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2,243 results on '"Biagio, A"'

1. COL1A1::PDGFB fusion-associated uterine fibrosarcoma: A case report and review of the literature.

Author

Rota, Simone, Franza, Andrea, Fabbroni, Chiara, Paolini, Biagio, Greco, Francesca, Alessi, Alessandra, Padovano, Barbara, Sanfilippo, Roberta, and Casali, Paolo

Subjects
COL1A1::PDGFB, Imatinib, fibrosarcoma, soft tissue sarcomas, translocation t(17, 22)(q22, q13), uterus, Female, Humans, Adult, Proto-Oncogene Proteins c-sis, Imatinib Mesylate, Dermatofibrosarcoma, In Situ Hybridization, Fluorescence, Leiomyosarcoma, Skin Neoplasms, Neoplasm Recurrence, Local, Fibrosarcoma, Soft Tissue Neoplasms, Translocation, Genetic, Uterus
Abstract

BACKGROUND: Mesenchymal neoplasms of the uterus encompass a diverse group of tumors, with varying characteristics and origins, collectively accounting for 8% of uterine malignancies. The most common variants include uterine leiomyosarcoma, low-grade and high-grade endometrial stromal sarcoma, adenosarcoma, and undifferentiated sarcoma. Clinical presentation is often nonspecific and can lead to delayed diagnosis. Uterine sarcomas are generally aggressive, resulting in poorer prognosis compared to carcinomas. Recent advances in molecular techniques, such as next-generation sequencing (NGS), have led to the identification of new subtypes of uterine sarcomas, including COL1A1::PDGFB fusion-associated fibrosarcoma, which has a specific chromosomal translocation t(17;22)(q22;q13). Imatinib, a tyrosine kinase inhibitor (TKI), is an effective treatment for dermatofibrosarcoma protuberans (DFSP), marked by this translocation. CASE: We present the case of a 42-year-old woman diagnosed with COL1A1::PDGFB fusion-associated uterine fibrosarcoma. The patient underwent total hysterectomy and excision of the tumor, initially misdiagnosed as a low-grade leiomyosarcoma. Subsequent histological examination, immunohistochemistry, and fluorescence in situ hybridization (FISH) confirmed the diagnosis. After 10 months, disease recurrence was detected, and Imatinib therapy was initiated at a dose of 400 mg daily. An allergic reaction led to a temporary discontinuation, but upon resumption with appropriate medication, a positive radiological response was observed. The patient achieved a complete remission after 2 years and is still on Imatinib treatment. CONCLUSIONS: COL1A1::PDGFB fusion-associated uterine fibrosarcoma is an extremely rare mesenchymal neoplasm. In a case we present herein, we treated a patient with imatinib as first-line medical therapy. The patient is currently in complete remission after 37 months from treatment start. To the best of our knowledge, this represents a unique observation. We also provide a detailed literature review of the published cases so far. Prospective case series are needed to further understand the natural history of these tumors and optimize treatment strategies.

Published
2024

2. Comutations and KRASG12C Inhibitor Efficacy in Advanced NSCLC.

Author

Negrao, Marcelo, Araujo, Haniel, Lamberti, Giuseppe, Cooper, Alissa, Akhave, Neal, Zhou, Teng, Delasos, Lukas, Hicks, J, Aldea, Mihaela, Minuti, Gabriele, Hines, Jacobi, Aredo, Jacqueline, Dennis, Michael, Scott, Susan, Bironzo, Paolo, Scheffler, Matthias, Christopoulos, Petros, Stenzinger, Albrecht, Riess, Jonathan, Kim, So, Goldberg, Sarah, Li, Mingjia, Wang, Qi, Qing, Yun, Ni, Ying, Do, Minh, Lee, Richard, Ricciuti, Biagio, Alessi, Joao, Wang, Jing, Resuli, Blerina, Landi, Lorenza, Tseng, Shu-Chi, Nishino, Mizuki, Digumarthy, Subba, Rinsurongkawong, Waree, Rinsurongkawong, Vadeerat, Vaporciyan, Ara, Blumenschein, George, Zhang, Jianjun, Owen, Dwight, Mountzios, Giannis, Shu, Catherine, Bestvina, Christine, Garassino, Marina, Marrone, Kristen, Gray, Jhanelle, Patel, Sandip, Cummings, Amy, Wakelee, Heather, Wolf, Juergen, Scagliotti, Giorgio, Cappuzzo, Federico, Barlesi, Fabrice, Patil, Pradnya, Drusbosky, Leylah, Gibbons, Don, Meric-Bernstam, Funda, Lee, J, Heymach, John, Hong, David, Heist, Rebecca, Awad, Mark, Skoulidis, Ferdinandos, Blakely, Collin, and Chakrabarti, Turja

Subjects
Humans, Carcinoma, Non-Small-Cell Lung, Lung Neoplasms, Kelch-Like ECH-Associated Protein 1, Phosphatidylinositol 3-Kinases, Mutation, NF-E2-Related Factor 2, DNA Helicases, Nuclear Proteins, Transcription Factors
Abstract

UNLABELLED: Molecular modifiers of KRASG12C inhibitor (KRASG12Ci) efficacy in advanced KRASG12C-mutant NSCLC are poorly defined. In a large unbiased clinicogenomic analysis of 424 patients with non-small cell lung cancer (NSCLC), we identified and validated coalterations in KEAP1, SMARCA4, and CDKN2A as major independent determinants of inferior clinical outcomes with KRASG12Ci monotherapy. Collectively, comutations in these three tumor suppressor genes segregated patients into distinct prognostic subgroups and captured ∼50% of those with early disease progression (progression-free survival ≤3 months) with KRASG12Ci. Pathway-level integration of less prevalent coalterations in functionally related genes nominated PI3K/AKT/MTOR pathway and additional baseline RAS gene alterations, including amplifications, as candidate drivers of inferior outcomes with KRASG12Ci, and revealed a possible association between defective DNA damage response/repair and improved KRASG12Ci efficacy. Our findings propose a framework for patient stratification and clinical outcome prediction in KRASG12C-mutant NSCLC that can inform rational selection and appropriate tailoring of emerging combination therapies. SIGNIFICANCE: In this work, we identify co-occurring genomic alterations in KEAP1, SMARCA4, and CDKN2A as independent determinants of poor clinical outcomes with KRASG12Ci monotherapy in advanced NSCLC, and we propose a framework for patient stratification and treatment personalization based on the comutational status of individual tumors. See related commentary by Heng et al., p. 1513. This article is highlighted in the In This Issue feature, p. 1501.

Published
2023

3. Mapping molecular landmarks of human skeletal ontogeny and pluripotent stem cell-derived articular chondrocytes.

Author

Ferguson, Gabriel B, Van Handel, Ben, Bay, Maxwell, Fiziev, Petko, Org, Tonis, Lee, Siyoung, Shkhyan, Ruzanna, Banks, Nicholas W, Scheinberg, Mila, Wu, Ling, Saitta, Biagio, Elphingstone, Joseph, Larson, A Noelle, Riester, Scott M, Pyle, April D, Bernthal, Nicholas M, Mikkola, Hanna Ka, Ernst, Jason, van Wijnen, Andre J, Bonaguidi, Michael, and Evseenko, Denis

Subjects
Chondrocytes, Osteoblasts, Myoblasts, Animals, Swine, Humans, Mice, Gene Expression Profiling, Sequence Analysis, RNA, Transcription, Genetic, Epigenesis, Genetic, Histone Code, Fetal Development, Chondrogenesis, Transcriptome, Biomarkers, Tenocytes, Sequence Analysis, RNA, Transcription, Genetic, Epigenesis, Stem Cell Research, Regenerative Medicine, Genetics, Stem Cell Research - Nonembryonic - Human, Stem Cell Research - Induced Pluripotent Stem Cell - Human, Stem Cell Research - Induced Pluripotent Stem Cell, Human Fetal Tissue, 1.1 Normal biological development and functioning, 5.2 Cellular and gene therapies, Musculoskeletal
Abstract

Tissue-specific gene expression defines cellular identity and function, but knowledge of early human development is limited, hampering application of cell-based therapies. Here we profiled 5 distinct cell types at a single fetal stage, as well as chondrocytes at 4 stages in vivo and 2 stages during in vitro differentiation. Network analysis delineated five tissue-specific gene modules; these modules and chromatin state analysis defined broad similarities in gene expression during cartilage specification and maturation in vitro and in vivo, including early expression and progressive silencing of muscle- and bone-specific genes. Finally, ontogenetic analysis of freshly isolated and pluripotent stem cell-derived articular chondrocytes identified that integrin alpha 4 defines 2 subsets of functionally and molecularly distinct chondrocytes characterized by their gene expression, osteochondral potential in vitro and proliferative signature in vivo. These analyses provide new insight into human musculoskeletal development and provide an essential comparative resource for disease modeling and regenerative medicine.

