet Abdussamet Bozkurt, Ali Kocataş, Semra Demirli Atici, Murat Akalin, Bulent Calik, Elif Colak, Yuksel Altinel, Serhat Meric, Yunus Emre Aktimur, Victoria Hudson, Jean-Luc Duval, Mansoor Khan, Ahmed Saad, Mandeep Kaur, Alison Bradley, Katherine Fox, Ivan Tomasi, Daniel Beasley, Alekhya Kotta Prasanti, Pinky Kotecha, Husam Ebied, Michaela Paul, Hemant Sheth, Ioannis Gerogiannis, Mohannad Gaber, Zara Sheikh, Shatadru Seth, Maria Kunitsyna, Cosimo Alex Leo, Vittoria Bellato, Noman - Zafar, Amr Elserafy, Giles Bond-smith, Giovanni Tebala, Pawan Mathur, Izza Abid, Nnaemeka Chidumije, Pardip Sandhar, Syed Osama Zohaib Ullah, Tamara Lezama, Muhammad Hassan Anwaar, Conor Magee, Salma Ahmed, Brooke Davies, Jeyakumar Apollos, Kieran McCormack, Hasham Choudhary, Triantafyllos Doulias, Tamsin Morrison, Anna Palepa, Fernando Bonilla Cal, Lianet Sánchez, Fabiana Domínguez, Ibrahim Al-Raimi, Haneen Alshargabi, Abdullah Meead, Podda, Mauro, Pacella, Daniela, Pellino, Gianluca, Coccolini, Federico, Giordano, Alessio, Di Saverio, Salomone, Pata, Francesco, Ielpo, Benedetto, Virdis, Francesco, Damaskos, Dimitrio, De Simone, Belinda, Agresta, Ferdinando, Sartelli, Massimo, Leppaniemi, Ari, Riboni, Cristiana, Agnoletti, Vanni, Mole, Damian, Kluger, Yoram, Catena, Fausto, Pisanu, Adolfo, de Manzini, Nicolo', Palmisano, Silvia, Podda, M, Pacella, D, Pellino, G, Coccolini, F, Giordano, A, Di Saverio, S, Pata, F, Ielpo, B, Virdis, F, Damaskos, D, De Simone, B, Agresta, F, Sartelli, M, Leppaniemi, A, Riboni, C, Agnoletti, V, Mole, D, Kluger, Y, Catena, F, Pisanu, A, Gerardi, C, Gourgiotis, S, Poillucci, G, Jayant, K, Ferrario, L, Calvo, M, Wilson, M, Soggiu, F, Hamdan, A, Gomes, C, Fraga, G, Ioannidis, A, Demetrashvili, Z, Sahani, S, Bains, L, Khamees, A, Ababneh, H, Aljaiuossi, O, Pimentel, S, Mohamad, I, Yusoff, A, Zarnescu, N, Calu, V, Litvin, A, Lesko, D, Elmehrath, A, Elshami, M, de Santibanes, M, Gundara, J, Alawadhi, K, Lui, R, Julianov, A, Ralon, S, Garzali, I, Machain, G, Quispe-Cruz, D, Orantia, A, Waledziak, M, Correia de Sa, T, Ali, S, Kovacevic, B, Noel, C, Abdalah, H, Kchaou, A, Isik, A, Ansaloni, L, Biffl, W, Guerrieri, M, Sartori, A, Abradelo, M, Nigri, G, Di Lorenzo, N, Mingoli, A, Chiarugi, M, Di Menno Stavron, J, Mazza, O, Valenzuela, J, Pantoja Pachajoa, D, Alvarez, F, Liano, J, Tefay, J, Alshaikh, A, Hasan, L, Augusto Gomes, C, Gomes, F, Calderan, T, Hirano, E, Dardanov, D, Saroglu, A, Atanasov, B, Belev, N, Kovachev, N, Chan, S, Lok, H, Salcedo, D, Robayo, D, Trivino, M, Manak, J, de Araujo, J, Sethi, A, Awad, A, Elbadawy, M, Farid, A, Hanafy, A, Nafea, A, Sherief-Ghozy, Salah - Abbas, A, Abdelsalam, W, Emile, S, Elfallal, A, Elfeki, H, Elghadban, H, Shoma, A, Shetiwy, M, Elbahnasawy, M, Mohamed, S, Hamed, E, Khalil, U, Chouillard, E, Gumbs, A, Police, A, Mabilia, A, Khutsishvili, K, Tvaladze, A, Ioannidis, O, Anestiadou, E, Loutzidou, L, Konstantinidis, K, Konstantinidou, S, Manatakis, D, Acheimastos, V, Tasis, N, Michalopoulos, N, Kokoropoulos, P, Papadoliopoulou, M, Sotiropoulou, M, Kapiris, S, Metaxas, P, Tsouknidas, I, Kefili, D, Petrakis, G, Dakis, K, Alexandridou, E, Synekidou, E, Papadopoulos, A, Chouliaras, C, Mouzakis, O, Mulita, F, Maroulis, I, Vailas, M, Triantafyllou, T, Theodorou, D, Lostoridis, E, Nagorni, E, Tourountzi, P, Baili, E, Charalabopoulos, A, Liakakos, T, Schizas, D, Kozadinos, A, Syllaios, A, Machairas, N, Kykalos, S, Stamopoulos, P, Delis, S, Farazi-Chongouki, C, Kalaitzakis, E, Giannarakis, M, Lasithiotakis, K, Petra, G, Gupta, A, Medappil, N, Muthukrishnan, V, Kamar, J, Lal, P, Agarwal, R, Magnoli, M, Aonzo, P, Serventi, A, Giuliani, A, Di Lascio, P, Pinto, M, Bergamini, C, Bottari, A, Fortuna, L, Martellucci, J, Cicako, A, Miglietta, C, Morino, M, Delogu, D, Picchetto, A, Assenza, M, D'Ambrosio, G, Argenio, G, Armellino, M, Ioia, G, Occhionorelli, S, Andreotti, D, Domenico, L, Luppi, D, Casadei, M, Di Donato, L, Manoochehri, F, Lucia Marchese, T, Sergi, W, Manca, R, Murgia, R, Piras, E, Conti, L, Gianazza, S, Rizzi, A, Segalini, E, Monti, M, Iiritano, E, Mariani, N, De Nicola, E, Scifo, G, Pignata, G, Andreuccetti, J, Fleres, F, Clarizia, G, Spolini, A, Biloslavo, A, Germani, P, Mastronardi, M, Bogoni, S, Palmisano, S, De Manzini, N, Marino, M, Martines, G, Trigiante, G, Lagouvardou, E, Anania, G, Bombardini, C, Oppici, D, Pilia, T, Murzi, V, Gessa, E, Bracale, U, Di Nuzzo, M, Peltrini, R, Salvetti, F, Vigano, J, Sganga, G, Bianchi, V, Fransvea, P, Fontana, T, Sarro, G, Dinuzzi, V, Scaravilli, L, Papa, M, Jovine, E, Ciabatti, G, Mastrangelo, L, Rottoli, M, Ricci, C, Russo, I, Aiolfi, A, Bona, D, Lombardo, F, Cianci, P, Bini, R, Chiara, O, Cioffi, S, Cantafio, S, Coretti, G, Licitra, E, Savino, G, Grimaldi, S, Porfidia, R, Moggia, E, Garino, M, Marafante, C, Pesce, A, Fabbri, N, Feo, C, Marra, E, Troian, M, Drigo, D, Nagliati, C, Andrea, M, Danna, R, Murgese, A, Crespi, M, Guerci, C, Frontali, A, Ferrari, L, Favi, F, Picariello, E, Rampini, A, D'Acapito, F, Ercolani, G, Solaini, L, Palmieri, F, Cali, M, Ferrara, F, Muttillo, I, Muttillo, E, Picardi, B, Galleano, R, Badran, A, Ghazouani, O, Cervellera, M, Campanella, G, Papa, G, Di Bella, A, Perrone, G, Petracca, G, Prioriello, C, Giuffrida, M, Cozzani, F, Rossini, M, Inama, M, Butturini, G, Moretto, G, Morelli, L, Di Candio, G, Guadagni, S, Cicuttin, E, Cremonini, C, Tartaglia, D, Genovese, V, Cillara, N, Cannavera, A, Deserra, A, Picciariello, A, Papagni, V, Vincenti, L, Bagaglini, G, Sica, G, Lapolla, P, Brachini, G, Bono, D, Nicotera, A, Zago, M, Sammartano, F, Benuzzi, L, Stella, M, Rossi, S, Cerioli, A, Puccioni, C, Olmi, S, Rubicondo, C, Uccelli, M, Balla, A, Guida, A, Lepiane, P, Sasia, D, Giraudo, G, Salomone, S, Belloni, E, Cossa, A, Lancellotti, F, Caronna, R, Chirletti, P, Saullo, P, Troiano, R, Mucilli, F, Barone, M, Ippoliti, M, Grande, M, Sensi, B, Siragusa, L, Ortenzi, M, Santini, A, Di Carlo, I, Veroux, M, Gioco, R, Veroux, G, Curro, G, Ammendola, M, Komaei, I, Navarra, G, Tonini, V, Sartarelli, L, Vaccari, S, Ceresoli, M, Perrone, S, Roccamatisi, L, Millo, P, Contul, R, Ponte, E, Zuin, M, Portale, G, Tonello, A, Fratini, G, Bianchini, M, Perotti, B, Doria, E, Lunghi, E, Visconti, D, Al-Shami, K, Awadi, S, Khalil Buwaitel, M, Naief Naffa', M, Samhouri, A, Sawalha, H, Ramzi Yusoff, A, Che Ani, M, Ahmed Fathil, I, Huei, J, Zakaria, A, Ya'Acob, M, Beristain-Hernandez, J, Garcia-Meza, A, Sepulveda-Rdriguez, R, Lozada Hernandez, E, Acuna Pinzon, C, Condoy, J, Becerra Garcia, F, Sadik, M, Jalpa, Kadir, B, Devi, J, Seerani, N, Zainab, Asghar, M, Afzal, A, Akbar, A, Lohse, H, Artidoro Quispe-Cruz, D, Leon Cabrera, Z, Yamamoto Seto, G, Chiuyari, J, Ordemar, J, Rodriguez, M, Orantia-Carlos, A, Quitoy, M, Kwiatkowski, A, Mawlichanow, M, Rocha, M, Soares, C, Muhammad Ali, S, Stoian, A, Diana Draghici, A, Draghici, A, Grigorean, V, Radulescu, R, Costea, R, Zarnescu, E, Kurtenkov, M, Gendrikson, G, Alla-Angelina, V, Arina, T, Kaldarov, A, Gachabayov, M, Abdullaev, A, Milentijevic, M, Karamarkovic, M, Panyko, A, Radonak, J, Soltes, M, Alvarez Moran, L, Garcia, H, Vega, P, Estevez, S, Ausania, F, Farguell, J, Gonzalez-Abos, C, Sanchez-Cabus, S, Martin, B, Molina, V, Oms, L, Ilzarbe, L, Feijoo, E, Perra, E, Rojas-Bonet, N, Penalba-Palmi, R, Perez-Bru, S, Tur-Martinez, J, Alvarez-Torrado, A, Domingo-Gonzalez, M, Tejedor-Tejada, J, Di Martino, M, Garcia del Alamo, Y, Mendoza-Moreno, F, Garcia-Moreno-Nisa, F, Matias-Garcia, B, Duran, M, Calleja-Lozano, R, Perez de Villar, J, Sanchez-Guillen, L, Caravaca, I, Triguero-Canovas, D, Maya Aparicio, A, Melendez, B, Palacios, A, Landaluce-olavarria, A, De Francisco, M, Estraviz-Mateos, B, Alconchel, F, Nicolas-Lopez, T, Ramirez, P, Munoz-Cruzado, V, Ciuro, F, Perea del Pozo, E, Pizarro, S, Cabrera, V, Bayo, J, Hamid, H, Roesel, R, Cristaudi, A, Abbas, K, Ali, I, Tlili, A, Bayhan, H, Turkoglu, M, Uzunoglu, M, Azamat, I, Omarov, N, Uymaz, D, Altintoprak, F, Akin, E, First, N, Das, K, Ozer, N, Seker, A, Kara, Y, Bozkurt, M, Kocatas, A, Atici, S, Akalin, M, Calik, B, Colak, E, Altinel, Y, Meric, S, Aktimur, Y, Hudson, V, Duval, J, Khan, M, Saad, A, Kaur, M, Bradley, A, Fox, K, Tomasi, I, Beasley, D, Prasanti, A, Kotecha, P, Ebied, H, Paul, M, Sheth, H, Gerogiannis, I, Gaber, M, Sheikh, Z, Seth, S, Kunitsyna, M, Leo, C, Bellato, V, Zafar, N, Elserafy, A, Bond-smith, G, Tebala, G, Mathur, P, Abid, I, Chidumije, N, Sandhar, P, Zohaib Ullah, S, Lezama, T, Anwaar, M, Magee, C, Ahmed, S, Davies, B, Apollos, J, Mccormack, K, Choudhary, H, Doulias, T, Morrison, T, Palepa, A, Cal, F, Sanchez, L, Dominguez, F, Al-Raimi, I, Alshargabi, H, and Meead, A

