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1. Erratum: Risk factors associated with adverse fetal outcomes in pregnancies affected by Coronavirus disease 2019 (COVID-19): A secondary analysis of the WAPM study on COVID-19 (Journal of Perinatal Medicine (2020) 48:9 (950-958) DOI: 10.1515/jpm-2020-0355)

Author: Di Mascio D., Sen C., Saccone G., Galindo A., Grunebaum A., Yoshimatsu J., Stanojevic M., Kurjak A., Chervenak F., Vena F., Giancotti A., Brunelli R., Muzii L., Panici P. B., Mollo A., Berghella V., Flacco M. E., Manzoli L., Esposito R., Coviello A., Cerbone M., Maruotti G. M., Nazzaro G., Locci M., Guida M., Di Spiezio Sardo A., Bifulco G., Zullo F., Herraiz I., Villalain C., Suarez M. J. R., Gambacorti-Passerini Z. M., De Los Angeles Anaya Baz M., Galan E. V. A., Carbone I. F., Lopez Y. C., De Leon Luis J. A., Hernandez I. C., Venturella R., Rizzo G., Mappa I., Gerosolima G., Hellmeyer L., Frusca T., Volpe N., Schera G. B. L., Fieni S., Esposito E., Simonazzi G., Di Donna G., Youssef A., Gatta A. N. D., Di Donna M. C., Chiantera V., Buono N., Sozzi G., Greco P., Morano D., Bianchi B., Marino M. G. L., Laraud F., Ramone A., Cagnacci A., Barra F., Gustavino C., Ferrero S., Ghezzi F., Cromi A., Lagana A. S., Longo V. L., Stollagli F., Puri L., Sirico A., Scambia G., Lanzone A., Driul L., Fabiana Cecchini D., Xodo S., Rodriguez B., Mercado-Olivares F., Elkafrawi D., Sisti G., Morlando M., Schiattarella A., Colacurci N., De Franciscis P., Valori E., Cataneo I., Lenzi M., Sandri F., Buscemi R., Gattei G., Della Sala F., Rovellotti M. C., Done E., Faron G., Gucciardo L., Luigi N., Sorrentino F., Vasciaveo L., Liberati M., Buca D., Leombroni M., Di Sebastiano F., Di Tizio L., D'Antonio F., Gazzolo D., Franchi M., Ianniciello Q. C., Garzon S., Petriglia G., Borrello L., Nieto-Calvache A. J., Burgos-Luna J. M., Kadji C., Carlin A., Bevilacqua E., Moucho M., Pinto P. V., Figueiredo R., Rosello J. M., Loscalzo G., Martinez-Varea A., Diago V., Lopez J. S. J., Aykanat A. Y., Cosma S., Carosso A., Benedetto C., Bermejo A., Feuerschuette O. H. M., Uyaniklar O., Ocakouglu S. R., Atak Z., Gunduz R., Haberal E. T., Froessler B., Parange A., Palm P., Samardjiski I., Okuyan E., Daskalakis G., Antsaklis P., De Sa R. A. M., Pittaro A., Gonzalez-Duran M. L., Guisan A. C., Genc S. O., Zlatohlavkova B., Piqueras A. L., Oliva D. E., Cil A. P., Api O., Ples L., Kyvernitakis I., Lila A., Granese R., Ercoli A., Zoccali G., Villasco A., Biglia N., Madalina C., Costa E., Daelemans C., Pintiaux A., Cueto E., Hadar E., Dollinger S., Sinai N. A. B., Huertas E., Arango P., Sanchez A., Schvartzman J. A., Cojocaru L., Turan S., Turan O., Di Dedda M. C., Molpeceres R. G., Zdjelar S., Premru-Srsen T., Cerar L. K., Druskovic M., De Robertis V., Stefanovic V., Nupponen I., Nelskyla K., Khodjaeva Z., Gorina K. A., Sukhikh G. T., Visentin S., Cosmi E., Ferrari J., Gatti A., Luvero D., Angioli R., Palumbo M., D'Urso G., Colaleo F., Rapisarda A. M. C., Di Mascio D., Sen C., Saccone G., Galindo A., Grunebaum A., Yoshimatsu J., Stanojevic M., Kurjak A., Chervenak F., Vena F., Giancotti A., Brunelli R., Muzii L., Panici P.B., Mollo A., Berghella V., Flacco M.E., Manzoli L., Esposito R., Coviello A., Cerbone M., Maruotti G.M., Nazzaro G., Locci M., Guida M., Di Spiezio Sardo A., Bifulco G., Zullo F., Herraiz I., Villalain C., Suarez M.J.R., Gambacorti-Passerini Z.M., De Los Angeles Anaya Baz M., Galan E.V.A., Carbone I.F., Lopez Y.C., De Leon Luis J.A., Hernandez I.C., Venturella R., Rizzo G., Mappa I., Gerosolima G., Hellmeyer L., Frusca T., Volpe N., Schera G.B.L., Fieni S., Esposito E., Simonazzi G., Di Donna G., Youssef A., Gatta A.N.D., Di Donna M.C., Chiantera V., Buono N., Sozzi G., Greco P., Morano D., Bianchi B., Marino M.G.L., Laraud F., Ramone A., Cagnacci A., Barra F., Gustavino C., Ferrero S., Ghezzi F., Cromi A., Lagana A.S., Longo V.L., Stollagli F., Puri L., Sirico A., Scambia G., Lanzone A., Driul L., Fabiana Cecchini D., Xodo S., Rodriguez B., Mercado-Olivares F., Elkafrawi D., Sisti G., Morlando M., Schiattarella A., Colacurci N., De Franciscis P., Valori E., Cataneo I., Lenzi M., Sandri F., Buscemi R., Gattei G., Della Sala F., Rovellotti M.C., Done E., Faron G., Gucciardo L., Luigi N., Sorrentino F., Vasciaveo L., Liberati M., Buca D., Leombroni M., Di Sebastiano F., Di Tizio L., D'Antonio F., Gazzolo D., Franchi M., Ianniciello Q.C., Garzon S., Petriglia G., Borrello L., Nieto-Calvache A.J., Burgos-Luna J.M., Kadji C., Carlin A., Bevilacqua E., Moucho M., Pinto P.V., Figueiredo R., Rosello J.M., Loscalzo G., Martinez-Varea A., Diago V., Lopez J.S.J., Aykanat A.Y., Cosma S., Carosso A., Benedetto C., Bermejo A., Feuerschuette O.H.M., Uyaniklar O., Ocakouglu S.R., Atak Z., Gunduz R., Haberal E.T., Froessler B., Parange A., Palm P., Samardjiski I., Okuyan E., Daskalakis G., Antsaklis P., De Sa R.A.M., Pittaro A., Gonzalez-Duran M.L., Guisan A.C., Genc S.O., Zlatohlavkova B., Piqueras A.L., Oliva D.E., Cil A.P., Api O., Ples L., Kyvernitakis I., Lila A., Granese R., Ercoli A., Zoccali G., Villasco A., Biglia N., Madalina C., Costa E., Daelemans C., Pintiaux A., Cueto E., Hadar E., Dollinger S., Sinai N.A.B., Huertas E., Arango P., Sanchez A., Schvartzman J.A., Cojocaru L., Turan S., Turan O., Di Dedda M.C., Molpeceres R.G., Zdjelar S., Premru-Srsen T., Cerar L.K., Druskovic M., De Robertis V., Stefanovic V., Nupponen I., Nelskyla K., Khodjaeva Z., Gorina K.A., Sukhikh G.T., Visentin S., Cosmi E., Ferrari J., Gatti A., Luvero D., Angioli R., Palumbo M., D'Urso G., Colaleo F., Rapisarda A.M.C., Di Mascio, D., Sen, C., Saccone, G., Galindo, A., Grunebaum, A., Yoshimatsu, J., Stanojevic, M., Kurjak, A., Chervenak, F., Vena, F., Giancotti, A., Brunelli, R., Muzii, L., Panici, P. B., Mollo, A., Berghella, V., Flacco, M. E., Manzoli, L., Esposito, R., Coviello, A., Cerbone, M., Maruotti, G. M., Nazzaro, G., Locci, M., Guida, M., Di Spiezio Sardo, A., Bifulco, G., Zullo, F., Herraiz, I., Villalain, C., Suarez, M. J. R., Gambacorti-Passerini, Z. M., De Los Angeles Anaya Baz, M., Galan, E. V. A., Carbone, I. F., Lopez, Y. C., De Leon Luis, J. A., Hernandez, I. C., Venturella, R., Rizzo, G., Mappa, I., Gerosolima, G., Hellmeyer, L., Frusca, T., Volpe, N., Schera, G. B. L., Fieni, S., Esposito, E., Simonazzi, G., Di Donna, G., Youssef, A., Gatta, A. N. D., Di Donna, M. C., Chiantera, V., Buono, N., Sozzi, G., Greco, P., Morano, D., Bianchi, B., Marino, M. G. L., Laraud, F., Ramone, A., Cagnacci, A., Barra, F., Gustavino, C., Ferrero, S., Ghezzi, F., Cromi, A., Lagana, A. S., Longo, V. L., Stollagli, F., Puri, L., Sirico, A., Scambia, G., Lanzone, A., Driul, L., Fabiana Cecchini, D., Xodo, S., Rodriguez, B., Mercado-Olivares, F., Elkafrawi, D., Sisti, G., Morlando, M., Schiattarella, A., Colacurci, N., De Franciscis, P., Valori, E., Cataneo, I., Lenzi, M., Sandri, F., Buscemi, R., Gattei, G., Della Sala, F., Rovellotti, M. C., Done, E., Faron, G., Gucciardo, L., Luigi, N., Sorrentino, F., Vasciaveo, L., Liberati, M., Buca, D., Leombroni, M., Di Sebastiano, F., Di Tizio, L., D'Antonio, F., Gazzolo, D., Franchi, M., Ianniciello, Q. C., Garzon, S., Petriglia, G., Borrello, L., Nieto-Calvache, A. J., Burgos-Luna, J. M., Kadji, C., Carlin, A., Bevilacqua, E., Moucho, M., Pinto, P. V., Figueiredo, R., Rosello, J. M., Loscalzo, G., Martinez-Varea, A., Diago, V., Lopez, J. S. J., Aykanat, A. Y., Cosma, S., Carosso, A., Benedetto, C., Bermejo, A., Feuerschuette, O. H. M., Uyaniklar, O., Ocakouglu, S. R., Atak, Z., Gunduz, R., Haberal, E. T., Froessler, B., Parange, A., Palm, P., Samardjiski, I., Okuyan, E., Daskalakis, G., Antsaklis, P., De Sa, R. A. M., Pittaro, A., Gonzalez-Duran, M. L., Guisan, A. C., Genc, S. O., Zlatohlavkova, B., Piqueras, A. L., Oliva, D. E., Cil, A. P., Api, O., Ples, L., Kyvernitakis, I., Lila, A., Granese, R., Ercoli, A., Zoccali, G., Villasco, A., Biglia, N., Madalina, C., Costa, E., Daelemans, C., Pintiaux, A., Cueto, E., Hadar, E., Dollinger, S., Sinai, N. A. B., Huertas, E., Arango, P., Sanchez, A., Schvartzman, J. A., Cojocaru, L., Turan, S., Turan, O., Di Dedda, M. C., Molpeceres, R. G., Zdjelar, S., Premru-Srsen, T., Cerar, L. K., Druskovic, M., De Robertis, V., Stefanovic, V., Nupponen, I., Nelskyla, K., Khodjaeva, Z., Gorina, K. A., Sukhikh, G. T., Visentin, S., Cosmi, E., Ferrari, J., Gatti, A., Luvero, D., Angioli, R., Palumbo, M., D'Urso, G., Colaleo, F., and Rapisarda, A. M. C.
Subjects: N.A
Abstract: Due to a technical error, the author list at the end of this article is unfortunately incorrect. Elif Gül Yapar Eyi is not a co-author, and therefore, his name and affiliation should not appear in the list. The correct author list and affiliations read as follows: Daniele Di Mascio, Cihat Sen, Gabriele Saccone, Alberto Galindo, Amos Grünebaum, Jun Yoshimatsu, Milan Stanojevic, AsimKurjak, Frank Chervenak, María Jos´e Rodríguez Suárez, Zita Maria Gambacorti-Passerini, María de los Angeles Anaya Baz, Esther Vanessa Aguilar Galán, Yolanda Cuñarro López, Juan Antonio De León Luis, Ignacio Cueto Hernández, Ignacio Herraiz, Cecilia Villalain, Roberta Venturella, Giuseppe Rizzo, Ilenia Mappa, Giovanni Gerosolima, Lars Hellmeyer, Josefine Königbauer, Giada Ameli, Tiziana Frusca, Nicola Volpe, Giovanni Battista Luca Schera, Stefania Fieni, Eutalia Esposito, Giuliana Simonazzi, Gaetana Di Donna, Aly Youssef, Anna Nunzia Della Gatta, Mariano Catello Di Donna, Vito Chiantera, Natalina Buono, Giulio Sozzi, Pantaleo Greco, Danila Morano, Beatrice Bianchi, Maria Giulia Lombana Marino, Federica Laraud, Arianna Ramone, Angelo Cagnacci, Fabio Barra, Claudio Gustavino, Simone Ferrero, Fabio Ghezzi, Antonella Cromi, Antonio Simone Laganá, Valentina Laurita Longo, Francesca Stollagli, Angelo Sirico, Antonio Lanzone, Lorenza Driul, Fabiana Cecchini D, Serena Xodo, Brian Rodriguez, Felipe Mercado-Olivares, Deena Elkafrawi, Giovanni Sisti, Rosanna Esposito, Antonio Coviello, Marco Cerbone, Maddalena Morlando, Antonio Schiattarella, Nicola Colacurci, Pasquale De Franciscis, Ilaria Cataneo, Marinella Lenzi, Fabrizio Sandri, Riccardo Buscemi, Giorgia Gattei, Francesca della Sala, Eleonora Valori, Maria Cristina Rovellotti, Elisa Done, Gilles Faron, Leonardo Gucciardo, Valentina Esposito, Flaminia Vena, Antonella Giancotti, Roberto Brunelli, Ludovico Muzii, Luigi Nappi, Felice Sorrentino, Lorenzo Vasciaveo, Marco Liberati, Danilo Buca, Martina Leombroni, Francesca Di Sebastiano, Luciano Di Tizio, Diego Gazzolo, Massimo Franchi, Quintino Cesare Ianniciello, Simone Garzon, Giuliano Petriglia, Leonardo Borrello, Albaro Jos´e Nieto-Calvache, Juan Manuel Burgos-Luna, Caroline Kadji, Andrew Carlin, Elisa Bevilacqua, Marina Moucho, Pedro Viana Pinto, Rita Figueiredo, Jos´e Morales Roselló, Gabriela Loscalzo, Alicia Martinez-Varea, Vincente Diago, Jesús S Jimenez Lopez, Alicia Yeliz Aykanat, Stefano Cosma, Andrea Carosso, Chiara Benedetto, Amanda Bermejo, Otto Henrique May Feuerschuette, Ozlem Uyaniklar, Sakine Rahimli Ocakouglu, Zeliha Atak, Reyhan Gündüz, Esra Tustas Haberal, Bernd Froessler, Anupam Parange, Peter Palm, Igor Samardjiski, Chiara Taccaliti, Erhan Okuyan, George Daskalakis, Renato Augusto Moreira de Sa, Alejandro Pittaro, Maria Luisa Gonzalez-Duran, Ana Concheiro Guisan, Serife Özlem Genç, Blanka Zlatohlávková, Anna Luengo Piqueras, Dolores Esteban Oliva, Aylin Pelin Cil, Olus Api, Panos Antsaklis, Liana Ples, Ioannis Kyvernitakis, Holger Maul, Marcel Malan, Albert Lila, Roberta Granese, Alfredo Ercoli, Giuseppe Zoccali, Andrea Villasco, Nicoletta Biglia, Ciuhodaru Madalina, Elena Costa, Caroline Daelemans, Axelle Pintiaux, Elisa Cueto, Eran Hadar, Sarah Dollinger, Noa A. Brzezinski Sinai, Erasmo Huertas, Pedro Arango, Amadeo Sanchez, Javier Alfonso Schvartzman, Liviu Cojocaru, Sifa Turan, Ozhan Turan, Maria Carmela Di Dedda, Rebeca Garrote Molpeceres, Snezana Zdjelar, Tanja Premru-Srsen, Lilijana Kornhauser Cerar, Mirjam Druškovic, Valentina De Robertis, Vedran Stefanovic, Irmeli Nupponen, Kaisa Nelskylä, Zulfiya Khodjaeva, Ksenia A. Gorina, Gennady T. Sukhikh, Giuseppe Maria Maruotti, Silvia Visentin, Erich Cosmi, Jacopo Ferrari, Alessandra Gatti, Daniela Luvero, Roberto Angioli, Ludovica Puri, Marco Palumbo, Giusella D’Urso, Francesco Colaleo, Agnese Maria Chiara Rapisarda, Ilma Floriana Carbone, Antonio Mollo, Giovanni Nazzaro, Mariavittoria Locci, Maurizio Guida, Attilio Di Spiezio Sardo, Pierluigi Benedetti Panici, Vincenzo Berghella, Maria Elena Flacco, Lamberto Manzoli, Giuseppe Bifulco, Giovanni Scambia, Fulvio Zullo and Francesco D’Antonio Flaminia Vena, Antonella Giancotti, Roberto Brunelli, Ludovico Muzii and Pierluigi Benedetti Panici, Department of Maternal and Child Health and Urological Sciences, Sapienza University of Rome, Rome, Italy Rosanna Esposito, Antonio Coviello, Marco Cerbone, Giuseppe Maria Maruotti, Giovanni Nazzaro, Mariavittoria Locci, Maurizio Guida, Attilio Di Spiezio Sardo, Giuseppe Bifulco and Fulvio Zullo, Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples Federico II, Naples, Italy Ignacio Herraiz and Cecilia Villalain, Department of Obstetrics and Gynaecology, Fetal Medicine Unit, Maternal and Child Health and Development Network, University Hospital 12 de Octubre, Complutense University of Madrid, Madrid, Spain María Jos´e Rodríguez Suárez, Hospital Universitario Central de Asturias, Asturias, Spain Zita Maria Gambacorti-Passerini, Department of Obstetrics and Gynaecology, Ciudad Real University General Hospital, Ciudad Real, Spain María de los Angeles Anaya Baz and Esther Vanessa Aguilar Galán, Department of Obstetrics and Gynaecology, Ciudad Real University General Hospital, Ciudad Real, Spain; University of Castilla-La Mancha, Ciudad Real, Spain Yolanda Cuñarro López, Juan Antonio De León Luis and Ignacio Cueto Hernández, Department of Obstetrics and Gynaecology, Fetal Medicine Unit, Maternal and Child Health and Development Network, Gregorio Marañón Hospital, Complutense University of Madrid, Madrid, Spain Roberta Venturella, Department of Obstetrics and Gynaecology, School of Medicine, Magna Graecia University of Catanzaro, Catanzaro, Italy Giuseppe Rizzo, University of Roma Tor Vergata, Division of Maternal Fetal Medicine, Ospedale Cristo Re Roma, Rome, Italy; Department of Obstetrics and Gynaecology, The First I.M. Sechenov Moscow State Medical University, Moscow, Russia Ilenia Mappa, University of Roma Tor Vergata, Division of Maternal Fetal Medicine, Ospedale Cristo Re Roma, Rome, Italy Giovanni Gerosolima, Department of Obstetrics and Gynaecology, Ospedale AOSG Moscati, Avellino, Italy Lars Hellmeyer, Josefine Königbauer and Giada Ameli, Department of Gynaecology and Obstetrics, Vivantes Klinikum im Friedrichshain, Berlin, Germany Tiziana Frusca, Nicola Volpe, Giovanni Battista Luca Schera and Stefania Fieni, Department of Obstetrics and Gynaecology, University of Parma, Parma, Italy Eutalia Esposito, Department of Obstetrics and Gynaecology, Ospedale di San Leonardo, Castellammare di Stabia, Italy Giuliana Simonazzi, Gaetana Di Donna, Aly Youssef and Anna Nunzia Della Gatta, Department of Obstetrics and Gynaecology, University of Bologna, Sant’Orsola- Malpighi University Hospital, Bologna, Italy Mariano Catello Di Donna, Vito Chiantera, Natalina Buono and Giulio Sozzi, Department of Gynaecologic Oncology, University of Palermo, Palermo, Sicilia, Italy Pantaleo Greco, Danila Morano, Beatrice Bianchi and Maria Giulia Lombana Marino, Department ofMedical Sciences, Section of Obstetrics and Gynaecology, Azienda Ospedaliera-Universitaria Sant’Anna, University of Ferrara, Ferrara, Italy Federica Laraud, Arianna Ramone, Angelo Cagnacci, Fabio Barra, Claudio Gustavino and Simone Ferrero, Academic Unit of Obstetrics and Gynaecology, IRCCS Ospedale Policlinico, San Martino, Genova, Italy Fabio Ghezzi, Antonella Cromi and Antonio Simone Laganà, Department of Obstetrics and Gynaecology, “Filippo Del Ponte” Hospita University of Insubria, Varese, Italy Valentina Laurita Longo, Department of Obstetrics and Gynaecology, Fondazione Policlinico Universitario A Gemelli IRCCS – Università Cattolica del Sacro Cuore, Rome, Italy; Istituto di Clinica Ostetrica e Ginecologica, Università Cattolica del Sacro Cuore, Rome, Italy; and Queen Margaret University, Institute for Global Health and Development, Edinburgh, UK Francesca Stollagli and Ludovica Puri, Istituto di Clinica Ostetrica e Ginecologica, Università Cattolica del Sacro Cuore, Rome, Italy Angelo Sirico and Giovanni Scambia, Department of Obstetrics and Gynaecology, Fondazione Policlinico Universitario A Gemelli IRCCS – Università Cattolica del Sacro Cuore, Rome, Italy Antonio Lanzone, Department of Obstetrics and Gynaecology, Fondazione Policlinico Universitario A Gemelli IRCCS – Università Cattolica del Sacro Cuore, Rome, Italy; Istituto di Clinica Ostetrica e Ginecologica, Università Cattolica del Sacro Cuore, Rome, Italy Lorenza Driul, Fabiana Cecchini D and Serena Xodo, Clinic of Obstetrics and Gynaecology, University of Udine, Udine, Italy Brian Rodriguez, Felipe Mercado-Olivares, Deena Elkafrawi and Giovanni Sisti, Department of Obstetrics and Gynaecology, New York Health and Hospitals/Lincoln Bronx, The Bronx, NY, USA Maddalena Morlando, Antonio Schiattarella, Nicola Colacurci and Pasquale De Franciscis, Department of Woman, Child and General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples, Italy Ilaria Cataneo, Marinella Lenzi and Fabrizio Sandri, Unit of Obstetrics and Gynaecology, Ospedale Maggiore, Bologna, Italy Riccardo Buscemi, Giorgia Gattei, Francesca della Sala and Maria Cristina Rovellotti, Department of Translational Medicine, University of Eastern Piedmont, Novara, Italy Eleonora Valori, Department of Translational Medicine, University of Eastern Piedmont, Novara, Italy; Hospital Castelli, Verbania, Italy Elisa Done, Gilles Faron and Leonardo Gucciardo, UZ Brussel, Universitair Ziekenhuis, Brussel, Belgium Valentina Esposito, University of Milan, Milan, Italy Luigi Nappi, Felice Sorrentino and Lorenzo Vasciaveo, Department of Obstetrics and Gynaecology, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy.
Published: 2021

2. Placenta Accreta Spectrum Disorders: Challenges, Risks, and Management Strategies

Author: Morlando, M, Collins, S, Morlando, Maddalena, and Collins, Sally
Subjects: placenta accreta spectrum, abnormal invasive placenta, • placenta accreta spectrum • placenta accreta • abnormal placentation • abnormal invasive placenta • morbidly adherent placenta, International Journal of Women's Health, placenta accreta, Review, abnormal placentation, lcsh:Gynecology and obstetrics, lcsh:RG1-991, morbidly adherent placenta
Abstract: Maddalena Morlando,1 Sally Collins2 1Department of Woman, Child and General and Specialized Surgery, Obstetrics and Gynecology Unit, University of Campania “Luigi Vanvitelli”, Naples, Italy; 2Nuffield Department of Women’s and Reproductive Health, University of Oxford, Fetal Medicine Unit, John Radcliffe Hospital, Oxford, UKCorrespondence: Sally CollinsNuffield Department of Women’s and Reproductive Health, University of Oxford, Fetal Medicine Unit, John Radcliffe Hospital, Oxford, UKTel +44 (0)1865 851165Fax +44 (0) 7958 656 885Email sally.collins@wrh.ox.ac.ukAbstract: The worldwide incidence of placenta accreta spectrum (PAS) is rapidly increasing, following the trend of rising cesarean delivery. PAS is an heterogeneous condition associated with a high maternal morbidity and mortality rate, presenting unique challenges in its diagnosis and management. So far, the rarity of this condition, together with the absence of high quality evidence and the lack of a standardized approach in reporting PAS cases for the ultrasound, clinical, and pathologic diagnosis, represented the main challenges for a deep understanding of this condition. The study of the available management strategies of PAS has been hampered by the heterogeneity of the available epidemiological data on this condition. The aim of this review is to provide a critical view of the current available evidence on the screening, the diagnosis, and the management options for PAS disorders, with a special focus on the challenges we foresee for the near future.Keywords: placenta accreta spectrum, placenta accreta, abnormal placentation, abnormal invasive placenta, morbidly adherent placenta
Published: 2020

3. Objective and quantitative evaluation of fetal hiccups by computerized cardiotocography: A prospective observational study

Author: La Verde M., Torella M., Lanza G., Rapisarda A. M. C., Morlando M., Cianci S., Colacurci N., Capristo C., Torre C., De Franciscis P., Riemma G., La Verde, M., Torella, M., Lanza, G., Rapisarda, A. M. C., Morlando, M., Cianci, S., Colacurci, N., Capristo, C., Torre, C., De Franciscis, P., and Riemma, G.
Subjects: Fetal movement, Fetal hiccups, Car-diotocography, Fetal heart rate, Computerised cardiotocography, Computerized analysi, Fetal hiccup, Computerized analysis
Abstract: The physiological function of fetal hiccup and its correlation with fetal well-being is a debated topic. We conducted a prospective observational study in a Tertiary care University Hospital to correlate the fetal hiccups with the antepartum computerized cardiotocography parameters. Fifty-one nonlaboring women with a term pregnancy were en-rolled. We collected data regarding maternal perception of fetal hiccups and the computerized cardiotocographic examination. The pregnant were divided into three groups depending on fetal hiccups perception. There was a statistical difference for the number of fetal movements in an hour between the group of daily perception and the group of no perception. Changes in fetal movements frequency are essential to recognize pregnancies at increased risk for adverse fetal outcomes. No one studies in the medical literature utilized the computerized cardiotocographic machine to explore fetal hiccups. Then our study showed that a mother with daily fetal hiccups could be considered a low risk considering the significant numbers of fetal movements revealed by computerized cardiotocography. Nevertheless, randomized controlled trials are required to evaluate the fetal hiccups evaluation and its influence on fetal outcomes.
Published: 2021

4. Intrahepatic cholestasis of pregnancy: A narrative review of the management

Author: Palmisano A., Morlando M., La Verde M., D'alessio A., Ambrosio D., Trotta C., Colacurci N., Maritato M., Palmisano, A., Morlando, M., La Verde, M., D'Alessio, A., Ambrosio, D., Trotta, C., Colacurci, N., and Maritato, M.
Published: 2021

5. Maternal and perinatal outcomes of pregnant women with SARS-CoV-2 infection

Author: Saccone, G. Sen, C. Di Mascio, D. Galindo, A. Grünebaum, A. Yoshimatsu, J. Stanojevic, M. Kurjak, A. Chervenak, F. Suárez, M.J.R. Gambacorti-Passerini, Z.M. de los Angeles Anaya Baz, M. Galán, E.V.A. López, Y.C. Luis, J.A.D.L. Hernández, I.C. Herraiz, I. Villalain, C. Venturella, R. Rizzo, G. Mappa, I. Gerosolima, G. Hellmeyer, L. Königbauer, J. Ameli, G. Frusca, T. Volpe, N. Schera, G.B.L. Fieni, S. Esposito, E. Simonazzi, G. Di Donna, G. Youssef, A. Gatta, A.N.D. Di Donna, M.C. Chiantera, V. Buono, N. Sozzi, G. Greco, P. Morano, D. Bianchi, B. Marino, M.G.L. Laraud, F. Ramone, A. Cagnacci, A. Barra, F. Gustavino, C. Ferrero, S. Ghezzi, F. Cromi, A. Laganà, A.S. Longo, V.L. Stollagli, F. Sirico, A. Lanzone, A. Driul, L. Cecchini, F. Xodo, S. Rodriguez, B. Mercado-Olivares, F. Elkafrawi, D. Sisti, G. Esposito, R. Coviello, A. Cerbone, M. Morlando, M. Schiattarella, A. Colacurci, N. De Franciscis, P. Cataneo, I. Lenzi, M. Sandri, F. Buscemi, R. Gattei, G. Sala, F.D. Valori, E. Rovellotti, M.C. Done, E. Faron, G. Gucciardo, L. Esposito, V. Vena, F. Giancotti, A. Brunelli, R. Muzii, L. Nappi, L. Sorrentino, F. Liberati, M. Buca, D. Leombroni, M. Di Sebastiano, F. Franchi, M. Ianniciello, Q.C. Garzon, S. Petriglia, G. Borrello, L. Nieto-Calvache, A.J. Burgos-Luna, J.M. Kadji, C. Carlin, A. Bevilacqua, E. Moucho, M. Viana Pinto, P. Figueiredo, R. Morales Roselló, J. Loscalzo, G. Martinez-Varea, A. Diago, V. Jimenez Lopez, J.S. Aykanat, A.Y. Cosma, S. Carosso, A. Benedetto, C. Bermejo, A. Feuerschuette, O.H.M. Uyaniklar, O. Ocakouglu, S.R. Atak, Z. Gündüz, R. Haberal, E.T. Froessler, B. Parange, A. Palm, P. Samardjiski, I. Taccaliti, C. Okuyan, E. Daskalakis, G. de Sa, R.A.M. Pittaro, A. Gonzalez-Duran, M.L. Guisan, A.C. Genç, S.Ö. Zlatohlávková, B. Piqueras, A.L. Oliva, D.E. Cil, A.P. Api, O. Antsaklis, P. Ples, L. Kyvernitakis, I. Maul, H. Malan, M. Lila, A. Granese, R. Ercoli, A. Zoccali, G. Villasco, A. Biglia, N. Madalina, C. Costa, E. Daelemans, C. Pintiaux, A. Cueto, E. Hadar, E. Dollinger, S. Brzezinski-Sinai, N.A. Huertas, E. Arango, P. Sanchez, A. Schvartzman, J.A. Cojocaru, L. Turan, S. Turan, O. Di Dedda, M.C. Molpeceres, R.G. Zdjelar, S. Premru-Srsen, T. Kornhauser-Cerar, L. Druškovic, M. De Robertis, V. Stefanovic, V. Nupponen, I. Nelskylä, K. Khodjaeva, Z. Gorina, K.A. Sukhikh, G.T. Maruotti, G.M. Visentin, S. Cosmi, E. Ferrari, J. Gatti, A. Luvero, D. Angioli, R. Puri, L. Palumbo, M. D'Urso, G. Colaleo, F. Rapisarda, A.M.C. Carbone, I.F. Manzoli, L. Flacco, M.E. Nazzaro, G. Locci, M. Guida, M. Sardo, A.D.S. Panici, P.B. Khalil, A. Berghella, V. Bifulco, G. Scambia, G. Zullo, F. D'Antonio, F. The WAPM (World Association of Perinatal Medicine) Working Group on COVID-19
Abstract: Objectives: To evaluate the maternal and perinatal outcomes of pregnancies affected by SARS-CoV-2 infection. Methods: This was a multinational retrospective cohort study including women with a singleton pregnancy and laboratory-confirmed SARS-CoV-2 infection, conducted in 72 centers in 22 different countries in Europe, the USA, South America, Asia and Australia, between 1 February 2020 and 30 April 2020. Confirmed SARS-CoV-2 infection was defined as a positive result on real-time reverse-transcription polymerase chain reaction (RT-PCR) assay of nasopharyngeal swab specimens. The primary outcome was a composite measure of maternal mortality and morbidity, including admission to the intensive care unit (ICU), use of mechanical ventilation and death. Results: In total, 388 women with a singleton pregnancy tested positive for SARS-CoV-2 on RT-PCR of a nasopharyngeal swab and were included in the study. Composite adverse maternal outcome was observed in 47/388 (12.1%) women; 43 (11.1%) women were admitted to the ICU, 36 (9.3%) required mechanical ventilation and three (0.8%) died. Of the 388 women included in the study, 122 (31.4%) were still pregnant at the time of data analysis. Among the other 266 women, six (19.4% of the 31 women with first-trimester infection) had miscarriage, three (1.1%) had termination of pregnancy, six (2.3%) had stillbirth and 251 (94.4%) delivered a liveborn infant. The rate of preterm birth before 37 weeks' gestation was 26.3% (70/266). Of the 251 liveborn infants, 69/251 (27.5%) were admitted to the neonatal ICU, and there were five (2.0%) neonatal deaths. The overall rate of perinatal death was 4.1% (11/266). Only one (1/251, 0.4%) infant, born to a mother who tested positive during the third trimester, was found to be positive for SARS-CoV-2 on RT-PCR. Conclusions: SARS-CoV-2 infection in pregnant women is associated with a 0.8% rate of maternal mortality, but an 11.1% rate of admission to the ICU. The risk of vertical transmission seems to be negligible. © 2020 International Society of Ultrasound in Obstetrics and Gynecology. © 2020 International Society of Ultrasound in Obstetrics and Gynecology
Published: 2021

6. Erratum: Risk factors associated with adverse fetal outcomes in pregnancies affected by Coronavirus disease 2019 (COVID-19): A secondary analysis of the WAPM study on COVID-19 (Journal of Perinatal Medicine (2020) 48:9 (950-958) DOI: 10.1515/jpm-2020-0355)