Published
2018

4. Surgery or Peroral Esophageal Myotomy for Achalasia

Author

Marano, Luigi, Pallabazzer, Giovanni, Solito, Biagio, Santi, Stefano, Pigazzi, Alessio, De Luca, Raffaele, Biondo, Francesco Giuseppe, Spaziani, Alessandro, Longaroni, Maurizio, Di Martino, Natale, Boccardi, Virginia, and Patriti, Alberto

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Patient Safety, Digestive Diseases, 6.4 Surgery, Evaluation of treatments and therapeutic interventions, Esophageal Achalasia, Esophageal Sphincter, Lower, Humans, Laparoscopy, Mouth, Natural Orifice Endoscopic Surgery, Treatment Outcome
Abstract

To date very few studies with small sample size have compared peroral esophageal myotomy (POEM) with the current surgical standard of care, laparoscopic Heller myotomy (LHM), in terms of efficacy and safety, and no recommendations have been proposed.To investigate the efficacy and safety of POEM compared with LHM, for the treatment of achalasia.The databases of Pubmed, Medline, Cochrane, and Ovid were systematically searched between January 1, 2005 and January 31, 2015, with the medical subject headings (MeSH) and keywords "achalasia," "POEM," "per oral endoscopic myotomy," and "peroral endoscopic myotomy," "laparoscopic Heller myotomy" (LHM), "Heller myotomy."All types of study designs including adult patients with diagnosis of achalasia were selected. Studies that did not report the comparison between endoscopic and surgical treatment, experimental studies in animal models, single case reports, technical reports, reviews, abstracts, and editorials were excluded.The total number of included patients was 486 (196 in POEM group and 290 in LHM group).There were no differences between POEM and LHM in reduction in Eckardt score (MD = -0.659, 95% CI: -1.70 to 0.38, P = 0.217), operative time (MD = -0.354, 95% CI: -1.12 to 0.41, P = 0.36), postoperative pain scores (MD = -1.86, 95% CI: -5.17 to 1.44, P = 0.268), analgesic requirements (MD = -0.74, 95% CI: -2.65 to 1.16, P = 0.445), and complications (OR = 1.11, 95% CI: 0.5-2.44, P = 0.796). Length of hospital stay was significantly lower for POEM (MD = -0.629, 95% CI: -1.256 to -0.002, P = 0.049). There was a trend toward significant reduction in symptomatic gastroesophageal reflux rate in favors of LHM compared to POEM group (OR = 1.81, 95% CI: 1.11-2.95, P = 0.017).All included studied were not randomized. Furthermore all selected studies did not report the results of follow-up longer than 1 year and most of them included patients who were both treatment naive and underwent previous endoscopic or surgical interventions for achalasia.POEM represents a safe and efficacy procedure comparable to the safety profile of LHM for achalasia at a short-term follow-up. Long-term clinical trials are urgently needed.

Published
2016

5. Glycolysis controls the induction of human regulatory T cells by modulating the expression of FOXP3 exon 2 splicing variants

Author

De Rosa, Veronica, Galgani, Mario, Porcellini, Antonio, Colamatteo, Alessandra, Santopaolo, Marianna, Zuchegna, Candida, Romano, Antonella, De Simone, Salvatore, Procaccini, Claudio, La Rocca, Claudia, Carrieri, Pietro Biagio, Maniscalco, Giorgia Teresa, Salvetti, Marco, Buscarinu, Maria Chiara, Franzese, Adriana, Mozzillo, Enza, La Cava, Antonio, and Matarese, Giuseppe

Subjects
Genetics, Aetiology, 2.1 Biological and endogenous factors, Adult, Alternative Splicing, Autoimmunity, Biomarkers, Tumor, CD4-Positive T-Lymphocytes, Case-Control Studies, DNA-Binding Proteins, Exons, Fatty Acids, Female, Forkhead Transcription Factors, Gene Knockdown Techniques, Genetic Variation, Glycolysis, Humans, In Vitro Techniques, Male, Metabolome, Middle Aged, Multiple Sclerosis, Relapsing-Remitting, Oxidation-Reduction, Phosphopyruvate Hydratase, RNA, Messenger, Receptors, Antigen, T-Cell, Signal Transduction, T-Lymphocytes, Regulatory, Tumor Suppressor Proteins, Young Adult, Immunology
Abstract

Human regulatory T cells (T(reg) cells) that develop from conventional T cells (T(conv) cells) following suboptimal stimulation via the T cell antigen receptor (TCR) (induced T(reg) cells (iT(reg) cells)) express the transcription factor Foxp3, are suppressive, and display an active proliferative and metabolic state. Here we found that the induction and suppressive function of iT(reg) cells tightly depended on glycolysis, which controlled Foxp3 splicing variants containing exon 2 (Foxp3-E2) through the glycolytic enzyme enolase-1. The Foxp3-E2-related suppressive activity of iT(reg) cells was altered in human autoimmune diseases, including multiple sclerosis and type 1 diabetes, and was associated with impaired glycolysis and signaling via interleukin 2. This link between glycolysis and Foxp3-E2 variants via enolase-1 shows a previously unknown mechanism for controlling the induction and function of T(reg) cells in health and in autoimmunity.

Published
2015

6. Two years later: Is the SARS-CoV-2 pandemic still having an impact on emergency surgery? An international cross-sectional survey among WSES members