Subjects
Acute pancreatitis, Biliary pancreatitis, Global surgery, Guidelines compliance, International audit, Hepatology, Endocrinology, Diabetes and Metabolism, Gastroenterology, Settore MED/18, Hospitalization, Enteral Nutrition, Pancreatitis, Acute Disease, Humans, Biliary pancreatiti, Cholecystectomy, Acute pancreatiti, Human
Abstract

Background/objectives: Reports about the implementation of recommendations from acute pancreatitis guidelines are scant. This study aimed to evaluate, on a patient-data basis, the contemporary practice patterns of management of biliary acute pancreatitis and to compare these practices with the recommendations by the most updated guidelines. Methods: All consecutive patients admitted to any of the 150 participating general surgery (GS), hepatopancreatobiliary surgery (HPB), internal medicine (IM) and gastroenterology (GA) departments with a diagnosis of biliary acute pancreatitis between 01/01/2019 and 31/12/2020 were included in the study. Categorical data were reported as percentages representing the proportion of all study patients or different and well-defined cohorts for each variable. Continuous data were expressed as mean and standard deviation. Differences between the compliance obtained in the four different subgroups were compared using the Mann-Whitney U, Student's t, ANOVA or Kruskal-Wallis tests for continuous data, and the Chi-square test or the Fisher's exact test for categorical data. Results: Complete data were available for 5275 patients. The most commonly discordant gaps between daily clinical practice and recommendations included the optimal timing for the index CT scan (6.1%, χ2 6.71, P = 0.081), use of prophylactic antibiotics (44.2%, χ2 221.05, P < 0.00001), early enteral feeding (33.2%, χ2 11.51, P = 0.009), and the implementation of early cholecystectomy strategies (29%, χ2 354.64, P < 0.00001), with wide variability based on the admitting speciality. Conclusions: The results of this study showed an overall poor compliance with evidence-based guidelines in the management of ABP, with wide variability based on the admitting speciality. Study protocol registered in ClinicalTrials.Gov (ID Number NCT04747990).

Published
2022

69. Changes in digestive cancer diagnosis during the SARS-CoV-2 pandemic in Italy: A nationwide survey

Author

Gian Luigi de’Angelis, Francesco Buttitta, Elisa Stasi, Socrate Pallio, Maria Antonia Bianco, S. Bargiggia, Costanza Alvisi, Monica Sbrancia, Giancarla Fiori, Maria Carla Di Paolo, Carmelo Luigiano, Carlo Manfrini, Guido Missale, Stefano Rodinò, Bastianello Germanà, Davide Checchin, L.M. Montalbano, Monica Cesarini, Michela Cameletti, Antonietta D'Errico, Franco Bazzoli, Eìlisabetta Buscarini, Adriano Lauri, Vincenzo Giorgio Mirante, Luigi Ricciardiello, Raffaele Manta, Sara Massironi, Cecilia Binda, Matteo Brunacci, Vincenzo Occhipinti, Simona Attardo, Salvatore Russo, Paolo Usai-Satta, Maurizio Giovannone, Giuseppe De Caro, Antonio Benedetti, Marco Di Marco, Giovanni Serio, Francesco Broglia, Clarissa Ferrari, Luca Ferraris, Marco Dal-Fante, Thomas Togliani, Maria Cristina Conti-Bellocchi, Osvaldo Burattini, Orazio La Bianca, Alessandro Mussetto, Luigi Pasquale, Fabio Monica, Andrea Anderloni, Domenica Alvaro, Manuele Dinca, Debora Berretti, Rosamaria Bozzi, Enrico Piras, Bruno Nipote, Buscarini E., Benedetti A., Monica F., Pasquale L., Buttitta F., Cameletti M., Ferrari C., Ricciardiello L., Massironi S., Bianco M.A., Germana B., Rodino S., Anderloni A., Mussetto A., Nipote B., Russo S., Manta R., Lauri A., Occhipinti V., Marco M.D., Giovannone M., Binda C., Sbrancia M., Paolo M.C.D., de'-Angelis G.L., Fiori G., Dal-Fante M., Caro G.D., Usai-Satta P., Cesarini M., Piras E., Stasi E., Serio G., Montalbano L.M., Mirante V.G., Burattini O., Attardo S., Bargiggia S., Dinca M., Missale G., Alvisi C., Broglia F., Ferraris L., Conti-Bellocchi M.C., Luigiano C., Pallio S., Brunacci M., Manfrini C., Bozzi R., Checchin D., Togliani T., D'errico A., Bazzoli F., La Bianca O., Berretti D., and Alvaro D.

Subjects
medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Colorectal cancer, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), COVID-19, Gastric cancer, Pancreatic cancer, SARS-CoV-2, Digestive System Neoplasms, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Surveys and Questionnaires, Pandemic, medicine, Diagnostic Techniques, Digestive System, Gastroenterology, Humans, Infection Control, Italy, Organizational Innovation, Delivery of Health Care, Early Detection of Cancer, Stomach cancer, Hepatology, business.industry, Stomach, Cancer, medicine.disease, Diagnostic Techniques, medicine.anatomical_structure, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, business, Settore SECS-S/01 - Statistica, Digestive System
Abstract

Background The SARS-CoV-2 pandemic has had a huge impact on healthcare systems, resulting in many routine diagnostic procedures either being halted or postponed. Aims To evaluate whether the diagnoses of colorectal, gastric and pancreatic cancers have been impacted by the SARS-CoV-2 pandemic in Italy. Methods A survey designed to collect the number of histologically-proven diagnoses of the three cancers in gastroenterology services across Italy from January 1 to October 31 in 2017–2020. Non-parametric ANOVA for repeated measurements was applied to compare distributions by years and macro-areas. Results Compared to 2019, in 2020 gastric cancer diagnoses decreased by 15.9%, CRC by 11.9% and pancreatic by 9.9%. CRC distributions showed significant differences between all years, stomach cancer between 2018 and 2020 and 2019–2020, and pancreatic cancer only between 2017 and 2019. The 2019–2020 comparison showed fewer CRC diagnoses in the North (-13.7%), Center (-16.5%) and South (-4.1%), fewer stomach cancers in the North (-19.0%) and South (-9.4%), and fewer pancreatic cancers in the North (-14.1%) and Center (-4.7%), with an increase in the South (+12.3%). Distributions of CRC and gastric cancer were significantly different between all years in the North. Conclusions This survey highlights the concerning effects of the COVID-19 pandemic on the diagnostic yield of gastroenterology services for stomach, colorectal and pancreatic cancers in Italy.