Author: Di Mascio, D. Sen, C. Saccone, G. Galindo, A. Grünebaum, A. Yoshimatsu, J. Stanojevic, M. Kurjak, A. Chervenak, F. Vena, F. Giancotti, A. Brunelli, R. Muzii, L. Panici, P.B. Mollo, A. Berghella, V. Flacco, M.E. Manzoli, L. Esposito, R. Coviello, A. Cerbone, M. Maruotti, G.M. Nazzaro, G. Locci, M. Guida, M. Di Spiezio Sardo, A. Bifulco, G. Zullo, F. Herraiz, I. Villalain, C. Suárez, M.J.R. Gambacorti-Passerini, Z.M. De Los Angeles Anaya Baz, M. Galán, E.V.A. Carbone, I.F. López, Y.C. De León Luis, J.A. Hernández, I.C. Venturella, R. Rizzo, G. Mappa, I. Gerosolima, G. Hellmeyer, L. Frusca, T. Volpe, N. Schera, G.B.L. Fieni, S. Esposito, E. Simonazzi, G. Di Donna, G. Youssef, A. Gatta, A.N.D. Di Donna, M.C. Chiantera, V. Buono, N. Sozzi, G. Greco, P. Morano, D. Bianchi, B. Marino, M.G.L. Laraud, F. Ramone, A. Cagnacci, A. Barra, F. Gustavino, C. Ferrero, S. Ghezzi, F. Cromi, A. Laganà, A.S. Longo, V.L. Stollagli, F. Puri, L. Sirico, A. Scambia, G. Lanzone, A. Driul, L. Fabiana Cecchini, D. Xodo, S. Rodriguez, B. Mercado-Olivares, F. Elkafrawi, D. Sisti, G. Morlando, M. Schiattarella, A. Colacurci, N. De Franciscis, P. Valori, E. Cataneo, I. Lenzi, M. Sandri, F. Buscemi, R. Gattei, G. Della Sala, F. Rovellotti, M.C. Done, E. Faron, G. Gucciardo, L. Luigi, N. Sorrentino, F. Vasciaveo, L. Liberati, M. Buca, D. Leombroni, M. Di Sebastiano, F. Di Tizio, L. D'Antonio, F. Gazzolo, D. Franchi, M. Ianniciello, Q.C. Garzon, S. Petriglia, G. Borrello, L. Nieto-Calvache, A.J. Burgos-Luna, J.M. Kadji, C. Carlin, A. Bevilacqua, E. Moucho, M. Pinto, P.V. Figueiredo, R. Roselló, J.M. Loscalzo, G. Martinez-Varea, A. Diago, V. Lopez, J.S.J. Aykanat, A.Y. Cosma, S. Carosso, A. Benedetto, C. Bermejo, A. Feuerschuette, O.H.M. Uyaniklar, O. Ocakouglu, S.R. Atak, Z. Gündüz, R. Haberal, E.T. Froessler, B. Parange, A. Palm, P. Samardjiski, I. Okuyan, E. Daskalakis, G. Antsaklis, P. De Sa, R.A.M. Pittaro, A. Gonzalez-Duran, M.L. Guisan, A.C. Genç, S.Ö. Zlatohlávková, B. Piqueras, A.L. Oliva, D.E. Cil, A.P. Api, O. Ples, L. Kyvernitakis, I. Lila, A. Granese, R. Ercoli, A. Zoccali, G. Villasco, A. Biglia, N. Madalina, C. Costa, E. Daelemans, C. Pintiaux, A. Cueto, E. Hadar, E. Dollinger, S. Sinai, N.A.B. Huertas, E. Arango, P. Sanchez, A. Schvartzman, J.A. Cojocaru, L. Turan, S. Turan, O. Di Dedda, M.C. Molpeceres, R.G. Zdjelar, S. Premru-Srsen, T. Cerar, L.K. Druškovic, M. De Robertis, V. Stefanovic, V. Nupponen, I. Nelskylä, K. Khodjaeva, Z. Gorina, K.A. Sukhikh, G.T. Visentin, S. Cosmi, E. Ferrari, J. Gatti, A. Luvero, D. Angioli, R. Palumbo, M. D'Urso, G. Colaleo, F. Rapisarda, A.M.C.
Abstract: Due to a technical error, the author list at the end of this article is unfortunately incorrect. Elif Gül Yapar Eyi is not a co-author, and therefore, his name and affiliation should not appear in the list. The correct author list and affiliations read as follows: Daniele Di Mascio, Cihat Sen, Gabriele Saccone, Alberto Galindo, Amos Grünebaum, Jun Yoshimatsu, Milan Stanojevic, AsimKurjak, Frank Chervenak, María Jos´e Rodríguez Suárez, Zita Maria Gambacorti-Passerini, María de los Angeles Anaya Baz, Esther Vanessa Aguilar Galán, Yolanda Cuñarro López, Juan Antonio De León Luis, Ignacio Cueto Hernández, Ignacio Herraiz, Cecilia Villalain, Roberta Venturella, Giuseppe Rizzo, Ilenia Mappa, Giovanni Gerosolima, Lars Hellmeyer, Josefine Königbauer, Giada Ameli, Tiziana Frusca, Nicola Volpe, Giovanni Battista Luca Schera, Stefania Fieni, Eutalia Esposito, Giuliana Simonazzi, Gaetana Di Donna, Aly Youssef, Anna Nunzia Della Gatta, Mariano Catello Di Donna, Vito Chiantera, Natalina Buono, Giulio Sozzi, Pantaleo Greco, Danila Morano, Beatrice Bianchi, Maria Giulia Lombana Marino, Federica Laraud, Arianna Ramone, Angelo Cagnacci, Fabio Barra, Claudio Gustavino, Simone Ferrero, Fabio Ghezzi, Antonella Cromi, Antonio Simone Laganá, Valentina Laurita Longo, Francesca Stollagli, Angelo Sirico, Antonio Lanzone, Lorenza Driul, Fabiana Cecchini D, Serena Xodo, Brian Rodriguez, Felipe Mercado-Olivares, Deena Elkafrawi, Giovanni Sisti, Rosanna Esposito, Antonio Coviello, Marco Cerbone, Maddalena Morlando, Antonio Schiattarella, Nicola Colacurci, Pasquale De Franciscis, Ilaria Cataneo, Marinella Lenzi, Fabrizio Sandri, Riccardo Buscemi, Giorgia Gattei, Francesca della Sala, Eleonora Valori, Maria Cristina Rovellotti, Elisa Done, Gilles Faron, Leonardo Gucciardo, Valentina Esposito, Flaminia Vena, Antonella Giancotti, Roberto Brunelli, Ludovico Muzii, Luigi Nappi, Felice Sorrentino, Lorenzo Vasciaveo, Marco Liberati, Danilo Buca, Martina Leombroni, Francesca Di Sebastiano, Luciano Di Tizio, Diego Gazzolo, Massimo Franchi, Quintino Cesare Ianniciello, Simone Garzon, Giuliano Petriglia, Leonardo Borrello, Albaro Jos´e Nieto-Calvache, Juan Manuel Burgos-Luna, Caroline Kadji, Andrew Carlin, Elisa Bevilacqua, Marina Moucho, Pedro Viana Pinto, Rita Figueiredo, Jos´e Morales Roselló, Gabriela Loscalzo, Alicia Martinez-Varea, Vincente Diago, Jesús S Jimenez Lopez, Alicia Yeliz Aykanat, Stefano Cosma, Andrea Carosso, Chiara Benedetto, Amanda Bermejo, Otto Henrique May Feuerschuette, Ozlem Uyaniklar, Sakine Rahimli Ocakouglu, Zeliha Atak, Reyhan Gündüz, Esra Tustas Haberal, Bernd Froessler, Anupam Parange, Peter Palm, Igor Samardjiski, Chiara Taccaliti, Erhan Okuyan, George Daskalakis, Renato Augusto Moreira de Sa, Alejandro Pittaro, Maria Luisa Gonzalez-Duran, Ana Concheiro Guisan, Serife Özlem Genç, Blanka Zlatohlávková, Anna Luengo Piqueras, Dolores Esteban Oliva, Aylin Pelin Cil, Olus Api, Panos Antsaklis, Liana Ples, Ioannis Kyvernitakis, Holger Maul, Marcel Malan, Albert Lila, Roberta Granese, Alfredo Ercoli, Giuseppe Zoccali, Andrea Villasco, Nicoletta Biglia, Ciuhodaru Madalina, Elena Costa, Caroline Daelemans, Axelle Pintiaux, Elisa Cueto, Eran Hadar, Sarah Dollinger, Noa A. Brzezinski Sinai, Erasmo Huertas, Pedro Arango, Amadeo Sanchez, Javier Alfonso Schvartzman, Liviu Cojocaru, Sifa Turan, Ozhan Turan, Maria Carmela Di Dedda, Rebeca Garrote Molpeceres, Snezana Zdjelar, Tanja Premru-Srsen, Lilijana Kornhauser Cerar, Mirjam Druškovic, Valentina De Robertis, Vedran Stefanovic, Irmeli Nupponen, Kaisa Nelskylä, Zulfiya Khodjaeva, Ksenia A. Gorina, Gennady T. Sukhikh, Giuseppe Maria Maruotti, Silvia Visentin, Erich Cosmi, Jacopo Ferrari, Alessandra Gatti, Daniela Luvero, Roberto Angioli, Ludovica Puri, Marco Palumbo, Giusella D’Urso, Francesco Colaleo, Agnese Maria Chiara Rapisarda, Ilma Floriana Carbone, Antonio Mollo, Giovanni Nazzaro, Mariavittoria Locci, Maurizio Guida, Attilio Di Spiezio Sardo, Pierluigi Benedetti Panici, Vincenzo Berghella, Maria Elena Flacco, Lamberto Manzoli, Giuseppe Bifulco, Giovanni Scambia, Fulvio Zullo and Francesco D’Antonio Flaminia Vena, Antonella Giancotti, Roberto Brunelli, Ludovico Muzii and Pierluigi Benedetti Panici, Department of Maternal and Child Health and Urological Sciences, Sapienza University of Rome, Rome, Italy Rosanna Esposito, Antonio Coviello, Marco Cerbone, Giuseppe Maria Maruotti, Giovanni Nazzaro, Mariavittoria Locci, Maurizio Guida, Attilio Di Spiezio Sardo, Giuseppe Bifulco and Fulvio Zullo, Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples Federico II, Naples, Italy Ignacio Herraiz and Cecilia Villalain, Department of Obstetrics and Gynaecology, Fetal Medicine Unit, Maternal and Child Health and Development Network, University Hospital 12 de Octubre, Complutense University of Madrid, Madrid, Spain María Jos´e Rodríguez Suárez, Hospital Universitario Central de Asturias, Asturias, Spain Zita Maria Gambacorti-Passerini, Department of Obstetrics and Gynaecology, Ciudad Real University General Hospital, Ciudad Real, Spain María de los Angeles Anaya Baz and Esther Vanessa Aguilar Galán, Department of Obstetrics and Gynaecology, Ciudad Real University General Hospital, Ciudad Real, Spain; University of Castilla-La Mancha, Ciudad Real, Spain Yolanda Cuñarro López, Juan Antonio De León Luis and Ignacio Cueto Hernández, Department of Obstetrics and Gynaecology, Fetal Medicine Unit, Maternal and Child Health and Development Network, Gregorio Marañón Hospital, Complutense University of Madrid, Madrid, Spain Roberta Venturella, Department of Obstetrics and Gynaecology, School of Medicine, Magna Graecia University of Catanzaro, Catanzaro, Italy Giuseppe Rizzo, University of Roma Tor Vergata, Division of Maternal Fetal Medicine, Ospedale Cristo Re Roma, Rome, Italy; Department of Obstetrics and Gynaecology, The First I.M. Sechenov Moscow State Medical University, Moscow, Russia Ilenia Mappa, University of Roma Tor Vergata, Division of Maternal Fetal Medicine, Ospedale Cristo Re Roma, Rome, Italy Giovanni Gerosolima, Department of Obstetrics and Gynaecology, Ospedale AOSG Moscati, Avellino, Italy Lars Hellmeyer, Josefine Königbauer and Giada Ameli, Department of Gynaecology and Obstetrics, Vivantes Klinikum im Friedrichshain, Berlin, Germany Tiziana Frusca, Nicola Volpe, Giovanni Battista Luca Schera and Stefania Fieni, Department of Obstetrics and Gynaecology, University of Parma, Parma, Italy Eutalia Esposito, Department of Obstetrics and Gynaecology, Ospedale di San Leonardo, Castellammare di Stabia, Italy Giuliana Simonazzi, Gaetana Di Donna, Aly Youssef and Anna Nunzia Della Gatta, Department of Obstetrics and Gynaecology, University of Bologna, Sant’Orsola- Malpighi University Hospital, Bologna, Italy Mariano Catello Di Donna, Vito Chiantera, Natalina Buono and Giulio Sozzi, Department of Gynaecologic Oncology, University of Palermo, Palermo, Sicilia, Italy Pantaleo Greco, Danila Morano, Beatrice Bianchi and Maria Giulia Lombana Marino, Department ofMedical Sciences, Section of Obstetrics and Gynaecology, Azienda Ospedaliera-Universitaria Sant’Anna, University of Ferrara, Ferrara, Italy Federica Laraud, Arianna Ramone, Angelo Cagnacci, Fabio Barra, Claudio Gustavino and Simone Ferrero, Academic Unit of Obstetrics and Gynaecology, IRCCS Ospedale Policlinico, San Martino, Genova, Italy Fabio Ghezzi, Antonella Cromi and Antonio Simone Laganà, Department of Obstetrics and Gynaecology, “Filippo Del Ponte” Hospita University of Insubria, Varese, Italy Valentina Laurita Longo, Department of Obstetrics and Gynaecology, Fondazione Policlinico Universitario A Gemelli IRCCS – Università Cattolica del Sacro Cuore, Rome, Italy; Istituto di Clinica Ostetrica e Ginecologica, Università Cattolica del Sacro Cuore, Rome, Italy; and Queen Margaret University, Institute for Global Health and Development, Edinburgh, UK Francesca Stollagli and Ludovica Puri, Istituto di Clinica Ostetrica e Ginecologica, Università Cattolica del Sacro Cuore, Rome, Italy Angelo Sirico and Giovanni Scambia, Department of Obstetrics and Gynaecology, Fondazione Policlinico Universitario A Gemelli IRCCS – Università Cattolica del Sacro Cuore, Rome, Italy Antonio Lanzone, Department of Obstetrics and Gynaecology, Fondazione Policlinico Universitario A Gemelli IRCCS – Università Cattolica del Sacro Cuore, Rome, Italy; Istituto di Clinica Ostetrica e Ginecologica, Università Cattolica del Sacro Cuore, Rome, Italy Lorenza Driul, Fabiana Cecchini D and Serena Xodo, Clinic of Obstetrics and Gynaecology, University of Udine, Udine, Italy Brian Rodriguez, Felipe Mercado-Olivares, Deena Elkafrawi and Giovanni Sisti, Department of Obstetrics and Gynaecology, New York Health and Hospitals/Lincoln Bronx, The Bronx, NY, USA Maddalena Morlando, Antonio Schiattarella, Nicola Colacurci and Pasquale De Franciscis, Department of Woman, Child and General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples, Italy Ilaria Cataneo, Marinella Lenzi and Fabrizio Sandri, Unit of Obstetrics and Gynaecology, Ospedale Maggiore, Bologna, Italy Riccardo Buscemi, Giorgia Gattei, Francesca della Sala and Maria Cristina Rovellotti, Department of Translational Medicine, University of Eastern Piedmont, Novara, Italy Eleonora Valori, Department of Translational Medicine, University of Eastern Piedmont, Novara, Italy; Hospital Castelli, Verbania, Italy Elisa Done, Gilles Faron and Leonardo Gucciardo, UZ Brussel, Universitair Ziekenhuis, Brussel, Belgium Valentina Esposito, University of Milan, Milan, Italy Luigi Nappi, Felice Sorrentino and Lorenzo Vasciaveo, Department of Obstetrics and Gynaecology, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy. © 2021 De Gruyter. All rights reserved.
Published: 2021

7. Maternal and perinatal outcomes in high compared to low risk pregnancies complicated by severe acute respiratory syndrome coronavirus 2 infection (phase 2): the World Association of Perinatal Medicine working group on coronavirus disease 2019

Author: D'Antonio, F. Sen, C. Mascio, D.D. Galindo, A. Villalain, C. Herraiz, I. Arisoy, R. Ovayolu, A. Eroğlu, H. Canales, M.G. Ladella, S. Cojocaru, L. Turan, O. Turan, S. Hadar, E. Brzezinski-Sinai, N.A. Dollinger, S. Uyaniklar, O. Ocakouglu, S.R. Atak, Z. Premru-Srsen, T. Kornhauser-Cerar, L. Druškovič, M. Ples, L. Gündüz, R. Ağaçayak, E. Schvartzman, J.A. Malbran, M.N. Liberati, M. Sebastiano, F.D. Oronzi, L. Cerra, C. Buca, D. Cagnacci, A. Ramone, A. Barra, F. Carosso, A. Benedetto, C. Cosma, S. Pintiaux, A. Daelemans, C. Costa, E. Özel, A. Muhçu, M. Lopez, J.S.J. Alvarado, C. Piqueras, A.L. Oliva, D.E. Schera, G.B.L. Volpe, N. Frusca, T. Samardjiski, I. Simeonova, S. Papestiev, I.A. Hojman, J. Turkcuoglu, I. Cromi, A. Laganà, A.S. Ghezzi, F. Sirico, A. Familiari, A. Scambia, G. Sukhikh, Z.K.G.T. Gorina, K.A. de Sa, R.A.M. Vaz, M. Feuerschuette, O.H.M. Gatta, A.N.D. Youssef, A. Donna, G.D. Martinez-Varea, A. Loscalzo, G. Roselló, J.M. Stefanovic, V. Nupponen, I. Nelskylä, K. Ayala, R. Molpeceres, R.G. Vázquez, A.P. Sandri, F. Cataneo, I. Lenzi, M. Haberal, E.T. Huertas, E. Sanchez, A. Arango, P. Bermejo, A. Alcantara, M.M.G. Göynümer, G. Okuyan, E. Madalina, C. Guisan, A.C. Schulte, A.M. Esposito, V. De Robertis, V. Zdjelar, S. Lackovic, M. Mihajlovic, S. Jekova, N. Saccone, G. Aslan, M.M. Dedda, M.C.D. Chalid, M. Canache, J.E.M. Daskalakis, G. Antsaklis, P. Vega, E.C. Cueto, E. Taccaliti, C. Aykanat, Y. Özlem Genç, Ş. Froessler, B. Radulova, P.A. Morano, D. Bianchi, B. Marino, M.G.L. Meccariello, G. Rohatgi, B. Schiattarella, A. Morlando, M. Colacurci, N. Villasco, A. Biglia, N. Marques, A.L.S. Gatti, A. Luvero, D. Angioli, R. Pittaro, A. Lila, A. Zlatohlávková, B. On the behalf of the World Association of Perinatal Medicine working group on coronavirus disease 2019
Abstract: BACKGROUND: It has still to be ascertained whether severe acute respiratory syndrome coronavirus 2 infection in pregnancy is associated with worse maternal and fetal outcomes compared to low risk gestations. OBJECTIVE: This study aimed to evaluate maternal and perinatal outcomes in high- and low-risk pregnancies complicated by severe acute respiratory syndrome coronavirus 2 infection. STUDY DESIGN: This was a multinational retrospective cohort study involving women with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection from 76 centers from 25 countries in Europe, the United States, South America, Asia, and Australia from April 4, 2020, to October 28, 2020. The primary outcome was a composite measure of maternal mortality and morbidity, including admission to the intensive care unit, use of mechanical ventilation, or death. The secondary outcome was a composite measure of adverse perinatal outcome, including miscarriage, fetal loss, neonatal and perinatal death, and admission to the neonatal intensive care unit. All outcomes were assessed in high- and low-risk pregnancies. Pregnancies were considered high risk in case of either preexisting chronic medical conditions in pregnancy or obstetrical disorders occurring in pregnancy. The Fisher exact test and logistic regression analysis were used to analyze the data. RESULTS: A total of 887 singleton pregnancies who tested positive for severe acute respiratory syndrome coronavirus 2 infection using reverse transcription-polymerase chain reaction of nasal and pharyngeal swab specimens were included in the study. The risk of composite adverse maternal outcomes was higher in high-risk pregnancies than in low-risk pregnancies (odds ratio, 1.52; 95% confidence interval, 1.03–2.24; P=.035). In addition, women carrying high-risk pregnancies were at higher risk of hospital admission (odds ratio, 1.48; 95% confidence interval, 1.07–2.04; P=.002), presence of severe respiratory symptoms (odds ratio, 2.13; 95% confidence interval, 0.41–3.21; P=.001), admission to the intensive care unit (odds ratio, 2.63; 95% confidence interval, 1.42–4.88), and invasive mechanical ventilation (odds ratio, 2.65; 95% confidence interval, 1.19–5.94; P=.002). When exploring perinatal outcomes, high-risk pregnancies were at high risk of adverse perinatal outcomes (odds ratio, 1.78; 95% confidence interval, 0.15–2.72; P=.009). However, such association was mainly because of the higher incidence of miscarriage in high-risk pregnancies compared with that in low-risk pregnancies (5.3% vs 1.6%, P=.008); furthermore, there was no difference in other explored outcomes between the 2 study groups. At logistic regression analysis, maternal age (odds ratio, 1.12; 95% confidence interval, 1.02–1.22; P=.023) and high-risk pregnancy (odds ratio, 4.21; 95% confidence interval, 3.90–5.11; P
Published: 2021

8. Evidence-based guidelines for the management of abnormally invasive placenta: recommendations from the International Society for Abnormally Invasive Placenta

Author: Collins, SL, Alemdar, B, van Beekhuizen, Heleen, Bertholdt, C, Braun, T, Calda, P, Delorme, P, Duvekot, J.J., Gronbeck, L, Kayem, G, Langhoff-Roos, J, Marcellin, L, Martinelli, P, Morel, O, Mhallem, M, Morlando, M, Noergaard, LN, Nonnenmacher, A, Pateisky, P, Petit, P, Rijken, MJ, Ropacka-Lesiak, M, Schlembach, D, Sentilhes, L, Stefanovic, V, Strindfors, G, Tutschek, B, Vangen, S, Weichert, A, Weizsacker, K, Chantraine, F, Is, AIP, Obstetrics & Gynecology, Obstetrics and Gynaecology, University of Helsinki, Department of Obstetrics and Gynecology, HUS Gynecology and Obstetrics, University of Oxford [Oxford], Karolinska University Hospital [Stockholm], Erasmus University Medical Center [Rotterdam] (Erasmus MC), Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service d'Obstétrique et de Gynécologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Freie Universität Berlin, Humboldt-Universität zu Berlin, Charles University [Prague] (CU), Maternité Port-Royal [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of Copenhagen = Københavns Universitet (KU), Service de Gynécologie-Obstétrique [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de Gynécologie et Obstétrique [Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Università degli studi di Napoli Federico II, Cliniques Universitaires Saint-Luc [Bruxelles], Medizinische Universität Wien = Medical University of Vienna, Centre Hospitalier Universitaire de Liège (CHU-Liège), University Medical Center [Utrecht], Poznan University of Medical Sciences [Poland] (PUMS), Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Institute of Clinical Medicine [Oslo], Faculty of Medicine [Oslo], University of Oslo (UiO)-University of Oslo (UiO), Collins, S. L., Alemdar, B., van Beekhuizen, H. J., Bertholdt, C., Braun, T., Calda, P., Delorme, P., Duvekot, J. J., Gronbeck, L., Kayem, G., Langhoff-Roos, J., Marcellin, L., Martinelli, P., Morel, O., Mhallem, M., Morlando, M., Noergaard, L. N., Nonnenmacher, A., Pateisky, P., Petit, P., Rijken, M. J., Ropacka-Lesiak, M., Schlembach, D., Sentilhes, L., Stefanovic, V., Strindfors, G., Tutschek, B., Vangen, S., Weichert, A., Weizsacker, K., Chantraine, F., Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM), UCL - SSS/IREC/SLUC - Pôle St.-Luc, and UCL - (SLuc) Service d'obstétrique
Subjects: Delphi Technique, Placenta, medicine.medical_treatment, increta, Guideline, Oxytocin, Conservative Treatment, placenta accreta spectrum, 0302 clinical medicine, PERIPARTUM HYSTERECTOMY, Uterine artery embolization, 3123 Gynaecology and paediatrics, Adrenal Cortex Hormones, Pregnancy, 030202 anesthesiology, Abnormally invasive placenta, Oxytocics, Obstetrics and Gynaecology, Medicine, 030212 general & internal medicine, Non-U.S. Gov't, ComputingMilieux_MISCELLANEOUS, reproductive and urinary physiology, accreta, 030219 obstetrics & reproductive medicine, medicine.diagnostic_test, Obstetrics, Mortality rate, Research Support, Non-U.S. Gov't, Obstetrics and Gynecology, Gestational age, Disease Management, Morbidly adherent placenta, 3. Good health, Hospitalization, medicine.anatomical_structure, Practice Guideline, SURGICAL-MANAGEMENT, Female, Stents, guideline, CESAREAN-SECTION, SEVERE POSTPARTUM HEMORRHAGE, medicine.medical_specialty, Evidence-based practice, placenta, Placenta Accreta/therapy, Accreta, Gestational Age, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, Placenta Accreta, Adrenal Cortex Hormones/therapeutic use, Research Support, Hysterectomy, Patient Positioning, 03 medical and health sciences, FIGO CONSENSUS GUIDELINES, abnormally invasive placenta, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, BAKRI BALLOON TAMPONADE, Journal Article, Humans, Intensive care medicine, Watchful Waiting, Oxytocics/therapeutic use, morbidly adherent placenta, Postpartum Hemorrhage/prevention & control, UTERINE ARTERY EMBOLIZATION, Increta, Cesarean Section, business.industry, Postpartum Hemorrhage, Balloon catheter, Cystoscopy, SUBSEQUENT PREGNANCIES, percreta, Percreta, HYSTEROSCOPIC RESECTION, Ureter, Oxytocin/therapeutic use, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, CONSERVATIVE MANAGEMENT
Abstract: The worldwide incidence of abnormally invasive placenta is rapidly rising, following the trend of increasing cesarean delivery. It is a heterogeneous condition and has a high maternal morbidity and mortality rate, presenting specific intrapartum challenges. Its rarity makes developing individual expertise difficult for the majority of clinicians. The International Society for Abnormally Invasive Placenta aims to improve clinicians’ understanding and skills in managing this difficult condition. By pooling knowledge, experience, and expertise gained within a variety of different healthcare systems, the Society seeks to improve the outcomes for women with abnormally invasive placenta globally. The recommendations presented herewith were reached using a modified Delphi technique and are based on the best available evidence. The evidence base for each is presented using a formal grading system. The topics chosen address the most pertinent questions regarding intrapartum management of abnormally invasive placenta with respect to clinically relevant outcomes, including the following: definition of a center of excellence; requirement for antenatal hospitalization; antenatal optimization of hemoglobin; gestational age for delivery; antenatal corticosteroid administration; use of preoperative cystoscopy, ureteric stents, and prophylactic pelvic arterial balloon catheters; maternal position for surgery; type of skin incision; position of the uterine incision; use of interoperative ultrasound; prophylactic administration of oxytocin; optimal method for intraoperative diagnosis; use of expectant management; adjuvant therapies for expectant management; use of local surgical resection; type of hysterectomy; use of delayed hysterectomy; intraoperative measures to treat life-threatening hemorrhage; and fertility after conservative management.
Published: 2019

9. Surgical management of endometrioma for ovarian safety

Author: Mele D., De Franciscis P., Cosenza C., Riemma G., D'eufemia M. D., Schettino M. T., Morlando M., Schiattarella A., Mele, D., De Franciscis, P., Cosenza, C., Riemma, G., D'Eufemia, M. D., Schettino, M. T., Morlando, M., and Schiattarella, A.
Subjects: AFC, Bipolar forcep, Fertilization in vitro, Infertility, FSH, AMH, Endometrioma, Laparoscopy, Endometriosi
Abstract: Objectives: The effect of laparoscopic surgery for endometrioma on ovarian function is debated and controversial. The aim of the study was to address the impact of preoperative parameters and surgical technique for the removal of endometrioma on the ovarian reserve.Methods: This was a retrospective cohort study of outpatient women referred to the Fertility Center of the University of Campania “Luigi Vanvitelli” in Naples undergoing laparoscopy for enucleation of endometriotic cysts. The evaluation of the ovarian reserve was performed before the intervention and at the third month after the intervention by the count of antral follicles (AFC), FSH and AMH dosage. Surgery was performed by operative laparoscopy by stripping technique and ablation. Hemostasis was performed with two kinds of bipolar forceps, according to the feasibility of self-regulating coagulation.Results: 46 patients were analyzed. The data showed a greater impact of the surgical technique on the ovarian reserve of patients in advanced reproductive age or with a recurrent endometrioma (
Published: 2019

10. Erratum: Value of third‐trimester cerebroplacental ratio and uterine artery Doppler indices as predictors of stillbirth and perinatal loss

Author: Khalil, A, Morales-Roselló, J, Townsend, R, Morlando, M, Papageorghiou, A, Bhide, A, and Thilaganathan, B
Published: 2019

11. Value of third-trimester cerebroplacental ratio and uterine artery Doppler indices as predictors of stillbirth and perinatal loss

Author: Khalil A., Morales-Rosello J., Townsend R., Morlando M., Papageorghiou A., Bhide A., Thilaganathan B., Khalil, A., Morales-Rosello, J., Townsend, R., Morlando, M., Papageorghiou, A., Bhide, A., and Thilaganathan, B.
Subjects: Adult, Middle Cerebral Artery, Perinatal Death, Placenta, Pregnancy Trimester, Third, Risk Assessment, Ultrasonography, Prenatal, Umbilical Arteries, Cohort Studies, Retrospective Studie, Pregnancy, Laser-Doppler Flowmetry, Humans, Retrospective Studies, cerebroplacental ratio, uterine artery Doppler, Infant, Newborn, birth weight, Ultrasonography, Doppler, Stillbirth, Placental Insufficiency, Umbilical Arterie, Uterine Artery, Fetal Weight, Pulsatile Flow, Female, Cohort Studie, Human
Abstract: Objective Placental insufficiency contributes to the risk of stillbirth. Cerebroplacental ratio (CPR) is an emerging marker of placental insufficiency. The aim of this study was to evaluate the association of third-trimester fetal CPR, uterine artery (UtA) Doppler and estimated fetal weight (EFW) with stillbirth and perinatal death. Methods This was a retrospective cohort study including 2812 women with a singleton pregnancy who underwent an ultrasound scan in the third trimester. EFWs were converted into centiles, and Doppler indices (UtA and CPR) were converted into multiples of the median (MoM), adjusting for gestational age. Regression analysis was performed to identify, and adjust for, potential confounders, and receiver-operating characteristics (ROC) curve analysis was used to assess the predictive value. Results When adjusting for EFW centile and UtA mean pulsatility index (UtA-PI) MoM, CPR-MoM remained an independent predictor of stillbirth (odds ratio (OR) = 0.003 (95% CI, 0.00-0.11), P = 0.003) and perinatal mortality (OR = 0.001 (95% CI, 0.00-0.03), P < 0.001). UtA-PI ≥ 1.5 MoM was significantly associated with low CPR-MoM, even after adjusting for EFW centile (OR = 5.22 (95% CI, 3.88-7.04), P < 0.001) or small-for-gestational age (SGA; OR = 4.73 (95% CI, 3.49-6.41), P < 0.001). These associations remained significant, even when excluding pregnancies with SGA or including only cases in which Doppler indices were recorded at term (P < 0.01). For prediction of stillbirth, the area under the ROC curve, using a combination of these three parameters, was 0.88 (95% CI, 0.77-0.99) with a sensitivity of 66.7%, specificity of 92.1%, positive likelihood ratio (LR) of 8.46 and negative LR of 0.36. Conclusions Third-trimester CPR is an independent predictor of stillbirth and perinatal mortality. The role of UtA Doppler, CPR and EFW in assessing risk of adverse pregnancy outcome should be evaluated prospectively.
Published: 2015

12. Maternal Body Mass Index influences Umbilical Artery Doppler Velocimetry in physiologic pregnancies

Author: SARNO, LAURA, MARUOTTI, GIUSEPPE MARIA, SACCONE, GABRIELE, Morlando M, Sirico A, MARTINELLI, PASQUALE, Sarno, Laura, Maruotti, GIUSEPPE MARIA, Saccone, Gabriele, Morlando, M, Sirico, A, and Martinelli, Pasquale
Subjects: Adult, Prospective Studie, Umbilical Arterie, Young Adult, Pregnancy, Pulsatile Flow, Female, Ultrasonography, Doppler, Color, Ultrasonography, Prenatal, Human, Body Mass Index
Abstract: OBJECTIVES: The aim of our study was to assess whether there is a relationship between maternal body mass index (BMI) and umbilical artery Doppler velocimetry in physiologic pregnancies. METHODS: Healthy pregnancy women, referred to our center at or before 32 weeks of gestation, were recruited. According to BMI, they were divided into underweight (BMI
Published: 2015

13. Poor neonatal acid-base status in term fetuses with low cerebroplacental ratio

Author: Morales-ROSELLOo J., Khalil A., Morlando M., Bhide A., Papageorghiou A., Thilaganathan B., Morales-ROSELLOo, J., Khalil, A., Morlando, M., Bhide, A., Papageorghiou, A., and Thilaganathan, B.
Subjects: Adult, Male, Middle Cerebral Artery, Adolescent, education, Cerebroplacental ratio, cord pH, Failure to reach growth potential, Ultrasonography, Prenatal, Umbilical Arteries, fetal growth restriction, Young Adult, fetal acid-base status, Retrospective Studie, Pregnancy, Risk Factors, Birth Weight, Humans, Ultrasonography, Doppler, Color, reproductive and urinary physiology, Retrospective Studies, Cord pH, Acid-Base Equilibrium, cerebroplacental ratio, Risk Factor, Fetal growth restriction, Fetal acid-base statu, Infant, Newborn, Middle Aged, Fetal Blood, Umbilical Arterie, failure to reach growth potential, Infant, Small for Gestational Age, fetal Doppler, Fetal Doppler, Female, Human
Abstract: ObjectiveTo determine whether small- and appropriate-for-gestational-age (SGA and AGA) term fetuses with a low cerebroplacental ratio (CPR) have worse neonatal acid-base status than those with normal CPR. MethodsThis was a retrospective study of 2927 term fetuses divided into groups according to birth-weight centile and CPR multiple of the median. The acid-base status at birth as determined by arterial and venous umbilical cord blood pH was compared between weight-centile groups with and without low CPR. ResultsCPR was better correlated with umbilical cord blood pH (arterial pH, r(2)=0.008, P
Published: 2015

14. Maternal body mass index influences umbilical artery Doppler velocimetry in physiologic pregnancies

Author: Sarno L., Maruotti G. M., Saccone G., Morlando M., Sirico A., Martinelli P., Sarno, L., Maruotti, G. M., Saccone, G., Morlando, M., Sirico, A., and Martinelli, P.
Subjects: Adult, nutritional and metabolic diseases, Ultrasonography, Prenatal, Umbilical Arteries, Body Mass Index, Prospective Studie, Umbilical Arterie, Young Adult, Pregnancy, Pulsatile Flow, Humans, Female, Prospective Studies, Ultrasonography, Doppler, Color, Human
Abstract: Objectives: The aim of our study was to assess whether there is a relationship between maternal body mass index (BMI) and umbilical artery Doppler velocimetry in physiologic pregnancies. Methods: Healthy pregnancy women, referred to our center at or before 32weeks of gestation, were recruited. According to BMI, they were divided into underweight (BMI+0weeks of gestation, maternal BMI and umbilical artery Doppler velocimetry were recorded. A correlation between pulsatility index of umbilical artery and BMI was assessed by one-way ANOVA test, multiple comparison test (Bonferroni correction) and polynomial regression. Results: One hundred eighty-five women were included. Mean pulsatility index of umbilical artery at 32+0 was significantly higher in obese women (0.95±0.01 vs 0.87±0.01 vs 0.67±0.01; p2=0.7; p
Published: 2014