Author

Reichert, Martin, Sartelli, Massimo, Weigand, Markus A, Hecker, Matthias, Oppelt, Philip U, Noll, Julia, Askevold, Ingolf H, Liese, Juliane, Padberg, Winfried, Coccolini, Federico, Catena, Fausto, Hecker, Andreas, Adam Peckham-Cooper, Adrian Camacho-Ortiz, Aikaterini T. Mastoraki, Aitor Landaluce-Olavarria, Ajay Kumar Pal, Akira Kuriyama, Alain Chichom-Mefire, Alberto Porcu, Aleix Martínez-Pérez, Aleksandar R. Karamarkovic, Aleksei V. Osipov, Alessandro Coppola, Alessandro Cucchetti, Alessandro Spolini, Alessio Giordano, Alexander Reinisch-Liese, Alfie J. Kavalakat, Alin Vasilescu, Amin Alamin, Amit Gupta, Ana Maria Dascalu, Ana-Maria Musina, Anargyros Bakopoulos, Andee Dzulkarnaen Zakaria, Andras Vereczkei, Andrea Balla, Andrea Bottari, Andreas Baumann, Andreas Fette, Andrey Litvin, Aniella Katharina Reichert, Anna Guariniello, Anna Paspala, Anne-Sophie Schneck, Antonio Brillantino, Antonio Pesce, Arda Isik, Ari Kalevi Leppäniemi, Aristeidis Papadopoulos, Aristotelis Kechagias, Ashraf Yehya Abdalla Mohamed, Ashrarur Rahman Mitul, Athanasios Marinis, Athanasios Syllaios, Baris Mantoglu, Belinda De Simone, Benjamin Stefan Weiss, Bernd Pösentrup, Biagio Picardi, Biagio Zampogna, Boris Eugeniev Sakakushev, Boyko Chavdarov Atanasov, Bruno Nardo, Bulent Calik, Camilla Cremonini, Carlos A. Ordoñez, Charalampos Seretis, Chiara Cascone, Christos Chouliaras, Cino Bendinelli, Claudia Lopes, Claudio Guerci, Clemens Weber, Constantinos Nastos, Cristian Mesina, Damiano Caputo, Damien Massalou, Davide Cavaliere, Deborah A. McNamara, Demetrios Demetriades, Desirè Pantalone, Diego Coletta, Diego Sasia, Diego Visconti, Dieter G. Weber, Diletta Corallino, Dimitrios Chatzipetris, Dimitrios K. Manatakis, Dimitrios Ntourakis, Dimitrios Papaconstantinou, Dimitrios Schizas, Dimosthenis Chrysikos, Dmitry Mikhailovich Adamovich, Doaa Elkafrawy, Dragos Seban, Edgar Fernando Hernandez García, Edoardo Baldini, Edoardo Picetti, Edward C. T. H. Tan, Efstratia Baili, Eftychios Lostoridis, Elena Adelina Toma, Elif Colak, Elisabetta Cerutti, Elmin Steyn, Elmuiz A. Hsabo, Emmanouil Ioannis Kapetanakis, Emmanouil Kaouras, Emmanuel Schneck, Emrah Akin, Emre Gonullu, Enes çelik, Enrico Cicuttin, Enrico Pinotti, Erik Johnsson, Ernest E. Moore, Ervis Agastra, Evgeni Nikolaev Dimitrov, Ewen A. Griffiths, Fabrizio D’Acapito, Federica Saraceno, Felipe Alconchel, Felix Alexander Zeppernick, Fernando Machado Rodríguez, Fikri Abu-Zidan, Francesca Pecchini, Francesco Favi, Francesco Ferrara, Francesco Fleres, Francesco Pata, Francesco Pietro Maria Roscio, Francesk Mulita, Frank J. M. F. Dor, Fredrik Linder, Gabriel Dimofte, Gabriel Rodrigues, Gabriela Nita, Gabriele Sganga, Gennaro Martines, Gennaro Mazzarella, Gennaro Perrone, George Velmahos, Georgios D. Lianos, Gia Tomadze, Gian Luca Baiocchi, Giancarlo D’Ambrosio, Gianluca Pellino, Gianmaria Casoni Pattacini, Giorgio Giraudo, Giorgio Lisi, Giovanni Domenico Tebala, Giovanni Pirozzolo, Giulia Montori, Giulio Argenio, Giuseppe Brisinda, Giuseppe Currò, Giuseppe Giuliani, Giuseppe Palomba, Giuseppe Roscitano, Gökhan Avşar, Goran Augustin, Guglielmo Clarizia, Gustavo M. Machain Vega, Gustavo P. Fraga, Harsheet Sethi, Hazim Abdulnassir Eltyeb, Helmut A. Segovia Lohse, Herald René Segovia Lohse, Hüseyin Bayhan, Hytham K. S. Hamid, Igor A. Kryvoruchko, Immacolata Iannone, Imtiaz Wani, Ioannis I. Lazaridis, Ioannis Katsaros, Ioannis Nikolopoulos, Ionut Negoi, Isabella Reccia, Isidoro Di Carlo, Iyiade Olatunde Olaoye, Jacek Czepiel, Jae Il Kim, Jeremy Meyer, Jesus Manuel Saenz Terrazas, Joel Noutakdie Tochie, Joseph M. Galante, Justin Davies, Kapil Sugand, Kebebe Bekele Gonfa, Kemal Rasa, Kenneth Y. Y. Kok, Konstantinos G. Apostolou, Konstantinos Lasithiotakis, Konstantinos Tsekouras, Kumar Angamuthu, Lali Akhmeteli, Larysa Sydorchuk, Laura Fortuna, Leandro Siragusa, Leonardo Pagani, Leonardo Solaini, Lisa A. Miller, Lovenish Bains, Luca Ansaloni, Luca Ferrario, Luigi Bonavina, Luigi Conti, Luis Antonio Buonomo, Luis Tallon-Aguilar, Lukas Tomczyk, Lukas Werner Widmer, Maciej Walędziak, Mahir Gachabayov, Maloni M. Bulanauca, Manu L. N. G. Malbrain, Marc Maegele, Marco Catarci, Marco Ceresoli, Maria Chiara Ranucci, Maria Ioanna Antonopoulou, Maria Papadoliopoulou, Maria Rosaria Valenti, Maria Sotiropoulou, Mario D’Oria, Mario Serradilla Martín, Markus Hirschburger, Massimiliano Veroux, Massimo Fantoni, Matteo Nardi, Matti Tolonen, Mauro Montuori, Mauro Podda, Maximilian Scheiterle, Maximos Frountzas, Mehmet Sarıkaya, Mehmet Yildirim, Michael Bender, Michail Vailas, Michel Teuben, Michela Campanelli, Michele Ammendola, Michele Malerba, Michele Pisano, Mihaela Pertea, Mihail Slavchev, Mika Ukkonen, Miklosh Bala, Mircea Chirica, Mirko Barone, Mohamed Maher Shaat, Mohammed Jibreel Suliman Mohammed, Mona Awad Akasha Abuelgasim, Monika Gureh, Mouaqit Ouadii, Mujdat Balkan, Mumin Mohamed, Musluh Hakseven, Natalia Velenciuc, Nicola Cillara, Nicola de’Angelis, Nicolò Tamini, Nikolaos J. Zavras, Nikolaos Machairas, Nikolaos Michalopoulos, Nikolaos N. Koliakos, Nikolaos Pararas, Noel E. Donlon, Noushif Medappil, Offir Ben-Ishay, Olmi Stefano, Omar Islam, Ömer Tammo, Orestis Ioannidis, Oscar Aparicio, Oussama Baraket, Pankaj Kumar, Pasquale Cianci, Per Örtenwall, Petar Angelov Uchikov, Philip de Reuver, Philip F. Stahel, Philip S. Barie, Micaela Piccoli, Piotr Major, Pradeep H. Navsaria, Prakash Kumar Sasmal, Raul Coimbra, Razrim Rahim, Recayi Çapoğlu, Renol M. Koshy, Ricardo Alessandro Teixeira Gonsaga, Riccardo Pertile, Rifat Ramadan Mussa Mohamed, Rıza Deryol, Robert G. Sawyer, Roberta Angelico, Roberta Ragozzino, Roberto Bini, Roberto Cammarata, Rosa Scaramuzzo, Rossella Gioco, Ruslan Sydorchuk, Salma Ahmed, Salomone Di Saverio, Sameh Hany Emile, Samir Delibegovic, Sanjay Marwah, Savvas Symeonidis, Scott G. Thomas, Sebahattin Demir, Selmy S. Awad, Semra Demirli Atici, Serge Chooklin, Serhat Meric, Sevcan Sarıkaya, Sharfuddin Chowdhury, Shaza Faycal Mirghani, Sherry M. Wren, Simone Gargarella, Simone Rossi Del Monte, Sofia Esposito, Sofia Xenaki, Soliman Fayez Ghedan Mohamed, Solomon Gurmu Beka, Sorinel Lunca, Spiros G. Delis, Spyridon Dritsas, Stefan Morarasu, Stefano Magnone, Stefano Rossi, Stefanos Bitsianis, Stylianos Kykalos, Suman Baral, Sumita A. Jain, Syed Muhammad Ali, Tadeja Pintar, Tania Triantafyllou, Tarik Delko, Teresa Perra, Theodoros A. Sidiropoulos, Thomas M. Scalea, Tim Oliver Vilz, Timothy Craig Hardcastle, Tongporn Wannatoop, Torsten Herzog, Tushar Subhadarshan Mishra, Ugo Boggi, Valentin Calu, Valentina Tomajer, Vanni Agnoletti, Varut Lohsiriwat, Victor Kong, Virginia Durán Muñoz-Cruzado, Vishal G. Shelat, Vladimir Khokha, Wagih Mommtaz Ghannam, Walter L. Biffl, Wietse Zuidema, Yasin Kara, Yoshiro Kobe, Zaza Demetrashvili, Ziad A. Memish, Zoilo Madrazo, Zsolt J. Balogh, Zulfu Bayhan, Surgery, AMS - Musculoskeletal Health, Other Research, APH - Quality of Care, Reichert, Martin, Sartelli, Massimo, Weigand, Markus A, Hecker, Matthia, Oppelt, Philip U, Noll, Julia, Askevold, Ingolf H, Liese, Juliane, Padberg, Winfried, Coccolini, Federico, Catena, Fausto, Hecker, Andrea, Adam Peckham-Cooper, Adrian Camacho-Ortiz, Aikaterini T. Mastoraki, Aitor Landaluce-Olavarria, Ajay Kumar Pal, Akira Kuriyama, Alain Chichom-Mefire, Alberto Porcu, Aleix Martínez-Pérez, Aleksandar R. Karamarkovic, Aleksei V. Osipov, Alessandro Coppola, Alessandro Cucchetti, Alessandro Spolini, Alessio Giordano, Alexander Reinisch-Liese, Alfie J. Kavalakat, Alin Vasilescu, Amin Alamin, Amit Gupta, Ana Maria Dascalu, Ana-Maria Musina, Anargyros Bakopoulos, Andee Dzulkarnaen Zakaria, Andras Vereczkei, Andrea Balla, Andrea Bottari, Andreas Baumann, Andreas Fette, Andrey Litvin, Aniella Katharina Reichert, Anna Guariniello, Anna Paspala, Anne-Sophie Schneck, Antonio Brillantino, Antonio Pesce, Arda Isik, Ari Kalevi Leppäniemi, Aristeidis Papadopoulos, Aristotelis Kechagias, Ashraf Yehya Abdalla Mohamed, Ashrarur Rahman Mitul, Athanasios Marinis, Athanasios Syllaios, Baris Mantoglu, Belinda De Simone, Benjamin Stefan Weiss, Bernd Pösentrup, Biagio Picardi, Biagio Zampogna, Boris Eugeniev Sakakushev, Boyko Chavdarov Atanasov, Bruno Nardo, Bulent Calik, Camilla Cremonini, Carlos A. Ordoñez, Charalampos Seretis, Chiara Cascone, Christos Chouliaras, Cino Bendinelli, Claudia Lopes, Claudio Guerci, Clemens Weber, Constantinos Nastos, Cristian Mesina, Damiano Caputo, Damien Massalou, Davide Cavaliere, Deborah A. McNamara, Demetrios Demetriades, Desirè Pantalone, Diego Coletta, Diego Sasia, Diego Visconti, Dieter G. Weber, Diletta Corallino, Dimitrios Chatzipetris, Dimitrios K. Manatakis, Dimitrios Ntourakis, Dimitrios Papaconstantinou, Dimitrios Schizas, Dimosthenis Chrysikos, Dmitry Mikhailovich Adamovich, Doaa Elkafrawy, Dragos Seban, Edgar Fernando Hernandez García, Edoardo Baldini, Edoardo Picetti, Edward C. T. H. Tan, Efstratia Baili, Eftychios Lostoridis, Elena Adelina Toma, Elif Colak, Elisabetta Cerutti, Elmin Steyn, Elmuiz A. Hsabo, Emmanouil Ioannis Kapetanakis, Emmanouil Kaouras, Emmanuel Schneck, Emrah Akin, Emre Gonullu, Enes çelik, Enrico Cicuttin, Enrico