Published
2021

70. La promozione della salute come forma di welfare aziendale: la co-costruzione di un'iniziativa di WHP tra prevenzione primaria e processi di simbolizzazione

Author

Enrico Maria Piras, Paolo Rossi, Francesco Miele, Piras, E, Rossi, P, Miele, F, Piras, Enrico Maria, Rossi, Paolo, and Miele, Francesco

Subjects
Economics and Econometric, Organizational Behavior and Human Resource Management, Economics and Econometrics, Sociology and Political Science, Organization studie, Case study, Workplace health promotion, Organization studies, Political science, Co-consruction, organization studies, workplace health promotion, co-consruction, case study, Humanities
Abstract

La promozione della salute sui luoghi di lavoro è oggetto di riflessione e analisi di discipline che vanno dalla medicina preventiva fino alle scienze aziendali, passando per la dietologia e le scienze motorie. Il nostro articolo si propone invece di contribuire al dibattito sulla promozione della salute sui luoghi di lavoro da una prospettiva organizzativista, indagandone gli aspetti processuali e la significazione simbolica nei contesti organizzativi. A questo scopo, il lavoro documenta e analizza la progettazione di Key to Health, un’iniziativa di Workplace Health Promotion condotta presso un grande istituto di ricerca con sede nella Provincia Autonoma di Trento. Tramite l’analisi dello studio di caso del progetto Key to Health, l’articolo intende riflettere sui processi di co-costruzione di un intervento di Workplace Health Promotion, soffermandosi sulle tensioni emergenti dai diversi modi di concepire e rappresentare la gestione della salute all’interno di un’organizzazione.

Published
2018

71. Data work in healthcare: An Introduction

Author

Gunnar Ellingsen, Federico Cabitza, Kathleen H. Pine, Claus Bossen, Enrico Maria Piras, Bossen, C, Pine, K, Cabitza, F, Ellingsen, G, and Piras, E

Subjects
Data Analysis, business.industry, ehealth, Data Work, Healthcare, MEDLINE, Health Informatics, Datafication, Data science, Data Accuracy, Health Care, Health Information Management, Work (electrical), VDP::Teknologi: 500::Medisinsk teknologi: 620, Data accuracy, Health care, Electronic Health Records, Humans, Data work, Business, Delivery of Health Care, VDP::Technology: 500::Medical technology: 620
Abstract

Why data work in healthcare? Healthcare organizations across the globe are currently grappling to implement tools and practices to transform data from “refuse to riches,” a movement propelled by mass adoption of electronic health records (EHRs), sensors, and servers that can hold an ever-expanding volume of digital data. Allegedly, “By digitizing, combining and effectively using big data, healthcare organizations ranging from single-physician offices and multi-provider groups to large hospital networks and accountable care organizations stand to realize significant benefits.” The potential is “. . . to improve care, save lives and lower costs.” As a consequence, organizations are struggling under massive institutional pressures to make healthcare “data-driven” against the messy reality of creating, managing, analyzing, and using data for management, decision-making, accountability, and medical research.

Published
2019

73. A new enzyme-linked immunosorbent assay for a total anti-T lymphocyte globulin determination: Development, analytical validation, and clinical applications

Author

Mario Regazzi, Giorgio La Nasa, Franco Locatelli, Maria Antonietta Avanzini, Michela Montagna, Maria Ester Bernardo, Eugenia Piras, Montagna, M., La Nasa, G., Bernardo, M. E., Piras, E., Avanzini, M. A., Regazzi, M., and Locatelli, F.

Subjects
Male, Globulin, Adolescent, medicine.medical_treatment, Lymphocyte, T-Lymphocytes, Graft vs Host Disease, Enzyme-Linked Immunosorbent Assay, Hematopoietic stem cell transplantation, Pharmacology, Antibodies, 03 medical and health sciences, Microtiter plate, 0302 clinical medicine, Pharmacokinetics, medicine, Humans, Transplantation, Homologous, Pharmacology (medical), Child, Saline, biology, business.industry, Hematopoietic Stem Cell Transplantation, Infant, ATG, Transplantation, medicine.anatomical_structure, Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA, Paediatric, 030220 oncology & carcinogenesis, Child, Preschool, Immunoglobulin G, biology.protein, Thalassemia, ELISA, Female, business, 030215 immunology, Blood sampling
Abstract

Background: Anti-T lymphocyte globulin (ATLG) modulates the alloreactivity of T lymphocytes, reducing the risk of immunological posttransplant complications, in particular rejection and graft-versushost disease, after allogeneic hematopoietic stem cell transplantation (HSCT). We developed and validated a new enzyme-linked immunosorbent assay (ELISA) method to measure serum levels of total ATLG and evaluate the pharmacokinetics (PK) of the drug in children with b-Thalassemia, receiving allogeneic HSCT. Methods: Diluted serum samples were incubated with Goat-anti- Rabbit IgG antibody coated on a microtiter plate and then, with Goat-anti-Human IgG labeled with horseradish peroxidase. After incubation and washings, substrate solution was added and absorbance was read at 492 nm. ATLG concentrations in samples were determined by interpolation from a standard curve (range: 200-0.095 ng/mL), prepared by diluting a known amount of ATLG in phosphate-buffered saline (PBS). Low, medium, and high-quality control concentrations were 1.56, 6.25, and 25 ng/ mL, respectively. This method was developed and validated within the acceptance criteria in compliance with the Guidelines for a biological method validation: the sensitivity of the method was 0.095 ng/mL. We analyzed serum samples from 14 children with b-Thalassemia who received ATLG (Grafalon) at a dose of 10 mg/kg administered as intravenous (IV) infusion on days 25, 24, and 23 before HSCT (day 0). Blood sampling for PK evaluation was performed on days 25, 24, and 23 before and after drug infusion; and then from day 22 to +56. Results: The median total ATLG levels pre-IVand post-IV were 0 and 118 mcg/mL on day 25; 85.9 and 199.2 mcg/mL on day 24; 153 and 270.9 mcg/mL on day 23, respectively. The median PK values of CL was 0.0029 (range: 0.0028-0.0057) L$kg21$d21, Vd was 0.088 (range: 0.025-0.448) L/kg and t1/2 was 20.2 (range: 5.8- 50.2) days. Conclusions: These data suggest that given the marked interindividual variability of total ATLG disposition, the development of a validated ELISA method and the possibility to measure PK parameters in paediatric populations are essential steps to optimize drug therapeutic regimens.

Published
2017

74. La medicina generale come lavoro di configurazione: gestire le terapie complesse nel paziente anziano

Author

Miele, Francesco, Piras, Enrico Maria, Bruni, Enrico, Coletta, Claudio, Zanutto, Alberto, Miele, Francesco, Piras, Enrico Maria, Bruni, A., Coletta, C., Zanutto, A., Auricchio A, Cruciani M, Rega A, Villani M, Miele F, Piras E, Bruni A, Coletta C, Zanutto A, A. Auricchio M. Cruciani A. Rega M. Villani, Bruni, Enrico, Coletta, Claudio, and Zanutto, Alberto

Subjects
N/A
Abstract

N/A

Published
2013

75. Allogeneic hematopoietic stem cell transplantation in thalassemia major: Results of a reduced-toxicity conditioning regimen based on the use of treosulfan

Author

Adriana Vacca, Maria Ester Bernardo, Daria Pagliara, Franco Locatelli, Eugenia Piras, Marco Zecca, Giovanna Giorgiani, Benedetta Contoli, Giovanni Caocci, Rita Maria Pinto, Giorgio La Nasa, Angela Mastronuzzi, Alice Bertaina, Bernardo, M. E., Piras, E., Vacca, A., Giorgiani, G., Zecca, M., Bertaina, A., Pagliara, D., Contoli, B., Pinto, R. M., Caocci, G., Mastronuzzi, A., La Nasa, G., and Locatelli, F.

Subjects
Male, Transplantation Conditioning, medicine.medical_treatment, Thalassemia, Graft vs Host Disease, Hematopoietic stem cell transplantation, Biochemistry, Cohort Studies, analogs /&/ derivatives/therapeutic use, Risk Factors, Cumulative incidence, Child, Adolescent, Adult, Busulfan, analogs /&/ derivatives/therapeutic use, Child, Child, Preschool, Cohort Studies, Female, Graft vs Host Disease, etiology, Hematopoietic Stem Cell Transplantation, adverse effects/methods/mortality, Humans, Infant, Male, Myeloablative Agonists, therapeutic use, Risk Factors, Thiotepa, therapeutic use, Transplantation Conditioning, methods, Transplantation, Homologous, Treatment Outcome, Vidarabine, analogs /&/ derivatives/therapeutic use, Young Adult, beta-Thalassemia, therapy, Hematopoietic Stem Cell Transplantation, Hematology, Fludarabine, surgical procedures, operative, Treatment Outcome, Child, Preschool, Female, Vidarabine, medicine.drug, Homologous, Adult, medicine.medical_specialty, Adolescent, etiology, Immunology, ThioTEPA, Treosulfan, methods, Young Adult, adverse effects/methods/mortality, Internal medicine, medicine, Humans, Transplantation, Homologous, Preschool, Busulfan, Transplantation, business.industry, beta-Thalassemia, Infant, Cell Biology, Myeloablative Agonists, medicine.disease, Surgery, Regimen, therapeutic use, business, Thiotepa
Abstract

Sixty thalassemia patients (median age, 7 years; range, 1-37) underwent allogeneic hematopoietic stem cell transplantation (HSCT) after a preparation combining thiotepa, treosulfan, and fludarabine. Before HSCT, 27 children were assigned to risk class 1 of the Pesaro classification, 17 to class 2, and 4 to class 3; 12 patients were adults. Twenty patients were transplanted from an HLA-identical sibling and 40 from an unrelated donor. The cumulative incidence of graft failure and transplantation-related mortality was 9% and 7%, respectively. Eight patients experienced grade II-IV acute GVHD, the cumulative incidence being 14%. Among 56 patients at risk, 1 developed limited chronic GVHD. With a median follow-up of 36 months (range, 4-72), the 5-year probability of survival and thalassemia-free survival are 93% and 84%, respectively. Neither the class of risk nor the donor used influenced outcome. This treosulfan-based preparation proved to be safe and effective for thalassemia patients given allogeneic HSCT.