15. Phosphorylation and Alternative Splicing of MEF2C, a Dual Switch Function in Muscle Regeneration

Author: Riuzzi, F., Beccafico, S., Sorci, G., Donato, R., Baruffaldi, F., Badodi, S., De Feo, L., Ganassi, M., Battini, R., Imbriano, C., Nicoletti, C., Musarò, A., Buckingham, M., Montarras, D., Molinari, S., Marroncelli, N., Noviello, C., Di Francescantonio, S., Consalvi, S., Saccone, V., Puri, P. L., Olson, E. N., Adamo, S., Moresi, V., Spada, F., Fuoco, C., Pirrò, S., Reggio, A., Paoluzi, S., Gargioli, C., Castagnoli, L., Cesareni, G., Basile, V., Dolfini, D., Ricci, L., Mantovani, R., Mancinelli, R., Guarnieri, S., Di Filippo, E.S., Pietrangelo, T., Fulle, S., Giordani, L., Le Grand, F., Giacomazzi, G., Quattrocelli, M., Sampaolesi, M., Serena, E., Zatti, S., Mattei, N., Vetralla, M., Giulitti, S., Selmin, G., Torchio, E., Vitiello, L., Elvassore, N., Marinkovic, M., Pavlidou, T., Ziraldo, G., Taccola, G., Coslovich, T., Lorenzon, P., Sciancalepore, M., Marcucci, L., Washio, T., Yanagida, T., Niewiadomski, P., Gawor, M., Bernadzki, K., Jóźwiak, J., Rojek, K., Rędowicz, M. Jolanta, Prószyński, T., Boncompagni, S., Michelucci, A., Pietrangelo, L., Dirksen, R.T., Protasi, F., Pisu, S., Rizzuto, E., Del Prete, Z., Nogara, L., Naber, N., Pate, E., Canton, M., Cooke, R., Reggiani, C., Bianco, P., Melli, L., Falorsi, G., Pertici, I., Coceano, G., Cojoc, D., Lombardi, V., Pierucci, F., Frati, A., Battistini, C., Bruzzone, E., Matteini, F., Penna, F., Costelli, P., Meacci, E., Passafaro, M., Madaro, L., Schirone, L., Berghella, L., Puri, P.L., Pin, F., Ballarò, R., Costamagna, D., Martinelli, G.B., Olivari, D., Talamini, L., Lecker, S.H., Ottoboni, L., Resovi, A., Giavazzi, R., Cervo, L., Piccirillo, R., Martinelli, G. B., Re Cecconi, A., Cerruti, F., Cascio, P., Bach, M. Beltrà, Guttridge, D.C., Giovarelli, M., Touvier, T., Clementi, E., DePalma, C., Pescatore, F., Albiero, M., Lutz, C., Schiaffino, S., Sandri, M., Conte, M., Armani, A., Franceschi, C., Salvioli, S., Petrilli, L.L., Codenotti, S., Faggi, F., Poliani, P. L., Cominelli, M., Chiarelli, N., Colombi, M., Vezzoli, M., Monti, E., Bono, F., Tulipano, G., Fiorentini, C., Zanola, A., Gavazzi, S., Lo, H. P., Parton, R. G., Keller, C., Fanzani, A., Mitola, S., Ronca, R., Bouche, M., Poliani, L., Longhena, F., Salani, B., Maggi, D., Kravic, B., Harbauer, A. B., Simeone, L., Kaiser, T., Romanello, V., Buttgereit, A., Neuhuber, W., Straubinger, M., Heuss, D., Rudolf, R., Friedrich, O., Meisinger, C., Hashemolhosseini, S., Huraskin, D., Eiber, N., Reichel, M., Zidek, L., Bernkopf, D., von Maltzahn, J., Behrens, J., Gherardi, G., Mammucari, C., Zamparo, I., Raffaello, A., Chemello, F., Cagnin, S., Braga, A., Zanin, S., Pallafacchina, G., Zentilin, L., De Stefani, D., Lanfranchi, G., Rizzuto, R., Perpetuini, A. Cerquone, Desiderio, G., Chrisam, M., Castagnaro, S., Spizzotin, M., Braghetta, P., Grumati, P., Cecconi, F., Bonaldo, P., Filomena, M.C., Yamamoto, D.L., Mastrototaro, G., Carullo, P., Caremani, M., Lieber, R., Nigro, V., Linari, M., Chen, J., Bang, M.L, Lo Verso, F., Soares, R., Albiero1, M., Guescini, M., Pelosi, L., Coggi, A., Forcina, L., Legnini, I., Di Timoteo, G., Rossi, F., Briganti, F., Sthandier, O., Morlando, M., Fatica, A., Andronache, A., Wade, M., Rajewsky, N., Bozzoni, I., Testa, S., Bianconi, V., Petrilli, L. L., Bernardini, S., Cannata, S., Torcinaro, A., De Santa, F., De Marco, A., Hamilton, S. L., Paolini, C., Canato, M., Salvadori, L., Sagheddu, R., Chiappalupi, S., Di Fonso, A., D’Onofrio, L., Camps, J., Carotenuto, F., Minieri, M., Di Nardo, P., Pigna, E., Coletti, D., Cescon, M., Gattazzo, F., Sabatelli, P., Megighian, A., Sanchez-Riera, C., Lahm, A., Guido, L., Cipriano, A., Tita, R., Bisceglie, L., Ballarino, M., Martini, M., Dobrowolny, G., Del Re, V., Spinozzi, S., Gamberucci, A., Barone, V., Sorrentino1, V., Sandonà, M., Tucciarone, L., Marsolier, J., Patissier, C., Gicquel, E., Adjali, O., Richard, I., Giambruno, R., Micheloni, S., Ferri, G., Jothi, M., Cabianca, D. S., Huber, J., Warner, S., and Gabellini, D.
Subjects: MyoNews, Article
Abstract: Muscle regeneration is a multistep process that is regulated by a restricted number of transcription factors whose activity is modulated at multiple levels. However, how different layers of regulation are coordinated to promote adult myogenesis is not yet understood. Here we show that the MEF2C transcription factor controls multiple steps of muscle regeneration, including myogenic progression of satellite cells and muscle maturation of newly generated myofibers, exhibiting multiple functions that depend on alternative splicing and post-translational modifications. Inclusion of the α1 exon in Mef2c transcripts is upregulated in proliferating mouse satellite cells and in the early phases of muscle regeneration. The encoded MEF2Cα1 isoform stimulates expansion of primary myoblasts ex vivo and in vivo. The pro-proliferative activity of MEF2C is mediated by phosphorylation of two phosphoserines located in exon α1. Subsequent terminal differentiation and growth of newly formed myofibers are promoted by dephosphorylated MEF2Cα1 and MEF2Cα2. Our results thus reveal an important role for regulatory interactions between alternative splicing and post translational modifications of a single transcription factor in the control of the multilayered regulatory programs required for adult myogenesis., Skeletal muscle exhibits a high capacity to regenerate, mainly due to the ability of satellite cells to replicate and differentiate in response to stimuli. Epigenetic control is effective at multiple steps of this process. The chromatin remodeling factor, HDAC4, is up-regulated in skeletal muscle upon injury, suggesting a role for this protein in muscle regeneration. With the aim to elucidate the role of HDAC4 in satellite cells and skeletal muscle regeneration, we generated inducible mice lacking HDAC4 in Pax7+ cells (HDAC4 KO mice). Despite having similar amount of satellite cells, HDAC4 KO mice show impaired muscle regeneration in vivo, and compromised satellite cell proliferation and differentiation in vitro. HDAC4 deletion in satellite cells is sufficient to block their differentiation, not acting via soluble factors, and possibly through the inhibition of Pax7 expression. The molecular mechanisms underling compromised muscle regeneration in HDAC4 KO mice are currently under investigation. All together, these data delineate the importance of HDAC4 in satellite cell differentiation and suggest a protective role of HDAC4 in response to muscle damage., The adult skeletal muscle has the ability to self-renew and repair in response to increased workload, stress conditions or limited damage. These properties rely on an array of different progenitor cell populations. While satellite cells play a central role in muscle regeneration, a variety of other mononuclear progenitor cells, either resident in the muscle or recruited from the blood stream, contribute to the complex crosstalk leading to muscle repair. In pathological conditions or with aging, the relative abundance and the activation stage of the different cell populations in the myogenic stem cell compartment vary. The ability to probe the heterogeneity and the dynamic of the muscle tissue is fundamental to achieve a complete understanding of muscle regeneration. To this end we have invested in a novel approach exploiting mass cytometry technology (CyTOF2 platform). CyTOF technology enables probing single cell events, by labelling intracellular and cell surface markers with up to 40 antibodies tagged with stable heavy metal isotopes. The sharp mass peaks obtained by TOF inductively coupled plasma mass spectrometry eliminates the problems of spectra overlap typical of fluorescence based flow cytometry. I will describe the panel of tagged antibodies that I have developed to characterize the heterogeneous muscle mononuclear cell populations and the advantages and limitations of mass cytometry. In addition I will present preliminary data on the dynamic of cell populations under different conditions and stimuli., The mechanisms that regulate skeletal muscle development involve the coordinated activity of transcription factors (TFs) and a precise timing of gene expression patterns. NF-Y is a heterotrimeric TF with a pioneer role in the transcriptional and epigenetic regulation of promoters containing the CCAAT-box. NF-Y activates the expression of various genes related to the cell cycle, particularly genes of the G2/M phase. NF-YA, the regulatory DNA-binding subunit of the complex, is expressed in proliferating myoblasts and down-regulated during terminal differentiation. The NF-YA gene encodes for two alternatively spliced isoforms, namely NF-YAs and NF-YAl, which are not functionally identical. Using mouse C2C12 cells, we provide evidence of a different role for NF-YA variants in the myogenic program. While NF-YAs enhances myoblasts proliferation, NF-YAl boosts their differentiation by up-regulating the transcription of novel target genes, among which Mef2D, Sixs and Cdkn1C, which are known to be involved in the differentiation program. We further demonstrate that NF-YA is expressed in resident stem cells (SCs) and the two isoforms are transcribed at different levels during SCs activation and differentiation. The inhibition of NF-Y activity impairs both proliferation and differentiation of SCs and the overexpression of the two NF-YA isoforms differentially affects their fate., Sarcopenia is the age-related loss of muscle leading to loss of muscle power, which in the end results in frailty and disability. At molecular level, sarcopenia is characterized by insufficient antioxidant defense mechanism, increased oxidative stress and altered function of respiratory chain. It has been hypothesized that the accumulation of oxidative stress is also related to an impaired regeneration cooperating to the atrophic state that characterizes muscle ageing. To the purpose, we investigated the myogenic process in satellite cells, the skeletal muscle stem cells, as myoblasts and myotubes collected by human Vastus Lateralis skeletal muscle of young and old subjects through needle-biopsies. To measure both the O2- and ROS level we used NBT and H2DCF-DA assays revealing higher concentration in elderly myoblasts compared to young ones. To evaluate if mitochondria are damaged by ROS we measured mitochondrial transmembrane potential after an oxidant insult as H2O2. We found that in elderly myoblasts mitochondrial transmembrane potential decreases much more than in young ones probably due to their lower endogenous antioxidant abilities. Specifically, MitoSOX™ Red reagent for direct measurements of O2- in mitochondria revealed that in elderly myoblasts O2- production is increased respect to young ones and the result is worsened in myotubes. Furthermore, the upregulation of the atrophic and ubiquitin-proteasome pathways together with a dysregulation of the proliferative one revealed an alteration at gene expression level in elderly myoblasts vs young ones. Overall our data confirm that oxidative stress impairs muscle regeneration in elderly subjects., Skeletal muscle is a complex structure endowed with extreme regenerative capability; this ability relies on the orchestrated interplay between different muscle populations that reside within the tissue. Functional changes occurring at the microenvironmental level during aging or pathological conditions however interfere with this ability leading to fibrosis and fat infiltration. Despite a large body of work still we are far from completely understanding these changes; even when genetic cause is known (e.g. Duchenne muscular Dystrophy) we are still unable to pin-point the steps that lead from the molecular cause to the outcome of the disease. The main reason for this bottleneck is that our knowledge has been limited so far by the lack of technical tools to dissect the heterogeneity of these populations. The use of bulk-scale methods able only to provide averaged information has frustrated our effort to characterize those pathological changes leaving those dysfunctional, disease-specific subpopulation to remain hidden within the bulk. Here we present a novel approach based on single cell mass spectrometry to study the populations that reside in the muscle. Using Cytof technology we would profile at single cell resolution the muscle resident populations during aging and in diseased state. This would allow us to identify dysfunctional subsets involved in the regeneration defect. This study would not only shed light on the mechanisms underpinning muscle regeneration but would provide a solid ground for the future identification of diagnostic biomarkers through the study of disease specific subpopulations., Hypertrophy and dystrophy are distinct, yet linked processes that remodel both skeletal and cardiac muscles in physiological or pathological settings. Not only is hypertrophy important during development, but it also plays major role upon acute or chronic damage. Muscular dystrophies (MDs) cause progressive degeneration and loss of functionality in both striated muscle types. In MD patients and animal models, an initial hypertrophic response occurs, with contrasting effects on skeletal and cardiac muscle. Recently it has been established that muscle fibers secrete exosomes, whose cargo acts as endocrine signals during myogenesis. We aim at deciphering the exosomal information guiding hypertrophy/dystrophy in both muscle in order to establish a new strategy based on miRNA modulation for novel myogenic regeneration. We performed ex vivo exosome analysis comparing age-matched WT, Sgcb-null (dystrophic), and MAGIC-F1+/+ (hypertrophic) mice. We detected several differentially regulated miRNAs, virtually relevant for striated muscle remodeling and de-/re-generation. We have preliminary results on the effects of ex vivo exosomes on cell types relevant for skeletal and cardiac muscle analysis. Moreover we are currently investigating the uptake routes of exosomes in both muscle types. In the future we will rely on miRNA-sequencing of ex vivo exosomes, to identify key mRNA/miRNA distinctive signatures by means of an high-throughput approach and place our ongoing results into a genome-wide setting. As a final goal, the hypertrophic/dystrophic signatures and tissue-specific information will further be integrated to establish skeletal- and cardiac-enhancing cocktails to selectively improve the regenerative outcome of patient-specific progenitors in vivo, into a xenograft-permissive murine model., Duchenne muscular dystrophy (DMD) is the most common, lethal, inherited myopathy, which results in muscle degeneration. In this work, we aimed at developing an innovative 3D satellite cell niche derived from human induced pluripotent stem cells (hiPSC) within their native sublaminal position in an engineered human skeletal muscle myofiber. One of the main limitations of cell therapy for DMD is the high number of myogenic cells required and the efficiency of engraftment in vivo. hiPSC ensure large amount of cells and the possibility of derive patient-specific cells, but obtaining myogenic cells in vitro from hiPSC is difficult and the yield is low. In this work, we induced the myogenic differentiation of hiPSC through multiple transfection of modified mRNA of the master transcription factors MYOD, PAX3 and PAX7. To this aim, we exploited a microfluidic platform that allows the downscaling of the process for performing cost-effective, multiparametric and highthroughput experimental investigations. We optimized the protocol for transfecting hiPSC colonies leading to a transfection efficiency of 60% per single transfection. After multiple transfections, exogenous MyoD is expressed in 95% of the cells and endogenous expression of desmin and myosin heavy chain was observed (4 days after the last transfection). Ongoing experiments are extending these results to Pax3 and Pax7. Another key factor for a successful cell therapy is the cell delivery. In this sight, we developed a 3D poly-acrilammide/hyaluronic acid hydrogel (HY) scaffold and optimized its biochemical and mechanical properties in order to sustain the myogenic differentiation of human primary myoblasts and to reproduce the protective microenvironment of the satellite cell niche. The scaffold was designed in order to control the cell topology: 3D parallel micro-channels (80-160 μm in diameter, 10-15 mm long) were produced inside the scaffold and functionalized with ECM proteins. To reproduce the physiological mechanobiology, HY chemical composition was optimized in order to obtain a soft scaffold with physiological elastic modulus, E≈12±4kPa. Human primary myoblasts were used to optimize the seeding, culture and differentiation protocols. At 10 days, we observed tightly packed myotubes bundles, expressing myosin heavy chain, α-actinin and dystrophin. We are now integrating hESC-derived myoblast and we observed differentiation into myoubes and expression of myosin heavy chai, α-actinin and desmin.We hypothesize that such engineered niche will provide, upon in vivo implantation, satellite cells able to regenerate the damaged muscle of DMD patients, and reconstitute the stem cell pool for future muscle damages. On the other hand, our 3D niche could be exploited as an in vitro tool to study the biology of the niche itself, the mechanism of the pathology or as a tool for testing new drugs and therapies in a personalized manner., Skeletal muscle regeneration is mediated by a complex crosstalk between various resident mononucleated cell populations. These cell interactions after fiber damage or stress are finely regulated in time and space. Satellite cells, skeletal muscle stem cells, play a pivotal role during regeneration being the main source of new myoblasts. However, their activation, proliferation and differentiation relies on environmental cues shaped by cell populations such as macrophages, pericytes, and fibro-adipogenic progenitors (FAPs). FAPs have a leading role in the regeneration process since they promote myotube formation by positively regulating satellite cell differentiation. However, in pathological conditions, such as muscular dystropies, these cells play a negative role since they are responsible for fibrosis and fatty tissue accumulation. In in vitro experiments we have observed an improvement in the maturation of myotubes derived from satellite cells, when co-cultured with FAPs. Furthermore, we have also observed that direct contact of these two cell populations inhibits adipogenic differentiation of FAPs while in the transwell system this inhibition does not occur. Even though there is a clear interaction between these two populations, it has not been thoroughly characterized yet. Thus exploiting Luminex technology we are aiming at identifying molecules affecting the differentiation process of these two cell types focusing on cytokines, chemokines and growth factors. In addition we are planning to include in these studies macrophages and pericytes in order to obtain a more complete picture of molecular networks involved in myogenesis and finally build a cell-cell interaction model of skeletal muscle regeneration., Electrical stimulation (ES) of skeletal muscle has been proposed to mimic the beneficial effects of physical training and to counteract the muscle atrophy associated with reduced motor activity. If properly used, it can be a potent tool to increase strength and endurance in patients affected by muscle weakness due to ageing or prolonged debilitating illness. However, classical ES exhibits several limitations, such as the unpleasant symptoms due to pulse strength and the occurrence of muscle fatigue. The most appropriate parameters of stimulation, such as intensity, frequency and pulse duration, are still under debate. Field ESs were given to mouse skeletal myotubes in culture. Changes in membrane potential were detected by perforated patch recordings and calcium dynamics was followed using fluorescent indicators. Different patterns of ES were tested. Tetanic high frequency stimulation at 45 Hz induced voltage changes invariably characterized by failures, and discontinuous firing preceding the complete disappearance of the electrical activity, whereas low-frequency stimulations at 1 Hz more efficiently elicited single action potentials. An innovative “noisy” waveform ES pattern was tested, obtained from a segment of electromyogram recording, sampled from a limb muscle of adult volunteers during the execution of a rhythmic motor activity. Using half of the intensity of stimulation employed for more stereotyped ES patterns, it was found to be more efficient in inducing repetitive cell firing, calcium transients and cell twitching. We suggest this approach as a new strategy for the design of new electrical devices able to provide a therapy option for injured muscles in human patients., Muscle contraction is generated by cyclical interactions of myosin heads with actin filaments to form the actomyosin complex. The stable configurations of the actomyosin complex have been described in detail, but whether in vivo, at physiological temperatures, these configurations are fixed to the ones observed in cryomicroscopy (at low temperature) or undergo thermal oscillations is unknown and not generally considered in mathematical modeling. By comparing three mathematical models, we analyze how this intrinsic property of the actomyosin complex affects muscle contraction at three level; namely, single cross-bridge, single fiber and organ levels, in a ceteris paribus analysis. We observed that state fluctuations allow the lever arm of myosin to easily and dynamically explore all possible minima in the energy landscape, generating several backward and forward jumps between states during the lifetime of the actomyosin complex, whereas the rigid case is characterized by fewer force generating events. Therefore, dynamical oscillations enable an efficient contraction mechanism, in which a higher force is sustained by fewer attached cross-bridges., Mammalian neuromuscular junctions (NMJs) undergo a postnatal topological transformation from a simple oval plaque to a complex branch-shaped structure often called a “pretzel”. Although abnormalities in NMJ maturation and/or maintenance are frequently observed in neuromuscular disorders, such as congenital myasthenic syndromes (CMSs), the mechanisms that govern synaptic developmental remodeling are poorly understood. It was reported that myotubes, when cultured aneurally on laminin-coated surfaces, form complex postsynaptic machinery, which resembles that at the NMJ. Interestingly, these assemblies of postsynaptic machinery undergo similar stages in developmental remodeling from “plaques” to “pretzels” as those formed in vivo. We have recently demonstrated that podosomes, actin-rich adhesive organelles, promote the remodeling process in cultured myotubes and showed a key role of one podosome component, Amotl2. We now provide evidence that several other known podosome-associated proteins are present at the NMJ in vivo and are located to the sites of synaptic remodeling. Additionally, we identified proteins that interact with Amotl2 in muscle cells. We show that two of them: Rassf8 and Homer1, together with other podosome components, are concentrated at postsynaptic areas of NMJs in the indentations between the AChR-rich branches. Our results provide further support for the hypothesis that podosome-like organelles are involved in synapse remodeling and that Rassf8 and Homer1 may regulate this process., Depletion of calcium (Ca2+) from intracellular stores (endoplasmic reticulum, ER), triggers Ca2+ entry across the plasma membrane, a process known as store-operated Ca2+ entry (SOCE). SOCE is mediated by the interaction between STIM1 (stromal interaction molecule 1), which functions as the Ca2+ sensor in the ER, and Ca2+ permeable Orai1 channels in the external membrane. In skeletal muscle, SOCE is the primary mechanism of Ca2+ entry during repetitive activity, a crucial step that prevents/delays fatigue. Despite the importance of this mechanism for proper muscle function during sustained activity, the subcellular sites for SOCE in skeletal fibers have not been identified. Here we show that prolonged muscle activity (treadmill running in mice) drives the formation of previously unidentified intracellular junctions between the sarcoplasmic reticulum (SR) and extensions of the external transverse tubule (TT) membrane. The activity-dependent formation of these unique SR-TT junctions reflects a striking and unexpected remodeling of the existing sarcotubular system at the I band of the sarcomere. Using immunochemistry and immuno-gold labeling we also demonstrate that these newly formed, activity-driven junctions contain the molecular machinery known to mediate SOCE in muscle: STIM1 Ca2+ sensor proteins in the SR, already present in the I band in control conditions, and Ca2+- permeable Orai1 channels, which move into the I band with TTs during prolonged muscle activity. Thus, we refer to these junctions as Ca2+ Entry Units, the first new, molecularly defined subcellular structure in skeletal muscle in over 30 years., The loss of connection between muscle and nerve is a crucial biological mechanism involved in Amyotrophic Lateral Sclerosis (ALS), a neurodegenerative disease associated with motor neuron degeneration, muscle atrophy and paralysis [1]. Recent studies showed the primary role of the skeletal muscle in the pathogenesis of the disease, pointing out the key role of the communication between muscle and nerve. In this context, we developed a protocol to measure, ex vivo, the neuromuscular junction (NMJ) functionality [2]. The experimental technique is based on the comparison between the muscle contractile response elicited by membrane stimulation and the response evoked by nerve stimulation. Since this latter stimulation bypasses the neuronal signalling, any difference between the two responses may be related to NMJ alterations. In particular, we started studying the Soleus-sciatic nerve preparation of one of the most studied ALS animal models, the SOD1G93A mouse [3], with the particular aim of following the pathology’s progress. We observed that the first functional alterations begin at 90 days of age, with an intrinsic damage of the muscle and defects in NMJ functionality who increase until the end-stage of the disease. Subsequently, we approached the study of the MLC/SOD1G93A mouse model, in which superoxyde dismutase-1 mutated gene is expressed exclusively in the skeletal muscle [4]. Our preliminary results highlighted defects in soleus muscle and NMJs functionality in MLC/SOD1G93A mouse model, compared to the wild type, suggesting a direct muscle impairment. Further analysis on this model will provide useful information about the NMJ alterations directly related to oxidative stress on skeletal muscles., Myosin is an abundant ATPase protein. It is estimated that 10% of muscle tissue weight is myosin. Due to its abundance, myosin can be a good target to raise basal metabolic rate in animals. A new low-ATP-consumption state of myosin has recently been proposed (1, 2). This new state has been called the “Super Relaxed State (SRX)” of Myosin. Structural evidence for the SRX state have recently been published showing a close complex formed by the two-myosin heads (3). It is characterized by an ATPase time constant in the order of 300 seconds versus the 15 seconds for the so-called “Disordered Relax State” (DRX)(1,2). The idea is that behind that large number of “dormant” ATPases, there is the key to raise basal metabolism in a physiological way. The amount of myosin in the SRX state is estimated to be approximately 60% of the total. Switching of the myosin heads from the SRX state to the DRX state is regulated by phosphorylation in a cooperativeness-driven-equilibrium. Controlling this equilibrium may lead to an increase in basal metabolism that would consume an additional energy of up to 1000 Kcal/day. We studied the effect of several Regulatory Light Chain mutants on the SRX state and we applied this information to the development of a high throughput screen. We are searching a molecule that is able to destabilize the SRX state in skeletal muscle fibers. We screened 2000 compound of an FDA approved library. Potential lead compounds will be discussed, The muscle cell is a biological machine where steady force and shortening are generated by arrays of the motor protein myosin II pulling the actin filament towards the centre of the sarcomere (the ~2 μm long structural unit of muscle) during cyclical ATP-driven interactions. The fraction of the time of the ATP hydrolysis cycle that myosin II spends attached to actin depends on the sarcomere load and at low load can be as small as 0.02. The array-type arrangement of the motors enhances and makes steady the production of force and shortening, but has so far limited the investigation of mechanics, energetics and structural dynamics of this collective motor to top-down approaches, such as single-cell mechanics and X-ray diffraction (Piazzesi et al. Cell 131:784-795, 2007). The laser trap technique in the Three Bead Assay (TBA) configuration allowed the recording of single actin-myosin interaction in vitro, but only when the duration of attachment was increased by reducing the ATP concentration to a few tens of micromolar (two orders of magnitude lower than that in situ in physiological conditions). In this project we use an alternative approach consisting in assembling molecular motor proteins on a nanostructured support to generate a synthetic sarcomere-scale machine, the mechanical output of which is measured with a double laser optical tweezers apparatus (Bianco et al. Biophys. J. 101:866-874, 2011). The shape, the material and the coating of the support carrying the motor array have been optimised using a preliminary version of the machine consisting of an ensemble of motor proteins randomly adsorbed on a flat surface and brought to interact with an actin filament attached to the trapped bead with the correct polarity. Tests on the density and the disposition of the myosin motors on the surface have been done using AFM. The most reproducible results have been obtained when the support for the motor ensemble is the lateral surface of a chemically etched single mode optical fibre (diameter 4 µm). In solution with physiological [ATP] (2 mM), the ensemble drives 350 nm of actin filament sliding developing a steady force of 50 pN. Supported by Italian Institute of Technology-SEED, project MYOMAC (Genova) and PRIN-MIUR, Italy., Skeletal muscle atrophy is caused by several and heterogeneous conditions, such as cancer (cachexia), neuromuscular disorders and aging. In most types of skeletal muscle atrophy overall rates of protein synthesis are suppressed, protein degradation is consistently elevated and atrogenes, such as the ubiquitin ligase Atrogin-1/MAFbx, are up-regulated. Sphingolipids represent a class of bioactive molecules capable of modulating the destiny of many cell types, including skeletal muscle cells. In particular, we and others have shown that sphingosine 1-phosphate (S1P), formed by sphingosine kinase (SphK), is able to act as trophic and morphogenic factor in myoblasts. Here, we report that the inhibition of SphK1 by specific gene silencing or pharmacological inhibition drastically reduced myotube size and myonuclei number, and increased Atrogin-1/MAFbx expression. Notably, the atrophic phenotype of C2C12 myotubes treated with dexamethasone and of muscle fibers obtained from cachectic mice inoculated with C26 adenocarcinoma, was characterized by increased expression of Atrogin-1/MAFbx and reduced levels of active SphK1. In addition, we found that C2C12 muscle cell atrophy was accomplished by changes in the pattern of expression of S1P receptor subtypes (S1PRs) and treatment of myotubes with S1P was able to prevent Dexa-induced atrophic marker expression. Finally, by using specific S1PR agonists and antagonists, we extended the investigation on the role played by S1PRs in the control of Atrogin-1/MAFbx expression. Altogether, these findings provide the first evidence that S1P/SphK1/S1PR axis acts as a molecular regulator of skeletal muscle atrophy, thereby representing a new possible target for therapy in many physiological and pathological conditions., Skeletal muscle is a dynamic tissue that can respond to external stimuli through both anabolic and catabolic processes. In a variety of conditions, including immobilization, AIDS and neuromuscular disorders, skeletal muscle mass is decreased (atrophy). Upon denervation or disuse, skeletal muscle undergoes atrophy, leading to reduced size of myofibers, impaired contractile and metabolic activities. Previous studies have identified key molecular pathways leading to protein breakdown and degradation of sarcomeric proteins; yet, it remains a gap of knowledge on whether muscle resident cell populations can regulate the response of muscle to atrophic stimuli. Indeed, the recent identification of muscle-derived interstitial cells, named fibro-adipogenic progenitors, that can adopt multiple lineages and contribute, either directly o indirectly, to muscle regeneration (Joe et al,2010; Uezumi et al,2010) indicates a previously unrecognized complexity in the regulation of muscle homeostasis (Saccone et al,2014). We have discovered an unexpected key role of specific muscle-derived mononuclear cells in the pathogenesis of muscle atrophy. The characterization of the mechanism by which these cells contribute to the loss of muscle mass may lead to the identification of new therapeutic targets to counteract muscolar atrophy., PGC-1α overexpression is able to protect skeletal muscle from fasting or denervation-induced atrophy (1) and to improve sarcopenia in old mice (2). Consistently, in the skeletal muscle of cachectic tumor-bearing mice, PGC-1α expression is reduced (3), in Association with the accumulation of PAX7+ cells, which is suggestive of an impairment of myogenesis (4). Preliminary observations obtained in mice overexpressing PGC-1α specifically in the skeletal muscle show that the number of CD34+/Sca1+ cells, both integrin-α7 positive (satellite cells) and negative (other myogenic precursors), was higher in the muscle of transgenic (TG) mice than in those of wild-type (wt) animals. Not only, myotubes originating from TG-derived myogenic precursors were increased in both number and size in comparison to those obtained from wt progenitors. Aim of the present study was to investigate if PGC-1α overexpression can improve the regenerative capacity in the muscle of tumor (C26)-bearing animals after chemically-induced injury. BaCl2 (30 μl, 1.2% w/v) was injected in the tibialis anterior muscle the day after tumor implantation. Thirteen days after injury, both wt and TG controls almost completely recovered the initial myofiber cross sectional area (CSA; 70% of uninjured muscle). By contrast, CSA recovery was markedly delayed in wt or TG tumor-bearing mice (30% of uninjured muscle). Such a lack of CSA rescue in TG C26 hosts occurred despite TG mice constitutively possess a number of myogenic precursors higher than wt animals. As an estimate of mitochondria number, cytochrome c expression was evaluated. The results show that cytochrome c levels were significantly reduced in the regenerating muscle of wt C26 hosts, while remained comparable to those of uninjured muscle in BaCl2-treated TG tumor bearers. Previous observations showed that inhibition of ERK activity improved muscle wasting and myogenesis in the C26 hosts (4). In this regard, muscle pERK levels were significantly lower in TG tumor bearers than in wt C26 hosts. In conclusion, the present study shows that PGC-1α overexpression in the regenerating muscle of tumor hosts resulted in improved mitochondrial mass, and likely, oxidative capacity, and in reduced pERK levels, however without obtaining a significant CSA rescue. These observations suggest that while PGC1α overexpression exerts positive effects on tumor-induced derangements at the molecular level, it does not appear able to impinge on the multifactorial nature of muscle wasting., Cancer cachexia is a life-threatening syndrome that affects most patients with advanced cancers and involves severe body weight loss, with rapid depletion of skeletal muscle. No effective treatment is available. We analyzed microarray datasets to identify a subset of genes whose expression is specifically altered in cachectic muscles of Yoshida hepatoma-bearing rodents, but not in those with diabetes, disuse, uremia or fasting. By Ingenuity Pathways Analysis, we found three genes belonging to the CXCR4 pathway downregulated only in muscles atrophying because of cancer: SDF1, PAK1 and ADCY7. Consistently, we show that the expression of all SDF1 isoforms declines also in Tibialis Anterior from cachectic mice bearing colon adenocarcinoma or renal cancer and anti-cachexia drugs such as sunitinib restore it. Overexpressing genes of this pathway (i.e. SDF1 or CXCR4) in cachectic muscles increases the fiber area by 20%, partially protecting them from wasting. The mechanisms behind this muscle preservation during cachexia include both reduced degradation of long-lived proteins, by either SDF1α or SDF1β on atrophying myotubes, and increased protein synthesis, mainly by SDF1α. However, inhibiting CXCR4 signaling with the antagonist AMD3100 does not affect protein homeostasis in atrophying myotubes at all, whereas normal myotubes treated with AMD3100 display decreased diameter in a time- and dose-dependent manner, until a plateau. This further confirms the involvement of a saturable pathway (i.e. CXCR4). Overall, these findings support the idea that activating the CXCR4 pathway in muscle suppresses the deleterious wasting associated with cancer., Cancer cachexia is a systemic syndrome that consists of a dramatic weight loss with rapid muscle depletion due to enhanced protein degradation, irrespective of food intake. Remarkably, 50% of advanced cancer patients are affected by cachexia, which accounts for approximately 20% of cancer deaths. No therapy is available. Interestingly, females are more resistant to cancer cachexia than males. We analyzed previous microarray datasets to identify genes whose expression is specifically altered in cachectic muscles of Yoshida hepatoma-bearing male rodents. Among these genes, we found that apelin was drastically downregulated to 8% of controls in cachectic gastrocnemius muscles (with 14% of weight loss) from male rats bearing Yoshida hepatoma for 5 days. We confirmed by Q-PCR that apelin was downregulated to 45% and 2% of controls also in Tibialis Anterior (TA) muscles in Lewis Lung Carcinoma and in Colon Adenocarcinoma 26 (C26)-bearing mice, respectively. Moreover, in TA from C26-bearing mice also the expression of apelin receptor (APJ), a member of G-protein coupled receptors, was reduced to 16%. Q-PCR analysis further confirmed that apelin downregulation occurred at all stages of cancer cachexia of C26-bearing male mice, while the expression of APJ was significantly reduced to 30% of controls only in early cachectic mice with less than 14% of body weight loss. Since apelin is expressed on X chromosome both in humans and mice and it is not downregulated in muscles from C26-bearing female mice, we believe that apelin could be a good candidate to explain the gender difference of cancer cachexia., Cachexia is a syndrome frequently occurring in cancer patients. It is characterized by body and skeletal muscle wasting and by metabolic abnormalities. These latter are mediated, partially at least, by humoral factors. Energy balance perturbations also contribute to the onset of cachexia. In this regard, impaired mitochondrial functions and altered energy expenditure likely play a role. Recent observations suggest that in addition to classical humoral factors such as hormones or cytokines, also tumor-derived microvesicles (MVs), circulating particles containing different molecules such as proteins, mRNAs and microRNAs, may contribute to derangements associated with cachexia (1). MVs were isolated by differential ultracentrifugation from the conditioned medium of LLC (Lewis Lung Carcinoma) cells and were quantified by a NanoSight apparatus. After five day culture in differentiation medium, C2C12 myotubes were treated for 24 h with LLC-derived MVs. In C2C12 myotubes tumor-derived MVs induce a reduction of PGC-1α, the master regulator of oxidative metabolisms and mitochondrial biogenesis, as well as of Cyt-c mRNA expression. These results are in agreement with previous observations showing decreased PGC1α expression in the skeletal muscle of cachectic mice. In myotubes oxygen consumption is significantly decreased while lactate levels in the culture medium are increased after treatment with MVs. BNIP3 mRNA expression is significantly increased, while no differences can be observed as for myotube size and mRNA expression of both Atrogin1 and MuRF-1, two muscle-specific ubiquitin ligases. These results suggest that tumor-derived MVs affect mitochondria in C2C12 cultures. The reduction of mitochondrial mass (decreased Cyt-c mRNA expression) and function is associated with down-regulation of PGC-1α expression and enhancement of selective autophagy (mitophagy). On the whole, MV-induced alterations could contribute to muscle wasting during cancer cachexia., High mobility group box 1 (HMGB1) is a nuclear protein that acts extracellularly as an alarmin to modulate inflammation and tissue repair by recruiting cells and promoting their migration and activation. Recently, we showed that HMGB1 orchestrates both processes by switching among mutually exclusive redox states. Fully reduced HMGB1 acts as a chemoattractant, whereas a disulfide bond makes it a proinflammatory cytokine and further cysteine oxidation by reactive oxygen species (ROS) abrogates both activities. The fully reduced HMGB1 is prevalent in the extracellular environment immediately after acute muscle injury, and disulfide- HMGB1 appears a few hours later. Thus, the generation of ROS during muscle damage might modulate the redox status of the protein and eventually limit its lifespan and functions. We created a mutant (3S-HMGB1) not susceptible to redox modifications and we evaluated its regenerative activity in a model of acute muscle injury induced by cardiotoxin. We demonstrated so far that HMGB1 has beneficial effects in skeletal muscle regeneration after acute injury by dramatically increasing the number of healthy fibers and the number of satellite cells and M2c macrophages, two cell types essential for muscle repair. Moreover, HMGB1 acts directly on primary myoblasts by inducing their migration and their fusion to form large myotubes. Remarkably, 3S-HMGB1 behaves as a superagonist of HMGB1 in vivo, suggesting that it is a promising candidate for muscle repair therapies. Our study will be extended to other models of muscle damage, in particular dystrophies, in order to evaluate the therapeutic potential of 3S-HMGB1 in chronic conditions., Atrophy is an active process controlled by specific signaling pathways and transcriptional programs. The identification of the precise signaling cascades that regulate muscle wasting remains poorly understood. The Ubiquitin Proteasome System (UPS) is one of the major systems that control protein breakdown during muscle wasting. The specificity of ubiquitin-dependent degradation derives from many E3s that recognize specific substrates. This work is focus on a novel muscle-specific circadian-rhythm dependent ubiquitin ligase named Asb2β. To dissect its role, we have generated muscle specific and tamoxifen-inducible muscle specific knock-out mice. We have characterized these knockout mice in physiological and in catabolic conditions. Asb2β defective muscles show normal muscle morphology and mitochondrial content but muscles display a fiber type switch and glycogen accumulation. Glucose tolerance test revealed an improved glucose uptake in knockout mice. Moreover, glycogen content dramatically decreased in Asb2β knockout mice during fasting. The changes in glucose homeostasis are Akt independent but TBC1D1and AS160 dependent. However, absence of nutrients triggers necrotic degeneration and appearance of abnormal mitochondria in Asb2β-null muscles. We have also started to characterize the tamoxifen-inducible knockout mice. Preliminary data show that acute inhibition of Asb2β induces a time dependent muscle growth. In conclusion, we have identified a novel muscle specific ubiquitin ligase, Asb2β, that plays an important role in glucose homeostasis and muscle hypertrophy., Aging is characterized by loss of skeletal muscle mass and function, condition known as sarcopenia. The mechanisms underlying sarcopenia are not completely understood, however a role for ectopic fat accumulation has been proposed. Skeletal muscle accumulates lipid in form of triglycerides within lipid droplets (LDs). LDs are characterized by the presence of Perilipins (Plins), that control lipid accumulation and metabolism under physiological and pathological conditions. In skeletal muscle one of the most representative is Plin2, particularly involved in lipid storage. However, the exact role of Plin2 is not still clear. We found that in human muscle the expression of Plin2 increases with aging and it is inversely associated with muscle mass and strength. Moreover, Plin2 expression is associated with atrophy-related genes, MuRF-1 and Atrogin, suggesting a role for Plin2 in muscle aging and atrophy. We also analysed the expression of Plin2 in adult mice where muscle atrophy was induced by denervation. Denervation of tibialis anterior muscle was compared with the contralateral intact side. After denervation, beside the expected increase of MuRF-1 and Atrogin, also Plin2 expression actually increases. This suggested that Plin2 expression is somehow associated with muscle atrophy. To support this hypothesis, we performed muscle-specific in vivo silencing experiments of Plin2. After 7 days from injection, a decrease of Plin2 was observed, and most interestingly the cross-sectional area (CSA) of Plin2-negative fibres resulted increased of about 30% with respect to Plin2-positive ones. As a whole, these data suggest that in skeletal muscle Plin2 is involved not only in muscle atrophy, but also in hypertrophy. Further studies are ongoing to better clarify this new role of Plin2 in skeletal muscle., The rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in people under 20 years of age. It can commonly arise anywhere in the body but the head and neck, the extremities and the genitourinary tract are predominant sites. Based on histology, RMS tumors are classified into two major subtypes, embryonal and alveolar, which also differ in the molecular pathogenesis of development. Despite these differences, the origin of