Pinotti, Erik Johnsson, Ernest E. Moore, Ervis Agastra, Evgeni Nikolaev Dimitrov, Ewen A. Griffiths, Fabrizio D’Acapito, Federica Saraceno, Felipe Alconchel, Felix Alexander Zeppernick, Fernando Machado Rodríguez, Fikri Abu-Zidan, Francesca Pecchini, Francesco Favi, Francesco Ferrara, Francesco Fleres, Francesco Pata, Francesco Pietro Maria Roscio, Francesk Mulita, Frank J. M. F. Dor, Fredrik Linder, Gabriel Dimofte, Gabriel Rodrigues, Gabriela Nita, Gabriele Sganga, Gennaro Martines, Gennaro Mazzarella, Gennaro Perrone, George Velmahos, Georgios D. Lianos, Gia Tomadze, Gian Luca Baiocchi, Giancarlo D’Ambrosio, Gianluca Pellino, Gianmaria Casoni Pattacini, Giorgio Giraudo, Giorgio Lisi, Giovanni Domenico Tebala, Giovanni Pirozzolo, Giulia Montori, Giulio Argenio, Giuseppe Brisinda, Giuseppe Currò, Giuseppe Giuliani, Giuseppe Palomba, Giuseppe Roscitano, Gökhan Avşar, Goran Augustin, Guglielmo Clarizia, Gustavo M. Machain Vega, Gustavo P. Fraga, Harsheet Sethi, Hazim Abdulnassir Eltyeb, Helmut A. Segovia Lohse, Herald René Segovia Lohse, Hüseyin Bayhan, Hytham K. S. Hamid, Igor A. Kryvoruchko, Immacolata Iannone, Imtiaz Wani, Ioannis I. Lazaridis, Ioannis Katsaros, Ioannis Nikolopoulos, Ionut Negoi, Isabella Reccia, Isidoro Di Carlo, Iyiade Olatunde Olaoye, Jacek Czepiel, Jae Il Kim, Jeremy Meyer, Jesus Manuel Saenz Terrazas, Joel Noutakdie Tochie, Joseph M. Galante, Justin Davies, Kapil Sugand, Kebebe Bekele Gonfa, Kemal Rasa, Kenneth Y. Y. Kok, Konstantinos G. Apostolou, Konstantinos Lasithiotakis, Konstantinos Tsekouras, Kumar Angamuthu, Lali Akhmeteli, Larysa Sydorchuk, Laura Fortuna, Leandro Siragusa, Leonardo Pagani, Leonardo Solaini, Lisa A. Miller, Lovenish Bains, Luca Ansaloni, Luca Ferrario, Luigi Bonavina, Luigi Conti, Luis Antonio Buonomo, Luis Tallon-Aguilar, Lukas Tomczyk, Lukas Werner Widmer, Maciej Walędziak, Mahir Gachabayov, Maloni M. Bulanauca, Manu L. N. G. Malbrain, Marc Maegele, Marco Catarci, Marco Ceresoli, Maria Chiara Ranucci, Maria Ioanna Antonopoulou, Maria Papadoliopoulou, Maria Rosaria Valenti, Maria Sotiropoulou, Mario D’Oria, Mario Serradilla Martín, Markus Hirschburger, Massimiliano Veroux, Massimo Fantoni, Matteo Nardi, Matti Tolonen, Mauro Montuori, Mauro Podda, Maximilian Scheiterle, Maximos Frountzas, Mehmet Sarıkaya, Mehmet Yildirim, Michael Bender, Michail Vailas, Michel Teuben, Michela Campanelli, Michele Ammendola, Michele Malerba, Michele Pisano, Mihaela Pertea, Mihail Slavchev, Mika Ukkonen, Miklosh Bala, Mircea Chirica, Mirko Barone, Mohamed Maher Shaat, Mohammed Jibreel Suliman Mohammed, Mona Awad Akasha Abuelgasim, Monika Gureh, Mouaqit Ouadii, Mujdat Balkan, Mumin Mohamed, Musluh Hakseven, Natalia Velenciuc, Nicola Cillara, Nicola de’Angelis, Nicolò Tamini, Nikolaos J. Zavras, Nikolaos Machairas, Nikolaos Michalopoulos, Nikolaos N. Koliakos, Nikolaos Pararas, Noel E. Donlon, Noushif Medappil, Offir Ben-Ishay, Olmi Stefano, Omar Islam, Ömer Tammo, Orestis Ioannidis, Oscar Aparicio, Oussama Baraket, Pankaj Kumar, Pasquale Cianci, Per Örtenwall, Petar Angelov Uchikov, Philip de Reuver, Philip F. Stahel, Philip S. Barie, Micaela Piccoli, Piotr Major, Pradeep H. Navsaria, Prakash Kumar Sasmal, Raul Coimbra, Razrim Rahim, Recayi Çapoğlu, Renol M. Koshy, Ricardo Alessandro Teixeira Gonsaga, Riccardo Pertile, Rifat Ramadan Mussa Mohamed, Rıza Deryol, Robert G. Sawyer, Roberta Angelico, Roberta Ragozzino, Roberto Bini, Roberto Cammarata, Rosa Scaramuzzo, Rossella Gioco, Ruslan Sydorchuk, Salma Ahmed, Salomone Di Saverio, Sameh Hany Emile, Samir Delibegovic, Sanjay Marwah, Savvas Symeonidis, Scott G. Thomas, Sebahattin Demir, Selmy S. Awad, Semra Demirli Atici, Serge Chooklin, Serhat Meric, Sevcan Sarıkaya, Sharfuddin Chowdhury, Shaza Faycal Mirghani, Sherry M. Wren, Simone Gargarella, Simone Rossi Del Monte, Sofia Esposito, Sofia Xenaki, Soliman Fayez Ghedan Mohamed, Solomon Gurmu Beka, Sorinel Lunca, Spiros G. Delis, Spyridon Dritsas, Stefan Morarasu, Stefano Magnone, Stefano Rossi, Stefanos Bitsianis, Stylianos Kykalos, Suman Baral, Sumita A. Jain, Syed Muhammad Ali, Tadeja Pintar, Tania Triantafyllou, Tarik Delko, Teresa Perra, Theodoros A. Sidiropoulos, Thomas M. Scalea, Tim Oliver Vilz, Timothy Craig Hardcastle, Tongporn Wannatoop, Torsten Herzog, Tushar Subhadarshan Mishra, Ugo Boggi, Valentin Calu, Valentina Tomajer, Vanni Agnoletti, Varut Lohsiriwat, Victor Kong, Virginia Durán Muñoz-Cruzado, Vishal G. Shelat, Vladimir Khokha, Wagih Mommtaz Ghannam, Walter L. Biffl, Wietse Zuidema, Yasin Kara, Yoshiro Kobe, Zaza Demetrashvili, Ziad A. Memish, Zoilo Madrazo, Zsolt J. Balogh, Zulfu Bayhan, Reichert, M, Sartelli, M, Weigand, M, Hecker, M, Oppelt, P, Noll, J, Askevold, I, Liese, J, Padberg, W, Coccolini, F, Catena, F, Hecker, A, Peckham-Cooper, A, Camacho-Ortiz, A, Mastoraki, A, Landaluce-Olavarria, A, Pal, A, Kuriyama, A, Chichom-Mefire, A, Porcu, A, Martinez-Perez, A, Karamarkovic, A, Osipov, A, Coppola, A, Cucchetti, A, Spolini, A, Giordano, A, Reinisch-Liese, A, Kavalakat, A, Vasilescu, A, Alamin, A, Gupta, A, Dascalu, A, Musina, A, Bakopoulos, A, Zakaria, A, Vereczkei, A, Balla, A, Bottari, A, Baumann, A, Fette, A, Litvin, A, Reichert, A, Guariniello, A, Paspala, A, Schneck, A, Brillantino, A, Pesce, A, Isik, A, Leppaniemi, A, Papadopoulos, A, Kechagias, A, Mohamed, A, Mitul, A, Marinis, A, Syllaios, A, Mantoglu, B, De Simone, B, Weiss, B, Posentrup, B, Picardi, B, Zampogna, B, Sakakushev, B, Atanasov, B, Nardo, B, Calik, B, Cremonini, C, Ordonez, C, Seretis, C, Cascone, C, Chouliaras, C, Bendinelli, C, Lopes, C, Guerci, C, Weber, C, Nastos, C, Mesina, C, Caputo, D, Massalou, D, Cavaliere, D, Mcnamara, D, Demetriades, D, Pantalone, D, Coletta, D, Sasia, D, Visconti, D, Weber, D, Corallino, D, Chatzipetris, D, Manatakis, D, Ntourakis, D, Papaconstantinou, D, Schizas, D, Chrysikos, D, Adamovich, D, Elkafrawy, D, Seban, D, Garcia, E, Baldini, E, Picetti, E, Tan, E, Baili, E, Lostoridis, E, Toma, E, Colak, E, Cerutti, E, Steyn, E, Hsabo, E, Kapetanakis, E, Kaouras, E, Schneck, E, Akin, E, Gonullu, E, Celik, E, Cicuttin, E, Pinotti, E, Johnsson, E, Moore, E, Agastra, E, Dimitrov, E, Griffiths, E, D'Acapito, F, Saraceno, F, Alconchel, F, Zeppernick, F, Rodriguez, F, Abu-Zidan, F, Pecchini, F, Favi, F, Ferrara, F, Fleres, F, Pata, F, Roscio, F, Mulita, F, Dor, F, Linder, F, Dimofte, G, Rodrigues, G, Nita, G, Sganga, G, Martines, G, Mazzarella, G, Perrone, G, Velmahos, G, Lianos, G, Tomadze, G, Baiocchi, G, D'Ambrosio, G, Pellino, G, Pattacini, G, Giraudo, G, Lisi, G, Tebala, G, Pirozzolo, G, Montori, G, Argenio, G, Brisinda, G, Curro, G, Giuliani, G, Palomba, G, Roscitano, G, Avsar, G, Augustin, G, Clarizia, G, Vega, G, Fraga, G, Sethi, H, Eltyeb, H, Lohse, H, Bayhan, H, Hamid, H, Kryvoruchko, I, Iannone, I, Wani, I, Lazaridis, I, Katsaros, I, Nikolopoulos, I, Negoi, I, Reccia, I, Di Carlo, I, Olaoye, I, Czepiel, J, Kim, J, Meyer, J, Terrazas, J, Tochie, J, Galante, J, Davies, J, Sugand, K, Gonfa, K, Rasa, K, Kok, K, Apostolou, K, Lasithiotakis, K, Tsekouras, K, Angamuthu, K, Akhmeteli, L, Sydorchuk, L, Fortuna, L, Siragusa, L, Pagani, L, Solaini, L, Miller, L, Bains, L, Ansaloni, L, Ferrario, L, Bonavina, L, Conti, L, Buonomo, L, Tallon-Aguilar, L, Tomczyk, L, Widmer, L, Waledziak, M, Gachabayov, M, Bulanauca, M, Malbrain, M, Maegele, M, Catarci, M, Ceresoli, M, Ranucci, M, Antonopoulou, M, Papadoliopoulou, M, Valenti, M, Sotiropoulou, M, D'Oria, M, Martin, M, Hirschburger, M, Veroux, M, Fantoni, M, Nardi, M, Tolonen, M, Montuori, M, Podda, M, Scheiterle, M, Frountzas, M, Sarikaya, M, Yildirim, M, Bender, M, Vailas, M, Teuben, M, Campanelli, M, Ammendola, M, Malerba, M, Pisano, M, Pertea, M, Slavchev, M, Ukkonen, M, Bala, M, Chirica, M, Barone, M, Shaat, M, Mohammed, M, Abuelgasim, M, Gureh, M, Ouadii, M, Balkan, M, Mohamed, M, Hakseven, M, Velenciuc, N, Cillara, N, De'Angelis, N, Tamini, N, Zavras, N, Machairas, N, Michalopoulos, N, Koliakos, N, Pararas, N, Donlon, N, Medappil, N, Ben-Ishay, O, Stefano, O, Islam, O, Tammo, O, Ioannidis, O, Aparicio, O, Baraket, O, Kumar, P, Cianci, P, Ortenwall, P, Uchikov, P, de Reuver, P, Stahel, P, Barie, P, Piccoli, M, Major, P, Navsaria, P, Sasmal, P, Coimbra, R, Rahim, R, Capoglu, R, Koshy, R, Gonsaga, R, Pertile, R, Mohamed, R, Deryol, R, Sawyer, R, Angelico, R, Ragozzino, R, Bini, R, Cammarata, R, Scaramuzzo, R, Gioco, R, Sydorchuk, R, Ahmed, S, Di Saverio, S, Emile, S, Delibegovic, S, Marwah, S, Symeonidis, S, Thomas, S, Demir, S, Awad, S, Atici, S, Chooklin, S, Meric, S, Sarikaya, S, Chowdhury, S, Mirghani, S, Wren, S, Gargarella, S, Del Monte, S, Esposito, S, Xenaki, S, Mohamed, S, Beka, S, Lunca, S, Delis, S, Dritsas, S, Morarasu, S, Magnone, S, Rossi, S, Bitsianis, S, Kykalos, S, Baral, S, Jain, S, Ali, S, Pintar, T, Triantafyllou, T, Delko, T, Perra, T, Sidiropoulos, T, Scalea, T, Vilz, T, Hardcastle, T, Wannatoop, T, Herzog, T, Mishra, T, Boggi, U, Calu, V, Tomajer, V, Agnoletti, V, Lohsiriwat, V, Kong, V, Munoz-Cruzado, V, Shelat, V, Khokha, V, Ghannam, W, Biffl, W, Zuidema, W, Kara, Y, Kobe, Y, Demetrashvili, Z, Memish, Z, Madrazo, Z, Balogh, Z, and Bayhan, Z