Published
2012

76. Considerazioni preliminari in tre punti di sutura: scienza, anatomia e discorso

Author

PIRAS, ANDREA, A. PIRAS, P. DELAINI, A. FOSCATI, F. MARCHETTI, E. CILLI, A. PIRAS E P. DELAINI, and A. Piras

Subjects
TERAPEUTICA, STORIA DELLA MEDICINA, METAFORE MEDICHE, ANATOMIA, ETNOSCIENZE
Abstract

relazione introduttiva dei lavori congressuali e punto di vista sulle recenti acquisizioni di antropologia medica e di etnoscienze, sia nell'ambito orientalistico del settore disciplinare dello scrivente, sia nel ripercorrere le concezioni mediche della scienza greco-ellenistica e romana, con considerazioni sul cristianesimo e sui paradigmi scientifici dell'occcidente medievale e moderno. **Si rimanda al volume qui inserito in pdf per una valutazione complessiva dell'opera**

Published
2010

77. Treosulfan-based conditioning regimen for allogeneic haematopoietic stem cell transplantation in patients with thalassaemia major

Author

Pietro Merli, Adriana Vacca, Angela Mastronuzzi, Marco Zecca, Maria Ester Bernardo, Giovanna Giorgiani, Giovanni Caocci, Patrizia Comoli, Eugenia Piras, Giorgio La Nasa, Chiara Cugno, Franco Locatelli, Bernardo, M. E., Zecca, M., Piras, E., Vacca, A., Giorgiani, G., Cugno, C., Caocci, G., Comoli, P., Mastronuzzi, A., Merli, P., La Nasa, G., and Locatelli, F.

Subjects
Adult, Graft Rejection, Male, medicine.medical_specialty, Transplantation Conditioning, Treosulfan, Adolescent, medicine.medical_treatment, Graft vs Host Disease, Hematopoietic stem cell transplantation, ThioTEPA, Young Adult, Conditioning regimen, Internal medicine, medicine, Humans, Cumulative incidence, Child, Busulfan, Toxicity, business.industry, beta-Thalassemia, Haematopoietic stem cell transplantation, Hematopoietic Stem Cell Transplantation, Infant, Thalassaemia major, Hematology, Myeloablative Agonists, medicine.disease, Surgery, Fludarabine, Transplantation, Regimen, Hemoglobinopathy, Treatment Outcome, Child, Preschool, Adolescent, Adult, Busulfan, adverse effects/analogs /&/ derivatives/therapeutic use, Child, Child, Preschool, Drug Therapy, Combination, Female, Graft Rejection, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation, Humans, Infant, Male, Myeloablative Agonists, adverse effects/therapeutic use, Thiotepa, adverse effects/therapeutic use, Transplantation Conditioning, adverse effects/methods, Treatment Outcome, Vidarabine, adverse effects/analogs /&/ derivatives/therapeutic use, Young Adult, beta-Thalassemia, drug therapy/therapy, Drug Therapy, Combination, Female, business, Thiotepa, Vidarabine, medicine.drug
Abstract

The safety and efficacy of a preparation with treosulfan/thiotepa/ fludarabine were explored in 20 thalassaemia patients given allogeneic marrow transplantation. Seventeen patients were transplanted from unrelated donors after receiving anti-thymocyte globulin. The regimen was well tolerated. Two patients experienced secondary graft failure; one died of acute graft-versus-host disease. Cumulative incidence (95% confidence interval, CI) of transplantation-related mortality and graft failure was 5% (95% CI, 0-34%) and 11% (95% CI, 3-43%), respectively. Two-year probability of survival and thalassaemia-free survival was 95% (95% CI, 85-100%) and 85% (95% CI, 66-100%), respectively. This regimen might find elective application in patients at high risk of developing life-threatening complications. © 2008 The Authors.

Published
2008

78. The human leucocyte antigen-G 14-basepair polymorphism correlates with graft-versus-host disease in unrelated bone marrow transplantation for thalassaemia

Author

F Alba, Eugenia Piras, Carlo Carcassi, Daniela Lisini, Adriana Vacca, Nesci S, Alessandra Di Cesare-Merlone, Sandro Orru, Franco Locatelli, Maria Ester Bernardo, Sara Lai, Giorgio La Nasa, Giovanni Caocci, Roberto Littera, La Nasa, G, Littera, R, Locatelli, F, Lai, S, Alba, F, Caocci, G, Lisini, D, Nesci, S, Vacca, A, Piras, E, Bernardo, M, Di Cesare-Merlone, A, Orrù, S, and Carcassi, C

Subjects
Hemolytic anemia, Adult, Male, medicine.medical_specialty, Bone marrow transplantation, Adolescent, Genes, MHC Class I, Graft vs Host Disease, Human leukocyte antigen, Biology, Risk Assessment, Immune tolerance, Immunopathology, Internal medicine, Genotype, medicine, Humans, Genetic Testing, Child, 14-basepair polymorphism, Bone Marrow Transplantation, Acute graft-versus-host disease, Hematology, Polymorphism, Genetic, Human leucocyte antigen-G, Thalassaemia, medicine.disease, medicine.anatomical_structure, Graft-versus-host disease, Treatment Outcome, Child, Preschool, Immunology, Thalassemia, Female, Bone marrow, Gene Deletion
Abstract

The presence of the 14-bp insertion polymorphism of the human leucocyte antigen (HLA)-G gene (HLA-G) promotes immune tolerance through increased synthesis of HLA-G molecules. We investigated this polymorphism in a large cohort of 53 thalassaemia patients transplanted from an unrelated donor. Sixteen patients (30.2%) homozygous for the 14-bp deletion had a higher risk of developing acute graft-versus-host disease (aGvHD) than patients homozygous for the 14-bp insertion (-14-bp/-14-bp vs +14-bp/+14-bp: Relative Risk = 15.0; 95% confidence interval 1.59-141.24; P = 0.008). Therefore, the 14-bp polymorphism could be an important predictive factor for aGvHD following bone marrow transplantation. © 2007 The Authors.

Published
2007

79. Ret, Abl1 (cAbl) and Trp53 gene fragmentations in comet-FISH assay act as in vivo biomarkers of radiation exposure in C57BL/6 and CBA/J mice

Author

Elena Piras, Giovanni Romeo, Anna Giovanetti, Emiliano Basso, Claudia Volpato, Pier Giorgio Pacifici, Roberto Amendola, Amendola R., Basso E., Pacifici PG., Piras E., Giovanetti A., Volpato C., and Romeo G.

Subjects
C57BL/6, Biophysics, DNA Fragmentation, Ionizing radiation, Mice, Dicentric chromosome, Radiation Monitoring, In vivo, Animals, Radiology, Nuclear Medicine and imaging, Cells, Cultured, In Situ Hybridization, Fluorescence, Adaptor Proteins, Signal Transducing, Radiation, ABL, biology, business.industry, Chemistry, Proto-Oncogene Proteins c-ret, DNA, Environmental Exposure, biology.organism_classification, Molecular biology, Mice, Inbred C57BL, Comet assay, Cytoskeletal Proteins, Micronucleus test, Leukocytes, Mononuclear, Mice, Inbred CBA, Comet Assay, Tumor Suppressor Protein p53, Radiation protection, Nuclear medicine, business, Biomarkers, DNA Damage
Abstract

The International Commission on Radiation Protection (ICRP) has lowered the dose limits for workers and for the general public exposed to ionizing radiation. Consequently, a reliable dosimetric method for monitoring possible radiation-induced damage is of great importance in radioprotection. The counting of dicentric chromosomal aberrations and of micronuclei in peripheral blood lymphocytes is unreliable when it is applied to in vivo biopsies and for low-dose exposures. Single-cell gel electrophoresis (SCGE or comet assay), although sensitive and rapid, shows high variability when applied in vivo, probably due to prompt repair of the DNA breaks and confounding environmental factors. In this paper, we describe specific in situ hybridization of Ret, Abl1 (cAbl), and Trp53 gene fragmentations on SCGE slides (comet-FISH assay) in peripheral blood cells from C57BL/6 and CBA/J mice as an indicator of radiation-induced DNA damage. The results obtained from four mice for each experimental point (0, 1, 2 and 4 Gy of X rays) discriminated in a statistically significant way the effects of all doses when fragmentations were analyzed for the Ret, Ab1 and Trp53 genes. SCGE alone, when applied to the same specimens, produced no significant results because of interindividual and experimental variability.

Published
2006

80. Unrelated bone marrow transplantation for β-thalassemia patients: The experience of the Italian bone marrow transplant group

Author

Andrea Pession, Eugenia Piras, Adriana Vacca, Antonio Ledda, Giorgio La Nasa, Piero De Stefano, Antonio Piroddi, Franca Argiolu, Roberto Littera, Giovanni Caocci, Claudio Giardini, Nesci S, Franca Fagioli, Franco Locatelli, La Nasa G., Argiolu F., Giardini C., Pession A., Fagioli F., Caocci G., Vacca A., De Stefano P., Piras E., Ledda A., Piroddi A., Littera R., Nesci S., and Locatelli F.