aRMS and eRMS seems to be the same but the precise cell type that triggers RMS is still unclear. Some evidence supports the notion that skeletal muscle precursors, probably satellite cells, may initiate RMS. Alternative theories propose mesenchymal stem cells, or even cells belonging to the adipocyte lineage, as possible tumor-initiating cells. In order to shed light on the origin of eRMS, we adopted the KrasG12D/+Trp53Fl/Fl conditional mouse model. This model allows us to generate eRMS in the hind limb of mice by infecting them with an adenovirus vector carrying the CRE recombinase. In a first approach we want to describe and rationalize the changes in the tumor mass cell populations by analyzing the tumor at different stages of development by using flow and mass cytometry techniques. In a second approach we aim at identifying the cell population(s) that are responsible for initiating the tumor. To this end we induce the gene mutations that are responsible for rhabdomyosarcoma development by infecting, with the CRE recombinase adenovirus, isolated muscle mononucleate cell populations and monitor their ability to develop rhabdomyosarcoma tumorigenic properties in vitro., The purpose of this study was to investigate whether MURC/cavin-4, a plasma membrane and Z-line associated protein exhibiting an overlapping distribution with Caveolin-3 (Cav-3) in heart and muscle tissues, may be expressed and play a role in rhabdomyosarcoma (RMS), an aggressive myogenic tumor affecting childhood. We found MURC/cavin-4 to be expressed, often concurrently with Cav3, in mouse and human RMS, as demonstrated through in silico analysis of gene datasets and immunohistochemical analysis of tumor samples. In vitro expression studies carried out using human cell lines and primary mouse tumor cultures showed that expression levels of both MURC/cavin-4 and Cav-3, while being low or undetectable during cell proliferation, became robustly increased during myogenic differentiation, as detected via semi-quantitative RT-PCR and immunoblotting analysis. Furthermore, confocal microscopy analysis performed on human RD and RH30 cell lines confirmed that MURC/cavin-4 mostly marks differentiated cell elements, colocalizing at the cell surface with Cav-3 and labeling myosin heavy chain (MHC) expressing cells. Finally, MURC/cavin-4 silencing prevented the differentiation in the RD cell line, leading to morphological cell impairment characterized by depletion of myogenin, Cav-3 and MHC protein levels. Overall, our data suggest that MURC/cavin-4, especially in combination with Cav-3, may play a consistent role in the differentiation process of RMS., Rhabdomyosarcoma (RMS) is a childhood soft tissue tumor with broad expression of markers that are typically found in skeletal muscle. Cavin-1 is a recently discovered protein actively cooperating with Caveolin-1 (Cav-1) in the morphogenesis of caveolae and whose role in cancer is drawing increasing attention. Using a combined in silico and in vitro analysis here we show that Cavin-1 is expressed in myogenic RMS tumors as well as in human and primary mouse RMS cultures, exhibiting a broad subcellular localization, ranging from nuclei and cytosol to plasma membrane. In particular, the coexpression and plasma membrane interaction between Cavin-1 and Cav-1 characterized the proliferation of human and mouse RMS cell cultures, while a downregulation of their expression levels was observed during the myogenic differentiation. Knockdown of Cavin-1 or Cav-1 in the human RD and RH30 cells led to impairment of cell proliferation and migration. Moreover, loss of Cavin-1 in RD cells impaired the anchorage-independent cell growth in soft agar. While the loss of Cavin-1 did not affect the Cav-1 protein levels in RMS cells, Cav-1 overexpression and knockdown triggered a rise or depletion of Cavin-1 protein levels in RD cells, respectively, in turn reflecting on increased or decreased cell proliferation, migration and anchorage-independent cell growth. Collectively, these data indicate that the interaction between Cavin-1 and Cav-1 underlies the cell growth, migration and differentiation grade in myogenic tumors., Recently, it was shown that in yeast CK2-dependent phosphorylation of the mitochondrial import receptor Tom22 promotes biogenesis of the TOM translocase and is required for import of mitochondrial proteins. We asked whether CK2-dependent phosphorylation of TOM proteins also occurs in mammals. Using CK2β-deficient skeletal muscle lysates, we observed less phosphorylation of Tom22. Moreover, we confirmed CK2 phosphorylating residues serine 15 and threonine 43 of murine Tom22. Further, CK2-dependent phosphorylation of Tom22 changes its binding affinity for proteins need to be imported into mitochondria. In the absence of CK2 mitochondrial protein import is impaired in muscle fibers and mitochondria are dysfunctional. Pink1, a mitochondria health sensor and involved in Parkinson s disease, accumulates within mutant muscle cells, and labels removal of dysfunctional mitochondria by mitophagy and involvement of autophagic adaptor protein p62/SQSTM1. Consequently, the metabolism of oxidative muscle fibers in mutant muscles shifted towards glycolytic. As proof of concept, removal of aggregated p62/SQSTM1 by muscular in vivo electroporation of phosphomimetic Tom22 was successful. This is the first evidence for both, regulated protein import into mammalian mitochondria, and muscle weaknes due to a mitochondrial protein import defect., Canonical Wnt/β-catenin signaling plays a role in myogenic differentiation, but its role in adult muscle fibers is completely unknown. We approached canonical Wnt signaling in adult myofibers by well-known reporter Axin2-lacZ mice, monitoring X-Gal staining in muscle stem cells, in adult muscle fibers and at their neuromuscular synapse. In muscle stem cells, canonical Wnt signalling is absent in quiescent cells and 72 h proliferating cells. In adult muscle fibers, canonical Wnt signaling is strongly detectable by Axin2- and β-catenin-positive skeletal muscle fibers, where it is expressed only in fast fiber types with small cross-sectional areas. In these fibers, canonical Wnt signaling is active together with Hippo signaling members, YAP/TAZ and TEAD1. During differentiation of C2C12 cells, Axin2 increases together with the expression of TEAD1-target genes: CTGF, Ankrd1 and Cyr61. In cultured primary muscle cells, we observed Axin1 and Axin2 being involved in proliferation and myotube formation in a Wnt1 and Wnt3a dependent manner. We present a model how canonical Wnt/β-catenin signaling, together with YAP/TAZ and TEAD1, influences muscle fiber diameter in fiber-type specific manner., Muscle atrophy contributes to the poor prognosis of many pathophysiological conditions, but pharmacological therapies are still limited. Muscle activity leads to major swings in mitochondrial [Ca2+] which control aerobic metabolism, cell death and survival pathways. We have investigated in vivo the effects of mitochondrial Ca2+ homeostasis in skeletal muscle function and trophism, by overexpressing or silencing the Mitochondrial Calcium Uniporter (MCU). The results demonstrate that both in developing and in adult muscles MCU-dependent mitochondrial Ca2+ uptake has a marked trophic effect that does not depend on aerobic control, but impinges on two major hypertrophic pathways of skeletal muscle, PGC-1α4 and IGF1-AKT/PKB. In addition, MCU overexpression protects from denervation-induced atrophy. These data reveal a novel Ca2+-dependent organelle-to-nucleus signaling route, which links mitochondrial function to the control of muscle mass and may represent a possible pharmacological target in conditions of muscle loss., PKC (protein kinase C) family is composed by 3 subgroups: conventional, novel and atypical PKC. These kinases are involved in a large number of biological processes (such as protein synthesis, glucose metabolism, apoptosis). PKCzeta and PKClambda/iota belong to the atypical PKC subgroup and differ from conventional and novel PKCs for their activation mechanism. Indeed atypical PKCs are calcium and diacylglycerol (DAG) insensitive, while classical PKCs are activated by calcium and DAG, and novel PKCs are activated by DAG but not by calcium (1,2). Little is known on the role of PKCzeta on skeletal muscle homeostasis. Thus, we overexpressed this kinase by in vivo transient transfection. We observed a marked hypertrophy in PKCzeta positive myofibers compared to surrounding not transfected fibers. In addition PKCzeta overexpression protected muscle from denervation-induced atrophy. Next, we studied the effects of 3 different PKCzeta mutants on fiber size: 1) PKCzeta-DN (a dominant negative isoform carrying a point mutation on the ATP-binding site); 2) PKCzeta-ΔNPS (a costitutive active mutant); 3) PKCzeta-InLoop (a dominant negative isoform mutated in the activation loop). Surprisingly all these mutants cause muscle hypertrophy and protect from denervation-induced atrophy suggesting a possible kinase-independent mechanism of PKCzeta on skeletal muscle trophism., P38 mitogen activated protein kinases (MAPKs) are required at several stages during differentiation of muscle progenitor cells. P38 phosphorylation initially accompanies satellite cells activation and triggers asymmetric division. At a later stage, it orchestrates myoblast differentiation promoting myotube formation. The signals that trigger or modulate p38 activation during the differentiation process are still debated. Both cellJtoJcell contact and TNFα prime p38α/β phosphorylation and activation during myogenesis. Cdo, a multifunctional surface protein has been implicated in myogenesis. Following cellJtoJcell contact and ligation to cadherin, Cdo binds JLP and BnipJ2 which act as scaffolds for recruitment of p38α/β and Cdc42. The formation of the complex leads to activation of Cdc42, which is fundamental to promote p38α/β phosphorylation and myogenic differentiation. However, the phosphorylation cascade leading to p38α/β activation has not been elucidated. We focused on Pak1, a member of the p21 activated kinase family, which is activated by Cdc42. We have observed that treatment of differentiating myogenic progenitors (mesoangioblasts) with the Pak1 inhibitor IPAJ3 negatively modulates p38α/β phosphorylation and myogenin expression without affecting cell proliferation. This inhibition of the myogenic differentiation program results in a lower efficiency of myotube formation. We followed these observations in vivo by monitoring regeneration efficiency in mice treated with IPA-3 and we observed that mice treated with IPA-3 displayed a delayed recovery after cardiotoxin injury. These results suggest the Pak1 contributes to myogenic differentiation of progenitor cells in vitro and participates in muscle regeneration in vivo., Ambra1 (activating molecule in Beclin 1-regulated autophagy) is an adaptor protein involved in a plethora of cellular processes. Studies in mice with a randomly mutated Ambra1 locus (Ambra1gt/gt) showed that this gene is essential for the development of the central nervous system. A recently published work by our team suggests that Ambra1 may also play a key role for muscle development in zebrafish and mouse. Indeed, Ambra1gt/gt E13.5 mouse embryos display severe defects of neck, tongue, dorsal and limb muscles, being characterized by increased cellularity and a marked disorganization of myofibers. To better clarify the role of Ambra1 in skeletal muscles, we generated mice with a floxed Ambra1 allele (Ambra1flox/flox). Ambra1flox/flox mice were then crossed with a CAG-Cre transgenic line, which express Cre recombinase in the oocytes, thus obtaining Ambra1+/- mice. Here we show that Ambra1–/– mice die at late developmental stages and display severe morphological defects, similar to Ambra1gt/gt embryos. Adult Ambra1+/- mice show an increased percentage of centrally nucleated fibers and a decreased proportion of oxidative fibers. Ambra1flox/flox mice were then bred with MLC-1f-Cre transgenic animals, which only express Cre recombinase in mature myofibers. Our preliminary data in adult Ambra1flox/flox;MLC-1f-Cre mice show a significant increase of centrally nucleated fibers, although we did not observe any overt defect of oxidative fibers. Altogether, our data suggest that Ambra1 is important for the development of skeletal muscle. Further studies in different muscles of Ambra1flox/flox;MLC-1f-Cre mice under different stress conditions will allow elucidating the role of this adaptor protein in myofiber homeostasis, Myopalladin (MYPN) is a striated muscle-specific sarcomeric protein belonging to a small family of actin-associated immunoglobulin-containing proteins. MYPN mutations have been identified in patients with dilated (DCM), hypertrophic, and restrictive cardiomyopathy. Furthermore, we identified three MYPN mutations in limb girdle muscular dystrophy (LGMD) patients with associated DCM. Within the sarcomeric Z-line, myopalladin binds to α-actinin, nebulin, and PDZ-LIM proteins. Furthermore, it is present in the nucleus and the I-band where it binds to the stress-inducible transcriptional cofactor CARP/Ankrd1, which, in turn, binds to the I-band region of titin, suggesting a role of MYPN in mechanosensing. In our preliminary studies, we found that MYPN can bind to and bundle filamentous actin, thereby promoting actin polymerization. Moreover, MYPN interacts with MRTF-A and strongly increases MRTF-A-mediated activation of serum response factor (SRF) signaling. In studies of MYPN knockout (MKO) mice, we found that MKO mice are significantly smaller compared to wildtype (WT) mice and have an about 30% reduction in skeletal muscle cross-sectional area (CSA) at all ages. Consistently, reduced differentiation rate and myotube width was observed in primary skeletal muscle cultures derived from MKO mice. Furthermore, studies of muscle performance in 2-month-old MKO mice showed reduced isometric force and power during isotonic shortening at any loads as a result of the reduced cross sectional area, whereas the force developed by each myosin molecular motor was unaffected. By up- and downhill treadmill running, MKO and WT mice performed similarly. However, while the performance of WT mice was unaffected following four consecutive days of downhill running, the performance of MKO mice decreased progressively and signs of muscle regeneration following muscle damage were observed. Consistent with a higher susceptibility to muscle damage, progressive Z-line widening was observed in MKO skeletal muscle from about 8 months of age. RNAseq revealed downregulation of actin isoforms and other SRF-target genes in MKO muscle both at 2 and 4 weeks of age, suggesting altered SRF signaling as a possible explanation for the reduced CSA in MKO mice., Impairment of autophagy in muscle leads to precocious ageing1. In particular, autophagy deficient mice are characterized by weakness are atrophy that are associated with alteration in Neuro Muscular Junction (NMJ) and loss of innervation. In order to investigate the cross-talk between muscle and nerve, we found that the expression of FGFBP1, a neurotrophic factor that is critical to preserve muscle-nerve interaction, is suppressed in muscle of autophagy deficient mice. FGFBP1 has been found to be regulated by miRNA206, the muscle-specific miRNA2. When we checked the level of miRNA206 expression, we found higher level of miRNA206 in serum of muscle specific autophagy deficient mice than in controls. Importantly, miRNA206 was detected in the heart of those mice. To understand whether autophagy deficient muscles released vesicles containing microRNAs, we analysed exosomes Quantitative RT-PCR analyses confirmed an increased expression of miRNA206 in purified exosomes from both denervated and autophagy deficient fibers. Moreover expression of BDNF in neurons treated with purified exosomes containing miRNA206 was down-regulated. This finding suggests a potential role of exosomes and miRNA206 in modulating synaptic plasticity. In order to mimic autophagy deficient mice condition, we systemically injected exosomes transfected with miRNA206 in wild-type animals. MiRNA206 was found in several tissues, in particular liver and heart. Moreover the treatment was sufficient to induce skeletal muscle atrophy and changes in the expression of several neurotrophic factors. These data support the role of exosome as a signaling mechanism that connects muscle with different tissues including motorneuron, heart and liver., Duchenne muscular dystrophy (DMD) is a genetic disease in which loss of functional dystrophin protein results in progressive skeletal muscle degeneration. Although the genetic defect is widely known, the mechanisms by which the absence of dystrophin leads to the complex pathophisiology of the disease is not completely understood. MiRNAs are small non coding RNA that are important regulatory elements for muscle development and function [1]. Altered levels of specific miRNAs were found in several muscular disorders, including DMD [2, 3]. In particular it has been identified a specific DMD-signature miRNAs that may serve as a marker for therapeutic purposes [4]. Moreover, in a recent work it has been defined a specific group of miRNAs strictly correlated to dystrophin levels and whose deregulated expression could explain several pathogenetic features of DMD [5]. Previously we have demonstrated that the local expression of mIGF-1 in mdx mice ameliorates the dystrophic phenotype reducing myonecrosis and upregulating survival pathways such as AKT pathway [6]. In this work, we show that a specific group of miRNAs, dystrophin-indipendent, are modulated by mIGF-1 expression. In particular, local expression of mIGF-1 promotes the modulation of miR-206 and miR-24 as well as muscle specific genes associated with maturation of regenerating muscle fibers and differentiation. These results indicates that local overexpression of the anabolic factor mIGF-1 in mdx mice ameliorates the dystrophic microenviroment modulating the expression of a specific group of miRNAs and inducing a partial rescue of the characteristic DMD-signature., Circular RNAs have been recently re-discovered as a large class of putative non-coding RNAs with a peculiar structure and poorly understood functions. Although their biogenesis, which proceeds via a back-splicing reaction, has been studied and dissected in the last years, their role in biologically relevant processes is still uncharacterized. Here, we performed expression profiling of circRNAs during in vitro differentiation of murine and human myoblasts, we selected and validated the expression of a subset of highly expressed, conserved circular RNAs and applied a high-content functional genomic screen in order to identify molecules that were able to impact on the differentiation process. We focused on three circRNAs whose down-regulation resulted in important phenotypes and further scrutinized one of them, named circ-ZNF609, with the aim of undestanding its molecular function. We found that circ-ZNF609 contains an open reading frame spanning from the native start codon of its host transcript and terminating at an in-frame stop codon that is created upon circularization. Circ-ZNF609 is associated to heavy polysomes and is translated into a 30-KDa peptide that is able to promote human myoblasts proliferation., Stem cells and regenerative medicine have greatly increased the expectations of the scientific community and the public for their potential in applications that aim at recovering or replacing injured, aged and diseased tissues. Nevertheless their clinical application is currently hindered by cell survival, inflammatory response, tissue engraftment, vascularization and efficient differentiation. Tissue engineering exploits biomaterials to improve stem cell engraftment and differentiation by mimicking organogenesis. Skeletal muscle tissue engineering is an up-and-coming biotechnology that could offer great potential, in the near future, for muscle repair. Reconstructing the skeletal muscle architecture and function is still a challenge requiring parallel alignment of myofibrils arranged into organized sarcomeres. We show that an “anatomical bioreactor-like” represented by the surface of mouse tibialis anterior muscle (TA), positively influences maturation and alignment of fibers derived from adult muscle stem/progenitor cells embedded into a poly-ethylene-glycol-fibrinogen (PF) hydrogel. This approach leads to the generation of an artificial normal muscle. Furthermore by the same approach we succeeded in replacing a complete mouse TA after massive muscle ablation, recovering morphology and function of the substituting artificial TA. Starting from these observations, we are now developing a novel approach for regeneration and/or reconstruction of skeletal muscle tissue segments human-like size in order to translate this technique to clinical application. For this purpose human derived muscle pericytes have been isolated from muscle biopsies and have been investigated for their myogenic potential. Moreover by exploiting the PF properties, we demonstrated the noteworthy potential of this cell population for human skeletal muscle tissue engineering., Histone deacetylases (HDACs) control the transcriptional networks underlying both muscle differentiation and progression of dystrophy. Considering that, HDAC inhibitors (HDACi) are important candidate drugs for pharmacological interventions in muscular dystrophies. Although the beneficial effects of HDACi in the treatment of muscular dystrophy are known, it remains to dissect the mechanism of action and the cellular mediators of these drugs. The goal of this project is to analyze the molecular mechanisms underlying the role of resident satellite cells and infiltrating macrophages in mediating the activity of HDACi ITF2357 (also referred to as Givinostat) in dystrophic muscle of mdx mice, the best animal model of Duchenne Muscular Dystrophy (DMD). We analyzed the dystrophic phenotype of mdx mice treated with Givinostat at different stages of disease, specifically 6, 12 and 36 weeks, corresponding to necrotic/inflammatory, regenerative and fibrotic stage, respectively. The histopathological and morphometric analyses show an amelioration of dystrophic phenotype with a significant increase of muscle fiber cross-sectional area and a consistent reduction of intramuscular fibrosis, surprisingly also at late stage of disease, suggest a positive outcome also in old mdx mice. Moreover, gene expression analysis of whole skeletal muscle and purified cell populations pointed out a modulation of fibrosis and inflammatory markers and fibroadipogenic differentiation. Overall, these data confirm the beneficial effects of Givinostat on dystrophic muscle and identify the involvement of macrophages in mediating Givinostat activity., Central Core Disease (CCD) and Malignant Hyperthermia (MH) are related disorders linked to mutations in the ryanodine receptopr-1 (RYR1) gene, encoding for the sarcoplasmic reticulum (SR) Ca2+ release channel. CCD is a congenital myopathy characterized by amorphous regions lacking mitochondrial activity (cores) in skeletal fibers. In humans, the RYR1-Y522S mutation is associated with MH and formation of structural cores. Skeletal fibers of knock-in RYR1Y522S/WT mice develop mitochondrial damage and cores, caused by excessive oxidative stress (Boncompagni et al. 2009 PNAS). We treated RYR1Y522S/WT mice with an antioxidant, N-acetylcysteine (NAC), provided ad-libitum in drinking water (1%w/v) for 2 months and verified reduction of oxidative stress: indeed, level of 3-nitrotyrosine was increased by 1.44-folds in RYR1Y522S/WT mice, but reduced to control levels after NAC treatment. Electron microscopy was used to assess mitochondrial integrity following NAC-treatment: a) mitochondria swelling and frequency of damaged mitochondria were both decreased (-24% and -10%, respectively); b) the number/100 µm2 of mitochondria (25.9 ± 0.7 vs 29.1 ± 0.6) and their proper association with the SR (+22%) were both increased. Using histological analysis, we also verified that NAC was effective in reducing the frequency of cores (-20% contracture cores; -30% unstructured cores). Finally, we evaluated muscle function in treated mice by grip strength test: NAC was able to improve muscle strength of about 80%. This work provides the bases for clinical trial as it demonstrate that NAC-administration prevents mitochondrial damage, development of cores, and improves muscle function in a mouse model of CCD., In humans, lethal hyperthermic episodes can be trigger by anesthetics (a disorder known as Malignant Hyperthermia, Susceptibility, MHS) and by high temperature and/or strenuous exercise (crises identified as Environmental/Exertional Heat Strokes, EHSs). The correlation between MHS and EHS is strongly supported by extensive work in animal models: indeed, both RYR1Y522S/WT knock-in and CASQ-1 knockout mice trigger similar lethal crises when exposed to both halothane and heat. Here we tested the following hypotheses: a) strenuous exercise is a stimulus capable to trigger EHS-lethal episodes; b) MHS and EHS share common molecular mechanisms underlying crises. When RYR1Y522S/WT and CASQ1-null mice were subjected to an exertional-stress (ES) protocol (executed on a treadmill placed in an environmental chamber), which was well tolerated by WT animals (0% of deaths), the mortality rate was dramatically increased (80% and 75%, respectively), with a rise in core temperature (hyperthermia) significantly higher than in WT at the end of the stimulus. During exertional-crises, most fibers from RYR1 Y522S/WT and CASQ1-null mice suffer severe structural damage (~99% and ~64% of fibers, respectively), indication of rhabdomyolysis. Importantly, pre-treatment of animals with azumolene (a more water soluble dantrolene analog, the only drug approved for treatment of MH crises in humans) almost completely abolished mortality rate in RYR1 Y522S/WT and CASQ1-null animals, by reducing hyperthermia, rhabdomyolysis, and Ca2+leak from the SR. All these results strongly suggest that EHS share common molecular mechanisms with anesthetic-induced MH episodes and that drugs used to treat classic MH should be considered for treatment of EHS., Duchenne muscular dystrophy (DMD) is an X-linked neuromuscular disorder characterized by progressive muscle degeneration due to lack of dystrophin, a protein essential for the integrity of sarcolemma during contraction. In DMD compensative degeneration/regeneration cycles determine a condition of chronic inflammation contributing to progressive muscle wasting. RAGE (receptor for advanced glycation end-products) is a multiligand receptor belonging to the immunoglobulin superfamily involved in physiological and pathological processes including inflammation and myogenesis [1]. RAGE is not expressed in adult muscle tissue, whereas it is expressed in regenerating myofibers during muscle regeneration [2,3], in dystrophic muscles and activated immune cells. To have information about the role of RAGE in the pathophysiology of DMD we generated a double mutant mdx/Ager–/– mouse lacking dystrophin and RAGE (Ager). We analyzed diaphragms and hind-limb muscles (i.e., tibialis anterior and quadriceps femoris) of mdx, mdx/Ager–/–, Ager–/– and WT mice at different ages (i.e., 2, 3, 4 and 5 weeks, and 3 and 6 months of age). We found that although the absence of RAGE in dystrophic mice did not affect the onset of the pathology, muscles of 5 week- and 6 month-old mdx/Ager–/– mice showed significantly reduced numbers of necrotic myofibers, and reduced areas of immune cell infiltrate compared with age-matched mdx mice. Also, muscles of mdx/Ager–/–mice showed strongly reduced expression of the marker of activated macrophages, MAC3, compared with mdx mice. Moreover, muscles of mdx/Ager–/– mice exhibited significantly reduced PAX7+ve and myogenin+ve cell numbers, pointing to a reduced recruitment of muscle precursor cells and a more efficient regeneration in dystrophic mice lacking RAGE. Our results suggest that RAGE has an important role in sustaining inflammatory and degenerative processes in dystrophic muscles, and that inhibition of RAGE expression/activity might represent a potential therapeutic approach in DMD patients., Ageing is associated to a dramatic increase in the incidence of heart failure, even if the existence of a real age-related cardiomyopathy remains controversial. As effective contraction and relaxation of cardiomyocytes also depends on Ca2+ supply to myofibrils (handled by calcium release units, CRUs) and on efficient ATP production (provided by mitochondria), in this study we performed a morphological study of cardiac cells in hearts from adult and old mice (4 months vs. ≥ 24 months of age) using confocal and electron microscopy. The analysis of CRUs indicates that couplons become shorter with age and that the number of CRUs/50 µm2 is decreased of about 24% (adults: 5.1±0.32; old: 3.9±0.19). Also mitochondria present structural modifications, with a significant increase in the percentage of organelles presenting severe alterations (3.5% vs. 16.5%). Importantly, both CRUs and mitochondria undergo a spatial re-organization with respect to sarcomeres/myofibrils: CRUs may be miss-oriented (longitudinal) or miss-placed (found at the A band instead of being correctly placed in proximity of Z-lines), while mitochondria are often grouped in an abnormal fashion. In addition, WB analysis shows that in aged mice, there is a significant reduced expression of junctophilin-2 (JP-2), a membrane protein involved in maintaining stability and morphometry of dyads. These age-related ultra-structural changes may underlie an inefficient supply of Ca2+ and ATP to contractile elements, providing a possible explanation for heart dysfunction associate to age., Progressive muscle degeneration followed by dilated cardiomyopathy is a hallmark of muscular dystrophy. Stem cell therapy is suggested to replace diseased by healthy myofibers, although so far we are faced by low efficiencies of migration, engraftment and differentiation of stem cells. Chemokines are signalling proteins guiding cell migration and have been shown to tightly regulate cardiac repair. We sought to determine which chemokines are expressed in a dystrophic heart that is undergoing cardiac remodelling. Therefor we analysed chemokine expression of Sarcoglycan-α (Sgcα) null, Sarcoglycan-β (Sgcβ) null and immunodeficient Sgcβ-null mice. High expression of all three monocyte-chemotactic proteins was observed, especially Ccl8 in both Sgcβ-null models and to a greater extent in Sgcα-null mice. Additionally, Fractalkine (Cx3cl1) was upregulated in both the immunocompetent and immunodeficient Sgcβ-null mice. In addition, we aim to evaluate the migration potential of cardiovascular progenitors derived from pluripotent stem cells in vitro, that have the potential to differentiate with high efficiency towards cardiomyocytes, smooth muscle cells and endothelial cells in vitro. We plan to test these cells for their in vivo differentiation and migration capacity towards the previously mentioned chemokines. This sheds perspective for an approachable mechanism, which could potentially improve stem cell homing towards the dystrophic myocardium., Cardiac dysfunction from cardiomyopathy is a frequent manifestation of muscular dystrophy. The primary defect common to most dystrophies involves the disruption of the dystrophin-glycoprotein complex (DGC) with subsequent sarcolemma instability and Ca2+ influx, inducing cellular necrosis. Defective Ca2+ uptake resulting from decreased expression and reduced activity of calcium-transporting ATPase (SERCA2a) and, recently, SERCA2a gene therapy has been demonstrated to mitigate dystrophic diseases. Our previous studies have demonstrated that the dystrophic phenotype observed in δ-sarcoglycan–null hamster is dramatically improved by a long-term dietary supplementation with flaxseeds (FS) (rich in n3-PUFAs), but the molecular mechanisms have not yet been fully understood. The present study was designed to test the hypothesis that FS enriched diet could regulate DGC and SERCA2a proteins that play an important structural and functional role in cardiomyocytes. Therefore, the levels of these proteins and mRNAs were analyzed in heart dystrophic hamsters fed with FS diet for long (five months) or short time (48 hours). Results showed that α- distroglycan, α-, β, γ-sarcoglycan and SERCA2a proteins were down-regulated in dystrophic hearts and FS-diet restored their normal expression pattern. The RT-PCR analysis showed that α-distroglycan, α-sarcoglycan and SERCA2a were up-regulated at the transcriptional level. Interestingly, the mRNAs increase was observed even when FS was administered for short periods suggesting the involvement of an epigenetic mechanism. Therefore, it seems plausible to consider the administration of plant-originated n-3 PUFAs as an adjuvant strategy for attenuating sarcolemma instability and defective Ca2+ uptake that represent major damages associated with dystrophic cardiomyopathies., Oxidative stress (OS) is an imbalance between the production of free radicals, in particular reactive oxygen species (ROS), and the ability of the cells to counteract them by antioxidant responses. ROS production in skeletal muscle occurs mainly in mitochondria, both following physiological stimuli (e.g. aging, physical exercise, or at birth) (1-3) and in response to pathological events, such as denervation (4). In all cases, high levels of ROS actively influence the maintenance of muscle homeostasis. Histone deacetylase 4 (HDAC4) is a member the class II of the HDAC superfamily that regulates many cellular processes (5-7). Following denervation, HDAC4 is upregulated in skeletal muscle: it induces muscle atrophy and represses reinnervation (8-9). Increased levels of ROS cause HDAC4 translocation from the nucleus to the cytoplasm, thus inducing the release of genes transcriptionally repressed by HDAC4(10). However, HDAC4 targets in skeletal muscle have not been discovered yet. In order to investigate the role of HDAC4 in response to OS in skeletal muscle, we use a mouse model with the selective deletion of HDAC4 in myogenin positive cells (HDAC4 mKO mice). HDAC4 mKO mice are viable and do not show gross abnormalities in skeletal muscle. We analyzed mice in two different conditions characterized by elevated OS: at birth and in adult mice following denervation. Molecular responses to oxidative stress are blunted in both newborn and adult HDAC4 mKO compared to control mice. Since elevated ROS contribute to mitochondrial damage and are important in redox signaling from the organelle to the rest of the cell, we analyzed mitochondrial ultrastructure. Both newborn and adult HDAC4 mKO muscles presented damaged mitochondria, altered mitochondrial dynamics and defects in myofiber organization. Our results indicate that HDAC4 is important in skeletal muscle to maintain muscle integrity and a proper response upon OS. Current studies are focused on the identification of HDAC4 targets in the OS response in skeletal muscle, Collagen VI (ColVI) is a major extracellular matrix component made of three genetically distinct α chains and abundantly deposited in the basement membrane of both skeletal muscles and peripheral nerves. Mutations in COL6A1, COL6A2 and COL6A3 genes are known to cause different forms of muscle diseases, including Bethlem myopathy, Ullrich congenital muscular dystrophy and myosclerosis myopathy. ColVI null (Col6a1–/–) mice display a myopathic phenotype characterized by latent mitochondrial dysfunction, spontaneous apoptosis, defective autophagy regulation and compromised muscle regeneration. We recently demonstrated that the absence of ColVI in peripheral nerves leads to hypermyelination, altered Remak bundles, sensory-motor functional deficits and decreased nerve conduction velocities, thus pointing at ColVI as a crucial molecule for peripheral nerve structure and function. Given the muscle and nerve defects displayed by Col6a1 null mice, we decided to explore the role of ColVI in the neuromuscular junction (NMJ). Our unpublished studies revealed that ColVI is indeed deposited at the synapse. Immunofluorescence analysis showed ColVI deposition in NMJs. Preliminary results revealed altered expression of synaptic genes and abnormal electrophysiological parameters in Col6a1–/– mice. These findings suggest a potential role for ColVI at the NMJ, and further studies will allow shedding new light on the roles of this extracellular matrix component in the nerve/muscle axis., Muscular dystrophies are non curable diseases. Recently, new strategies shed light to an increase of muscle regeneration. These strategies focus on epigenetic drugs. TSA (HDACi) achieve to enhance the regeneration rate in both mice and humans. However, new challenges stay on the horizon. Monitoring and controlling the changes of the treatment in muscle without invasive techniques are one of that’s. In our research we identified seven microRNAs differential expressed in FAPs population. FAPs are Key players of muscle regeneration under HDACi treatment. From these seven microRNA, miR-143 has been validated with qRT-PCR, and Chip techniques. This miR-143 form part of a cluster with miR-145 that locates into a long non coding RNA non characterized until that moment. The overexpression of this miR-143 turns FAPs into a non adipogenic phenotype, whereas the inhibition of it recovershe adipogenic behavior. Thus, in this work we are trying to characterize the role of this microRNA and their host gene to understand if it could be a good candidate to be used as marker during the treatment., The central dogma of gene expression is that DNA is transcribed into messenger RNAs, which in turn serve as the template for protein synthesis. In recent years, it has been discovered that genomes of multicellular organisms are characterized by the pervasive expression of different types of non-coding RNAs (ncRNA) and, among them, long non-coding RNAs (IncRNAs). In particular the mammalian genome contains many thousands of lncRNAs, which have been proposed to be fundamental in the regulation of many biological processes such as cellular differentiation and show an aberrant regulation in a variety of diseases. A transcriptome analysis performed during in vitro murine muscle differentiation allowed us to identify a subset of new lncRNAs differentially expressed during myogenesis (1). These transcripts were classified on the basis of their expression in proliferating versus differentiated conditions, muscle-restricted activation and subcellular localization. We are now focusing on the characterization of a nuclear lncRNA conserved in human, lnc-405, up-regulated during differentiation, whose expression is cardiac and skeletal muscle restricted. To dissect its role in myogenesis, we performed loss of function experiments using LNA-Gapmers followed by a transcriptome analysis. This approach revealed a strong down-regulation of a subset of genes involved in fiber contraction, cell fusion and related to several cardiomyopathies. With the idea to better explain its crucial role during myogenesis, we are now focusing on the molecular mechanism by which lnc-405 exerts its function in the nucleus by RIP, ChIRP and RNA pull-down assays that are on going., The functional connection between muscle and nerve is affected in several neuromuscular diseases, including Amyotrophic Lateral Sclerosis (ALS) whose major pathological processes are motor neuron degeneration. However, other cells may be involved in the pathogenesis of ALS and open the possibility that alteration in skeletal muscle homeostasis represents one of the principal mediators of motor neuron degeneration. We have evidences that indicate that muscle selective expression of SOD1G93A mutant gene modulates, at the level of spinal cord of MLC/SOD1G93A mice, relevant mRNA and microRNA associated with myelin homeostasis. Our study provided insights into the pathophysiological interplay between muscle and nerve and supports the hypothesis that skeletal muscle is a source of signals that can affect the nervous system., Calsequestrin (CASQ) is the major protein of the sarcoplasmic reticulum of striated muscle that binds Ca2+ with high capacity and moderate affinity. CASQ exist as a monomer and polymers, depending on Ca2+ concentration. CASQ switches from an unfolded state to a folded monomer when the ionic strength increases allowing the formation of front-to-front first and then back-to-back interactions in higher Ca2+ concentrations. In humans, mutations in the cardiac isoform CASQ2 lead to catecholamine-induced polymorphic ventricular tachycardia. Recently we reported one mutation in the skeletal CASQ1 gene in a group of patients with a vacuolar myopathy characterized by the presence of inclusions containing CASQ1 and other SR proteins. The CASQ1 mutation (CASQ1D244G) affects one of the high-affinity Ca2+-binding sites of the protein and alters the kinetics of Ca2+ release in muscle fibers from patients. Expression of the CASQ1D244G in myotubes and in mouse fibers causes the appearance of SR vacuoles containing aggregates of the mutant CASQ1 protein that resemble those observed in patients. Studies of Ca2+ release showed an increase in Ca2+ storage in CASQ1WT COS-7 transfected cells whereas no increase was observed in CASQ1D244G. Moreover both CASQ1WT and CASQ1D244G were expressed in bacteria, purified and analysed for their ability to polymerize at increasing Ca2+ concentrations. The results obtained indicate that the CASQ1D244G protein polymerizes at lower Ca2+ levels and more rapidly than CASQ1WT. These results suggest that the CASQ1D244G mutation interferes with the correct process of Ca2+ -dependent protein polymerization causing altered intracellular calcium storage and the formation of protein aggregates., Muscle regeneration is dependent upon a complex interplay of different cell types in the muscle stem cell niche. In particular, the recently described population of interstitial fibro-adipogenic progenitors (FAPs) and satellite cells (MuSCs) establish a complex network of interactions to coordinate muscle regeneration. FAPs are able to promote satellite cell differentiation and compensate for muscle necrosis. In our recent studies, we demonstrated that FAPs are the key cellular mediators of the beneficial effect of HDAC inhibitors at early stages of Duchenne Muscular Dystrophy (DMD). Indeed, FAPs, from young mdx mice HDACi, induce myogenesis at expense of adipogenesis and enhance their ability to support MuSCs differentiation. Conversely, FAPs from old mdx mice are resistant to HDACi and repress MuSCs differentiation (Mozzetta et al., 2013; Saccone et al., 2014). Given the importance of the cross-talk between FAPs and MuSCs in DMD progression, we are currently deciphering the role of FAP-released extracellular vesicles (and in particular the exosomes - endosome derived vesicles) as mediators of the functional interactions between mononuclear cell types that contribute to muscle regeneration., Limb Girdle Muscular Dystrophies are rare genetic diseases, characterized by weakness and progressive muscular atrophy. A subfamily of LGMD2 regroups sarcoglycanopathies caused by mutations in genes coding for sarcoglycans. These transmembrane proteins are part of the dystrophin complex that protects muscle fibers against mechanical stress due to contraction. There is no treatment available for these diseases.In order to understand the molecular mechanisms implicated in sarcoglycanopathies and to identify new therapeutic targets, we are conducting two studies: 1 - SG mutants are not present at the muscle fiber membrane because they are retained in the endoplasmic reticulum by the quality control (ERQC) and they are prematurely degraded by the proteasome. To study the ERCQ pathways responsible for sarcoglycan disposal at molecular level, we first generated cell lines expressing clonally one SG mutant. Those clones are now used to investigate the SGs cellular trafficking mechanisms and then to test pharmacological compounds modulating ERCQ pathways. 2 – In these diseases, muscular atrophy affects limb muscles and infrequently head muscles. To investigate mechanisms underlying the fact that some muscles are more affected than other, we analyzed different muscles to search for molecular differences that may sign their relative sensitivity to the genetic defects. The content in micro-RNA of muscles from the limbs and face of Macaca fascicularis was explored. Experiments are in progress to analyze the function of identified micro-RNAs and to evaluate their therapeutic potential for sarcoglycanopathies. These projects will improve the knowledge on physio-pathological mechanisms of sarcoglycanopathies in order to identify new therapies for patients., Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common human myopathies and arises with progressive wasting of facial mimic muscles as well as upper arms and shoulder girdle muscles. In 95% of the cases, FSHD is associated with the copy number reduction of D4Z4 macrosatellite repeats at the subtelomeric region of chromosome 4 (4q35). This change is associated with an epigenetic deregulation of the region that ultimately leads to the de-repression of nearby genes, such as DUX4 and FRG1 that have been reported to contribute to the muscular dystrophic phenotype observed in FSHD patients. The chromatin-associated lncRNA DBE-T, encoded by the FSHD locus, has been shown to be one of the main players of such event, though the molecular mechanism has not been yet fully elucidated. DBE-T is preferentially expressed in FSHD patients where it favors the transcription of the 4q35 genes thanks to the recruitment of the histone methyl transferase of the Trithorax group of epigenetic activators ASH1L. Interestingly, through a structural/functional analysis, we have recognized several DBE-T functional domains that can be exploited as new molecular targets for therapeutic purposes. Specifically, we have identified a region and the molecular mechanism required for DBE-T tethering to the chromatin. In addition, we have mapped the minimal binding domains in ASH1L and DBE-T. Finally, we have highlighted a portion of DBE-T required to positively promote transcription. In agreement, a DBE-T mutant lacking this region is unable to trigger transcription. Currently, through proteomic approaches, we are investigating DBE-T protein partners that are specific for each DBE-T functional domain. Our goal is to identify unknown molecular players that, similarly to ASH1L, are recruited by DBE-T to the FSHD locus and can play a role in the disease. Overall, our study elucidates the molecular mechanism of DBE-T in FSHD and might unveil new therapeutic targets for the treatment of the disease.
Published: 2016