Subjects
Cross-Sectional Studie, ddc:610, Capacity, Pandemic, SARS-CoV-2, COVID-19, WSES, Time to intervention, Appendicitis, Reconstructive and regenerative medicine Radboud Institute for Health Sciences [Radboudumc 10], Cross-Sectional Studies, Emergency, Quarantine, Emergency Medicine, Emergency surgery, Humans, Surgery, Appendiciti, COVID-19, SARS-CoV-2, Pandemic, Emergency surgery, Emergency, Appendicitis, WSES, Time to intervention, Capacity, Quarantine, Pandemics, Diverticulitis, Human
Abstract

Background The SARS-CoV-2 pandemic is still ongoing and a major challenge for health care services worldwide. In the first WSES COVID-19 emergency surgery survey, a strong negative impact on emergency surgery (ES) had been described already early in the pandemic situation. However, the knowledge is limited about current effects of the pandemic on patient flow through emergency rooms, daily routine and decision making in ES as well as their changes over time during the last two pandemic years. This second WSES COVID-19 emergency surgery survey investigates the impact of the SARS-CoV-2 pandemic on ES during the course of the pandemic. Methods A web survey had been distributed to medical specialists in ES during a four-week period from January 2022, investigating the impact of the pandemic on patients and septic diseases both requiring ES, structural problems due to the pandemic and time-to-intervention in ES routine. Results 367 collaborators from 59 countries responded to the survey. The majority indicated that the pandemic still significantly impacts on treatment and outcome of surgical emergency patients (83.1% and 78.5%, respectively). As reasons, the collaborators reported decreased case load in ES (44.7%), but patients presenting with more prolonged and severe diseases, especially concerning perforated appendicitis (62.1%) and diverticulitis (57.5%). Otherwise, approximately 50% of the participants still observe a delay in time-to-intervention in ES compared with the situation before the pandemic. Relevant causes leading to enlarged time-to-intervention in ES during the pandemic are persistent problems with in-hospital logistics, lacks in medical staff as well as operating room and intensive care capacities during the pandemic. This leads not only to the need for triage or transferring of ES patients to other hospitals, reported by 64.0% and 48.8% of the collaborators, respectively, but also to paradigm shifts in treatment modalities to non-operative approaches reported by 67.3% of the participants, especially in uncomplicated appendicitis, cholecystitis and multiple-recurrent diverticulitis. Conclusions The SARS-CoV-2 pandemic still significantly impacts on care and outcome of patients in ES. Well-known problems with in-hospital logistics are not sufficiently resolved by now; however, medical staff shortages and reduced capacities have been dramatically aggravated over last two pandemic years.