Subjects
Graft Rejection, Male, Genetics and Molecular Biology (all), Transplantation Conditioning, Thalassemia, medicine.medical_treatment, Graft vs Host Disease, Biochemistry, Living Donors, Life Tables, Child, Bone Marrow Transplantation, HLA compatibility criteria, General Neuroscience, Incidence, Beta thalassemia, Immunosuppression, Middle Aged, Combined Modality Therapy, surgical procedures, operative, Treatment Outcome, Italy, Child, Preschool, Histocompatibility, Unrelated bone marrow transplantation, Adolescent, Adult, Blood Transfusion, Disease-Free Survival, Female, Humans, Retrospective Studies, Risk Assessment, Survival Analysis, Transplantation, Homologous, beta-Thalassemia, Neuroscience (all), Biochemistry, Genetics and Molecular Biology (all), History and Philosophy of Science, Homologous, medicine.medical_specialty, General Biochemistry, Genetics and Molecular Biology, Internal medicine, medicine, Preschool, Survival analysis, Immunosuppression Therapy, Transplantation, Donor selection, business.industry, Retrospective cohort study, medicine.disease, Surgery, business
Abstract

Bone marrow transplantation (BMT) remains the only potentially curative treatment for patients with thalassemia major. However, most candidates for BMT do not have a suitable family donor. In order to evaluate whether BMT from an HLA-matched unrelated volunteer donor can offer a probability of cure comparable to that obtained when the donor is a compatible sibling, we carried out a study involving 68 thalassemia patients transplanted in six Italian BMT Centers. Thirty-three males and 35 females (age range, 2-37 years; median age, 15) were transplanted from unrelated volunteer donors, all selected using high-resolution molecular typing of both HLA class I and II loci. Fourteen patients were classified in risk class 1; 16 in risk class 2; and 38 in risk class III of the Pesaro classification system. Nine patients (13%) had either primary or secondary graft failure. Fourteen patients (20%) died from transplant-related causes. Grade II-IV acute graft-versus-host disease (GVHD) developed in 24 cases (40%), and chronic GVHD in 10 cases (18%). Overall survival (OS) in the cohort of 68 patients was 79.3% (CI 67-88%), whereas the Kaplan-Meier estimates of disease-free survival (DFS) with transfusion independence was 65.8% (CI 54-77%). In the group of 30 thalassemic patients in risk classes 1 and 2, the probability of OS and DFS were 96.7% (CI 90-100%) and 80.0% (CI 65-94%), respectively, whereas in the 38 patients in class 3 OS was 65.2% (CI 49-80%) and DFS was 54.5% (CI 38-70%). These data show that when donor selection is based on stringent compatibility criteria, the results of unrelated transplantation in thalassemia patients are comparable to those obtained when the donor is a compatible sibling.

Published
2005

82. Feasibility, safety, and efficacy of a new percutaneous interspinous device: a retrospective multicenter study.

Author

Marcia S, Hirsch JA, Bellini M, Sadotti G, Manfré L, De Vivo AE, Piras E, Zini G, and Zini C

Subjects
Humans, Male, Aged, Female, Middle Aged, Aged, 80 and over, Retrospective Studies, Lumbar Vertebrae surgery, Lumbar Vertebrae diagnostic imaging, Tomography, X-Ray Computed, Treatment Outcome, Prostheses and Implants, Decompression, Surgical methods, Feasibility Studies, Spinal Stenosis surgery, Spinal Stenosis diagnostic imaging
Abstract

Purpose: To evaluate safety and efficacy of the novel percutaneous interspinous device (PID) for the treatment of symptomatic degenerative lumbar spinal stenosis (DLSS) in 3 different centers., Methods: From November 2016 to March 2020, 255 patients (male 125, mean age 71.2 years old range 49-91 years old) with neurogenic claudication, confirmed by electromyography, related to mono or bi-segmental lumbar central canal and/or foraminal stenosis were enrolled in the study. Magnetic resonance (MR) and/or computer tomography (CT), physical exam, and Visual Analogue Scale (VAS) and Zurich Claudication Questionnaire (ZCQ) were performed before and 6 months after the procedure. All treatments were performed under fluoroscopic guidance with local anesthesia and mild sedation. Technical success was defined as correct placement of the Lobster® (Demetrios Medical, Firenze, Italy) PID as demonstrated by computer tomography (CT) performed immediately after treatment; spinoplasty was performed in selected patients., Results: PID placement was accomplished with a 99.6% success rate (257/258). The one device that was not implanted was due to a spinous process fracture. In 28 patients, more than 1 device was implanted in the same session (max 3 PIDs); 6 patients required a second implant in different session. A total of 172 prophylactic spinoplasties were performed (59.3%). No major complications occurred; 3 device misplacements were successfully treated with percutaneous retrieval and new device deployment. 99.6% of patients experienced clinical improvement., Conclusion: Lobster PID is an effective and safe minimally invasive decompression method for central canal and neural foraminal stenosis when patients are correctly selected., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Published
2024
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83. Health-Related Quality-of-Life Profile of Pediatric Patients with β Thalassemia after Hematopoietic Stem Cell Transplantation.

Author

Mulas O, Efficace F, Orofino MG, Piroddi A, Piras E, Vacca A, Barella S, Costa A, Giesinger JM, La Nasa G, and Caocci G

Abstract

Matched hematopoietic stem cell transplantation (HSCT) is a feasible and curative treatment in pediatric patients with beta thalassemia major (β-TM). However, little data are available regarding patients and their parents' health-related quality of life (HRQoL) after the procedure. As such, we investigated the HRQoL of pediatric patients with β-TM after HSCT compared to that of patients treated with blood transfusions and iron chelation. The health-related quality of life of 43 β-TM pediatric patients and 43 parents were evaluated using the Pediatric Quality of Life Inventory (PedsQL). A total of 25 patients underwent HSCT: 15 from a sibling and 10 from an HLA-matched donor. The median follow-up time from HSCT was 5 years (range 1-13 years). The mean ages at the survey were 10.1 years (range 5-15) and 9.6 years (range 5-15) for transfused and transplanted patients, respectively. A significant reduction in HRQoL was reported in the group of transfused patients compared with that of patients transplanted in the following PedsQL domains: children's and parents' physical functions, Δ = -15.4, p = 0.009 and Δ = -11.3, p = 0.002, respectively; children's and parents' emotional functioning, Δ = -15.2, p = 0.026 and Δ = -15.2, p = 0.045, respectively; child's and parents' school functioning, Δ = -25, p = 0.005 and Δ = -22.5, p = 0.011, respectively; total child and parents scores, Δ = -14.5, p = 0.004 and Δ = -13.2, p = 0.005, respectively. The results of a multivariable analysis showed that the HSCT procedure was significantly associated with a higher total child PedsQL score (adjusted mean difference = 15.3, p = 0.001) and a higher total parent PedsQL score (adjusted mean difference = 14.1, p = 0.006). We found no significant difference in the HRQoL measured after sibling or unrelated human leukocyte antigen (HLA)-matched HSCT. Finally, a significant positive correlation across all the PedsQL domains was found between the scores reported by the children and those reported by their parents. In conclusion, our study shows that HSCT in pediatric patients with β-TM is associated with a good overall HRQoL profile. This information further supports physicians when counseling patients and their parents before the HSCT procedure.

Published
2023
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84. Gut and oral microbiome modulate molecular and clinical markers of schizophrenia-related symptoms: A transdiagnostic, multilevel pilot study.

Author

Lee JJ, Piras E, Tamburini S, Bu K, Wallach DS, Remsen B, Cantor A, Kong J, Goetz D, Hoffman KW, Bonner M, Joe P, Mueller BR, Robinson-Papp J, Lotan E, Gonen O, Malaspina D, and Clemente JC

Subjects
Humans, Pilot Projects, Biomarkers, Cytokines, Gastrointestinal Microbiome, Schizophrenia microbiology, Microbiota
Abstract

Although increasing evidence links microbial dysbiosis with the risk for psychiatric symptoms through the microbiome-gut-brain axis (MGBA), the specific mechanisms remain poorly characterized. In a diagnostically heterogeneous group of treated psychiatric cases and nonpsychiatric controls, we characterized the gut and oral microbiome, plasma cytokines, and hippocampal inflammatory processes via proton magnetic resonance spectroscopic imaging ( 1 H-MRSI). Using a transdiagnostic approach, these data were examined in association with schizophrenia-related symptoms measured by the Positive and Negative Syndrome Scale (PANSS). Psychiatric cases had significantly greater heterogeneity of gut alpha diversity and an enrichment of pathogenic taxa, like Veillonella and Prevotella, in the oral microbiome, which was an accurate classifier of phenotype. Cases exhibited significantly greater positive, negative, and general PANSS scores that uniquely correlated with bacterial taxa. Strong, positive correlations of bacterial taxa were also found with cytokines and hippocampal gliosis, dysmyelination, and excitatory neurotransmission. This pilot study supports the hypothesis that the MGBA influences psychiatric symptomatology in a transdiagnostic manner. The relative importance of the oral microbiome in peripheral and hippocampal inflammatory pathways was highlighted, suggesting opportunities for probiotics and oral health to diagnose and treat psychiatric conditions., Competing Interests: Declaration of Competing Interest JCC, OG, and DM were supported by NIH NIMH grant 5R01MH110418. JJL is supported by NIH TL1 grant 5TL1RR029886. OG and EL are also supported by NIH NIBIB grant P41 EB017183. Computational analysis was supported by Mount Sinai's Scientific Computing through an allocation to JCC. All authors declare no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Published
2023
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86. An integrative study of the microbiome gut-brain-axis and hippocampal inflammation in psychosis: Persistent effects from mode of birth.

Author

Joe P, Clemente JC, Piras E, Wallach DS, Robinson-Papp J, Boka E, Remsen B, Bonner M, Kimhy D, Goetz D, Hoffman K, Lee J, Ruby E, Fendrich S, Gonen O, and Malaspina D

Subjects
Cesarean Section, Cytokines, Glutamates, Hippocampus diagnostic imaging, Hippocampus pathology, Humans, Inflammation diagnostic imaging, Magnetic Resonance Imaging methods, Delivery, Obstetric methods, Gastrointestinal Microbiome, Psychotic Disorders diagnosis, Schizophrenia diagnosis
Abstract

The mechanism producing psychosis appears to include hippocampal inflammation, which could be associated with the microbiome-gut-brain-axis (MGBS). To test this hypothesis we are conducting a multidisciplinary study, herein described. The procedures are illustrated with testing of a single subject and group level information on the impact of C-section birth are presented., Method: Study subjects undergo research diagnostic interviews and symptom assessments to be categorized into one of 3 study groups: psychosis, nonpsychotic affective disorder or healthy control. Hippocampal volume and metabolite concentrations are assessed using 3-dimensional, multi-voxel H1 Magnetic Resonance Imaging (MRSI) encompassing all gray matter in the entire hippocampal volume. Rich self-report information is obtained with the PROMIS interview, which was developed by the NIH Commons for research in chronic conditions. Early trauma is assessed and cognition is quantitated using the MATRICS. The method also includes the most comprehensive autonomic nervous system (ANS) battery used to date in psychiatric research. Stool and oral samples are obtained for microbiome assessments and cytokines and other substances are measured in blood samples., Results: Group level preliminary data shows that C-section birth is associated with higher concentrations of GLX, a glutamate related hippocampal neurotransmitter in psychotic cases, worse symptoms in affective disorder cases and smaller hippocampal volume in controls., Conclusion: Mode of birth appears to have persistent influences through adulthood. The methodology described for this study will define pathways through which the MGBA may influence the risk for psychiatric disorders., Competing Interests: Declaration of competing interest None., (Copyright © 2021. Published by Elsevier B.V.)