16. The lack of the Celf2a splicing factor converts a Duchenne genotype into a Becker phenotype

Author: Martone J, Briganti F, Legnini I, Morlando M, Picillo E, Sthandier O, Politano L, Bozzoni I.
Subjects: musculoskeletal diseases, Duchenne muscular dystrophy, congenital, hereditary, and neonatal diseases and abnormalities, exon 45, exon skipping
Abstract: Substitutions, deletions and duplications in the dystrophin gene lead to either the severe Duchenne muscular dystrophy (DMD) or mild Becker muscular dystrophy depending on whether out-of-frame or in-frame transcripts are produced. We identified a DMD case (GSΔ44) where the correlation between genotype and phenotype is not respected, even if carrying a typical Duchenne mutation (exon 44 deletion) a Becker-like phenotype was observed. Here we report that in this patient, partial restoration of an in-frame transcript occurs by natural skipping of exon 45 and that this is due to the lack of Celf2a, a splicing factor that interacts with exon 45 in the dystrophin pre-mRNA. Several experiments are presented that demonstrate the central role of Celf2a in controlling exon 45 splicing; our data point to this factor as a potential target for the improvement of those DMD therapeutic treatments, which requires exon 45 skipping.
Published: 2016

17. Novel RNAs during in vitro myogenesis: a lncRNA overlapped to miR-31 controls the timing of murine myoblast differentiation

Author: Ballarino, Monica, Morlando, M., Cipriano, A., Bisceglie, L., and Bozzoni, I.
Published: 2014

18. An ALS-associated mutation in the FUS 3′2-UTR disrupts a microRNA-FUS regulatory circuitry

Author: Dini Modigliani, S., Morlando, M., Errichelli, L., Sabatelli, M., and Bozzoni, I.
Subjects: Homeodomain Proteins, MicroRNAs, Gene Expression Regulation, Amyotrophic Lateral Sclerosis, Mutation, 3' Untranslated Regions, Humans, RNA-Binding Protein FUS, Transcription Factors, Zinc Finger E-box-Binding Homeobox 1
Published: 2014

19. Identification of novel lncRNAs modulated during myogenic differentiation in mouse

Author: Ballarino, Monica, Cazzella, Valentina, Morlando, M., Bisceglie, L., Cipriano, A., Pinnarò, C., Tramontano, A., and Bozzoni, Irene
Published: 2014

20. The interplay between the HUR protein and the long non-coding RNA linc-MD1 drives the progression from early to late muscle differentiation stages

Author: Morlando, M., Legnini, I., Mangiavacchi, A., Ballarino, Monica, Cazzella, Valentina, Fatica, Alessandro, and Bozzoni, Irene
Published: 2014

21. Tight coupling between transcription and processing of microRNA precursors

Author: Morlando, M, Ballarino, Monica, Giradi, E, Pagano, Francesca, DINI MODIGLIANI, S, Cacchiarelli, D, Marchioni, M, Proudfoot, N. J., and Bozzoni, Irene
Published: 2010

22. Coupling between transcription and processing promotes efficient expression of independently transcribed microRNA genes

Author: Morlando, M., Ballarino, Monica, Pagano, Francesca, Girardi, E., Cacchiarelli, D., Marchioni, M., Proudfoot, N. J., and Bozzoni, Irene
Published: 2009

23. Coupled RNA processing and transcription of intergenic primary miRNAs

Author: Ballarino M., Pagano F., Girardi E., Morlando M., Cacchiarelli D., Marchioni M., Proudfoot N., and Bozzoni I.
Published: 2009

24. RNA processing and transcription are tightly coupled for the intergenic miRNAs biogenesis

Author: Morlando, M., Ballarino, Monica, Pagano, Francesca, Girardi, E., Cacchiarelli, D., Proudfoot, N. J., and Bozzoni, I.
Published: 2009

25. The RNAseIII drosha controls miRNA biogenesis during transcription

Author: Pagano, F., Girardi, Erika, Ballarino, M., Morlando, M., Marchioni, M., Fatica, A., and Bozzoni, I.
Published: 2007

26. Risk factors associated with adverse fetal outcomes in pregnancies affected by Coronavirus disease 2019 (COVID-19): a secondary analysis of the WAPM study on COVID-19

Author: Eran Hadar, Chiara Benedetto, Agnese Maria Chiara Rapisarda, Renato Augusto Moreira de Sá, Deena Elkafrawi, Daniela Luvero, Noa A Brzezinski Sinai, Alicia Martínez-Varea, Antonio Schiattarella, Anna Nunzia Della Gatta, Giovanni Scambia, Albert Lila, Luciano Di Tizio, Andrea Carosso, Giovanni Nazzaro, G. Schera, Giuseppe Rizzo, Giuseppe Maria Maruotti, Giusella D'Urso, Albaro José Nieto-Calvache, Ilenia Mappa, Ozlem Uyaniklar, Fabio Barra, Gilles Faron, Luigi Nappi, Jacopo Ferrari, Giulio Sozzi, Simone Ferrero, Mirjam Druškovič, Tanja Premru-Srsen, Leonardo Borrello, Fabiana Cecchini D, George Daskalakis, Giuliano Petriglia, Caroline Kadji, Felipe Mercado-Olivares, Zeliha Atak, Aylin Pelin Cil, Claudio Gustavino, Axelle Pintiaux, Pantaleo Greco, Rita Figueiredo, Stefano Cosma, Ludovica Puri, Valentina Esposito, Anupam Parange, Simone Garzon, Alessandra Gatti, Ioannis Kyvernitakis, Roberto Brunelli, Maddalena Morlando, Attilio Di Spiezio Sardo, Ignacio Cueto Hernández, Giuseppe Zoccali, Brian Rodriguez, Antonio Mollo, Flaminia Vena, Cihat Sen, Ciuhodaru Madalina, Felice Sorrentino, Francesca Di Sebastiano, Gennady T. Sukhikh, Ilma Floriana Carbone, Andrea Villasco, Blanka Zlatohlavkova, Gabriele Saccone, Erasmo Huertas, Marcel Malan, Leonardo Gucciardo, Eutalia Esposito, Otto Henrique May Feuerschuette, Sarah Dollinger, María de Los Angeles Anaya Baz, Jun Yoshimatsu, Sifa Turan, Vincente Diago, Alicia Yeliz Aykanat, Ignacio Herraiz, Javier Alfonso Schvartzman, Diego Gazzolo, Natalina Buono, Milan Stanojević, Erich Cosmi, Valentina De Robertis, Elena Costa, Angelo Cagnacci, Eleonora Valori, Nicoletta Biglia, Şerife Özlem Genç, Vincenzo Berghella, Francesco Maria Colaleo, Esther Vanessa Aguilar Galán, Gabriela Loscalzo, Marco Palumbo, Fabrizio Sandri, Irmeli Nupponen, Antonio Lanzone, Juan Antonio De León Luis, Amos Grunebaum, Giuseppe Bifulco, Marinella Lenzi, Serena Xodo, Fulvio Zullo, Ozhan Turan, Josefine Königbauer, Anna Luengo Piqueras, Nicola Volpe, Holger Maul, Chiara Taccaliti, Juan Manuel Burgos-Luna, Giovanni Sisti, Rosanna Esposito, Alfredo Ercoli, Panos Antsaklis, Dolores Esteban Oliva, Aly Youssef, Pedro Viana Pinto, Alberto Galindo, Asim Kurjak, Erhan Okuyan, Roberto Angioli, Maria Luisa Gonzalez-Duran, Ana Concheiro Guisan, Massimo Franchi, Maria Carmela Di Dedda, Giovanni Gerosolima, Francesco D'Antonio, Caroline Daelemans, Quintino Cesare Ianniciello, Pasquale De Franciscis, Maurizio Guida, Maria Cristina Rovellotti, Liana Ples, Frank A. Chervenak, Nicola Colacurci, Lilijana Kornhauser Cerar, Zulfiya Khodjaeva, Valentina Longo, Francesca Stollagli, Daniele Di Mascio, Mariavittoria Locci, Amadeo Sanchez, Angelo Sirico, Stefania Fieni, Rebeca Garrote Molpeceres, Pierluigi Benedetti Panici, Vito Chiantera, Esra Tustas Haberal, Liviu Cojocaru, Maria Elena Flacco, Antonella Cromi, Roberta Granese, Antonio Simone Laganà, Maria Giulia Lombana Marino, Silvia Visentin, Beatrice Bianchi, Roberta Venturella, Federica Laraud, Amanda Bermejo, Reyhan Gündüz, Marina Moucho, Zita Maria Gambacorti-Passerini, Danila Morano, Pedro Arango, Francesca Della Sala, Gaetana Di Donna, Jesús S Jimenez Lopez, Mariano Catello Di Donna, Giuliana Simonazzi, Snezana Zdjelar, Vedran Stefanovic, Cecilia Villalain, Antonio Coviello, Lars Hellmeyer, Antonella Giancotti, Elisa Bevilacqua, Igor Samardjiski, Riccardo Buscemi, Arianna Ramone, Marco Cerbone, Lorenza Driul, Danilo Buca, Tiziana Frusca, Elisa Done, Marco Liberati, José Morales Roselló, Fabio Ghezzi, Lorenzo Vasciaveo, Bernd Froessler, Alejandro Pittaro, Yolanda Cuñarro López, Andrew Carlin, Sakine Rahimli Ocakouglu, Giorgia Gattei, I. Cataneo, María José Suárez, Giada Ameli, Lamberto Manzoli, Kaisa Nelskylä, Ludovico Muzii, Peter Palm, Olus Api, Elisa Cueto, Martina Leombroni, Ksenia A. Gorina, HUS Gynecology and Obstetrics, Department of Obstetrics and Gynecology, Children's Hospital, HUS Children and Adolescents, HUS Perioperative, Intensive Care and Pain Medicine, Anestesiologian yksikkö, Department of Diagnostics and Therapeutics, Dicle Üniversitesi, Tıp Fakültesi, Cerrahi Tıp Bilimleri Bölümü, Kadın Hastalıkları ve Doğum Ana Bilim Dalı, Gündüz, Reyhan, Di Mascio D., Sen C., Saccone G., Galindo A., Grunebaum A., Yoshimatsu J., Stanojevic M., Kurjak A., Chervenak F., Suarez M.J.R., Gambacorti-Passerini Z.M., De Los Angeles Anaya Baz M., Galan E.V.A., Lopez Y.C., De Leon Luis J.A., Hernandez I.C., Herraiz I., Villalain C., Venturella R., Rizzo G., Mappa I., Gerosolima G., Hellmeyer L., Konigbauer J., Ameli G., Frusca T., Volpe N., Schera G.B.L., Fieni S., Esposito E., Simonazzi G., Di Donna G., Youssef A., Della Gatta A.N., Di Donna M.C., Chiantera V., Buono N., Sozzi G., Greco P., Morano D., Bianchi B., Marino M.G.L., Laraud F., Ramone A., Cagnacci A., Barra F., Gustavino C., Ferrero S., Ghezzi F., Cromi A., Lagana A.S., Longo V.L., Stollagli F., Sirico A., Lanzone A., Driul L., Fabiana Cecchini D., Xodo S., Rodriguez B., Mercado-Olivares F., Elkafrawi D., Sisti G., Esposito R., Coviello A., Cerbone M., Morlando M., Schiattarella A., Colacurci N., De Franciscis P., Cataneo I., Lenzi M., Sandri F., Buscemi R., Gattei G., Della Sala F., Valori E., Rovellotti M.C., Done E., Faron G., Gucciardo L., Esposito V., Vena F., Giancotti A., Brunelli R., Muzii L., Nappi L., Sorrentino F., Vasciaveo L., Liberati M., Buca D., Leombroni M., Di Sebastiano F., Di Tizio L., Gazzolo D., Franchi M., Ianniciello Q.C., Garzon S., Petriglia G., Borrello L., Nieto-Calvache A.J., Burgos-Luna J.M., Kadji C., Carlin A., Bevilacqua E., Moucho M., Pinto P.V., Figueiredo R., Rosello J.M., Loscalzo G., Martinez-Varea A., Diago V., Lopez J.S.J., Aykanat A.Y., Cosma S., Carosso A., Benedetto C., Bermejo A., Feuerschuette O.H.M., Uyaniklar O., Ocakouglu S.R., Atak Z., Gunduz R., Haberal E.T., Froessler B., Parange A., Palm P., Samardjiski I., Taccaliti C., Okuyan E., Daskalakis G., De Sa R.A.M., Pittaro A., Gonzalez-Duran M.L., Guisan A.C., Genc S.O., Zlatohlavkova B., Piqueras A.L., Oliva D.E., Cil A.P., Api O., Antsaklis P., Ples L., Kyvernitakis I., Maul H., Malan M., Lila A., Granese R., Ercoli A., Zoccali G., Villasco A., Biglia N., Madalina C., Costa E., Daelemans C., Pintiaux A., Cueto E., Hadar E., Dollinger S., Sinai N.A.B., Huertas E., Arango P., Sanchez A., Schvartzman J.A., Cojocaru L., Turan S., Turan O., Di Dedda M.C., Molpeceres R.G., Zdjelar S., Premru-Srsen T., Cerar L.K., Druskovie M., De Robertis V., Stefanovic V., Nupponen I., Nelskyla K., Khodjaeva Z., Gorina K.A., Sukhikh G.T., Maruotti G.M., Visentin S., Cosmi E., Ferrari J., Gatti A., Luvero D., Angioli R., Puri L., Palumbo M., D'Urso G., Colaleo F., Rapisarda A.M.C., Carbone I.F., Mollo A., Nazzaro G., Locci M., Guida M., Di Spiezio Sardo A., Panici P.B., Berghella V., Flacco M.E., Manzoli L., Bifulco G., Scambia G., Zullo F., D'Antonio F., Di Mascio D, Sen C, Saccone G, Galindo A, Grünebaum A, Yoshimatsu J, Stanojevic M, Kurjak A, Chervenak F, Rodríguez Suárez MJ, Gambacorti-Passerini ZM, Baz MLAA, Aguilar Galán EV, López YC, De León Luis JA, Hernández IC, Herraiz I, Villalain C, Venturella R, Rizzo G, Mappa I, Gerosolima G, Hellmeyer L, Königbauer J, Ameli G, Frusca T, Volpe N, Luca Schera GB, Fieni S, Esposito E, Simonazzi G, Di Donna G, Youssef A, Della Gatta AN, Di Donna MC, Chiantera V, Buono N, Sozzi G, Greco P, Morano D, Bianchi B, Lombana Marino MG, Laraud F, Ramone A, Cagnacci A, Barra F, Gustavino C, Ferrero S, Ghezzi F, Cromi A, Laganà AS, Laurita Longo V, Stollagli F, Sirico A, Lanzone A, Driul L, Cecchini D F, Xodo S, Rodriguez B, Mercado-Olivares F, Elkafrawi D, Sisti G, Esposito R, Coviello A, Cerbone M, Morlando M, Schiattarella A, Colacurci N, De Franciscis P, Cataneo I, Lenzi M, Sandri F, Buscemi R, Gattei G, Sala FD, Valori E, Rovellotti MC, Done E, Faron G, Gucciardo L, Esposito V, Vena F, Giancotti A, Brunelli R, Muzii L, Nappi L, Sorrentino F, Vasciaveo L, Liberati M, Buca D, Leombroni M, Di Sebastiano F, Di Tizio L, Gazzolo D, Franchi M, Ianniciello QC, Garzon S, Petriglia G, Borrello L, Nieto-Calvache AJ, Burgos-Luna JM, Kadji C, Carlin A, Bevilacqua E, Moucho M, Pinto PV, Figueiredo R, Roselló JM, Loscalzo G, Martinez-Varea A, Diago V, Jimenez Lopez JS, Aykanat AY, Cosma S, Carosso A, Benedetto C, Bermejo A, May Feuerschuette OH, Uyaniklar O, Ocakouglu SR, Atak Z, Gündüz R, Haberal ET, Froessler B, Parange A, Palm P, Samardjiski I, Taccaliti C, Okuyan E, Daskalakis G, Moreira de Sa RA, Pittaro A, Gonzalez-Duran ML, Guisan AC, Genç ŞÖ, Zlatohlávková B, Piqueras AL, Oliva DE, Cil AP, Api O, Antsaklis P, Ples L, Kyvernitakis I, Maul H, Malan M, Lila A, Granese R, Ercoli A, Zoccali G, Villasco A, Biglia N, Madalina C, Costa E, Daelemans C, Pintiaux A, Cueto E, Hadar E, Dollinger S, Brzezinski Sinai NA, Huertas E, Arango P, Sanchez A, Schvartzman JA, Cojocaru L, Turan S, Turan O, Di Dedda MC, Molpeceres RG, Zdjelar S, Premru-Srsen T, Cerar LK, Druškovič M, De Robertis V, Stefanovic V, Nupponen I, Nelskylä K, Khodjaeva Z, Gorina KA, Sukhikh GT, Maruotti GM, Visentin S, Cosmi E, Ferrari J, Gatti A, Luvero D, Angioli R, Puri L, Palumbo M, D'Urso G, Colaleo F, Chiara Rapisarda AM, Carbone IF, Mollo A, Nazzaro G, Locci M, Guida M, Di Spiezio Sardo A, Panici PB, Berghella V, Flacco ME, Manzoli L, Bifulco G, Scambia G, Zullo F, D'Antonio F, Di Mascio, D., Sen, C., Saccone, G., Galindo, A., Grunebaum, A., Yoshimatsu, J., Stanojevic, M., Kurjak, A., Chervenak, F., Suarez, M. J. R., Gambacorti-Passerini, Z. M., De Los Angeles Anaya Baz, M., Galan, E. V. A., Lopez, Y. C., De Leon Luis, J. A., Hernandez, I. C., Herraiz, I., Villalain, C., Venturella, R., Rizzo, G., Mappa, I., Gerosolima, G., Hellmeyer, L., Konigbauer, J., Ameli, G., Frusca, T., Volpe, N., Schera, G. B. L., Fieni, S., Esposito, E., Simonazzi, G., Di Donna, G., Youssef, A., Della Gatta, A. N., Di Donna, M. C., Chiantera, V., Buono, N., Sozzi, G., Greco, P., Morano, D., Bianchi, B., Marino, M. G. L., Laraud, F., Ramone, A., Cagnacci, A., Barra, F., Gustavino, C., Ferrero, S., Ghezzi, F., Cromi, A., Lagana, A. S., Longo, V. L., Stollagli, F., Sirico, A., Lanzone, A., Driul, L., Fabiana Cecchini, D., Xodo, S., Rodriguez, B., Mercado-Olivares, F., Elkafrawi, D., Sisti, G., Esposito, R., Coviello, A., Cerbone, M., Morlando, M., Schiattarella, A., Colacurci, N., De Franciscis, P., Cataneo, I., Lenzi, M., Sandri, F., Buscemi, R., Gattei, G., Della Sala, F., Valori, E., Rovellotti, M. C., Done, E., Faron, G., Gucciardo, L., Esposito, V., Vena, F., Giancotti, A., Brunelli, R., Muzii, L., Nappi, L., Sorrentino, F., Vasciaveo, L., Liberati, M., Buca, D., Leombroni, M., Di Sebastiano, F., Di Tizio, L., Gazzolo, D., Franchi, M., Ianniciello, Q. C., Garzon, S., Petriglia, G., Borrello, L., Nieto-Calvache, A. J., Burgos-Luna, J. M., Kadji, C., Carlin, A., Bevilacqua, E., Moucho, M., Pinto, P. V., Figueiredo, R., Rosello, J. M., Loscalzo, G., Martinez-Varea, A., Diago, V., Lopez, J. S. J., Aykanat, A. Y., Cosma, S., Carosso, A., Benedetto, C., Bermejo, A., Feuerschuette, O. H. M., Uyaniklar, O., Ocakouglu, S. R., Atak, Z., Gunduz, R., Haberal, E. T., Froessler, B., Parange, A., Palm, P., Samardjiski, I., Taccaliti, C., Okuyan, E., Daskalakis, G., De Sa, R. A. M., Pittaro, A., Gonzalez-Duran, M. L., Guisan, A. C., Genc, S. O., Zlatohlavkova, B., Piqueras, A. L., Oliva, D. E., Cil, A. P., Api, O., Antsaklis, P., Ples, L., Kyvernitakis, I., Maul, H., Malan, M., Lila, A., Granese, R., Ercoli, A., Zoccali, G., Villasco, A., Biglia, N., Madalina, C., Costa, E., Daelemans, C., Pintiaux, A., Cueto, E., Hadar, E., Dollinger, S., Sinai, N. A. B., Huertas, E., Arango, P., Sanchez, A., Schvartzman, J. A., Cojocaru, L., Turan, S., Turan, O., Di Dedda, M. C., Molpeceres, R. G., Zdjelar, S., Premru-Srsen, T., Cerar, L. K., Druskovie, M., De Robertis, V., Stefanovic, V., Nupponen, I., Nelskyla, K., Khodjaeva, Z., Gorina, K. A., Sukhikh, G. T., Maruotti, G. M., Visentin, S., Cosmi, E., Ferrari, J., Gatti, A., Luvero, D., Angioli, R., Puri, L., Palumbo, M., D'Urso, G., Colaleo, F., Rapisarda, A. M. C., Carbone, I. F., Mollo, A., Nazzaro, G., Locci, M., Guida, M., Di Spiezio Sardo, A., Panici, P. B., Berghella, V., Flacco, M. E., Manzoli, L., Bifulco, G., Scambia, G., Zullo, F., D'Antonio, F., Di Mascio, Daniele, Sen, Cihat, Saccone, Gabriele, Galindo, Alberto, Grünebaum, Amo, Yoshimatsu, Jun, Stanojevic, Milan, Kurjak, Asım, Chervenak, Frank, Rodríguez Suárez, María José, Gambacorti-Passerini, Zita Maria, Baz, María de Los Angeles Anaya, Aguilar Galán, Esther Vanessa, López, Yolanda Cuñarro, De León Luis, Juan Antonio, Hernández, Ignacio Cueto, Herraiz, Ignacio, Villalain, Cecilia, Venturella, Roberta, Rizzo, Giuseppe, Mappa, Ilenia, Gerosolima, Giovanni, Hellmeyer, Lar, Königbauer, Josefine, Ameli, Giada, Frusca, Tiziana, Volpe, Nicola, Luca Schera, Giovanni Battista, Fieni, Stefania, Esposito, Eutalia, Simonazzi, Giuliana, Di Donna, Gaetana, Youssef, Aly, Della Gatta, Anna Nunzia, Di Donna, Mariano Catello, Chiantera, Vito, Buono, Natalina, Sozzi, Giulio, Greco, Pantaleo, Morano, Danila, Bianchi, Beatrice, Lombana Marino, Maria Giulia, Laraud, Federica, Ramone, Arianna, Cagnacci, Angelo, Barra, Fabio, Gustavino, Claudio, Ferrero, Simone, Ghezzi, Fabio, Cromi, Antonella, Laganà, Antonio Simone, Longo, Valentina Laurita, Stollagli, Francesca, Sirico, Angelo, Lanzone, Antonio, Driul, Lorenza, Cecchini D, Fabiana, Xodo, Serena, Rodriguez, Brian, Mercado-Olivares, Felipe, Elkafrawi, Deena, Sisti, Giovanni, Esposito, Rosanna, Coviello, Antonio, Cerbone, Marco, Morlando, Maddalena, Schiattarella, Antonio, Colacurci, Nicola, De Franciscis, Pasquale, Cataneo, Ilaria, Lenzi, Marinella, Sandri, Fabrizio, Buscemi, Riccardo, Gattei, Giorgia, Sala, Francesca Della, Valori, Eleonora, Rovellotti, Maria Cristina, Done, Elisa, Faron, Gille, Gucciardo, Leonardo, Esposito, Valentina, Vena, Flaminia, Giancotti, Antonella, Brunelli, Roberto, Muzii, Ludovico, Nappi, Luigi, Sorrentino, Felice, Vasciaveo, Lorenzo, Liberati, Marco, Buca, Danilo, Leombroni, Martina, Di Sebastiano, Francesca, Di Tizio, Luciano, Gazzolo, Diego, Franchi, Massimo, Ianniciello, Quintino Cesare, Garzon, Simone, Petriglia, Giuliano, Borrello, Leonardo, Nieto-Calvache, Albaro Josè, Burgos-Luna, Juan Manuel, Kadji, Caroline, Carlin, Andrew, Bevilacqua, Elisa, Moucho, Marina, Pinto, Pedro Viana, Figueiredo, Rita, Roselló, José Morale, Loscalzo, Gabriela, Martinez-Varea, Alicia, Diago, Vincente, Jimenez Lopez, Jesús S, Aykanat, Alicia Yeliz, Cosma, Stefano, Carosso, Andrea, Benedetto, Chiara, Bermejo, Amanda, May Feuerschuette, Otto Henrique, Uyaniklar, Ozlem, Ocakouglu, Sakine Rahimli, Atak, Zeliha, Haberal, Esra Tusta, Froessler, Bernd, Parange, Anupam, Palm, Peter, Samardjiski, Igor, Taccaliti, Chiara, Okuyan, Erhan, Daskalakis, George, Moreira de Sa, Renato Augusto, Pittaro, Alejandro, Gonzalez-Duran, Maria Luisa, Guisan, Ana Concheiro, Genç, Şerife Özlem, Zlatohlávková, Blanka, Piqueras, Anna Luengo, Oliva, Dolores Esteban, Cil, Aylin Pelin, Api, Olu, Antsaklis, Pano, Ples, Liana, Kyvernitakis, Ioanni, Maul, Holger, Malan, Marcel, Lila, Albert, Granese, Roberta, Ercoli, Alfredo, Zoccali, Giuseppe, Villasco, Andrea, Biglia, Nicoletta, Madalina, Ciuhodaru, Costa, Elena, Daelemans, Caroline, Pintiaux, Axelle, Yapar Eyi, Elif Gül, Cueto, Elisa, Hadar, Eran, Dollinger, Sarah, Brzezinski Sinai, Noa A, Huertas, Erasmo, Arango, Pedro, Sanchez, Amadeo, Schvartzman, Javier Alfonso, Cojocaru, Liviu, Turan, Sifa, Turan, Ozhan, Di Dedda, Maria Carmela, Molpeceres, Rebeca Garrote, Zdjelar, Snezana, Premru-Srsen, Tanja, Cerar, Lilijana Kornhauser, Druškovič, Mirjam, De Robertis, Valentina, Stefanovic, Vedran, Nupponen, Irmeli, Nelskylä, Kaisa, Khodjaeva, Zulfiya, Gorina, Ksenia A, Sukhikh, Gennady T, Maruotti, Giuseppe Maria, Visentin, Silvia, Cosmi, Erich, Ferrari, Jacopo, Gatti, Alessandra, Luvero, Daniela, Angioli, Roberto, Puri, Ludovica, Palumbo, Marco, D'Urso, Giusella, Colaleo, Francesco, Chiara Rapisarda, Agnese Maria, Carbone, Ilma Floriana, Mollo, Antonio, Nazzaro, Giovanni, Locci, Mariavittoria, Guida, Maurizio, Di Spiezio Sardo, Attilio, Panici, Pierluigi Benedetti, Berghella, Vincenzo, Flacco, Maria Elena, Manzoli, Lamberto, Bifulco, Giuseppe, Scambia, Giovanni, Zullo, Fulvio, and D'Antonio, Francesco
Subjects: COVID-19 Vaccine, Infectious Disease Transmission, Perinatal Death, Abortion, Clinical Laboratory Technique, Miscarriage, Cohort Studies, 0302 clinical medicine, COVID-19 Testing, Pregnancy, Risk Factors, 3123 Gynaecology and paediatrics, Secondary analysis, Perinatal medicine, Abortion, Spontaneou, Medicine, Vertical, 030212 general & internal medicine, Viral, Pregnancy Complications, Infectious, coronavirus, perinatal morbidity, perinatal mortality, covid-19, Coronavirus, Abortion, Spontaneous, COVID-19, COVID-19 Vaccines, Clinical Laboratory Techniques, Coronavirus Infections, Female, Gestational Age, Humans, Infant, Newborn, Infant, Premature, Infectious Disease Transmission, Vertical, Pandemics, Pneumonia, Viral, Pregnancy Outcome, Reverse Transcriptase Polymerase Chain Reaction, SARS-CoV-2, Betacoronavirus, Fetal Death, 030219 obstetrics & reproductive medicine, Obstetrics, Infectious, Gestational age, Obstetrics and Gynecology, 3. Good health, Settore MED/40, Gestation, Human, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Coronaviru, Socio-culturale, Intrauterine device, 03 medical and health sciences, PARVOVIRUS B19 INFECTION, Coronavirus, perinatal morbidity, perinatal mortality, Adverse effect, Premature, Fetus, Betacoronaviru, Pandemic, Coronavirus Infection, business.industry, Risk Factor, Spontaneous, MORTALITY, Infant, Odds ratio, Pneumonia, medicine.disease, Newborn, Pregnancy Complications, Pediatrics, Perinatology and Child Health, Pregnancy Complications, Infectiou, Cohort Studie, business
Abstract: Objectives To evaluate the strength of association between maternal and pregnancy characteristics and the risk of adverse perinatal outcomes in pregnancies with laboratory confirmed COVID-19. Methods Secondary analysis of a multinational, cohort study on all consecutive pregnant women with laboratory-confirmed COVID-19 from February 1, 2020 to April 30, 2020 from 73 centers from 22 different countries. A confirmed case of COVID-19 was defined as a positive result on real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay of nasal and pharyngeal swab specimens. The primary outcome was a composite adverse fetal outcome, defined as the presence of either abortion (pregnancy loss before 22 weeks of gestations), stillbirth (intrauterine fetal death after 22 weeks of gestation), neonatal death (death of a live-born infant within the first 28 days of life), and perinatal death (either stillbirth or neonatal death). Logistic regression analysis was performed to evaluate parameters independently associated with the primary outcome. Logistic regression was reported as odds ratio (OR) with 95% confidence interval (CI). Results Mean gestational age at diagnosis was 30.6±9.5 weeks, with 8.0% of women being diagnosed in the first, 22.2% in the second and 69.8% in the third trimester of pregnancy. There were six miscarriage (2.3%), six intrauterine device (IUD) (2.3) and 5 (2.0%) neonatal deaths, with an overall rate of perinatal death of 4.2% (11/265), thus resulting into 17 cases experiencing and 226 not experiencing composite adverse fetal outcome. Neither stillbirths nor neonatal deaths had congenital anomalies found at antenatal or postnatal evaluation. Furthermore, none of the cases experiencing IUD had signs of impending demise at arterial or venous Doppler. Neonatal deaths were all considered as prematurity-related adverse events. Of the 250 live-born neonates, one (0.4%) was found positive at RT-PCR pharyngeal swabs performed after delivery. The mother was tested positive during the third trimester of pregnancy. The newborn was asymptomatic and had negative RT-PCR test after 14 days of life. At logistic regression analysis, gestational age at diagnosis (OR: 0.85, 95% CI 0.8–0.9 per week increase; p Conclusions Early gestational age at infection, maternal ventilatory supports and low birthweight are the main determinants of adverse perinatal outcomes in fetuses with maternal COVID-19 infection. Conversely, the risk of vertical transmission seems negligible.
Published: 2021