Published
2022

7. Perceptions of U = U Among Italian Infectious Diseases Specialists: A Nationwide Survey on Providers' Attitudes Toward the Risk of HIV Transmission in Virologically Suppressed Patients

Author

Diego Ripamonti, Mariacristina Poliseno, Giovanni Mazzola, Pietro Colletti, Antonio Di Biagio, Benedetto Maurizio Celesia, Andrea Gori, Rita Bellagamba, Giordano Madeddu, Silvia Nozza, Stefano Rusconi, Antonio Cascio, Sergio Lo Caputo, Ripamonti, Diego, Poliseno, Mariacristina, Mazzola, Giovanni, Colletti, Pietro, Di Biagio, Antonio, Celesia, Benedetto Maurizio, Gori, Andrea, Bellagamba, Rita, Madeddu, Giordano, Nozza, Silvia, Rusconi, Stefano, Cascio, Antonio, and Lo Caputo, Sergio

Subjects
HIV, HIV providers, PEP, U = U, survey, Humans, Surveys and Questionnaires, Attitude, RNA, Anti-HIV Agents, HIV Infections, Physicians, Settore MED/17 - Malattie Infettive, Immunology, Anti-HIV Agent, Infectious Diseases, Virology, HIV provider, Surveys and Questionnaire, HIV Infection, Human
Abstract

This survey aimed to understand how far the Italian infectious diseases (ID) specialists are confident in the "Undetectable = Untransmittable" (U = U) message and translate this concept into clinical practice. An anonymous survey was distributed by e-mail to 286 clinicians to collect their opinions regarding six situations potentially at risk of HIV transmission between virologically suppressed patients and seronegative individuals who possibly require postexposure prophylaxis (PEP). Overall, 51% of ID specialists deemed zero risk of HIV transmission through condomless sex for undetectable patients. This answer was more frequent among HIV specialists (30% vs. 21%, p = .01) and clinicians working in teaching hospitals (35% vs. 16%, p = .03). Remarkably, 61% of participants would advise taking PEP for the HIV-negative partner in case of sexual intercourse with a seropositive person with a recent blip occurrence or absence of an HIV RNA test performed within the last 6 months (63%). Seventy-three percent of respondents deemed it essential to know patients' history of adherence to interpreting an HIV RNA test, regardless of its timing. When applying the U = U concept to daily clinical decisions, we observed an overall cautious attitude among physicians. Concerns mainly regarded the timing of the last HIV RNA test to the exposure event, especially in the absence of details on the patient's adherence. Wider diffusion and application of the U = U message are needed.

Published
2022

8. Premature ejaculation in the era of mobile health application: A current analysis and evaluation of adherence to EAU guidelines

Author

Luigi Napolitano, Luigi Cirillo, Giovanni Maria Fusco, Marco Abate, Alfonso Falcone, Vincenzo Morgera, Gianluigi Cacace, Luigi De Luca, Pasquale Reccia, Claudia Mirone, Felice Crocetto, Giuseppe Celentano, Simone Morra, Biagio Barone, Ciro Imbimbo, Nicola Longo, Vincenzo Mirone, Roberto La Rocca, Napolitano, Luigi, Cirillo, Luigi, Fusco, Giovanni Maria, Abate, Marco, Falcone, Alfonso, Morgera, Vincenzo, Cacace, Gianluigi, De Luca, Luigi, Reccia, Pasquale, Mirone, Claudia, Crocetto, Felice, Celentano, Giuseppe, Morra, Simone, Barone, Biagio, Imbimbo, Ciro, Longo, Nicola, Mirone, Vincenzo, and La Rocca, Roberto

Subjects
Male, Urology, Quality of Life, Humans, Premature Ejaculation, Mobile Applications, Telemedicine
Abstract

Introduction: Several mobile health applications (MHAs) have been developed to assist and improve the quality of life of patients affected by premature ejaculation, but the scientific quality and adherence to guidelines are not yet addressed. Materials and methods: On 25 May 2022, we conducted a search in the Apple App Store and Google Play Store. We reviewed all mobile apps from Apple App Store and Google Play Store for premature ejaculation and evaluated their usage in screening, prevention, management, and adherence to EAU guidelines. Results: In total 9 MHA were reviewed. All MHAs are geared towards the patient and provide information about diagnoses and treatment of PE. The mean score were 2.87, 3.69, 2.77, 2.55, 2.86 for Engagement, Functionality, Aesthetics, Information, and Subjective quality respectively. MHAs reported low and medium adherence to EAU guidelines. Conclusions: MHAs provide different services in many medical fields, including male sexual dysfunction. Their development is constantly increasing, but the problems of scientific validation, content, and quality are not yet solved. Much future research is necessary to improve the quality of the apps and promote new user designed, and high-quality apps.

Published
2022

9. Safety and efficacy of anti-SARS-CoV-2 monoclonal antibodies in pregnancy

Author

Antonio Riccardo Buonomo, Nunzia Esposito, Isabella Di Filippo, Gabriele Saccone, Biagio Pinchera, Riccardo Scotto, Giuseppe Bifulco, Ivan Gentile, Buonomo, Antonio Riccardo, Esposito, Nunzia, Di Filippo, Isabella, Saccone, Gabriele, Pinchera, Biagio, Scotto, Riccardo, Bifulco, Giuseppe, and Gentile, Ivan

Subjects
maternal infection, Pregnancy, Humans, COVID-19, Antibodies, Monoclonal, Female, Pharmacology (medical), General Medicine, Pregnancy Complications, Infectious, Antibodies, Viral, monoclonal antibodie, Human
Published
2022