Published
2022
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87. Proinflammatory mucosal-associated invariant CD8+ T cells react to gut flora yeasts and infiltrate multiple sclerosis brain.

Author

Gargano F, Guerrera G, Piras E, Serafini B, Di Paola M, Rizzetto L, Buscarinu MC, Annibali V, Vuotto C, De Bardi M, D'Orso S, Ruggieri S, Gasperini C, Pavarini L, Ristori G, Picozza M, Rosicarelli B, Ballerini C, Mechelli R, Vitali F, Cavalieri D, Salvetti M, Angelini DF, Borsellino G, De Filippo C, and Battistini L

Subjects
Animals, Brain, CD8-Positive T-Lymphocytes pathology, Saccharomyces cerevisiae, Gastrointestinal Microbiome, Mucosal-Associated Invariant T Cells, Multiple Sclerosis
Abstract

The composition of the intestinal microbiota plays a critical role in shaping the immune system. Modern lifestyle, the inappropriate use of antibiotics, and exposure to pollution have significantly affected the composition of commensal microorganisms. The intestinal microbiota has been shown to sustain inappropriate autoimmune responses at distant sites in animal models of disease, and may also have a role in immune-mediated central nervous system (CNS) diseases such as multiple sclerosis (MS). We studied the composition of the gut mycobiota in fecal samples from 27 persons with MS (pwMS) and in 18 healthy donors (HD), including 5 pairs of homozygous twins discordant for MS. We found a tendency towards higher fungal abundance and richness in the MS group, and we observed that MS twins showed a higher rate of food-associated strains, such as Saccharomyces cerevisiae . We then found that in pwMS, a distinct population of cells with antibacterial and antifungal activity is expanded during the remitting phase and markedly decreases during clinically and/or radiologically active disease. These cells, named MAIT (mucosal-associated invariant T cells) lymphocytes, were significantly more activated in pwMS compared to HD in response to S. cerevisiae and Candida albicans strains isolated from fecal samples. This activation was also mediated by fungal-induced IL-23 secretion by innate immune cells. Finally, immunofluorescent stainings of MS post-mortem brain tissues from persons with the secondary progressive form of the disease showed that MAIT cells cross the blood-brain barrier (BBB) and produce pro-inflammatory cytokines in the brain. These results were in agreement with the hypothesis that dysbiosis of the gut microbiota might determine the inappropriate response of a subset of pathogenic mucosal T cells and favor the development of systemic inflammatory and autoimmune diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gargano, Guerrera, Piras, Serafini, Di Paola, Rizzetto, Buscarinu, Annibali, Vuotto, De Bardi, D’Orso, Ruggieri, Gasperini, Pavarini, Ristori, Picozza, Rosicarelli, Ballerini, Mechelli, Vitali, Cavalieri, Salvetti, Angelini, Borsellino, De Filippo and Battistini.)

Published
2022
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88. Infant gut microbiome is enriched with Bifidobacterium longum ssp. infantis in Old Order Mennonites with traditional farming lifestyle.

Author

Seppo AE, Bu K, Jumabaeva M, Thakar J, Choudhury RA, Yonemitsu C, Bode L, Martina CA, Allen M, Tamburini S, Piras E, Wallach DS, Looney RJ, Clemente JC, and Järvinen KM

Subjects
Child, Farms, Humans, Infant, Life Style, Milk, Human, Oligosaccharides, RNA, Ribosomal, 16S genetics, Bifidobacterium longum subspecies infantis, Gastrointestinal Microbiome
Abstract

Background: Growing up on traditional, single-family farms is associated with protection against asthma in school age, but the mechanisms against early manifestations of atopic disease are largely unknown. We sought determine the gut microbiome and metabolome composition in rural Old Order Mennonite (OOM) infants at low risk and Rochester, NY urban/suburban infants at high risk for atopic diseases., Methods: In a cohort of 65 OOM and 39 Rochester mother-infant pairs, 101 infant stool and 61 human milk samples were assessed by 16S rRNA gene sequencing for microbiome composition and qPCR to quantify Bifidobacterium spp. and B. longum ssp. infantis (B. infantis), a consumer of human milk oligosaccharides (HMOs). Fatty acids (FAs) were analyzed in 34 stool and human 24 milk samples. Diagnoses and symptoms of atopic diseases by 3 years of age were assessed by telephone., Results: At a median age of 2 months, stool was enriched with Bifidobacteriaceae, Clostridiaceae, and Aerococcaceae in the OOM compared with Rochester infants. B. infantis was more abundant (p < .001) and prevalent, detected in 70% of OOM compared with 21% of Rochester infants (p < .001). Stool colonized with B. infantis had higher levels of lactate and several medium- to long/odd-chain FAs. In contrast, paired human milk was enriched with a distinct set of FAs including butyrate. Atopic diseases were reported in 6.5% of OOM and 35% of Rochester children (p < .001)., Conclusion: A high rate of B. infantis colonization, similar to that seen in developing countries, is found in the OOM at low risk for atopic diseases., (© 2021 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Published
2021
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89. Viral Inactivation Impacts Microbiome Estimates in a Tissue-Specific Manner.

Author

Boix-Amorós A, Piras E, Bu K, Wallach D, Stapylton M, Fernández-Sesma A, Malaspina D, and Clemente JC

Abstract

The global emergence of novel pathogenic viruses presents an important challenge for research, as high biosafety levels are required to process samples. While inactivation of infectious agents facilitates the use of less stringent safety conditions, its effect on other biological entities of interest present in the sample is generally unknown. Here, we analyzed the effect of five inactivation methods (heat, ethanol, formaldehyde, psoralen, and TRIzol) on microbiome composition and diversity in samples collected from four different body sites (gut, nasal, oral, and skin) and compared them against untreated samples from the same tissues. We performed 16S rRNA gene sequencing and estimated abundance and diversity of bacterial taxa present in all samples. Nasal and skin samples were the most affected by inactivation, with ethanol and TRIzol inducing the largest changes in composition, and heat, formaldehyde, TRIzol, and psoralen inducing the largest changes in diversity. Oral and stool microbiomes were more robust to inactivation, with no significant changes in diversity and only moderate changes in composition. Firmicutes was the taxonomic group least affected by inactivation, while Bacteroidetes had a notable enrichment in nasal samples and moderate enrichment in fecal and oral samples. Actinobacteria were more notably depleted in fecal and skin samples, and Proteobacteria exhibited a more variable behavior depending on sample type and inactivation method. Overall, our results demonstrate that inactivation methods can alter the microbiome in a tissue-specific manner and that careful consideration should be given to the choice of method based on the sample type under study. IMPORTANCE Understanding how viral infections impact and are modulated by the microbiome is an important problem in basic research but is also of high clinical relevance under the current pandemic. To facilitate the study of interactions between microbial communities and pathogenic viruses under safe conditions, the infectious agent is generally inactivated prior to processing samples. The effect of this inactivation process in the microbiome is, however, unknown. Further, it is unclear whether biases introduced by inactivation methods are dependent on the sample type under study. Estimating the magnitude and nature of the changes induced by different methods in samples collected from various body sites thus provides important information for current and future studies that require inactivation of pathogenic agents.

Published
2021
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90. Traditional Farming Lifestyle in Old Older Mennonites Modulates Human Milk Composition.

Author

Seppo AE, Choudhury R, Pizzarello C, Palli R, Fridy S, Rajani PS, Stern J, Martina C, Yonemitsu C, Bode L, Bu K, Tamburini S, Piras E, Wallach DS, Allen M, Looney RJ, Clemente JC, Thakar J, and Järvinen KM

Subjects
Child, Preschool, Female, Gastrointestinal Microbiome genetics, Humans, Hypersensitivity, Immediate epidemiology, Life Style, Male, Milk, Human immunology, Religion, United States epidemiology, Up-Regulation, Agriculture, Gastrointestinal Microbiome immunology, Hypersensitivity, Immediate immunology, Immunoglobulin A metabolism, Maternal Exposure adverse effects, Milk, Human metabolism, Rural Population
Abstract

Background: In addition to farming exposures in childhood, maternal farming exposures provide strong protection against allergic disease in their children; however, the effect of farming lifestyle on human milk (HM) composition is unknown., Objective: This study aims to characterize the maternal immune effects of Old Order Mennonite (OOM) traditional farming lifestyle when compared with Rochester (ROC) families at higher risk for asthma and allergic diseases using HM as a proxy., Methods: HM samples collected at median 2 months of lactation from 52 OOM and 29 ROC mothers were assayed for IgA 1 and IgA 2 antibodies, cytokines, endotoxin, HM oligosaccharides (HMOs), and targeted fatty acid (FA) metabolites. Development of early childhood atopic diseases in children by 3 years of age was assessed. In addition to group comparisons, systems level network analysis was performed to identify communities of multiple HM factors in ROC and OOM lifestyle., Results: HM contains IgA 1 and IgA 2 antibodies broadly recognizing food, inhalant, and bacterial antigens. OOM HM has significantly higher levels of IgA to peanut, ovalbumin, dust mites, and Streptococcus equii as well TGF-β2, and IFN-λ3. A strong correlation occurred between maternal antibiotic use and levels of several HMOs. Path-based analysis of HMOs shows lower activity in the path involving lactoneohexaose (LNH) in the OOM as well as higher levels of lacto- N -neotetraose (LNnT) and two long-chain FAs C-18OH (stearic acid) and C-23OH (tricosanoic acid) compared with Rochester HM. OOM and Rochester milk formed five different clusters, e.g., butyrate production was associated with Prevotellaceae , Veillonellaceae , and Micrococcaceae cluster. Development of atopic disease in early childhood was more common in Rochester and associated with lower levels of total IgA, IgA 2 to dust mite, as well as of TSLP., Conclusion: Traditional, agrarian lifestyle, and antibiotic use are strong regulators of maternally derived immune and metabolic factors, which may have downstream implications for postnatal developmental programming of infant's gut microbiome and immune system., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Seppo, Choudhury, Pizzarello, Palli, Fridy, Rajani, Stern, Martina, Yonemitsu, Bode, Bu, Tamburini, Piras, Wallach, Allen, Looney, Clemente, Thakar and Järvinen.)