27. Maternal and perinatal outcomes of pregnant women with SARS-CoV-2 infection

Author: Di Mascio Daniele, Gabriele, Saccone, Cihat, Sen, Daniele Di Mascio, Alberto, Galindo, Amos, Grünebaum, Jun, Yoshimatsu, Milan, Stanojevic, Asım, Kurjak, Frank, Chervenak, María José Rodríguez Suárez, Zita Maria Gambacorti-Passerini, María de Los Angeles Anaya Baz, Esther Vanessa Aguilar Galán, Yolanda Cuñarro López, Juan Antonio De León Luis, Ignacio Cueto Hernández, Ignacio, Herraiz, Cecilia, Villalain, Roberta, Venturella, Rizzo, GIUSEPPE DAVIDE, Ilenia, Mappa, Giovanni, Gerosolima, Lars, Hellmeyer, Josefine, Königbauer, Giada, Ameli, Tiziana, Frusca, Nicola, Volpe, Giovanni Battista Luca Schera, Stefania, Fieni, Eutalia, Esposito, Giuliana, Simonazzi, Gaetana Di Donna, Aly, Youssef, Anna Nunzia Della Gatta, Mariano Catello Di Donna, Vito, Chiantera, Natalina, Buono, Giulio, Sozzi, Pantaleo, Greco, Danila, Morano, Beatrice, Bianchi, Maria Giulia Lombana Marino, Federica, Laraud, Arianna, Ramone, Angelo, Cagnacci, Fabio, Barra, Claudio, Gustavino, Ferrero, Simone, Fabio, Ghezzi, Antonella, Cromi, Antonio Simone Laganà, Valentina Laurita Longo, Francesca, Stollagli, Angelo, Sirico, Antonio, Lanzone, Lorenza, Driul, Fabiana, Cecchini, Serena, Xodo, Brian, Rodriguez, Felipe, Mercado-Olivares, Deena, Elkafrawi, Giovanni, Sisti, Rosanna, Esposito, Antonio, Coviello, Marco, Cerbone, Maddalena, Morlando, Antonio, Schiattarella, Nicola, Colacurci, Pasquale De Franciscis, Ilaria, Cataneo, Marinella, Lenzi, Fabrizio, Sandri, Riccardo, Buscemi, Giorgia, Gattei, Francesca Della Sala, Eleonora, Valori, Maria Cristina Rovellotti, Elisa, Done, Gilles, Faron, Leonardo, Gucciardo, Esposito, Valentina, Flaminia, Vena, Antonella, Giancotti, Roberto, Brunelli, Ludovico, Muzii, Luigi, Nappi, Felice, Sorrentino, Marco, Liberati, Danilo, Buca, Martina, Leombroni, Francesca Di Sebastiano, Massimo, Franchi, Quintino Cesare Ianniciello, Simone, Garzon, Giuliano, Petriglia, Leonardo, Borrello, Albaro Josè Nieto-Calvache, Juan Manuel Burgos-Luna, Caroline, Kadji, Andrew, Carlin, Elisa, Bevilacqua, Marina, Moucho, Pedro, Viana, Rita, Figueiredo, José Morales Roselló, Gabriela, Loscalzo, Alicia, Martinez-Varea, Vincente, Diago, Jesús, S Jimenez Lopez, Alicia Yeliz Aykanat, Cosma, Stefano Domenico, Carosso, ANDREA ROBERTO, Benedetto, Chiara, Amanda, Bermejo, Otto Henrique May Feuerschuette, Ozlem, Uyaniklar, Sakine Rahimli Ocakouglu, Zeliha, Atak, Reyhan, Gündüz, Esra Tustas Haberal, Bernd, Froessler, Anupam, Parange, Peter, Palm, Igor, Samardjiski, Chiara, Taccaliti, Erhan, Okuyan, George, Daskalakis, Renato Augusto Moreira de Sa, Alejandro, Pittaro, Maria Luisa Gonzalez-Duran, Ana Concheiro Guisan, Şerife Özlem Genç, Blanka, Zlatohlávková, Anna Luengo Piqueras, Dolores Esteban Oliva, Aylin Pelin Cil, Olus, Api, Panos, Antsaklis, Liana, Ples, Ioannis, Kyvernitakis, Holger, Maul, Marcel, Malan, Albert, Lila, Roberta, Granese, Alfredo, Ercoli, Giuseppe, Zoccali, Villasco, Andrea, Biglia, Nicoletta, Ciuhodaru, Madalina, Costa, Elena, Caroline, Daelemans, Axelle, Pintiaux, Elif Gül Yapar Eyi, Elisa, Cueto, Eran, Hadar, Sarah, Dollinger, Noa, A Brzezinski-Sinai, Erasmo, Huertas, Pedro, Arango, Amadeo, Sanchez, Javier Alfonso Schvartzman, Liviu, Cojocaru, Sifa, Turan, Ozhan, Turan, Maria Carmela Di Dedda, Rebeca Garrote Molpeceres, Snezana, Zdjelar, Tanja, Premru-Srsen, Lilijana, Kornhauser-Cerar, Mirjam, Druškovič, Valentina De Robertis, Vedran, Stefanovic, Irmeli, Nupponen, Kaisa, Nelskylä, Zulfiya, Khodjaeva, Ksenia, A Gorina, Gennady, T Sukhikh, Giuseppe Maria Maruotti, Silvia, Visentin, Erich, Cosmi, Jacopo, Ferrari, Alessandra, Gatti, Daniela, Luvero, Roberto, Angioli, Ludovica, Puri, Marco, Palumbo, Giusella, D'Urso, Francesco, Colaleo, Agnese Maria Chiara Rapisarda, Ilma Floriana Carbone, Manzoli, Lamberto, Maria Elena Flacco, Giovanni, Nazzaro, Mariavittoria, Locci, Maurizio, Guida, Attilio Di Spiezio Sardo, Pierluigi Benedetti Panici, Asma, Khalil, Vincenzo, Berghella, Giuseppe, Bifulco, Giovanni, Scambia, Fulvio, Zullo, Francesco, D'Antonio, Saccone, Gabriele, Sen, Cihat, Di Mascio, Daniele, Galindo, Alberto, Grünebaum, Amo, Yoshimatsu, Jun, Stanojevic, Milan, Kurjak, Asım, Chervenak, Frank, Suárez, María José Rodríguez, Gambacorti‐Passerini, Zita Maria, de los Angeles Anaya Baz, María, Galán, Esther Vanessa Aguilar, López, Yolanda Cuñarro, Luis, Juan Antonio De León, Hernández, Ignacio Cueto, Herraiz, Ignacio, Villalain, Cecilia, Venturella, Roberta, Rizzo, Giuseppe, Mappa, Ilenia, Gerosolima, Giovanni, Hellmeyer, Lar, Königbauer, Josefine, Ameli, Giada, Frusca, Tiziana, Volpe, Nicola, Schera, Giovanni Battista Luca, Fieni, Stefania, Esposito, Eutalia, Simonazzi, Giuliana, Di Donna, Gaetana, Youssef, Aly, Gatta, Anna Nunzia Della, Di Donna, Mariano Catello, Chiantera, Vito, Buono, Natalina, Sozzi, Giulio, Greco, Pantaleo, Morano, Danila, Bianchi, Beatrice, Marino, Maria Giulia Lombana, Laraud, Federica, Ramone, Arianna, Cagnacci, Angelo, Barra, Fabio, Gustavino, Claudio, Ferrero, Simone, Ghezzi, Fabio, Cromi, Antonella, Laganà, Antonio Simone, Longo, Valentina Laurita, Stollagli, Francesca, Sirico, Angelo, Lanzone, Antonio, Driul, Lorenza, Cecchini, Fabiana, Xodo, Serena, Rodriguez, Brian, Mercado‐Olivares, Felipe, Elkafrawi, Deena, Sisti, Giovanni, Esposito, Rosanna, Coviello, Antonio, Cerbone, Marco, Morlando, Maddalena, Schiattarella, Antonio, Colacurci, Nicola, De Franciscis, Pasquale, Cataneo, Ilaria, Lenzi, Marinella, Sandri, Fabrizio, Buscemi, Riccardo, Gattei, Giorgia, Sala, Francesca Della, Valori, Eleonora, Rovellotti, Maria Cristina, Done, Elisa, Faron, Gille, Gucciardo, Leonardo, Esposito, Valentina, Vena, Flaminia, Giancotti, Antonella, Brunelli, Roberto, Muzii, Ludovico, Nappi, Luigi, Sorrentino, Felice, Liberati, Marco, Buca, Danilo, Leombroni, Martina, Di Sebastiano, Francesca, Franchi, Massimo, Ianniciello, Quintino Cesare, Garzon, Simone, Petriglia, Giuliano, Borrello, Leonardo, Nieto‐Calvache, Albaro Josè, Burgos‐Luna, Juan Manuel, Kadji, Caroline, Carlin, Andrew, Bevilacqua, Elisa, Moucho, Marina, Viana Pinto, Pedro, Figueiredo, Rita, Morales Roselló, José, Loscalzo, Gabriela, Martinez‐Varea, Alicia, Diago, Vincente, Jimenez Lopez, Jesús S, Aykanat, Alicia Yeliz, Cosma, Stefano, Carosso, Andrea, Benedetto, Chiara, Bermejo, Amanda, Feuerschuette, Otto Henrique May, Uyaniklar, Ozlem, Ocakouglu, Sakine Rahimli, Atak, Zeliha, Gündüz, Reyhan, Haberal, Esra Tusta, Froessler, Bernd, Parange, Anupam, Palm, Peter, Samardjiski, Igor, Taccaliti, Chiara, Okuyan, Erhan, Daskalakis, George, de Sa, Renato Augusto Moreira, Pittaro, Alejandro, Gonzalez‐Duran, Maria Luisa, Guisan, Ana Concheiro, Genç, Şerife Özlem, Zlatohlávková, Blanka, Piqueras, Anna Luengo, Oliva, Dolores Esteban, Cil, Aylin Pelin, Api, Olu, Antsaklis, Pano, Ples, Liana, Kyvernitakis, Ioanni, Maul, Holger, Malan, Marcel, Lila, Albert, Granese, Roberta, Ercoli, Alfredo, Zoccali, Giuseppe, Villasco, Andrea, Biglia, Nicoletta, Madalina, Ciuhodaru, Costa, Elena, Daelemans, Caroline, Pintiaux, Axelle, Eyi, Elif Gül Yapar, Cueto, Elisa, Hadar, Eran, Dollinger, Sarah, Brzezinski‐Sinai, Noa A., Huertas, Erasmo, Arango, Pedro, Sanchez, Amadeo, Schvartzman, Javier Alfonso, Cojocaru, Liviu, Turan, Sifa, Turan, Ozhan, Di Dedda, Maria Carmela, Molpeceres, Rebeca Garrote, Zdjelar, Snezana, Premru‐Srsen, Tanja, Kornhauser‐Cerar, Lilijana, Druškovič, Mirjam, De Robertis, Valentina, Stefanovic, Vedran, Nupponen, Irmeli, Nelskylä, Kaisa, Khodjaeva, Zulfiya, Gorina, Ksenia A., Sukhikh, Gennady T., Maruotti, Giuseppe Maria, Visentin, Silvia, Cosmi, Erich, Ferrari, Jacopo, Gatti, Alessandra, Luvero, Daniela, Angioli, Roberto, Puri, Ludovica, Palumbo, Marco, D'Urso, Giusella, Colaleo, Francesco, Rapisarda, Agnese Maria Chiara, Carbone, Ilma Floriana, Manzoli, Lamberto, Flacco, Maria Elena, Nazzaro, Giovanni, Locci, Mariavittoria, Guida, Maurizio, Sardo, Attilio Di Spiezio, Panici, Pierluigi Benedetti, Khalil, Asma, Berghella, Vincenzo, Bifulco, Giuseppe, Scambia, Giovanni, Zullo, Fulvio, D'Antonio, Francesco, Dicle Üniversitesi, Tıp Fakültesi, Cerrahi Tıp Bilimleri Bölümü, Kadın Hastalıkları ve DoğumAna Bilim Dalı, University of Helsinki, Department of Obstetrics and Gynecology, HUS Gynecology and Obstetrics, HUS Children and Adolescents, Children's Hospital, HUS Perioperative, Intensive Care and Pain Medicine, Anestesiologian yksikkö, Department of Diagnostics and Therapeutics, Saccone, G., Sen, C., Di Mascio, D., Galindo, A., Grunebaum, A., Yoshimatsu, J., Stanojevic, M., Kurjak, A., Chervenak, F., Suarez, M. J. R., Gambacorti-Passerini, Z. M., de los Angeles Anaya Baz, M., Galan, E. V. A., Lopez, Y. C., Luis, J. A. D. L., Hernandez, I. C., Herraiz, I., Villalain, C., Venturella, R., Rizzo, G., Mappa, I., Gerosolima, G., Hellmeyer, L., Konigbauer, J., Ameli, G., Frusca, T., Volpe, N., Schera, G. B. L., Fieni, S., Esposito, E., Simonazzi, G., Di Donna, G., Youssef, A., Gatta, A. N. D., Di Donna, M. C., Chiantera, V., Buono, N., Sozzi, G., Greco, P., Morano, D., Bianchi, B., Marino, M. G. L., Laraud, F., Ramone, A., Cagnacci, A., Barra, F., Gustavino, C., Ferrero, S., Ghezzi, F., Cromi, A., Lagana, A. S., Longo, V. L., Stollagli, F., Sirico, A., Lanzone, A., Driul, L., Cecchini, F., Xodo, S., Rodriguez, B., Mercado-Olivares, F., Elkafrawi, D., Sisti, G., Esposito, R., Coviello, A., Cerbone, M., Morlando, M., Schiattarella, A., Colacurci, N., De Franciscis, P., Cataneo, I., Lenzi, M., Sandri, F., Buscemi, R., Gattei, G., Sala, F. D., Valori, E., Rovellotti, M. C., Done, E., Faron, G., Gucciardo, L., Esposito, V., Vena, F., Giancotti, A., Brunelli, R., Muzii, L., Nappi, L., Sorrentino, F., Liberati, M., Buca, D., Leombroni, M., Di Sebastiano, F., Franchi, M., Ianniciello, Q. C., Garzon, S., Petriglia, G., Borrello, L., Nieto-Calvache, A. J., Burgos-Luna, J. M., Kadji, C., Carlin, A., Bevilacqua, E., Moucho, M., Viana Pinto, P., Figueiredo, R., Morales Rosello, J., Loscalzo, G., Martinez-Varea, A., Diago, V., Jimenez Lopez, J. S., Aykanat, A. Y., Cosma, S., Carosso, A., Benedetto, C., Bermejo, A., Feuerschuette, O. H. M., Uyaniklar, O., Ocakouglu, S. R., Atak, Z., Gunduz, R., Haberal, E. T., Froessler, B., Parange, A., Palm, P., Samardjiski, I., Taccaliti, C., Okuyan, E., Daskalakis, G., de Sa, R. A. M., Pittaro, A., Gonzalez-Duran, M. L., Guisan, A. C., Genc, S. O., Zlatohlavkova, B., Piqueras, A. L., Oliva, D. E., Cil, A. P., Api, O., Antsaklis, P., Ples, L., Kyvernitakis, I., Maul, H., Malan, M., Lila, A., Granese, R., Ercoli, A., Zoccali, G., Villasco, A., Biglia, N., Madalina, C., Costa, E., Daelemans, C., Pintiaux, A., Cueto, E., Hadar, E., Dollinger, S., Brzezinski-Sinai, N. A., Huertas, E., Arango, P., Sanchez, A., Schvartzman, J. A., Cojocaru, L., Turan, S., Turan, O., Di Dedda, M. C., Molpeceres, R. G., Zdjelar, S., Premru-Srsen, T., Kornhauser-Cerar, L., Druskovic, M., De Robertis, V., Stefanovic, V., Nupponen, I., Nelskyla, K., Khodjaeva, Z., Gorina, K. A., Sukhikh, G. T., Maruotti, G. M., Visentin, S., Cosmi, E., Ferrari, J., Gatti, A., Luvero, D., Angioli, R., Puri, L., Palumbo, M., D'Urso, G., Colaleo, F., Rapisarda, A. M. C., Carbone, I. F., Manzoli, L., Flacco, M. E., Nazzaro, G., Locci, M., Guida, M., Sardo, A. D. S., Panici, P. B., Khalil, A., Berghella, V., Bifulco, G., Scambia, G., Zullo, F., D'Antonio, F., José Rodríguez Suárez, María, Maria Gambacorti-Passerini, Zita, de Los Angeles Anaya Baz, María, Vanessa Aguilar Galán, Esther, Cuñarro López, Yolanda, Antonio De León Luis, Juan, Cueto Hernández, Ignacio, Battista Luca Schera, Giovanni, Nunzia Della Gatta, Anna, Catello Di Donna, Mariano, Giulia Lombana Marino, Maria, Simone Laganà, Antonio, Laurita Longo, Valentina, Mercado-Olivares, Felipe, Della Sala, Francesca, Cristina Rovellotti, Maria, Cesare Ianniciello, Quintino, Josè Nieto-Calvache, Albaro, Manuel Burgos-Luna, Juan, Viana, Pedro, Martinez-Varea, Alicia, S Jimenez Lopez, Jesú, Yeliz Aykanat, Alicia, DI BENEDETTO, Chiara, Henrique May Feuerschuette, Otto, Rahimli Ocakouglu, Sakine, Tustas Haberal, Esra, Augusto Moreira de Sa, Renato, Luisa Gonzalez-Duran, Maria, Concheiro Guisan, Ana, Özlem Genç, Şerife, Luengo Piqueras, Anna, Esteban Oliva, Dolore, Pelin Cil, Aylin, Gül Yapar Eyi, Elif, A Brzezinski-Sinai, Noa, Alfonso Schvartzman, Javier, Carmela Di Dedda, Maria, Garrote Molpeceres, Rebeca, Premru-Srsen, Tanja, Kornhauser-Cerar, Lilijana, A Gorina, Ksenia, T Sukhikh, Gennady, Maruotti, GIUSEPPE MARIA, Maria Chiara Rapisarda, Agnese, Floriana Carbone, Ilma, Elena Flacco, Maria, DI SPIEZIO SARDO, Attilio, Benedetti Panici, Pierluigi, Saccone G., Sen C., Di Mascio D., Galindo A., Grunebaum A., Yoshimatsu J., Stanojevic M., Kurjak A., Chervenak F., Suarez M.J.R., Gambacorti-Passerini Z.M., de los Angeles Anaya Baz M., Galan E.V.A., Lopez Y.C., Luis J.A.D.L., Hernandez I.C., Herraiz I., Villalain C., Venturella R., Rizzo G., Mappa I., Gerosolima G., Hellmeyer L., Konigbauer J., Ameli G., Frusca T., Volpe N., Schera G.B.L., Fieni S., Esposito E., Simonazzi G., Di Donna G., Youssef A., Gatta A.N.D., Di Donna M.C., Chiantera V., Buono N., Sozzi G., Greco P., Morano D., Bianchi B., Marino M.G.L., Laraud F., Ramone A., Cagnacci A., Barra F., Gustavino C., Ferrero S., Ghezzi F., Cromi A., Lagana A.S., Longo V.L., Stollagli F., Sirico A., Lanzone A., Driul L., Cecchini F., Xodo S., Rodriguez B., Mercado-Olivares F., Elkafrawi D., Sisti G., Esposito R., Coviello A., Cerbone M., Morlando M., Schiattarella A., Colacurci N., De Franciscis P., Cataneo I., Lenzi M., Sandri F., Buscemi R., Gattei G., Sala F.D., Valori E., Rovellotti M.C., Done E., Faron G., Gucciardo L., Esposito V., Vena F., Giancotti A., Brunelli R., Muzii L., Nappi L., Sorrentino F., Liberati M., Buca D., Leombroni M., Di Sebastiano F., Franchi M., Ianniciello Q.C., Garzon S., Petriglia G., Borrello L., Nieto-Calvache A.J., Burgos-Luna J.M., Kadji C., Carlin A., Bevilacqua E., Moucho M., Viana Pinto P., Figueiredo R., Morales Rosello J., Loscalzo G., Martinez-Varea A., Diago V., Jimenez Lopez J.S., Aykanat A.Y., Cosma S., Carosso A., Benedetto C., Bermejo A., Feuerschuette O.H.M., Uyaniklar O., Ocakouglu S.R., Atak Z., Gunduz R., Haberal E.T., Froessler B., Parange A., Palm P., Samardjiski I., Taccaliti C., Okuyan E., Daskalakis G., de Sa R.A.M., Pittaro A., Gonzalez-Duran M.L., Guisan A.C., Genc S.O., Zlatohlavkova B., Piqueras A.L., Oliva D.E., Cil A.P., Api O., Antsaklis P., Ples L., Kyvernitakis I., Maul H., Malan M., Lila A., Granese R., Ercoli A., Zoccali G., Villasco A., Biglia N., Madalina C., Costa E., Daelemans C., Pintiaux A., Cueto E., Hadar E., Dollinger S., Brzezinski-Sinai N.A., Huertas E., Arango P., Sanchez A., Schvartzman J.A., Cojocaru L., Turan S., Turan O., Di Dedda M.C., Molpeceres R.G., Zdjelar S., Premru-Srsen T., Kornhauser-Cerar L., Druskovic M., De Robertis V., Stefanovic V., Nupponen I., Nelskyla K., Khodjaeva Z., Gorina K.A., Sukhikh G.T., Maruotti G.M., Visentin S., Cosmi E., Ferrari J., Gatti A., Luvero D., Angioli R., Puri L., Palumbo M., D'Urso G., Colaleo F., Rapisarda A.M.C., Carbone I.F., Manzoli L., Flacco M.E., Nazzaro G., Locci M., Guida M., Sardo A.D.S., Panici P.B., Khalil A., Berghella V., Bifulco G., Scambia G., Zullo F., D'Antonio F., Mother and Child, Surgical clinical sciences, Obstetrics, and Clinical sciences
Subjects: COVID19, medicine.medical_treatment, coronavirus, COVID-19, infection, pregnancy, SARS-CoV-2, Abortion, infectious diseases, law.invention, Cohort Studies, 0302 clinical medicine, law, 3123 Gynaecology and paediatrics, Pregnancy, Obstetrics and Gynaecology, 030212 general & internal medicine, Pregnancy Complications, Infectious, 030219 obstetrics & reproductive medicine, Radiological and Ultrasound Technology, Transmission (medicine), Obstetrics, Pregnancy Outcome, Obstetrics and Gynecology, Coronavirus, SARS-COV-2, General Medicine, Disease 2019 Covid-19, Intensive care unit, 3. Good health, Hospitalization, Intensive Care Units, Maternal Mortality, Settore MED/40, Radiology Nuclear Medicine and imaging, Gestation, Female, coronavirus, Pandemics, Pregnancy, Pregnancy Complications, Infectious, Pregnancy Outcome, Respiration, Artificial, Retrospective Studies, SARS-CoV-2, COVID-19, Infant, Newborn, Intensive Care Units,Maternal Mortality, Infection, Cohort study, Adult, medicine.medical_specialty, NO, 03 medical and health sciences, medicine, Humans, Radiology, Nuclear Medicine and imaging, Pandemics, Retrospective Studies, Mechanical ventilation, business.industry, Infant, Newborn, Infant, Retrospective cohort study, medicine.disease, Respiration, Artificial, coronaviru, Reproductive Medicine, business
Abstract: WOS:000613461600006 PubMed ID: 32926494 Objectives To evaluate the maternal and perinatal outcomes of pregnancies affected by SARS-CoV-2 infection. Methods This was a multinational retrospective cohort study including women with a singleton pregnancy and laboratory-confirmed SARS-CoV-2 infection, conducted in 72 centers in 22 different countries in Europe, the USA, South America, Asia and Australia, between 1 February 2020 and 30 April 2020. Confirmed SARS-CoV-2 infection was defined as a positive result on real-time reverse-transcription polymerase chain reaction (RT-PCR) assay of nasopharyngeal swab specimens. The primary outcome was a composite measure of maternal mortality and morbidity, including admission to the intensive care unit (ICU), use of mechanical ventilation and death. Results In total, 388 women with a singleton pregnancy tested positive for SARS-CoV-2 on RT-PCR of a nasopharyngeal swab and were included in the study. Composite adverse maternal outcome was observed in 47/388 (12.1%) women; 43 (11.1%) women were admitted to the ICU, 36 (9.3%) required mechanical ventilation and three (0.8%) died. Of the 388 women included in the study, 122 (31.4%) were still pregnant at the time of data analysis. Among the other 266 women, six (19.4% of the 31 women with first-trimester infection) had miscarriage, three (1.1%) had termination of pregnancy, six (2.3%) had stillbirth and 251 (94.4%) delivered a liveborn infant. The rate of preterm birth before 37 weeks' gestation was 26.3% (70/266). Of the 251 liveborn infants, 69/251(27.5%) were admitted to the neonatal ICU, and there were five (2.0%) neonatal deaths. The overall rate of perinatal death was 4.1% (11/266). Only one (1/251, 0.4%) infant, born to a mother who tested positive during the third trimester, was found to be positive for SARS-CoV-2 on RT-PCR. Conclusions SARS-CoV-2 infection in pregnant women is associated with a 0.8% rate of maternal mortality, but an 11.1% rate of admission to the ICU. The risk of vertical transmission seems to be negligible. (C) 2020 International Society of Ultrasound in Obstetrics and Gynecology.
Published: 2021

28. Recurrent Cesarean scar pregnancy: case series and literature review

Author: Judith Chervenak, G Horwitz, Ilan E. Timor-Tritsch, Giuseppe Calì, Maddalena Morlando, Francesco D'Antonio, Eran Bornstein, L Messina, Ana Monteagudo, Timor-Tritsch, Ie, Horwitz, G, D'Antonio, F, Monteagudo, A, Bornstein, E, Chervenak, J, Messina, L, Morlando, M, Cali, G, Timor-Tritsch, I. E., Horwitz, G., D'Antonio, F., Monteagudo, A., Bornstein, E., Chervenak, J., Messina, L., Morlando, M., and Cali, G.
Subjects: Adult, medicine.medical_specialty, animal structures, Databases, Factual, Cesarean Scar Pregnancy, complex mixtures, Ultrasonography, Prenatal, Cicatrix, Combined treatment, Postoperative Complications, CSP, Obstetrics and gynaecology, Pregnancy, Recurrence, Risk Factors, parasitic diseases, Medicine, Humans, Radiology, Nuclear Medicine and imaging, Medical diagnosis, Retrospective Studies, Radiological and Ultrasound Technology, Ectopic pregnancy, ultrasound, business.industry, Obstetrics, Cesarean Section, fungi, scar pregnancy, Obstetrics and Gynecology, General Medicine, Cesarean scar pregnancy, medicine.disease, Pregnancy, Ectopic, Reproductive Medicine, Gestation, Female, business, After treatment
Abstract: Objectives To determine the rate of recurrent Cesarean scar pregnancy (CSP) in our clinical practices and to evaluate whether the mode of treatment of a CSP is associated with the risk of recurrent CSP, as well as to review the published literature on recurrent CSP. Methods We performed a retrospective search of our six obstetric and gynecological departmental ultrasound databases for all CSPs and recurrent CSPs between 2010 and 2019. We extracted various data, including number of CSPs with follow-up, number of cases attempting and number achieving pregnancy following treatment of CSP and number of recurrent CSPs, as well as details of the treatment of the original CSP. After analyzing the clinical data, we evaluated whether the mode of treatment terminating the previous CSP was associated with the risk of recurrent CSP. We also performed a PubMed search for: 'recurrent Cesarean scar pregnancy' and 'recurrent Cesarean scar ectopic pregnancy'. Articles were reviewed for year of publication, and extraction and analysis of the same data as those obtained from our departmental databases were performed. Results Our database search identified 252 cases of CSP. The overall rate of clinical follow-up ranged between 71.4% and 100%, according to treatment site (mean, 90.9%). Among these, 105 women had another pregnancy after treatment of the previous CSP. Of these, 36 (34.3%) pregnancies were recurrent CSP, with 27 women having a single recurrence and three women having multiple recurrences, one with two, one with three and one with four. We did not find any particular single or combination treatment mode terminating the previous CSP to be associated with recurrent CSP. The literature search identified 17 articles that yielded sufficient information for us to evaluate their reported prevalence of recurrent CSP. These reported 1743 primary diagnoses of CSP, of which 944 had reliable follow-up. Data were available for 489 cases that attempted to conceive again after treatment of a previous CSP, and on the 327 pregnancies achieved. Of these, 67 (20.5%) were recurrent CSP. Conclusions On the basis of our pooled clinical data and review of the literature, recurrent CSP is apparently more common than was previously assumed based upon mostly single-case reports or series with few cases. This should be borne in mind when counseling patients undergoing treatment for CSP regarding their risk of recurrence. We found no obvious causal relationship or association between the type of treatment of the previous CSP and recurrence of CSP. Patients who become pregnant after treatment of a CSP should be encouraged to have an early (5-7-week) first-trimester transvaginal scan to determine the location of the gestation. (c) 2021 International Society of Ultrasound in Obstetrics and Gynecology.
Published: 2020