10. A first update on mapping the human genetic architecture of COVID-19

Author

COVID-19 Host Genetics Initiative, Pathak, GA, Karjalainen, J, Stevens, C, Neale, BM, Daly, M, Ganna, A, Andrews, SJ, Kanai, M, Cordioli, M, Polimanti, R, Harerimana, N, Pirinen, M, Liao, RG, Chwialkowska, K, Trankiem, A, Balaconis, MK, Nguyen, H, Solomonson, M, Veerapen, K, Wolford, B, Roberts, G, Park, D, Ball, CA, Coignet, M, McCurdy, S, Knight, S, Partha, R, Rhead, B, Zhang, M, Berkowitz, N, Gaddis, M, Noto, K, Ruiz, L, Pavlovic, M, Hong, EL, Rand, K, Girshick, A, Guturu, H, Baltzell, AH, Niemi, MEK, Rahmouni, S, Guntz, J, Beguin, Y, Pigazzini, S, Nkambule, L, Georges, M, Moutschen, M, Misset, B, Darcis, G, Guiot, J, Azarzar, S, Gofflot, S, Claassen, S, Malaise, O, Huynen, P, Meuris, C, Thys, M, Jacques, J, Leonard, P, Frippiat, F, Giot, J-B, Sauvage, A-S, Frenckell, CV, Belhaj, Y, Lambermont, B, Nakanishi, T, Morrison, DR, Mooser, V, Richards, JB, Butler-Laporte, G, Forgetta, V, Li, R, Ghosh, B, Laurent, L, Belisle, A, Henry, D, Abdullah, T, Adeleye, O, Mamlouk, N, Kimchi, N, Afrasiabi, Z, Rezk, N, Vulesevic, B, Bouab, M, Guzman, C, Petitjean, L, Tselios, C, Xue, X, Afilalo, J, Afilalo, M, Oliveira, M, Brenner, B, Brassard, N, Durand, M, Schurr, E, Lepage, P, Ragoussis, J, Auld, D, Chassé, M, Kaufmann, DE, Lathrop, GM, Adra, D, Hayward, C, Glessner, JT, Shaw, DM, Campbell, A, Morris, M, Hakonarson, H, Porteous, DJ, Below, J, Richmond, A, Chang, X, Polikowski, H, Lauren, PE, Chen, H-H, Wanying, Z, Fawns-Ritchie, C, North, K, McCormick, JB, Glessner, JR, Gignoux, CR, Wicks, SJ, Crooks, K, Barnes, KC, Daya, M, Shortt, J, Rafaels, N, Chavan, S, Timmers, PRHJ, Wilson, JF, Tenesa, A, Kerr, SM, D’Mellow, K, Shahin, D, El-Sherbiny, YM, von Hohenstaufen, KA, Sobh, A, Eltoukhy, MM, Nkambul, L, Elhadidy, TA, Abd Elghafar, MS, El-Jawhari, JJ, Mohamed, AAS, Elnagdy, MH, Samir, A, Abdel-Aziz, M, Khafaga, WT, El-Lawaty, WM, Torky, MS, El-shanshory, MR, Yassen, AM, Hegazy, MAF, Okasha, K, Eid, MA, Moahmed, HS, Medina-Gomez, C, Ikram, MA, Uitterlinden, AG, Mägi, R, Milani, L, Metspalu, A, Laisk, T, Läll, K, Lepamets, M, Esko, T, Reimann, E, Naaber, P, Laane, E, Pesukova, J, Peterson, P, Kisand, K, Tabri, J, Allos, R, Hensen, K, Starkopf, J, Ringmets, I, Tamm, A, Kallaste, A, Alavere, H, Metsalu, K, Puusepp, M, Batini, C, Tobin, MD, Venn, LD, Lee, PH, Shrine, N, Williams, AT, Guyatt, AL, John, C, Packer, RJ, Ali, A, Free, RC, Wang, X, Wain, LV, Hollox, EJ, Bee, CE, Adams, EL, Palotie, A, Ripatti, S, Ruotsalainen, S, Kristiansson, K, Koskelainen, S, Perola, M, Donner, K, Kivinen, K, Kaunisto, M, Rivolta, C, Bochud, P-Y, Bibert, S, Boillat, N, Nussle, SG, Albrich, W, Quinodoz, M, Kamdar, D, Suh, N, Neofytos, D, Erard, V, Voide, C, Friolet, R, Vollenweider, P, Pagani, JL, Oddo, M, zu Bentrup, FM, Conen, A, Clerc, O, Marchetti, O, Guillet, A, Guyat-Jacques, C, Foucras, S, Rime, M, Chassot, J, Jaquet, M, Viollet, RM, Lannepoudenx, Y, Portopena, L, Bochud, PY, Desgranges, F, Filippidis, P, Guéry, B, Haefliger, D, Kampouri, EE, Manuel, O, Munting, A, Papadimitriou-Olivgeris, M, Regina, J, Rochat-Stettler, L, Suttels, V, Tadini, E, Tschopp, J, Van Singer, M, Viala, B, Boillat-Blanco, N, Brahier, T, Hügli, O, Meuwly, JY, Pantet, O, Gonseth Nussle, S, Bochud, M, D’Acremont, V, Estoppey Younes, S, Albrich, WC, Cerny, A, O’Mahony, L, von Mering, C, Frischknecht, M, Kleger, G-R., Filipovic, M, Kahlert, CR, Wozniak, H, Negro, TR, Pugin, J, Bouras, K, Knapp, C, Egger, T, Perret, A, Montillier, P, di Bartolomeo, C, Barda, B, de Cid, R, Carreras, A, Moreno, V, Kogevinas, M, Galván-Femenía, I, Blay, N, Farré, X, Sumoy, L, Cortés, B, Mercader, JM, Guindo-Martinez, M, Torrents, D, Garcia-Aymerich, J, Castaño-Vinyals, G, Dobaño, C, Gori, M, Renieri, A, Mari, F, Mondelli, MU, Castelli, F, Vaghi, M, Rusconi, S, Montagnani, F, Bargagli, E, Franchi, F, Mazzei, MA, Cantarini, L, Tacconi, D, Feri, M, Scala, R, Spargi, G, Nencioni, C, Bandini, M, Caldarelli, GP, Canaccini, A, Ognibene, A, D’Arminio Monforte, A, Girardis, M, Antinori, A, Francisci, D, Schiaroli, E, Scotton, PG, Panese, S, Scaggiante, R, Monica, MD, Capasso, M, Fiorentino, G, Castori, M, Aucella, F, Biagio, AD, Masucci, L, Valente, S, Mandalà, M, Zucchi, P, Giannattasio, F, Coviello, DA, Mussini, C, Tavecchia, L, Crotti, L, Rizzi, M, Rovere, MTL, Sarzi-Braga, S, Bussotti, M, Ravaglia, S, Artuso, R, Perrella, A, Romani, D, Bergomi, P, Catena, E, Vincenti, A, Ferri, C, Grassi, D, Pessina, G, Tumbarello, M, Pietro, MD, Sabrina, R, Luchi, S, Furini, S, Dei, S, Benetti, E, Picchiotti, N, Sanarico, M, Ceri, S, Pinoli, P, Raimondi, F, Biscarini, F, Stella, A, Zguro, K, Capitani, K, Tanfoni, M, Fallerini, C, Daga, S, Baldassarri, M, Fava, F, Frullanti, E, Valentino, F, Doddato, G, Giliberti, A, Tita, R, Amitrano, S, Bruttini, M, Croci, S, Meloni, I, Mencarelli, MA, Rizzo, CL, Pinto, AM, Beligni, G, Tommasi, A, Sarno, LD, Palmieri, M, Carriero, ML, Alaverdian, D, Busani, S, Bruno, R, Vecchia, M, Belli, MA, Mantovani, S, Ludovisi, S, Quiros-Roldan, E, Antoni, MD, Zanella, I, 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M., van Blokland, Irene, Lanting, Pauline, Ori, Anil P. S., Feng, Yen-Chen Anne, Mercader, Josep, Weiss, Scott T., Karlson, Elizabeth W., Smoller, Jordan W., Murphy, Shawn N., Meigs, James B., Woolley, Ann E., Green, Robert C., Perez, Emma F., Zöllner, Sebastian, Wang, Jiongming, Beck, Andrew, Sloofman, Laura G., Ascolillo, Steven, Sebra, Robert P., Collins, Brett L., Levy, Te, Buxbaum, Joseph D., Sealfon, Stuart C., Jordan, Daniel M., Thompson, Ryan C., Gettler, Kyle, Chaudhary, Kumardeep, Belbin, Gillian M., Preuss, Michael, Hoggart, Clive, Choi, Sam, Underwood, Slayton J., Salib, Irene, Britvan, Bari, Keller, Katherine, Tang, Lara, Peruggia, Michael, Hiester, Liam L., Niblo, Kristi, Aksentijevich, Alexandra, Labkowsky, Alexander, Karp, Avromie, Zlatopolsky, Menachem, Zyndorf, Marissa, Charney, Alexander W., Beckmann, Noam D., Schadt, Eric E., Abul-Husn, Noura S., Cho, Judy H., Itan, Yuval, Kenny, Eimear E., Loos, Ruth J. F., Nadkarni, Girish N., Do, Ron, O’Reilly, Paul, Huckins, Laura M., Ferreira, Manuel A. R., Abecasis, Goncalo R., Leader, Joseph B., Cantor, Michael N., Justice, Anne E., Carey, Dave J., Chittoor, Geetha, Josyula, Navya Shilpa, Kosmicki, Jack A., Horowitz, Julie E., Baras, Ari, Gass, Matthew C., Yadav, Ashish, Mirshahi, Tooraj, Hottenga, Jouke Jan, Bartels, Meike, de geus, Eco E. J. C., Nivard, Michel M. G., Verma, Anurag, Ritchie, Marylyn D., Rader, Daniel, Li, Binglan, Verma, Shefali S., Lucas, Anastasia, Bradford, Yuki, Abedalthagafi, Malak, Alaamery, Manal, Alshareef, Abdulraheem, Sawaji, Mona, Massadeh, Salam, AlMalik, Abdulaziz, Alqahtani, Saleh, Baraka, Dona, Harthi, Fawz Al, Alsolm, Ebtehal, Safieh, Leen Abu, Alowayn, Albandary M., Alqubaishi, Fatimah, Mutairi, Amal Al, Mangul, Serghei, Almutairi, Mansour, Aljawini, Nora, Albesher, Nour, Arabi, Yaseen M., Mahmoud, Ebrahim S., Khattab, Amin K., Halawani, Roaa T., Alahmadey, Ziab Z., Albakri, Jehad K., Felemban, Walaa A., Suliman, Bandar A., Hasanato, Rana, Al-Awdah, Laila, Alghamdi, Jahad, AlZahrani, Deema, AlJohani, Sameera, Al-Afghani, Hani, AlDhawi, Nouf, AlBardis, Hadeel, Alkwai, Sarah, Alswailm, Moneera, Almalki, Faisal, Albeladi, Maha, Almohammed, Iman, Barhoush, Eman, Albader, Anoud, Alotaibi, Sara, Alghamdi, Bader, Jung, Junghyun, fawzy, Mohammad S., Alrashed, May, Zeberg, Hugo, Nkambul, Lindo, Frithiof, Robert, Hultström, Michael, Lipcsey, Miklo, Tardif, Nicola, Rooyackers, Olav, Grip, Jonathan, Maricic, Tomislav, Helgeland, Øyvind, Magnus, Per, Trogstad, Lill-Iren S., Lee, Yunsung, Harris, Jennifer R., Mangino, Massimo, Spector, Tim D., Emma, Duncan, Moutsianas, Louka, Caulfield, Mark J., Scott, Richard H., Kousathanas, Athanasio, Pasko, Dorota, Walker, Susan, Stuckey, Alex, Odhams, Christopher A., Rhodes, Daniel, Fowler, Tom, Rendon, Augusto, Chan, Georgia, Arumugam, Prabhu, Karczewski, Konrad J., Martin, Alicia R., Wilson, Daniel J., Spencer, Chris C. A., Crook, Derrick W., Wyllie, David H., O’Connell, Anne Marie, Atkinson, Elizabeth G., Tsuo, Kristin, Baya, Nikola, Turley, Patrick, Gupta, Rahul, Walters, Raymond K., Palmer, Duncan S., Sarma, Gopal, Cheng, Nathan, Lu, Wenhan, Churchhouse, Claire, Goldstein, Jacqueline I., King, Daniel, Seed, Cotton, Daly, Mark J., Finucane, Hilary, Bryant, Sam, Satterstrom, F. Kyle, Band, Gavin, Earle, Sarah G., Lin, Shang-Kuan, Arning, Nicola, Koelling, Nil, Armstrong, Jacob, Rudkin, Justine K., Callier, Shawneequa, Cusick, Caroline, Soranzo, Nicole, Zhao, Jing Hua, Danesh, John, Angelantonio, Emanuele Di, Butterworth, Adam S., Sun, Yan V., Huffman, Jennifer E., Cho, Kelly, O’Donnell, Christopher J., Tsao, Phil, Gaziano, J. Michael, Peloso, Gina, Ho, Yuk-Lam, Smieszek, Sandra P., Polymeropoulos, Christo, Polymeropoulos, Vasilio, Polymeropoulos, Mihael H., Przychodzen, Bartlomiej P., Fernandez-Cadenas, Israel, Planas, Anna M., Perez-Tur, Jordi, Llucià-Carol, Laia, Cullell, Natalia, Muiño, Elena, Cárcel-Márquez, Jara, DeDiego, Marta L., Iglesias, Lara Lloret, Soriano, Alex, Rico, Veronica, Agüero, Daiana, Bedini, Josep L., Lozano, Francisco, Domingo, Carlo, Robles, Veronica, Ruiz-Jaén, Francisca, Márquez, Leonardo, Gomez, Juan, Coto, Eliecer, Albaiceta, Guillermo M., García-Clemente, Marta, Dalmau, David, Arranz, Maria J., Dietl, Beatriz, Serra-Llovich, Alex, Soler, Pere, Colobrán, Roger, Martín-Nalda, Andrea, Martínez, Alba Parra, Bernardo, David, Rojo, Silvia, Fiz-López, Aida, Arribas, Elisa, de la Cal-Sabater, Paloma, Segura, Tomá, González-Villa, Esther, Serrano-Heras, Gemma, Martí-Fàbregas, Joan, Jiménez-Xarrié, Elena, de Felipe Mimbrera, Alicia, Masjuan, Jaime, García-Madrona, Sebastian, Domínguez-Mayoral, Anna, Villalonga, Joan Montaner, Menéndez-Valladares, Paloma, Chasman, Daniel I., Sesso, Howard D., Manson, JoAnn E., Buring, Julie E., Ridker, Paul M., Franco, Giulianini, Davis, Lea, Lee, Sulggi, Priest, Jame, Sankaran, Vijay G., van Heel, David, Biesecker, Le, Kerchberger, V. Eric, Baillie, J. Kenneth, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, Biological Psychology, APH - Mental Health, AMS - Sports, AMS - Ageing & Vitality, APH - Methodology, Mccurdy, Shannon, Mccormick, Joseph B., Macarthur, Daniel, Maclaughlin, Bev, Lefaive, Jonathon, Almalik, Abdulaziz, Alzahrani, Deema, Aljohani, Sameera, Aldhawi, Nouf, Albardis, Hadeel, Fawzy, Mohammad S., Dediego, Marta L., Stem Cell Aging Leukemia and Lymphoma (SALL), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Life Course Epidemiology (LCE), Groningen Research Institute for Asthma and COPD (GRIAC), University of Zurich, COVID-19 Host Genetics Initiative, Barcelona Supercomputing Center, COVID-19 Genetics Initiative, including authors, Institute for Molecular Medicine Finland, and Data Science Genetic Epidemiology Lab