Published
2021
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91. Sexually Dimorphic Immune and Neuroimmune Changes Following Peripheral Nerve Injury in Mice: Novel Insights for Gender Medicine.

Author

Vacca V, Marinelli S, De Angelis F, Angelini DF, Piras E, Battistini L, Pavone F, and Coccurello R

Subjects
Animals, Cytokines, Female, Gliosis etiology, Hyperalgesia etiology, Inflammation etiology, Male, Mice, Neuralgia etiology, Sex Factors, Gliosis pathology, Hyperalgesia pathology, Inflammation pathology, Macrophages pathology, Neuralgia pathology, Peripheral Nerve Injuries complications, Sciatic Nerve pathology
Abstract

Neuropathic pain (NeP) in humans is often a life-long condition with no effective therapy available. The higher incidence of female gender in NeP onset is worldwide reported, and although the cause is generally attributed to sex hormones, the actual mechanisms and the players involved are still unclear. Glial and immune cells take part in NeP development, and orchestrate the neuroimmune and inflammatory response, releasing pro-inflammatory factors with chemoattractant properties that activate resident immune cells and recruit immune cells from circulation. The neuro-immune crosstalk is a key contributor to pain hypersensitivity following peripheral nervous system injury. Our previous works showed that in spite of the fact that female mice had an earlier analgesic response than males following nerve lesion, the recovery from NeP was never complete, suggesting that this difference could occur in the very early stages after injury. To further investigate gender differences in immune and neuroimmune responses to NeP, we studied the main immune cells and mediators elicited both in plasma and sciatic nerves by peripheral nerve lesion. After injury, we found a different pattern of distribution of immune cell populations showing either a higher infiltration of T cells in nerves from females or a higher infiltration of macrophages in nerves from males. Moreover, in comparison to male mice, the levels of cytokines and chemokines were differently up- and down-regulated in blood and nerve lysates from female mice. Our study provides some novel insights for the understanding of gender-associated differences in the generation and perseveration of NeP as well as for the isolation of specific neurodegenerative mechanisms underlying NeP. The identification of gender-associated inflammatory profiles in neuropathy is of key importance for the development of differential biomarkers and gender-specific personalized medicine.

Published
2021
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92. Corrigendum: Very Early Involvement of Innate Immunity in Peripheral Nerve Degeneration in SOD1-G93A Mice.

Author

Angelini DF, De Angelis F, Vacca V, Piras E, Parisi C, Nutini M, Spalloni A, Pagano F, Longone P, Battistini L, Pavone F, and Marinelli S

Abstract

[This corrects the article DOI: 10.3389/fimmu.2020.575792.]., (Copyright © 2021 Angelini, De Angelis, Vacca, Piras, Parisi, Nutini, Spalloni, Pagano, Longone, Battistini, Pavone and Marinelli.)

Published
2021
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93. Correction to: Appendectomy versus conservative treatment with antibiotics for patients with uncomplicated acute appendicitis: a propensity score-matched analysis of patient-centered outcomes (the ACTUAA prospective multicenter trial).

Author

Podda M, Poillucci G, Pacella D, Mortola L, Canfora A, Aresu S, Pisano M, Erdas E, Pisanu A, Cillara N, Serventi F, Marini S, Sirigu D, Piga M, Coppola M, Balestra F, De Nisco C, Pazzona M, Anania M, Pulighe F, Lai A, Ottonello R, De Angelis R, Piro S, Calò PG, Podda F, Saba L, Bottino V, Dalla Caneva P, Canu L, Piras E, Deserra A, Virdis F, Gerardi C, Gordini L, and Sanna S

Published
2021
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94. Efficacy of a Novel Vertebral Body Augmentation System in the Treatment of Patients with Symptomatic Vertebral Body Fractures.

Author

Marcia S, Piras E, Hirsch JA, Mereu A, Marras M, Spinelli A, and Saba L

Subjects
Aged, Aged, 80 and over, Female, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Middle Aged, Osteoporotic Fractures diagnostic imaging, Prospective Studies, Prostheses and Implants, Quality of Life, Spinal Fractures diagnostic imaging, Tomography, X-Ray Computed, Treatment Outcome, Vertebral Body diagnostic imaging, Vertebral Body surgery, Fracture Fixation, Internal methods, Osteoporotic Fractures surgery, Spinal Fractures surgery, Vertebral Body injuries
Abstract

Purpose: To evaluate the safety and efficacy of a novel augmentation implant in the treatment of patients with symptomatic vertebral body fractures., Materials and Methods: Thirty consecutive patients (seven males and 23 females), mean age of 70 years (range 56 to 89) with osteoporotic fractures and/or low-energy trauma fractures (osteoporosis confirmed by CT), were enrolled in an IRB-approved prospective study. The type of fracture was classified according to the Magerl classification. The patients were treated with the Tektona ® dedicated vertebral body augmentation system. Visual analogue scale (VAS) and Oswestry Disability Index (ODI) scores were obtained after 1, 6 and 12 months. Quality of life was assessed with the SF36 score., Results: A total of 37 vertebral bodies, mostly from T6 to L5, were treated in the 30 enrolled patients. In 67.6% of the cases (n = 25), lumbar fractures were treated. Most of the fractures (43%; n = 16) were A1.1 according to the Magerl classification. A significant pain reduction evaluated by VAS scores (p < 0.0001) was observed on average 7.6 (before the procedure) to 2.8 (immediately post-treatment), 2.1 and 2.7 (after 6 and 12 months later, respectively). The mean ODI score was 55.5% before treatment, and this was statistically significant reduced to 22.3% and 26.9%, respectively, at 6 and 12 months after treatment (p < 0.0001). The SF36 scores, both physical and mental components, showed statistically significant variations (p < 0.0001) whose direction was subpopulation dependent., Conclusion: Patients with confirmed osteoporosis, suffering from symptomatic vertebral body fractures (osteoporotic and/or low-energy traumatic), were treated safely and effectively using this novel implant.

Published
2021
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95. Very Early Involvement of Innate Immunity in Peripheral Nerve Degeneration in SOD1-G93A Mice.

Author

Angelini DF, De Angelis F, Vacca V, Piras E, Parisi C, Nutini M, Spalloni A, Pagano F, Longone P, Battistini L, Pavone F, and Marinelli S

Subjects
Animals, Male, Disease Progression, Genetic Predisposition to Disease, Interleukin-10 metabolism, Interleukin-6 metabolism, Macrophages immunology, Macrophages metabolism, Mast Cells immunology, Mast Cells metabolism, Mice, Inbred C57BL, Mice, Transgenic, Mutation, NF-kappa B metabolism, Phenotype, Signal Transduction, Time Factors, Disease Models, Animal, Amyotrophic Lateral Sclerosis enzymology, Amyotrophic Lateral Sclerosis genetics, Amyotrophic Lateral Sclerosis immunology, Amyotrophic Lateral Sclerosis pathology, Immunity, Innate, Neuroimmunomodulation, Neuromuscular Junction enzymology, Neuromuscular Junction immunology, Neuromuscular Junction pathology, Sciatic Nerve enzymology, Sciatic Nerve immunology, Sciatic Nerve pathology, Spinal Cord enzymology, Spinal Cord immunology, Spinal Cord pathology, Superoxide Dismutase-1 genetics, Superoxide Dismutase-1 metabolism, Wallerian Degeneration
Abstract

Recent preclinical and clinical evidence suggest that immune system has a role in the progression and prognosis of Amyotrophic Lateral Sclerosis (ALS), but the identification of a clear mechanism and immune players remains to be elucidated. Here, we have investigated, in 30 and 60 days (presymptomatic) and 120 days (symptomatic) old SOD1-G93A mice, systemic, peripheral, and central innate and adaptive immune and inflammatory response, correlating it with the progression of the neurodegeneration in neuromuscular junction, sciatic nerves, and spinal cord. Surprisingly, we found a very initial (45-60 days) presence of IgG in sciatic nerves together with a gradual enhancement of A20/TNFAIP3 (protein controlling NF-κB signalling) and a concomitantly significant increase and activation of circulating mast cells (MCs) as well as MCs and macrophages in sciatic nerve and an enhancement of IL-6 and IL-10. This immunological frame coincided with a myelin aggregation. The 30-60 days old SOD1-G93A mice didn't show real elements of neuroinflammation and neurodegeneration in spinal cord. In 120 days old mice macrophages and monocytes are widely diffused in sciatic nerves, peripheral neurodegeneration reaches the tip, high circulating levels of TNFα and IL-2 were found and spinal cord exhibits clear signs of neural damage and infiltrating immune cells. Our results underpin a clear immunological disorder at the origin of ALS axonopathy, in which MCs are involved in the initiation and sustaining of inflammatory events. These data cannot be considered a mere epiphenomenon of motor neuron degeneration and reveal new potential selective immune targets in ALS therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Angelini, De Angelis, Vacca, Piras, Parisi, Nutini, Spalloni, Pagano, Longone, Battistini, Pavone and Marinelli.)

Published
2020
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96. EBV-specific CD8 T lymphocytes and B cells during glatiramer acetate therapy in patients with MS.