29. Use of routine ureteral stents in cesarean hysterectomy for placenta accreta

Author: Rosanna Esposito, Sonia Migliorini, Francesco Paolo Improda, Laura Sarno, Luigi Della Corte, Felice Crocetto, Pietro D'Alessandro, Ciro Imbimbo, Pasquale Martinelli, Giuseppe Bifulco, Bruno Arduino, Fulvio Zullo, Antonio Travaglino, Gabriele Saccone, Maddalena Morlando, Giuseppe Maria Maruotti, Antonio Raffone, Crocetto, F, Esposito, R, Saccone, G, Della Corte, L, Sarno, L, Morlando, M, Maruotti, Gm, Migliorini, S, D'Alessandro, P, Arduino, B, Raffone, A, Travaglino, A, Improda, Fp, Bifulco, G, Martinelli, P, Imbimbo, C, Zullo, F, Crocetto, F., Esposito, R., Saccone, G., Della Corte, L., Sarno, L., Morlando, M., Maruotti, G. M., Migliorini, S., D'Alessandro, P., Giuliani, Arduino, Raffone, A., Travaglino, A., Improda, F. P., Bifulco, G., Martinelli, P., Imbimbo, C., and Zullo, F.
Subjects: medicine.medical_specialty, placenta, Placenta accreta, Placenta Previa, Accreta, Placenta Accreta, Hysterectomy, Single Center, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Pregnancy, cesarean delivery, Placenta, medicine, Humans, 030212 general & internal medicine, Cesarean delivery, reproductive and urinary physiology, Retrospective Studies, 030219 obstetrics & reproductive medicine, Cesarean Section, Obstetrics, business.industry, Obstetrics and Gynecology, Ureteral stents, medicine.disease, female genital diseases and pregnancy complications, medicine.anatomical_structure, surgical procedures, operative, postpartum hemorrhage, Pediatrics, Perinatology and Child Health, previa, Female, Stents, business, Clinical record, Cesarean hysterectomy, Cohort study
Abstract: OBJECTIVE: To evaluate benefits of use of ureteral stents in association with cesarean hysterectomy in case of placenta accreta. METHODS: This was a single center, cohort study. Clinical records of singleton pregnancies with placenta accreta who underwent cesarean hysterectomy were included in the study. For this study, pregnancies with diagnoses of placenta accreta, increta, or percreta were considered under the umbrella term of placenta accreta. For all women with placenta accreta, delivery was planned via cesarean hysterectomy at 340-356 weeks, without any attempt to remove the placenta. Reasons for earlier delivery included vaginal bleeding and spontaneous onset of labor. The primary outcome was the incidence of unintentional urinary tract injury. Outcomes were compared in a cohort of women who had planned the placement of ureteral stents and in those who did not. RESULTS: Forty-four singleton gestations with confirmed placenta accreta at the time of cesarean hysterectomy were included in the study. Twenty-four (54.5%) of the included women had the placing of ureteral stents prior to cesarean, while 20 (45.5%) did not. At histological confirmation, most of them had placenta accreta (17/44, 38.6%), 14 placenta increta (31.8%), and 13 placenta percreta (29.6%). Urinary tract injuries occurred in eight cases (18.2%), six in the ureteral stents and two in the non-ureteral stents group (25 versus 10%; p = .21). All the injuries were bladder injuries, while no cases of ureteral injury were recorded. All injuries were recognized intraoperatively. CONCLUSION: In case of placenta accreta, the use of ureteral stents in association with cesarean hysterectomy does not reduce the risk of urinary tract injury.
Published: 2019

30. Fetal aortic isthmus Doppler assessment to predict the adverse perinatal outcomes associated with fetal growth restriction: systematic review and meta-analysis

Author: M. La Verde, F. Savoia, G. Riemma, A. Schiattarella, A. Conte, S. Hidar, M. Torella, N. Colacurci, P. De Franciscis, M. Morlando, La Verde, M, Savoia, F, Riemma, G, Schiattarella, A, Conte, A, Hidar, S, Torella, M, Colacurci, N, De Franciscis, P, and Morlando, M
Subjects: Fetal growth retardation, IUGR, Doppler, Obstetrics and Gynecology, General Medicine, Fetu, Aortic isthmu
Abstract: Purpose Fetal growth restriction (FGR) management and delivery planning is based on a multimodal approach. This meta-analysis aimed to evaluate the prognostic accuracies of the aortic isthmus Doppler to predict adverse perinatal outcomes in singleton pregnancies with FGR. Methods PubMed, EMBASE, the Cochrane Library, ClinicalTrials.gov and Google scholar were searched from inception to May 2021, for studies on the prognostic accuracy of anterograde aortic isthmus flow compared with retrograde aortic isthmus flow in singleton pregnancy with FGR. The meta-analysis was registered on PROSPERO and was assessed according to PRISMA and Newcastle–Ottawa Scale. DerSimonian and Laird’s random-effect model was used for relative risks, Freeman-Tukey Double Arcsine for pooled estimates and exact method to stabilize variances and CIs. Heterogeneity was quantified using I2 statistics. Results A total of 2933 articles were identified through the electronic search, of which 6 studies (involving 240 women) were included. The quality evaluation of studies revealed an overall acceptable score for study group selection and comparability and substantial heterogeneity. The risk of perinatal death was significantly greater in fetuses with retrograde Aortic Isthmus blood flow, with a RR of 5.17 (p value 0.00001). Similarly, the stillbirth rate was found to have a RR of 5.39 (p value 0.00001). Respiratory distress syndrome had a RR of 2.64 (p value = 0.03) in the group of fetuses with retrograde Aortic Isthmus blood flow. Conclusion Aortic Isthmus Doppler study may add information for FGR management. However, additional clinical trial are required to assess its applicability in clinical practice.
Published: 2023

31. Transversus abdominis plane block versus wound infiltration for post‐cesarean section analgesia: A systematic review and meta‐analysis of randomized controlled trials

Author: Antonio Schiattarella, Pasquale De Franciscis, Gaetano Riemma, Marco La Verde, Irene Esposito, Maddalena Morlando, Luigi Della Corte, Giovanni Sisti, Stefano Cianci, Pasquale Sansone, Riemma, Gaetano, Schiattarella, Antonio, Cianci, Stefano, La Verde, Marco, Morlando, Maddalena, Sisti, Giovanni, Esposito, Irene, DELLA CORTE, Luigi, Sansone, Pasquale, De Franciscis, Pasquale, Riemma, G., Schiattarella, A., Cianci, S., La Verde, M., Morlando, M., Sisti, G., Esposito, I., Della Corte, L., Sansone, P., and De Franciscis, P.
Subjects: Sedation, Cochrane Library, transversus abdominis plane block, analgesia, cesarean delivery, TAP block, wound infiltration, Abdominal Muscles, Analgesia, Obstetrical, Anesthetics, Local, Female, Humans, Pain, Postoperative, Pregnancy, Randomized Controlled Trials as Topic, Cesarean Section, Nerve Block, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, Transversus Abdominis Plane Block, law, medicine, 030212 general & internal medicine, Adverse effect, 030219 obstetrics & reproductive medicine, business.industry, Obstetrics and Gynecology, General Medicine, Confidence interval, Anesthesia, Relative risk, Meta-analysis, Abdominal Muscle, TAP block, analgesia, cesarean delivery, transversus abdominis plane block, wound infiltration, medicine.symptom, business, Human
Abstract: Background: Transversus abdominis plane (TAP) block and wound infiltration (WI) with local anesthetics are used for postoperative analgesia after cesarean section (CS), reducing the need for administration of opioids. Objective: To compare the analgesic effect of TAP block related to WI. Search strategy: MEDLINE, Scopus, ClinicalTrials.gov, EMBASE, Cochrane Library, and CINAHL were searched from inception until April 2020. Selection criteria: Randomized controlled trials (RCTs) about women who underwent TAP block or WI after CS. Data collection and analysis: Relevant data were extracted and tabulated. Review Manager 5.3 was used for data analysis. Primary outcome was cumulative opioid consumption (COC) 24 and 48 h after CS. Main results: Five RCTs, enrolling 268 women, were included. There were no significant differences between the interventions regarding COC at 24 (mean difference [MD] -1.68, 95% confidence interval [CI] -6.29 to 2.93) and 48 hours (MD 1.28, 95% CI -10.44 to 13.00). Adverse effects (relative risk [RR] 0.93, 95% CI 0.75-1.16), gastrointestinal reactions (RR 1.30, 95% CI 0.46-3.68), or mild-moderate sedation (RR 1.12, 95% CI 0.72-1.74), pain scores, satisfaction of women, and withdrawals were similar between groups. Conclusions: There might be no significant advantages selecting TAP block over WI for post-CS analgesia.
Published: 2021

32. Efficacy of hyoscine butyl-bromide in shortening the active phase of labor: Systematic review and meta-analysis of randomized trials

Author: Pasquale De Franciscis, Antonio Schiattarella, Gaetano Riemma, Nicola Colacurci, Maddalena Morlando, Luigi Cobellis, Marco La Verde, Riemma, G., La Verde, M., Schiattarella, A., Cobellis, L., De Franciscis, P., Colacurci, N., and Morlando, M.
Subjects: Bromides, medicine.medical_specialty, Antispasmodics, medicine.drug_class, Antispasmodic, Scopolamine, Active phase, Cochrane Library, Placebo, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, Pregnancy, law, Internal medicine, Butylscopolammonium Bromide, medicine, Anticholinergic, Humans, 030212 general & internal medicine, Butyl bromide, Randomized Controlled Trials as Topic, Labor, Obstetric, 030219 obstetrics & reproductive medicine, business.industry, Infant, Newborn, Obstetrics and Gynecology, medicine.disease, Labor, Confidence interval, Shortening, Duration, Reproductive Medicine, Meta-analysis, Female, business, Hyoscine butyl-bromide
Abstract: Introduction Prolonged labor increases the risk of maternal and fetal complications. The active management of labor has been proven effective in lowering neonatal and maternal morbidity by shortening the duration of labor. Several pharmaceutical and non-pharmaceutical approaches are currently being used in the active management of labor. Hyoscine Butyl-bromide (HBB) is an antispasmodic and anticholinergic drug that acts as a cervical spasmolytic agent. It has been widely used in everyday practice for shortening the active phase of labor. Nonetheless, only a few trials have been conducted on the topic. Objective This review aimed to evaluate whether HBB is effective in decreasing the mean duration of the active phase of labor. Study design An electronic search was conducted on Medline (through PubMed), Scopus, ClinicalTrials.gov, EMBASE, PROSPERO, and Cochrane Library from the beginning of all databases to December 2019. Results were limited to randomized trials. Restriction for English language was applied. Inclusion criteria were: randomized clinical trials regarding primiparae or multiparae women with a singleton vertex pregnancy at term who were randomized to HBB versus placebo or other drugs. Primary outcome evaluated was the mean reduction of the active phase of labor. Data collection and analysis Eight randomized clinical trials, including 1159 pregnant women, were analyzed. Significant heterogeneity (I2 = 99 %) between studies was noted for the primary outcome. The active phase of labor duration was significantly reduced in the treatment arm compared to controls [mean difference (MD) −83.93 min (95 % confidence interval (CI) −163.61, −4.25)]. Achieved reduction in primiparae women was −55.09 min [95 % CI −68.83, −41.35; I2 = 37 %]. Conclusion HBB is an effective treatment to shorten the duration of the active phase of labor in primiparae and multiparae women.
Published: 2020

33. Incidence of gestational diabetes mellitus before and after the Covid-19 lockdown: A retrospective cohort study

Author: Marco La Verde, Marco Torella, Gaetano Riemma, Giuliana Narciso, Irene Iavarone, Ligia Gliubizzi, Marica Palma, Maddalena Morlando, Nicola Colacurci, Pasquale De Franciscis, La Verde, M., Torella, M., Riemma, G., Narciso, G., Iavarone, I., Gliubizzi, L., Palma, M., Morlando, M., Colacurci, N., and De Franciscis, P.
Subjects: Male, SARS-CoV-2, Incidence, Pregnancy Outcome, Obstetrics and Gynecology, COVID-19, Gestational Weight Gain, gestational diabete, lockdown, Diabetes, Gestational, Retrospective Studie, Pregnancy, Communicable Disease Control, Humans, Female, diabetes gestational mellitu, Human, Retrospective Studies
Abstract: Aim To evaluate whether the first Covid-19 lockdown for Italian citizens (March to July 2021) might have altered the incidence of gestational diabetes mellitus (GDM). Methods A retrospective single-center study in a tertiary referral center. Primary outcome was the incidence of GDM among pregnant women. GDM incidence, from June 11, 2019 to December 4, 2020, was compared by dividing the study time as follows: from the beginning of the study to before Covid-19 lockdown (from June 11, 2019, to March 9, 2020) and lockdown period (from March 10, 2020, to December 4, 2020). GDM was diagnosed with a 75-g, 2-h oral glucose tolerance test (OGTT) at 24-28 gestational weeks. Results Concerning 1295 women, GDM incidence increased during the lockdown period (9.3% vs. 3.4%, p < 0.001). Higher pregnancy weight gain with an increased body mass index (BMI) at the delivery was reported during the lockdown (31.3 vs. 28.4 kg/m(2), p = 0.02 and mean weight gain of 9.3 vs. 6.6 kg, p = 0.007). There was no difference in other comorbidity incidence and OGTT values between the two groups. Conclusions Pregnant women during the Covid-19 lockdown might have experienced higher BMI and pregnancy weight gain with increased GDM diagnoses. This may be related to physical limitations and emotional distress experienced during the lockdown. However, evidence is limited due to restricted study duration and random variations of outcomes across time. More studies are needed to understand the dietary patterns and the physical activity changes during the Covid-19 lockdown and its impact on fetal outcomes.
Published: 2022

34. Successfulness of the Bakri Intrauterine Balloon For Uterotonic-Unresponsive Postpartum Haemorrhage Treatment: Systematic Review and Meta-Analysis

Author: Marco La Verde, Gaetano Riemma, Marco Torella, Nicola COLACURCI, Salvatore Annona, Anna Conte, Vittorio Simeon, Agnese MariaChiara Rapisarda, Pasquale De Franciscis, Maddalena Morlando, La Verde, M., Riemma, G., Torella, M., Colacurci, N., Annona, S., Conte, A., Simeon, V., Rapisarda, A. M., De Franciscis, P., and Morlando, M.
Subjects: General Medicine
Published: 2022

35. Is Uterine Myomectomy a Real Contraindication to Vaginal Delivery? Results from a Prospective Study

Author: Antonio Schiattarella, Maddalena Morlando, Marco Torella, Nicola Colacurci, Anna Conte, Domenico Ambrosio, Gaetano Riemma, Pasquale De Franciscis, Marco La Verde, Luigi Cobellis, La Verde, Marco, Cobellis, Luigi, Torella, Marco, Morlando, Maddalena, Riemma, Gaetano, Schiattarella, Antonio, Conte, Anna, Ambrosio, Domenico, Colacurci, Nicola, De Franciscis, Pasquale, La Verde, M., Cobellis, L., Torella, M., Morlando, M., Riemma, G., Schiattarella, A., Conte, A., Ambrosio, D., Colacurci, N., and De Franciscis, P.
Subjects: medicine.medical_specialty, medicine.medical_treatment, laparoscopy, Contraindications, Procedure, 03 medical and health sciences, 0302 clinical medicine, laparotomy, Pregnancy, Retrospective Studie, Laparotomy, Uterine Myomectomy, medicine, Humans, In patient, Prospective Studies, Prospective cohort study, Laparoscopy, Contraindication, myomectomy, Retrospective Studies, medicine.diagnostic_test, Obstetrics, Vaginal delivery, business.industry, Cesarean Section, medicine.disease, Delivery, Obstetric, Labor, Uterine myomectomy, Prospective Studie, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Surgery, Female, vaginal delivery, business, Human
Abstract: Objectives: The main goal of our research was to explore correlations between a history of uterine myomectomy and maternal-fetal outcomes, throughout a comparison between vaginal deliveries in patients with or without a history of uterine myoma excision. Materials and methods: A prospective study was carried out at two tertiary care hospitals between January 2019 and January 2020. Women were assigned into two groups according to the history of laparoscopic or laparotomic myomectomy (Group 1) or without myomectomy (Group 2). Results: 80 women successfully delivered after myomectomy. Pregnancies with previous laparoscopic or laparotomic myomectomy were associated with a minor rate of spontaneous labor onset (RR 1.17; 95% CI 1.04 − 1.31) and with an increased rate of emergency cesarean section (RR 1.22; 95% CI 1.09 − 1.36). Moreover, myomectomy group had a significant number of indications to emergency cesarean section correlated to suspected uterine rupture (RR 1.19; 95% CI 1.02–1.39). There were no uterine ruptures or neonatal deaths recorded. First stage of labor was longer in the myomectomy group (316 vs 204 mins, p = 0.01). No differences in the rates of the prolonged first and second stage of labor, postpartum hemorrhage and vaginal laceration, and no neonatal adverse outcomes were found between groups. Conclusions: Pregnancies after myomectomy might be associated with an elevated rate of emergency cesarean section only due to a higher percentage of suspected uterine rupture, without a real hazard of adverse obstetric or neonatal outcomes.
Published: 2022

36. Maternal and Fetal Outcomes in Women with Diabetes in Pregnancy Treated before and after the Introduction of a Standardized Multidisciplinary Management Protocol

Author: Katherine Esposito, Maddalena Morlando, Antonio Schiattarella, Fabiana Savoia, Carlo Capristo, Mauro Carpentieri, Anna Conte, Nicola Colacurci, Michela Petrizzo, Marco La Verde, Morlando, M., Savoia, F., Conte, A., Schiattarella, A., La Verde, M., Petrizzo, M., Carpentieri, M., Capristo, C., Esposito, K., and Colacurci, N.
Subjects: Adult, medicine.medical_specialty, Time Factors, Article Subject, Endocrinology, Diabetes and Metabolism, MEDLINE, Pregnancy in Diabetics, Diseases of the endocrine glands. Clinical endocrinology, Fetal Macrosomia, Endocrinology, Clinical Protocols, Neonatologists, Multidisciplinary approach, Pregnancy, Fetal macrosomia, medicine, Humans, Labor, Induced, Cooperative Behavior, Retrospective Studies, Protocol (science), Patient Care Team, Fetus, business.industry, Vaginal delivery, Obstetrics, Pregnancy Outcome, Retrospective cohort study, medicine.disease, RC648-665, Delivery, Obstetric, Diabetes, Gestational, Endocrinologists, Treatment Outcome, Gestation, Female, Interdisciplinary Communication, business, Research Article
Abstract: Background. Diabetes in pregnancy is associated with an increased risk to the woman and to the developing fetus. Currently, there is no consensus on the optimal management strategies for the follow-up and the timing of delivery of pregnancies affected by gestational and pregestational diabetes, with different international guidelines suggesting different management options. Materials and Methods. We conducted a retrospective cohort study from January 2017 to January 2021, to compare maternal and neonatal outcomes of pregnancies complicated by gestational and pregestational diabetes, followed-up and delivered in a third level referral center before and after the introduction of a standardized multidisciplinary management protocol including diagnostic, screening, and management criteria. Results. Of the 131 women included, 55 were managed before the introduction of the multidisciplinary management protocol and included in group 1 (preprotocol), while 76 were managed according to the newly introduced multidisciplinary protocol and included in group 2 (after protocol). We observed an increase in the rates of vaginal delivery, rising from 32.7% to 64.5% ( P < 0.001 ). No differences were found in neonatal outcomes, and the only significant difference was demonstrated for the rates of fetal macrosomia (20% versus 5.3%, P : 0.012). Therefore, the improvements observed in the maternal outcomes did not impact negatively on fetal and neonatal outcomes. Conclusion. The introduction of a standardized multidisciplinary management protocol led to an improvement in the rates of vaginal delivery and in the rate of successful induction of labor in our center. A strong cooperation between obstetricians, diabetologists, and neonatologists is crucial to obtain a successful outcome in women with diabetes in pregnancy.
Published: 2021
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37. Impact of Braxton-Hicks contractions on fetal wellbeing; a prospective analysis through computerised cardiotocography

Author: Clelia Torre, Maddalena Morlando, Nicola Colacurci, Carlo Capristo, Pasquale De Franciscis, Marco Torella, Gaetano Riemma, Anna Conte, Stefano Cianci, Marco La Verde, La Verde, M., Riemma, G., Torella, M., Torre, C., Cianci, S., Conte, A., Capristo, C., Morlando, M., Colacurci, N., and De Franciscis, P.
Subjects: medicine.medical_specialty, Braxton–Hicks contraction, Cardiotocography, Pregnancy Trimester, Third, Foetal heart rate, Prospective analysis, Fetus, Braxton–Hicks contractions, computerised cardiotocography, foetal heart rate, foetal wellbeing, pregnancy, uterine contractions, medicine, Humans, Braxton Hicks contractions, Prospective Studies, Pregnancy, medicine.diagnostic_test, business.industry, Term pregnancy, Obstetrics, Obstetrics and Gynecology, Heart Rate, Fetal, medicine.disease, Observational study, Female, business
Abstract: To estimate the correlation between the maternal perception of Braxton-Hicks contractions (BHC) and foetal wellbeing throughout antepartum computerised cardiotocography (cCTG) parameters, we performed a prospective observational study between April 2019 and March 2020. Non-labouring women with a term pregnancy were recruited. We collected data regarding maternal perception of BHC in the last two weeks before delivery. For each patient, an external computerised cardiotocography (cCTG) was registered. Women were subdivided in accordance with perception or non-perception of BHC. Fifty women were recruited. Women who felt BHC showed higher foetal heart rate (135 bpm vs 128 bpm, p = .008), lower long-term variability (47.2 ms vs 57.7 ms, p = .02) and reduced number of accelerations (7.8 vs 11.4, p = .04). In conclusion, the absence of mother's perception of BHC showed lower baseline foetal heart rate, increased number of accelerations and higher long-term variability related to mothers who perceived BHC.IMPACT STATEMENTWhat is already known on this subject? BHC are common painful contractions that start in the third trimester. They are random spots of uterine action that happen in the absence of sufficient gap-junction connectivity. BHC have a significant impact on foetal wellbeing.What do the results of this study add? BHC are associated with reduced long-term variability during cCTG examination. Moreover, baseline foetal heart rate seems lower, and accelerations are less frequent when BHC are felt by pregnant women.What are the implications of these findings for clinical practice and/or further research? These findings could be related to a cumulative effect on the uterine flow mediated by BHC. Further researches are needed to state the impact of BHC on the foetal wellbeing. What is already known on this subject? BHC are common painful contractions that start in the third trimester. They are random spots of uterine action that happen in the absence of sufficient gap-junction connectivity. BHC have a significant impact on foetal wellbeing. What do the results of this study add? BHC are associated with reduced long-term variability during cCTG examination. Moreover, baseline foetal heart rate seems lower, and accelerations are less frequent when BHC are felt by pregnant women. What are the implications of these findings for clinical practice and/or further research? These findings could be related to a cumulative effect on the uterine flow mediated by BHC. Further researches are needed to state the impact of BHC on the foetal wellbeing.
Published: 2021

38. Maternal and perinatal outcomes in high compared to low risk pregnancies complicated by severe acute respiratory syndrome coronavirus 2 infection (phase 2): the World Association of Perinatal Medicine working group on coronavirus disease 2019

Author: D'Antonio, Francesco, Sen, Cihat, Mascio, Daniele Di, Galindo, Alberto, Villalain, Cecilia, Herraiz, Ignacio, Arisoy, Resul, Ovayolu, Ali, Eroğlu, Hasan, Canales, Manuel Guerra, Ladella, Subhashini, Cojocaru, Liviu, Turan, Ozhan, Turan, Sifa, Hadar, Eran, Brzezinski-Sinai, Noa A, Dollinger, Sarah, Uyaniklar, Ozlem, Ocakouglu, Sakine Rahimli, Atak, Zeliha, Premru-Srsen, Tanja, Kornhauser-Cerar, Lilijana, Druškovič, Mirjam, Ples, Liana, Gündüz, Reyhan, Ağaçayak, Elif, Schvartzman, Javier Alfonso, Malbran, Mercedes Negri, Liberati, Marco, Sebastiano, Francesca Di, Oronzi, Ludovica, Cerra, Chiara, Buca, Danilo, Cagnacci, Angelo, Ramone, Arianna, Barra, Fabio, Carosso, Andrea, Benedetto, Chiara, Cosma, Stefano, Pintiaux, Axelle, Daelemans, Caroline, Costa, Elena, Özel, Ayşegül, Muhçu, Murat, Lopez, Jesús S Jimenez, Alvarado, Clara, Piqueras, Anna Luengo, Oliva, Dolores Esteban, Schera, Giovanni Battista Luca, Volpe, Nicola, Frusca, Tiziana, Samardjiski, Igor, Simeonova, Slagjana, Papestiev, Irena Aleksioska, Hojman, Javier, Turkcuoglu, Ilgin, Cromi, Antonella, Laganà, Antonio Simone, Ghezzi, Fabio, Sirico, Angelo, Familiari, Alessandra, Scambia, Giovanni, Sukhikh, Zulfiya Khodjaeva Gennady T, Gorina, Ksenia A, de Sa, Renato Augusto Moreira, Vaz, Mariana, Feuerschuette, Otto Henrique May, Gatta, Anna Nunzia Della, Youssef, Aly, Donna, Gaetana Di, Martinez-Varea, Alicia, Loscalzo, Gabriela, Morales Roselló, José, Stefanovic, Vedran, Nupponen, Irmeli, Nelskylä, Kaisa, Ayala, Rodrigo, Molpeceres, Rebeca Garrote, Vázquez, Asunción Pino, Sandri, Fabrizio, Cataneo, Ilaria, Lenzi, Marinella, Haberal, Esra Tustas, Huertas, Erasmo, Sanchez, Amadeo, Arango, Pedro, Bermejo, Amanda, Alcantara, María Monica Gonzalez, Göynümer, Gökhan, Okuyan, Erhan, Madalina, Ciuhodaru, Guisan, Ana Concheiro, Schulte, Alejandra Martínez, Esposito, Valentina, De Robertis, Valentina, Zdjelar, Snezana, Lackovic, Milan, Mihajlovic, Sladjana, Jekova, Nelly, Saccone, Gabriele, Aslan, Mehmet Musa, Dedda, Maria Carmela Di, Chalid, Maisuri, Canache, Jose Enrique Moros, Daskalakis, George, Antsaklis, Panos, Vega, Enrique Criado, Cueto, Elisa, Taccaliti, Chiara, Aykanat, Yeliz, Özlem Genç, Şerife, Froessler, Bernd, Radulova, Petya Angelova, Morano, Danila, Bianchi, Beatrice, Marino, Maria Giulia Lombana, Meccariello, Gabriella, Rohatgi, Bindu, Schiattarella, Antonio, Morlando, Maddalena, Colacurci, Nicola, Villasco, Andrea, Biglia, Nicoletta, Marques, Ana Luiza Santos, Gatti, Alessandra, Luvero, Daniela, Angioli, Roberto, Pittaro, Alejandro, Lila, Albert, Zlatohlávková, Blanka, On the behalf of the World Association of Perinatal Medicine working group on coronavirus disease 2019, Dicle Üniversitesi, Tıp Fakültesi, Cerrahi Tıp Bilimleri Bölümü, Kadın Hastalıkları ve Doğum Ana Bilim Dalı, Gündüz, Reyhan, Ağaçayak, Elif, [Belirlenecek], D'Antonio, F., Sen, C., Mascio, D. D., Galindo, A., Villalain, C., Herraiz, I., Arisoy, R., Ovayolu, A., Eroglu, H., Canales, M. G., Ladella, S., Cojocaru, L., Turan, O., Turan, S., Hadar, E., Brzezinski-Sinai, N. A., Dollinger, S., Uyaniklar, O., Ocakouglu, S. R., Atak, Z., Premru-Srsen, T., Kornhauser-Cerar, L., Druskovic, M., Ples, L., Gunduz, R., Agacayak, E., Schvartzman, J. A., Malbran, M. N., Liberati, M., Sebastiano, F. D., Oronzi, L., Cerra, C., Buca, D., Cagnacci, A., Ramone, A., Barra, F., Carosso, A., Benedetto, C., Cosma, S., Pintiaux, A., Daelemans, C., Costa, E., Ozel, A., Muhcu, M., Lopez, J. S. J., Alvarado, C., Piqueras, A. L., Oliva, D. E., Schera, G. B. L., Volpe, N., Frusca, T., Samardjiski, I., Simeonova, S., Papestiev, I. A., Hojman, J., Turkcuoglu, I., Cromi, A., Lagana, A. S., Ghezzi, F., Sirico, A., Familiari, A., Scambia, G., Sukhikh, Z. K. G. T., Gorina, K. A., de Sa, R. A. M., Vaz, M., Feuerschuette, O. H. M., Gatta, A. N. D., Youssef, A., Donna, G. D., Martinez-Varea, A., Loscalzo, G., Rosello, J. M., Stefanovic, V., Nupponen, I., Nelskyla, K., Ayala, R., Molpeceres, R. G., Vazquez, A. P., Sandri, F., Cataneo, I., Lenzi, M., Haberal, E. T., Huertas, E., Sanchez, A., Arango, P., Bermejo, A., Alcantara, M. M. G., Goynumer, G., Okuyan, E., Madalina, C., Guisan, A. C., Schulte, A. M., Esposito, V., De Robertis, V., Zdjelar, S., Lackovic, M., Mihajlovic, S., Jekova, N., Saccone, G., Aslan, M. M., Dedda, M. C. D., Chalid, M., Canache, J. E. M., Daskalakis, G., Antsaklis, P., Vega, E. C., Cueto, E., Taccaliti, C., Aykanat, Y., Ozlem Genc, S., Froessler, B., Radulova, P. A., Morano, D., Bianchi, B., Marino, M. G. L., Meccariello, G., Rohatgi, B., Schiattarella, A., Morlando, M., Colacurci, N., Villasco, A., Biglia, N., Marques, A. L. S., Gatti, A., Luvero, D., Angioli, R., Pittaro, A., Lila, A., and Zlatohlavkova, B.
Subjects: Neonatal intensive care unit, coronavirus, Miscarriage, law.invention, 0302 clinical medicine, Retrospective Studie, law, Pregnancy, Neonatal, Severe acute respiratory syndrome coronavirus 2, 030212 general & internal medicine, Pregnancy Complications, Infectious, 030219 obstetrics & reproductive medicine, coronavirus disease 2019, infection, pregnancy, severe acute respiratory syndrome coronavirus 2, Asia, Australia, Europe, Female, Humans, Infant, Newborn, Intensive Care Units, Neonatal, Retrospective Studies, SARS-CoV-2, South America, COVID-19, Pregnancy Outcome, Coronavirus disease 2019, Obstetrics, Incidence (epidemiology), Infectious, General Medicine, Intensive care unit, 3. Good health, Intensive Care Units, Covid-19, Infection, Human, medicine.medical_specialty, 03 medical and health sciences, medicine, business.industry, Infant, Retrospective cohort study, Odds ratio, medicine.disease, Newborn, Confidence interval, coronaviru, Pregnancy Complications, Coronavirus, Pregnancy Complications, Infectiou, business
Abstract: BACKGROUND: It has still to be ascertained whether severe acute respiratory syndrome coronavirus 2 infection in pregnancy is associated with worse maternal and fetal outcomes compared to low risk gestations. OBJECTIVE: This study aimed to evaluate maternal and perinatal outcomes in high- and low-risk pregnancies complicated by severe acute respiratory syndrome coronavirus 2 infection. STUDY DESIGN: This was a multinational retrospective cohort study involving women with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection from 76 centers from 25 countries in Europe, the United States, South America, Asia, and Australia from April 4, 2020, to October 28, 2020. The primary outcome was a composite measure of maternal mortality and morbidity, including admission to the intensive care unit, use of mechanical ventilation, or death. The secondary outcome was a composite measure of adverse perinatal outcome, including miscarriage, fetal loss, neonatal and perinatal death, and admission to the neonatal intensive care unit. All outcomes were assessed in high- and low-risk pregnancies. Pregnancies were considered high risk in case of either preexisting chronic medical conditions in pregnancy or obstetrical disorders occurring in pregnancy. The Fisher exact test and logistic regression analysis were used to analyze the data. RESULTS: A total of 887 singleton pregnancies who tested positive for severe acute respiratory syndrome coronavirus 2 infection using reverse transcription-polymerase chain reaction of nasal and pharyngeal swab specimens were included in the study. The risk of composite adverse maternal outcomes was higher in high-risk pregnancies than in low-risk pregnancies (odds ratio, 1.52; 95% confidence interval, 1.03-2.24; P=.035). In addition, women carrying high-risk pregnancies were at higher risk of hospital admission (odds ratio, 1.48; 95% confidence interval, 1.07-2.04; P=.002), presence of severe respiratory symptoms (odds ratio, 2.13; 95% confidence interval, 0.41-3.21; P=.001), admission to the intensive care unit (odds ratio, 2.63; 95% confidence interval, 1.42-4.88), and invasive mechanical ventilation (odds ratio, 2.65; 95% confidence interval, 1.19-5.94; P=.002). When exploring perinatal outcomes, high-risk pregnancies were at high risk of adverse perinatal outcomes (odds ratio, 1.78; 95% confidence interval, 0.15-2.72; P=.009). However, such association was mainly because of the higher incidence of miscarriage in high-risk pregnancies compared with that in low-risk pregnancies (5.3% vs 1.6%, P=.008); furthermore, there was no difference in other explored outcomes between the 2 study groups. At logistic regression analysis, maternal age (odds ratio, 1.12; 95% confidence interval, 1.02-1.22; P=.023) and high-risk pregnancy (odds ratio, 4.21; 95% confidence interval, 3.90-5.11; P
Published: 2021

39. Efficacy of phloroglucinol in shortening the first stage of labor: systematic review and meta-analysis of randomized controlled trials

Author: Agnese Maria Chiara Rapisarda, Fabiana Savoia, Maddalena Morlando, Gaetano Riemma, Pasquale De Franciscis, Antonio Schiattarella, Giovanni Sisti, Schiattarella, A., Riemma, G., Sisti, G., Savoia, F., Rapisarda, A., De Franciscis, P., and Morlando, M.
Subjects: medicine.medical_specialty, shortening, Phloroglucinol, labor, law.invention, chemistry.chemical_compound, Randomized controlled trial, Pregnancy, law, Active phase, Internal medicine, active management, medicine, Humans, Stage (cooking), reproductive and urinary physiology, Randomized Controlled Trials as Topic, Labor, Obstetric, business.industry, Parasympatholytics, Obstetrics and Gynecology, active phase, duration, chemistry, Meta-analysis, Pediatrics, Perinatology and Child Health, Female, business
Abstract: Background: Protracted labor is associated with an elevated risk of maternal and fetal complications. Results of randomized controlled trials on the efficacy in labor of phloroglucinol (PHL), a pure antispasmodic drug, are uncertain. Objectives: To evaluate whether PHL is effective in shortening the first stage of labor. Search strategy: MEDLINE, EMBASE, LILACS, Scopus, ClinicalTrials.gov, and the Cochrane Library were searched from inception to July 2020. Selection criteria: Randomized controlled trials (RCTs) concerning women with a singleton vertex pregnancy at term who were treated with PHL. Data collection and analysis: Relevant data were extracted and tabulated. Review Manager 5.3 was used for data analysis. Primary outcome evaluated was the mean reduction of the first stage of labor. Main results: Five RCTs, including 487 pregnant women, were analyzed. The first stage of labor duration was significantly shorter in the treatment arm compared to the control group [MD−113.21 min (95% CI−119.63,–106.79)]. A significant shortening of the second stage was achieved in the PHL group [MD−11.12 min (95% CI−12.64,–9.75)] while no differences were reported for the third stage. Conclusions: PHL might represent an effective treatment to shorten the duration of the first and second stage of labor. Synopsis: A meta‐analysis of 5 trials found that Phloroglucinol favorably impacts on the total duration of the labor in primiparae and multiparae women with a singleton pregnancy.
Published: 2021

40. Mediterranean Diet for the Prevention of Gestational Diabetes in the Covid-19 Era: Implications of Il-6 In Diabesity

Author: Antonio Schiattarella, Elisabetta Toti, Ilaria Peluso, Maddalena Morlando, Anna Raguzzini, Anna Lucia Fedullo, Pasquale De Franciscis, Fedullo, A. L., Schiattarella, A., Morlando, M., Raguzzini, A., Toti, E., De Franciscis, P., and Peluso, I.
Subjects: Mediterranean diet, Review, Diet, Mediterranean, lcsh:Chemistry, chemistry.chemical_compound, 0302 clinical medicine, Pregnancy, oxidative stress, plant foods, 030212 general & internal medicine, lcsh:QH301-705.5, Spectroscopy, chemistry.chemical_classification, nutraceuticals, biology, General Medicine, Plant food, Gestational Weight Gain, Computer Science Applications, Gestational diabetes, Female, Nutraceutical, Polyunsaturated fatty acid, Human, medicine.medical_specialty, 030209 endocrinology & metabolism, Catalysis, Inorganic Chemistry, 03 medical and health sciences, Insulin resistance, Diabetes mellitus, Internal medicine, medicine, Animals, Humans, Obesity, Physical and Theoretical Chemistry, cardio-diabesity, Interleukin 6, Molecular Biology, Life Style, business.industry, Animal, Interleukin-6, Organic Chemistry, COVID-19, medicine.disease, Diabetes, Gestational, Endocrinology, chemistry, lcsh:Biology (General), lcsh:QD1-999, inflammation, biology.protein, Oxidative stre, Glycated hemoglobin, business
Abstract: The aim of this review is to highlight the influence of the Mediterranean Diet (MedDiet) on Gestational Diabetes Mellitus (GDM) and Gestational Weight Gain (GWG) during the COVID-19 pandemic era and the specific role of interleukin (IL)-6 in diabesity. It is known that diabetes, high body mass index, high glycated hemoglobin and raised serum IL-6 levels are predictive of poor outcomes in coronavirus disease 2019 (COVID-19). The immunopathological mechanisms of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection include rising levels of several cytokines and in particular IL-6. The latter is associated with hyperglycemia and insulin resistance and could be useful for predicting the development of GDM. Rich in omega-3 polyunsaturated fatty acids, vitamins, and minerals, MedDiet improves the immune system and could modulate IL-6, C reactive protein and Nuclear Factor (NF)-κB. Moreover, polyphenols could modulate microbiota composition, inhibit the NF-κB pathway, lower IL-6, and upregulate antioxidant enzymes. Finally, adhering to the MedDiet prior to and during pregnancy could have a protective effect, reducing GWG and the risk of GDM, as well as improving the immune response to viral infections such as COVID-19.
Published: 2021

41. Aberrant right subclavian artery: the association with chromosomal defects and the related post-natal outcomes in a third level referral centre

Author: Carmela Morelli, Antonio Schiattarella, Adelaide Fusco, Maria Giovanna Russo, Gianfranco Moccia, Fortuna Del Gaizo, Federica De Fazio, Maddalena Morlando, Nicola Colacurci, Laura Di Pietto, Ludovica Spinelli Barrile, Pasquale De Franciscis, Morlando, M., Morelli, C., Del Gaizo, F., Fusco, A., De Fazio, F., Di Pietto, L., Moccia, G., Spinelli Barrile, L., Schiattarella, A., De Franciscis, P., Colacurci, N., and Russo, M. G.
Subjects: Heart Defects, Congenital, Pediatrics, medicine.medical_specialty, Down syndrome, arteria lusoria, Stridor, Cardiovascular Abnormalities, Dysphagia lusoria, Subclavian Artery, fetal echocardiography, Ultrasonography, Prenatal, 03 medical and health sciences, 0302 clinical medicine, Pregnancy, Aberrant right subclavian artery, dysphagia lusoria, medicine, Humans, Arteria lusoria, Referral and Consultation, 030219 obstetrics & reproductive medicine, medicine.diagnostic_test, Respiratory distress, business.industry, Infant, Newborn, Obstetrics and Gynecology, medicine.disease, Dysphagia, 030220 oncology & carcinogenesis, ARSA, Female, medicine.symptom, business, Trisomy, Fetal echocardiography
Abstract: Aberrant right subclavian artery (ARSA) is the most common embryologic abnormality of the aortic arch. The presence of ARSA has been previously associated with an increased risk of Down syndrome. ARSA at birth may be associated with dysphagia, respiratory distress and stridor and there is no clear evidence‐based management. The aim of this study was to describe the associations with chromosomal abnormalities and the postnatal outcome of fetuses diagnosed with ARSA. We analysed fetuses diagnosed antenatally with ARSA between January 2013 and September 2019 in the fetal echocardiography unit of the Hospital Monaldi, University ‘Vanvitelli’ of Naples, Italy. The results showed fifty fetuses diagnosed with ARSA, all confirmed after birth. The ARSA was an isolated finding in 46 fetuses (92%), while in 4 fetuses the ARSA was associated with other cardiac and/or extra-cardiac anomalies. Only one fetus was diagnosed with trisomy 21 (2%). In this fetus the ARSA was the only ultrasound anomaly identified. There were no cases necessitating referral due to the presence of compression symptoms at birth. The presence of ARSA was associated with trisomy 21 in the 2% of cases in our series and there were no neonatal complications due to airway compression at birth.IMPACT STATEMENTWhat is already known on this subject? Aberrant right subclavian artery (ARSA) is the most common embryologic abnormality of the aortich arch. ARSA at birth could be associated with dysphagia, respiratory distress and stridor and no evidence-based management of these fetuses has been described yet. The presence of ARSA has been previously associated with an increased risk of Down syndrome. What do the results of this study add? This study confirms known data on association with chromosomal defects and provides some original data on the absence of symptomatology due to tracheal compression with a postnatal follow-up up to three years of age. What are the implications of these findings for clinical practice and/or further research? Our findings suggest that in cases with adequate prenatal assessment performed by experienced clinicians, delivery can safely take place at local hospitals, with no need of referral soon after birth. The use of transthoracic echocardiography to confirm the diagnoses of ARSA after birth and to plan the next follow-up appointments can be supported.
Published: 2021

42. Maternal death related to COVID-19: A systematic review and meta-analysis focused on maternal co-morbidities and clinical characteristics

Author: Federico Licciardi, Nicola Colacurci, Marco Torella, Serena Scida, Gaetano Riemma, Marco La Verde, Fabiana Savoia, Stefano Cianci, Maddalena Morlando, Pasquale De Franciscis, La Verde, M., Riemma, G., Torella, M., Cianci, S., Savoia, F., Licciardi, F., Scida, S., Morlando, M., Colacurci, N., and De Franciscis, P.
Subjects: medicine.medical_specialty, Comorbidity, Cochrane Library, neonatal outcome, 03 medical and health sciences, co-morbiditie, 0302 clinical medicine, Pregnancy, Intensive care, medicine, Humans, 030212 general & internal medicine, Obesity, Pregnancy Complications, Infectious, Pandemics, 030219 obstetrics & reproductive medicine, Pandemic, Obstetrics, business.industry, SARS-CoV-2, co-morbidities, COVID-19, maternal death, neonatal outcomes, pregnancy, Asthma, Diabetes, Gestational, Female, Infant, Newborn, Postpartum Period, Maternal Death, Maternal Mortality, Obstetrics and Gynecology, General Medicine, medicine.disease, Confidence interval, Gestational diabetes, Relative risk, Pregnancy Complications, Infectiou, Maternal death, business, Postpartum period, Human
Abstract: Background: Besides reducing the quality of obstetric care, the direct impact of COVID-19 on pregnancy and postpartum is uncertain. Objective: To evaluate the characteristics of pregnant women who died due to COVID-19. Search strategy: Cochrane Library, Embase, MEDLINE, Scopus, and Google Scholar were searched from inception to February 2021. Selection criteria: Studies that compared deceased and survived pregnant women with COVID-19. Data collection and analysis: Relevant data were extracted and tabulated. The primary outcome was maternal co-morbidity. Main results: Thirteen studies with 154 deceased patients were included. Obesity doubled the risk of death (relative risk [RR] 2.48, 95% confidence interval [CI] 1.41–4.36, I2=0%). No differences were found for gestational diabetes (RR 5.71; 95% CI 0.77–42.44, I2=94%) or asthma (RR 2.05, 95% CI 0.81–5.15, I2=0%). Overall, at least one severe co-morbidity showed a twofold increased risk of death (RR 2.26, 95% CI 1.77–2.89, I2=76%). Admission to intensive care was related to a fivefold increased risk of death (RR 5.09, 95% CI 2.00–12.98, I2=56%), with no difference in need for respiratory support (RR 0.53, 95% CI 0.23–1.48, I2=95%) or mechanical ventilation (RR 4.34, 95% CI 0.96–19.60, I2=58%). Conclusion: COVID-19 with at least one co-morbidity increases risk of intensive care and mortality.
Published: 2021

43. Reproductive and pregnancy outcomes following embryo transfer in women with previous cesarean section: A systematic review and meta-analysis

Author: Giuliana Narciso, Nicola Colacurci, Gaetano Riemma, Maddalena Morlando, Marco Torella, Marco La Verde, Pasquale De Franciscis, Luigi Cobellis, Riemma, G., De Franciscis, P., Torella, M., Narciso, G., La Verde, M., Morlando, M., Cobellis, L., and Colacurci, N.
Subjects: medicine.medical_specialty, medicine.medical_treatment, Subgroup analysis, medicine, Humans, Pregnancy, fresh embryo transfer, In vitro fertilisation, Vaginal delivery, Obstetrics, business.industry, Cesarean Section, Pregnancy Outcome, assisted reproduction, Obstetrics and Gynecology, General Medicine, medicine.disease, Embryo Transfer, Embryo transfer, perinatal outcome, Meta-analysis, Relative risk, previous cesarean delivery, Female, frozen embryo transfer, pregnancy, business, Live birth, Infertility, Female, in vitro fertilization
Abstract: Introduction: Cesarean section affects subsequent spontaneous pregnancies because of implantation issues. However, its impact on post-embryo transfer pregnancies is still debated. This review aimed to evaluate the impact of a previous cesarean section on fertility and pregnancy outcomes of women undergoing fresh or frozen embryo transfer. Material and methods: MEDLINE, Scopus, ClinicalTrials.gov, Scielo, EMBASE, Cochrane Library at the CENTRAL, and LILACS were searched from inception to February 2021. Studies were included if they evaluated reproductive or pregnancy outcomes after fresh or frozen embryo transfer in infertile women with a previous cesarean section relative to women with a previous vaginal delivery. Random-effect meta-analyses to calculate risk ratio (RR) or mean differences with 95% confidence intervals (CI) followed by subgroup analysis for fresh and frozen embryo transfer were performed. Risk of bias and quality assessment were conducted using Newcastle–Ottawa scale and GRADE criteria. The review was registered in the International Prospective Register of Systematic Reviews (CRD42021226297). Results: Ten studies, with data provided for 13696 participants, were eligible. For embryo transfers after cesarean section, compared with vaginal delivery, there was a significant reduction of the live birth rate (RR 0.88, 95% CI 0.79–0.99) and biochemical pregnancy rate (RR 0.89, 95% CI 0.82–0.96). No statistically significant differences were found for clinical pregnancy rate (RR 0.92, 95% CI 0.84–1.02), ectopic pregnancies (RR 1.00, 95% CI 0.68–1.46), pregnancy loss (RR 1.05, 95% CI 0.94–1.18), multiple pregnancies (RR 0.80, 95% CI 0.63–1.02), stillbirths (RR 0.86, 95% CI 0.27–2.69), birth defects (RR 1.71, 95% CI 0.49–5.96) or birthweight (mean difference 46.82, 95% CI −40.16 to 133.80). Subgroup analysis revealed an increased risk for preterm birth in post-cesarean section fresh embryo transfer pregnancies (RR 1.59, 95% CI 1.16–2.19). Conclusions: Low-grade evidence shows that post-embryo transfer pregnancies in infertile women who had a previous cesarean delivery result in reduced biochemical pregnancy and live birth rates relative to women with a previous vaginal delivery. An increased risk for preterm birth is notable in post-fresh embryo transfer pregnancies.
Published: 2021

44. Usefulness of atosiban for tocolysis during external cephalic version: Systematic review and meta-analysis

Author: Marco La Verde, Antonio Schiattarella, Fabiana Savoia, Maddalena Morlando, Nicola Colacurci, Pasquale De Franciscis, Luigi Cobellis, Gaetano Riemma, Stefano Cianci, Riemma, G., Schiattarella, A., La Verde, M., Cianci, S., Savoia, F., De Franciscis, P., Cobellis, L., Colacurci, N., and Morlando, M.
Subjects: medicine.medical_specialty, medicine.medical_treatment, Tractocile, Tocolysis, Atosiban, External cephalic version, Vaginal delivery, Cesarean Section, Female, Humans, Pregnancy, Vasotocin, Breech Presentation, Version, Fetal, Tocolysi, medicine, Obstetrics, business.industry, Cephalic presentation, Obstetrics and Gynecology, Confidence interval, Reproductive Medicine, Relative risk, Gestation, Apgar score, business, medicine.drug
Abstract: Introduction Breech/transverse presentation is responsible for about 30–50 % of cesarean sections in the world. Cesarean section carries a five-fold greater morbidity than vaginal delivery, deeply impacting on women’s health. External Cephalic Version (ECV) is an external manipulation used to convert a non-cephalic to a cephalic presentation. The use of tocolysis might facilitate this procedure; however, it is still controversial which drug should be considered as first choice. Objective To assess the effectiveness of tocolysis with atosiban, a competitive oxytocin receptor antagonist, in order to increase the rate of successful ECV. Study design Nine databases (including MEDLINE, CINAHL, LILACS, EMBASE, Scopus, ClinicalTrials.gov, Scielo, PROSPERO, Cochrane at CENTRAL) were searched from the inception to August 2020 using a combination of MeSH terms and keywords regarding “atosiban” and “external cephalic version”. We included trials of women with a singleton pregnancy who reached at least 36 weeks of gestation and were scheduled to ECV and tocolysis with atosiban (intervention group) compared to beta-agonists or other drugs (control group). The primary outcome was the incidence of successful ECV. Summary measures were reported as relative risk (RR) with 95 % confidence interval (CI). Data collection and analysis Four studies (1534 women) were eligible for analysis. ECV success rate was significantly lower in women randomized to atosiban (36.7 % vs 45.3 %; RR 0.78 [95 % CI 0.6 to 0.98]). Cesarean section and vaginal delivery rates did not differ between intervention and control group ((59.8 % vs 52.6 %; RR 1.17 [0.98–1.38] and (38.6 % vs 45.0 %; RR 0.83 [95 % CI 0.69–1.01] respectively). Cephalic (36.9 % vs 44.6 %; RR 0.81 [95 % CI 0.65 to 1.01], or breech/transverse presentation at labor (63.4 % vs 55.1 %; RR 1.18 [95 % CI 0.99–1.40]), APGAR score less than 7 at 5 min (1.6 % vs 2.0 %; RR 1.14 [95 % CI 0.27–4.73], NICU admissions (44.2 % vs 48.1 %; RR 0.92 [95 % CI 0.58–1.46] and Umbilical cord pH were similar in both groups. Drug-related side effects were lower in women randomized to atosiban, compared with control group (16.0 % vs 42.9 %; RR 0.38 [95 % CI 0.31 to 0.47]. Conclusion The use of atosiban for tocolysis does not improve the rate of successful ECVs when compared to beta-agonists. However, atosiban was associated with a significantly lower incidence of side effects and comparable cesarean section rates.
Published: 2021

45. Emerging Role for Linear and Circular Spermine Oxidase RNAs in Skeletal Muscle Physiopathology

Author: Giulia Baroli, Roberta Ceci, Cristiana Valle, Irene Bozzoni, Jonathan Fernando Reinoso-Sánchez, Paolo Mariottini, Silvia Scaricamazza, Robert Anthony Casero Casero, Mariangela Morlando, Manuela Cervelli, Stefania Sabatini, Guglielmo Duranti, Reinoso-Sanchez, J. F., Baroli, G., Duranti, G., Scaricamazza, S., Sabatini, S., Valle, C., Morlando, M., Casero, R. A., Bozzoni, I., Mariottini, P., Ceci, R., and Cervelli, M.
Subjects: Male, RNA, Untranslated, Muscle Fibers, Skeletal, lcsh:Chemistry, Mice, Superoxide Dismutase-1, circRNA, Amyotrophic lateral sclerosis, lcsh:QH301-705.5, Spectroscopy, Cells, Cultured, Oxidoreductases Acting on CH-NH Group Donors, Myogenesis, Cell Differentiation, General Medicine, Muscle atrophy, Computer Science Applications, Cell biology, CircRNA, Muscular Atrophy, medicine.anatomical_structure, Spermine oxidase, Female, medicine.symptom, C2C12, Mice, Transgenic, Biology, Catalysis, Article, Inorganic Chemistry, Atrophy, skeletal muscle atrophy, amyotrophic lateral sclerosis murine models, medicine, Animals, RNA, Messenger, Physical and Theoretical Chemistry, spermine oxidase, Muscle, Skeletal, Molecular Biology, Amyotrophic lateral sclerosis murine model, Organic Chemistry, Amyotrophic Lateral Sclerosis, Skeletal muscle, RNA, RNA, Circular, medicine.disease, Mice, Inbred C57BL, Disease Models, Animal, lcsh:Biology (General), lcsh:QD1-999, RNA-Binding Protein FUS, Skeletal muscle atrophy
Abstract: Skeletal muscle atrophy is a pathological condition so far without eective treatment and poorly understood at a molecular level. Emerging evidence suggest a key role for circular RNAs (circRNA) during myogenesis and their deregulation has been reported to be associated with muscle diseases. Spermine oxidase (SMOX), a polyamine catabolic enzyme plays a critical role in muscle dierentiation and the existence of a circRNA arising from SMOX gene has been recently identified. In this study, we evaluated the expression profile of circular and linear SMOX in both C2C12 dierentiation and dexamethasone-induced myotubes atrophy. To validate our findings in vivo their expression levels were also tested in two murine models of amyotrophic lateral sclerosis: SOD1G93A and hFUS+/+, characterized by progressive muscle atrophy. During C2C12 dierentiation, linear and circular SMOX show the same trend of expression. Interestingly, in atrophy circSMOX levels significantly increased compared to the physiological state, in both in vitro and in vivo models. Our study demonstrates that SMOX represents a new player in muscle physiopathology and provides a scientific basis for further investigation on circSMOX RNA as a possible new therapeutic target for the treatment of muscle atrophy.
Published: 2020
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46. The impact of obesity on haemodynamic profiles of pregnant women beyond 34 weeks’ gestation

Author: Supreet Sidhu, Pasquale Martinelli, Maddalena Morlando, Maurizio Guida, Giuseppe Maria Maruotti, Antonia Giudicepietro, Laura Sarno, Marta Campanile, Annunziata Carlea, Sarno, L., Morlando, M., Giudicepietro, A., Carlea, A., Sidhu, S., Campanile, M., Maruotti, G. M., Martinelli, P., Guida, M., Sarno, Laura, Morlando, Maddalena, Giudicepietro, Antonia, Carlea, Annunziata, Sidhu, Supreet, Campanile, Marta, Maruotti, Giuseppe Maria, Martinelli, Pasquale, and Guida, Maurizio
Subjects: Adult, Body surface area, medicine.medical_specialty, Cardiac output, Pregnancy Trimester, Third, Cardiac index, Hemodynamics, 030204 cardiovascular system & hematology, Body Mass Index, 03 medical and health sciences, 0302 clinical medicine, Pregnancy, Internal medicine, Internal Medicine, medicine, Humans, Prospective Studies, Obesity, Cardiac Output, Hypertensive disorder of pregnancy, 030219 obstetrics & reproductive medicine, business.industry, Obstetrics and Gynecology, Stroke volume, Hypertension, Pregnancy-Induced, medicine.disease, Haemodynamic, Prospective Studie, medicine.anatomical_structure, Case-Control Studies, Vascular resistance, Cardiology, Gestation, Female, Vascular Resistance, business, Case-Control Studie, Human
Abstract: Objective: We aimed to compare the haemodynamic profiles of obese and non-obese pregnant women, alongside describing the haemodynamic changes that occur in hypertensive disorders of pregnancies with an Appropriate for Gestational Age Fetus (HDP-AGA) beyond 34 weeks' gestation.Study design: In this prospective case-control study, maternal haemodynamic assessment was carried out by a trained operator using an UltraSonic Cardiac Output Monitor during a routine clinical assessment after 34 weeks of gestation. Indexed and non-indexed parameters were evaluated.Main outcome measures: Maternal hemodynamic parameters.Results: Obese and non-obese women did not differ for non-indexed parameters (Cardiac Output, Stroke Volume, Systemic Vascular Resistance). Using indexed parameters, corrected for Body Surface Area, obese women presented significantly lower Cardiac Index z-score (-0.23 +/- 0.5 vs 0.26 +/- 1.2; p = 0.004), Stroke Volume Index z-score (-0.27 +/- 0.8 vs 0.31 +/- 1.0; p < 0.0001) and significantly higher Systemic Vascular Resistance Index (0.16 +/- 0.8 vs -0.36 +/- 0.7; p < 0.0001). In obese women, HDP-AGA (n = 19) had significantly higher Systemic Vascular Resistance Index z-score (1.26 +/- 1.7 vs 0.16 +/- 0.8; P = 0.009) and significantly lower Stroke Volume Index (-0.68 +/- 0.8 vs -0.27 +/- 0.8; 0.049).Conclusion: Using indexed parameters, differences in haemodynamic profiles between obese and non obese women can be highlighted. Obese women seem to present a cardiac maladapation to the pregnancy (reduced cardiac index and stroke volume and increased vascular resistance) that could explain the increased risk of complications in this subgroup.
Published: 2020

47. Fetal cerebral and umbilical Doppler in pregnancies complicated by late-onset placental abruption

Author: José Morales-Roselló, Janani Sivanathan, Silvia Salvi, Farida Akhoundova, Asma Khalil, Basky Thilaganathan, Alfredo Perales-Marín, David Hervas-Marín, José Alberola-Rubio, Victoria Fornés-Ferrer, Maddalena Morlando, Morales-Rosello, J., Khalil, A., Akhoundova, F., Salvi, S., Morlando, M., Sivanathan, J., Alberola-Rubio, J., Hervas-Marin, D., Fornes-Ferrer, V., Perales-Marin, A., and Thilaganathan, B.
Subjects: Adult, Male, Middle Cerebral Artery, medicine.medical_specialty, Logistic Model, Birth weight, Fetal middle cerebral artery Doppler, Reproducibility of Result, late-onset fetal growth restriction, Gestational Age, Logistic regression, Ultrasonography, Prenatal, Umbilical Arteries, 03 medical and health sciences, Fetus, 0302 clinical medicine, Retrospective Studie, Pregnancy, medicine.artery, medicine, Birth Weight, Humans, Fetu, 030212 general & internal medicine, Abruptio Placentae, Retrospective Studies, umbilical artery Doppler, 030219 obstetrics & reproductive medicine, Placental abruption, business.industry, Obstetrics, Infant, Newborn, Reproducibility of Results, Obstetrics and Gynecology, Gestational age, Umbilical artery, medicine.disease, placental abruption, Umbilical Arterie, Logistic Models, Case-Control Studies, Pediatrics, Perinatology and Child Health, Middle cerebral artery, Female, Case-Control Studie, business, Human
Abstract: Objective: To evaluate whether changes in the cerebroplacental Doppler and birth weight (BW) suggestive of chronic fetal hypoxemia, precede the development of late-onset placental abruption (PA) after 32 weeks. Methods: In a multicenter retrospective study, the Doppler examinations of the fetal umbilical artery (UA) and middle cerebral artery (MCA) recorded after 32 weeks were collected in pregnancies subsequently developing PA. The BW centiles were calculated and the MCA pulsatility indices (PI), and UA PI were converted into multiples of the median (MoM). Afterwards, a comparison was made with a group of fetuses, which did not develop PA. Logistic regression was used to adjust for potential confounders and evaluate the feasibility of the prediction model. Results: Pregnancies complicated by late-onset PA (n = 31) presented lower MCA PI (p = 0.015) and were smaller (p < 0.001) than those who did not (n = 1294). Logistic regression analysis indicated that cerebral vasodilation was more important than umbilical flow in the explanation of PA (MCA PI OR = 0.106, p = 0.014 and UA PI OR 1.901, p = 0.32). In addition, the influence of BW exerted was residual (BW centile OR = 0.989, p = 0.15). Conclusions: Fetuses developing late-onset PA demonstrate significant cerebral vasodilation with scarce placental dysfunction, suggesting the existence of some kind of chronic hypoxemia that follows the late-onset pattern.
Published: 2016

48. Diagnostic accuracy of magnetic resonance imaging in assessing placental adhesion disorder in patients with placenta previa: Correlation with histological findings

Author: Mario Petretta, G. Frauenfelder, Arturo Brunetti, P.P. Mainenti, Simone Maurea, M. I. Ginocchio, Maddalena Morlando, Valeria Romeo, Raffaele Liuzzi, Francesco Verde, Maria D'Armiento, Laura Sarno, Pasquale Martinelli, Maurea, S., Romeo, V., Mainenti, P. P., Ginocchio, M. I., Frauenfelder, G., Verde, Francesco, Liuzzi, R., D'Armiento, M., Sarno, L., Morlando, M., Petretta, M., Martinelli, P., Brunetti, A., Verde, F., Liuzzi, Rosa, and Morlando, Maddalena
Subjects: Prenatal Diagnosi, Adult, Radiology, Nuclear Medicine and Imaging, Placenta, Placenta Previa, Reproducibility of Result, Adhesion (medicine), Placenta Accreta, Focal interruption of myometrial border, 030218 nuclear medicine & medical imaging, Correlation, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Vascularity, Pregnancy, Prenatal Diagnosis, Medicine, Humans, In patient, Magnetic resonance imaging (MRI), Prospective Studies, 030219 obstetrics & reproductive medicine, medicine.diagnostic_test, Receiver operating characteristic, business.industry, Ultrasound, Reproducibility of Results, Magnetic resonance imaging, General Medicine, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Placenta previa, Prospective Studie, Myometrium, Intraplacental dark band, Female, medicine.symptom, business, Nuclear medicine, Human, Placental adhesion disorder (PAD)
Abstract: Objective: To evaluate MRI accuracy in assessing placental adhesion disorders (PAD) in patients with placenta previa correlating imaging results with histological findings. Materials and methods: Sixty-one patients who underwent abdomino-pelvic magnetic resonance imaging (MRI) for ultrasound suspicion of PAD were prospectively evaluated. T1- and T2-weighted images, with and without fat suppression, were obtained in the three conventional planes using a 1.5 T MRI scanner. MRI accuracy to evaluate the presence of PAD was assessed on the basis of the occurrence of the following abnormal MRI signs: 1) intraplacental dark bands; 2) focal interruption of myometrial border; 3) intraplacental abnormal vascularity; 4) uterine bulging; 5) tenting of the bladder and/or 6) direct visualization of adjacent tissues invasion only in case of percretism. Imaging results were classified as suggestive or not of PAD using histological data as standard of reference; two methods of imaging analysis were used represented by the presence of at least one (Method A) or two (Method B) abnormal MRI signs; the correlation between the presence of each abnormal MRI sign of PAD and the corresponding histological finding was also assessed. Results: The accuracy, as the area under the receiver operating characteristic curve, was significantly (p = 0.001) higher for Method B (0.92, C.I. 95%: 0.82–0.97) compared to Method A (0.764, C.I. 95%: 0.64–0.86). Among the abnormal MRI signs, intraplacental dark bands and focal interruption of myometrial border were those highly correlated with histological proof of PAD (ρ > 0.71, p < 0.001, for both); as result, a modified version of Method B (Method C) was identified considering as criterion for PAD the combined presence of the two abnormal MRI signs highly correlated with histologically proven PAD; however, the accuracy of Method C was significantly (p = 0.005) lower (0.80, C.I. 95%: 0.67–0.89) than Method B and comparable to Method A. Conclusions: MRI is a useful imaging technique to assess PAD in patients with placenta previa; in particular, the presence of at least two among all the abnormal MRI signs represents the most accurate criterion (Method B) to identify PAD. Although intraplacental dark bands and focal interruption of myometrial border showed the highest correlation with histological proof of PAD as well as this association was the most frequent in PAD, the combination of these latter MRI signs along with other abnormal signs should be considered diagnostic for PAD.
Published: 2018

49. The association between prenatal atrioventricular septal defects and chromosomal abnormalities

Author: José Morales-Roselló, Asma Khalil, Alessandra Familiari, A T Papageorghiou, Julene S. Carvalho, Maddalena Morlando, Amarnath Bhide, Morlando, M., Bhide, A., Familiari, A., Khalil, A., Morales-Rosello, J., Papageorghiou, A. T., and Carvalho, J. S.
Subjects: Trisomy 21, Tertiary Care Center, Chromosome Disorders, Screening Result, Tertiary Care Centers, 0302 clinical medicine, Pregnancy, Prenatal Diagnosis, London, Prevalence, Electronic Health Records, Atrioventricular Septal Defect, Genetics, 030219 obstetrics & reproductive medicine, First trimester risk, Obstetrics, Pregnancy Outcome, Obstetrics and Gynecology, Pregnancy Trimester, Second, Electronic Health Record, Heart Septal Defect, Female, Low risk group, AVSD, Human, Adult, Risk, medicine.medical_specialty, Atrioventricular septal defect, Chromosomal abnormalitie, Ultrasonography, Prenatal, Follow-Up Studie, 03 medical and health sciences, Combined risk, Second trimester, 030225 pediatrics, Chromosomal Abnormality, medicine, Humans, Abnormalities, Multiple, Genetic Testing, Fetus, business.industry, Heart Septal Defects, medicine.disease, Aneuploidy, First trimester, Pregnancy Trimester, First, Chromosome Disorder, Reproductive Medicine, Karyotyping, Down Syndrome, Trisomy, business, Follow-Up Studies
Abstract: Objectives Atrioventricular septal defect is associated with a high risk of a chromosomal abnormality, particularly trisomy 21. The aim of this study is to assess the rate of trisomy 21 in fetuses diagnosed with an atrioventricular septal defect and to examine the influence of prior screening on the rate of trisomy 21. Methods Electronic ultrasound database was searched to identify fetuses diagnoses with an atrioventricular septal defect from 2002 to 2014. Rate of trisomy 21 and other aneuploidies was calculated among fetuses with normal situs. The prevalence of trisomy 21 and other aneuploidies was assessed in women with low and high first trimester risk for trisomy 21, using a cut-off value of 1:150 and 1:250. Results total 110 fetuses with a diagnosis of atrioventricular septal defect were identified. Among the 98 fetuses with normal situs, the prevalence of trisomy 21 was 46% (95% CI: 36–56%). Using a 1:150 threshold, the rate of trisomy 21 within the low-risk group was 41% (95% CI: 27–57%) while in the high-risk group it was 70% (95% CI: 52–83%), significantly higher than in the low risk group (p = 0.028). Similar results were obtained when the 1:250 threshold was applied (66% versus 41%, p = 0.055). Conclusions The rate of trisomy 21 among fetuses identified with an atrioventricular septal defect in the second trimester is high even in those that undergo first trimester combined screening. Some fetuses with a high-risk screening result show a normal karyotype. Therefore, an offer of an invasive procedure to check fetal karyotyping is indicated. Knowledge of these rates may be helpful for parents in the decision making process.
Published: 2018

50. Response to Letter Regarding Article, 'Risk Factors for Coarctation of the Aorta on Prenatal Ultrasound: A Systematic Review and Meta-Analysis'

Author: Maddalena Morlando, Alessandra Familiari, Giuseppe Rizzo, Sven-Erik Sonesson, Ganesh Acharya, Francesco D'Antonio, Lamberto Manzoli, Familiari, A., Morlando, M., Sonesson, S. -E., Rizzo, G., Acharya, G., Manzoli, L., and D'Antonio, F.
Subjects: medicine.medical_specialty, Weakness, Coarctation of the aorta, 030204 cardiovascular system & hematology, Aortic Coarctation, Ultrasonography, Prenatal, 03 medical and health sciences, Prenatal ultrasound, 0302 clinical medicine, Pregnancy, Risk Factors, Physiology (medical), medicine.artery, Internal medicine, Ascending aorta, medicine, Humans, Aorta, 030219 obstetrics & reproductive medicine, business.industry, Risk Factor, medicine.disease, Surgery, Meta-analysis, Cardiology, Settore MED/40 - Ginecologia e Ostetricia, Female, medicine.symptom, Cardiology and Cardiovascular Medicine, business, Human
Abstract: We thank Ceylan for his interest in our work and the interesting points he raised. We agree that the size of the ascending aorta did not signal coarctation (CoA) because of problems associated with diameter measurements (which are frequently measured on long-axis images) and the small number of cases included. We acknowledge this major weakness of our systematic review.1 Although not statistically significant, a trend toward smaller ascending aorta …
Published: 2017

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