Author

Guerrera G, Ruggieri S, Picozza M, Piras E, Gargano F, Placido R, Gasperini C, Salvetti M, Buscarinu MC, Battistini L, Borsellino G, and Angelini DF

Subjects
Adult, Aged, Cross-Sectional Studies, Female, Humans, Longitudinal Studies, Male, Middle Aged, Young Adult, B-Lymphocytes drug effects, CD8-Positive T-Lymphocytes drug effects, Glatiramer Acetate pharmacology, Herpesvirus 4, Human immunology, Immunologic Factors pharmacology, Multiple Sclerosis, Relapsing-Remitting blood, Multiple Sclerosis, Relapsing-Remitting drug therapy
Abstract

Objective: Infection with Epstein-Barr virus (EBV) has been associated with clinical activity and risk of developing MS. The purpose of this study is to investigate the impact of glatiramer acetate (GA) therapy on EBV-specific immune responses and disease course., Methods: We characterized EBV-specific CD8 T lymphocytes and B cells during disease-modifying treatments in 2 groups of patients with MS. We designed a 2-pronged approach consisting of a cross-sectional study (39 untreated patients, 38 patients who had undergone 12 months of GA treatment, and 48 healthy donors compatible for age and sex with the patients with MS) and a 12-month longitudinal study (35 patients treated with GA). CD8 EBV-specific T cells and B lymphocytes were studied using pentamers and multiparametric flow cytometry., Results: We find that treatment with GA enhances viral recognition by inducing an increased number of circulating virus-specific CD8 T cells ( p = 0.0043) and by relieving their features of exhaustion ( p = 0.0053) and senescence ( p < 0.0001, p = 0.0001). B cells, phenotypically and numerically tracked along the 1-year follow-up study, show a steady decrease in memory B-cell frequencies ( p = 0.025), paralleled by an increase of the naive B subset., Conclusion: GA therapy acts as a disease-modifying therapy restoring homeostasis in the immune system, including anti-EBV responses., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Published
2020
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97. The cyanobacterial neurotoxin β-N-methylamino-L-alanine (BMAA) targets the olfactory bulb region.

Author

Pierozan P, Piras E, Brittebo E, and Karlsson O

Subjects
Administration, Intranasal, Amino Acids, Diamino administration & dosage, Amino Acids, Diamino metabolism, Animals, Bacterial Toxins administration & dosage, Bacterial Toxins metabolism, Cell Survival drug effects, Cells, Cultured, Cyanobacteria Toxins, Glutamic Acid metabolism, Male, Mice, Inbred C57BL, Neuroglia metabolism, Neuroglia pathology, Neuronal Outgrowth drug effects, Neurons metabolism, Neurons pathology, Olfactory Bulb metabolism, Olfactory Bulb pathology, Olfactory Mucosa metabolism, Amino Acids, Diamino toxicity, Bacterial Toxins toxicity, Cyanobacteria metabolism, Neuroglia drug effects, Neurons drug effects, Olfactory Bulb drug effects
Abstract

Olfactory dysfunction is implicated in neurodegenerative disorders and typically manifests years before other symptoms. The cyanobacterial neurotoxin β-N-methylamino-L-alanine (BMAA) is suggested as a risk factor for neurodegenerative disease. Detection of BMAA in air filters has increased the concern that aerosolization may lead to human BMAA exposure through the air. The aim of this study was to determine if BMAA targets the olfactory system. Autoradiographic imaging showed a distinct localization of radioactivity in the right olfactory mucosa and bulb following a unilateral intranasal instillation of 3 H-BMAA (0.018 µg) in mice, demonstrating a direct transfer of BMAA via the olfactory pathways to the brain circumventing the blood-brain barrier, which was confirmed by liquid scintillation. Treatment of mouse primary olfactory bulb cells with 100 µM BMAA for 24 h caused a disruption of the neurite network, formation of dendritic varicosities and reduced cell viability. The NMDA receptor antagonist MK-801 and the metabotropic glutamate receptor antagonist MCPG protected against the BMAA-induced alterations, demonstrating the importance of glutamatergic mechanisms. The ionotropic non-NMDA receptor antagonist CNQX prevented the BMAA-induced decrease of cell viability in mixed cultures containing both neuronal and glial cells, but not in cultures with neurons only, suggesting a role of neuron-glial interactions and glial AMPA receptors in the BMAA-induced toxicity. The results show that the olfactory region may be a target for BMAA following inhalation exposure. Further studies on the relations between environmental olfactory toxicants and neurodegenerative disorders are warranted.

Published
2020
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98. Efficacy of an ethyl alcohol gel in symptomatic disc herniation.

Author

Marcia S, Bellini M, Hirsch JA, Chandra RV, Piras E, Marras M, Sanna AM, and Saba L

Subjects
Adult, Aged, Aged, 80 and over, Back Pain etiology, Feasibility Studies, Female, Gels, Humans, Lumbar Vertebrae surgery, Magnetic Resonance Imaging methods, Male, Middle Aged, Pain Measurement, Retrospective Studies, Treatment Outcome, Back Pain therapy, Central Nervous System Depressants administration & dosage, Ethanol administration & dosage, Intervertebral Disc Chemolysis methods, Intervertebral Disc Displacement therapy
Abstract

Purpose: To evaluate the clinical outcome of DiscoGel® chemonucleolysis for symptomatic disc herniation in patients who fail conservative treatment., Material and Methods: Consecutive patients with symptomatic disc herniation confirmed on MRI who failed conservative management for at least 6 months were included. Visual analogue scale (VAS), Oswestry Disability Index (ODI) scores, and analgesic use were recorded at baseline, and 12 months after treatment. Multidetector CT (MDCT) was performed at baseline, and 12 months after treatment to assess for DiscoGel® extravasation and alteration in treated disc volume. In a unique long-term subgroup analysis of 31 patients, telephonic follow-up was performed utilizing VAS and ODI parameters 7 years after the procedure., Results: A total of 87 disc herniations were treated in 71 patients; majority (54%) were treated at L4/5 and L5/S1. VAS score of 8 before treatment was reduced to 3 at 12 months after treatment (p = 0.0001); ODI score of 51 before treatment was reduced to 15 at 12 months after treatment (p = 0.0001). Analgesic use of 70.4% was reduced to 29.6% after treatment. There were no symptomatic procedural complications; MDCT revealed 1 asymptomatic peri-neural DiscoGel® extravasation. In the 31 subjects that underwent telephonic follow-up the VAS and ODI parameters maintained their values without statistically significant differences when compared with the 12-month follow-up., Conclusion: Patients with symptomatic disc herniation who failed conservative treatment and were treated with DiscoGel® chemonucleolysis achieved significant gains in pain relief and reduced disability without symptomatic complication. DiscoGel® chemonucleolysis is a feasible, minimally invasive technique for treatment of symptomatic disc herniation., (Copyright © 2018. Published by Elsevier B.V.)

Published
2018
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99. Detection of HHV-6 and EBV and Cytokine Levels in Saliva From Children With Seizures: Results of a Multi-Center Cross-Sectional Study.

Author

Bartolini L, Piras E, Sullivan K, Gillen S, Bumbut A, Lin CM, Leibovitch EC, Graves JS, Waubant EL, Chamberlain JM, Gaillard WD, and Jacobson S

Abstract

Background and Objective: One third of children with epilepsy are refractory to medications. Growing data support a role of common childhood infections with neurotropic viruses and inflammation in epileptogenesis. Our objective was to determine the frequency of Human Herpesvirus-6 (HHV-6) and Epstein-Barr Virus (EBV) infection and cytokine levels in saliva from children with seizures compared to healthy controls and to controls with a febrile illness without seizures. Methods: In this cross-sectional multi-center study, we collected saliva from 115 consecutive children with acute seizures (cases), 51 children with a fever and no seizures or underlying neurological disease (fever controls) and 46 healthy children (healthy controls). Specimens were analyzed by a novel droplet digital PCR for HHV-6 and EBV viral DNA and a bead-based immunoassay for neuroinflammatory cytokines. Results: Cases included febrile seizures ( n = 30), acute seizures without ( n = 53) and with fever ( n = 4) in chronic epilepsy, new onset epilepsy ( n = 13), febrile status epilepticus ( n = 3), and first lifetime seizure ( n = 12). HHV-6 DNA was found in 40% of cases vs. 37% fever controls and 35% healthy controls, with no statistically significant differences. EBV DNA was also detected with no differences in 17% cases, 16% fever controls, and 28% healthy controls. IL-8 and IL-1β were increased in saliva of 32 random samples from cases compared with 30 fever controls: IL-8 cases mean (SD): 1158.07 pg/mL (1427.41); controls 604.92 (754.04); p = 0.02. IL-1β 185.76 (230.57); controls 86.99 (187.39); p = 0.0002. IL-1β level correlated with HHV6 viral load ( p = 0.007). Conclusion: Increase in inflammatory cytokines may play a role in the onset of acute seizures and saliva could represent an inexpensive and non-invasive method for detection of viral DNA and cytokines.

Published
2018
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100. What is the role of vertebral augmentation for osteoporotic fractures? A review of the recent literature.

Author

Marcia S, Muto M, Hirsch JA, Chandra RV, Carter N, Crivelli P, Piras E, and Saba L

Subjects
Humans, Outcome and Process Assessment, Health Care, Quality of Life, Cementoplasty methods, Fractures, Compression surgery, Osteoporotic Fractures surgery, Spinal Fractures surgery
Abstract

Purpose: Vertebral augmentation procedures such as vertebroplasty and kyphoplasty are utilized in the treatment of vertebral compression fractures (VCFs). However, their capacity for providing analgesia, reducing disability, and improving quality of life in patients with osteoporotic VCFs remains a topic of debate. The objective of this narrative review is to summarize the latest evidence for the safety and efficacy of vertebral augmentation for osteoporotic vertebral compression fractures (VCFs)., Methods: A systematic literature search was conducted using the PubMed and Cochrane electronic databases for systematic reviews, review articles, meta-analyses, and randomized clinical trials prior to May 2017. The keywords were "vertebroplasty," "kyphoplasty," and "vertebral augmentation.", Results: Thirty-three papers (7 systematic reviews, 6 cohort studies, 15 randomized clinical trials, and 5 international guidelines) were included in this narrative review., Conclusion: Vertebral augmentation is a safe procedure, with low rates of serious complications and no increase in subsequent post-treatment fracture risk.

Published
2018
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