Subjects
Informàtica::Aplicacions de la informàtica::Bioinformàtica [Àrees temàtiques de la UPC], Quantitative Trait Loci, MUC5B PROMOTER POLYMORPHISM, Genome-wide association studies, COVID-19 (Malaltia), UFSP13-7 Evolution in Action: From Genomes to Ecosystems, COVID-19 (Disease), Settore BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA, SDG 3 - Good Health and Well-being, Humans, genetics, Genetic variation, Genomes, Medicinsk genetik, 1000 Multidisciplinary, Multidisciplinary, Chromosome Mapping, COVID-19, Human Genetics, 10124 Institute of Molecular Life Sciences, covid-19, 3121 General medicine, internal medicine and other clinical medicine, 570 Life sciences, biology, Medical Genetics
Abstract

Matters arising from: Mapping the human genetic architecture of COVID-19 Original Article published on 08 July 2021 https://www.nature.com/articles/s41586-021-03767-x The COVID-19 pandemic continues to pose a major public health threat, especially in countries with low vaccination rates. To better understand the biological underpinnings of SARS-CoV-2 infection and COVID-19 severity, we formed the COVID-19 Host Genetics Initiative1. Here we present a genome-wide association study meta-analysis of up to 125,584 cases and over 2.5 million control individuals across 60 studies from 25 countries, adding 11 genome-wide significant loci compared with those previously identified2. Genes at new loci, including SFTPD, MUC5B and ACE2, reveal compelling insights regarding disease susceptibility and severity. Here we present meta-analyses bringing together 60 studies from 25 countries (Fig. 1 and Supplementary Table 1) for three COVID-19-related phenotypes: (1) individuals critically ill with COVID-19 on the basis of requiring respiratory support in hospital or who died as a consequence of the disease (9,376 cases, of which 3,197 are new in this data release, and 1,776,645 control individuals); (2) individuals with moderate or severe COVID-19 defined as those hospitalized due to symptoms associated with the infection (25,027 cases, 11,386 new and 2,836,272 control individuals); and (3) all cases with reported SARS-CoV-2 infection regardless of symptoms (125,584 cases, 76,022 new and 2,575,347 control individuals). Most studies have reported results before the roll out of the COVID-19 vaccination campaign. An overview of the study design is provided in Supplementary Fig. 1. We found a total of 23 genome-wide significant loci (P

Published
2022

12. Rapid Diagnosis of XDR and Pre-XDR TB: A Systematic Review of Available Tools

Author

Laura Saderi, Mariangela Puci, Biagio Di Lorenzo, Rosella Centis, Lia D’Ambrosio, Onno W. Akkerman, Jan-Willem C. Alffenaar, José A. Caminero, Jeremiah Muhwa Chakaya, Justin T. Denholm, Xhevat Kurhasani, Catherine W.M. Ong, Adrian Rendon, Denise Rossato Silva, Simon Tiberi, Dominik Zenner, Andrea M. Cabibbe, Giovanni Battista Migliori, and Giovanni Sotgiu

Subjects
Pulmonary and Respiratory Medicine, Genotype, Predictive Value of Tests, Extensively Drug-Resistant Tuberculosis, Tuberculosis, Multidrug-Resistant, Humans, Mycobacterium tuberculosis, Rifampin, Sensitivity and Specificity
Abstract

INTRODUCTION: No previous systematic reviews have comprehensively investigated the features of Xpert MTB/XDR and other rapid tests to diagnose pre-XDR/XDR-TB. The aim of this systematic review is to assess existing rapid diagnostics for pre-XDR/XDR-TB from a point-of-care perspective and describe their technical characteristics (i.e., sensitivity, specificity, positive and negative predictive values). METHODS: Embase, PubMed, Scopus, and Web of Science were searched to detect the articles focused on the accuracy of commercially available rapid molecular diagnostic tests for XDR-TB according to PRISMA guidelines. The analysis compared the diagnostic techniques and approaches in terms of sensitivity, specificity, laboratory complexity, time to confirmed diagnosis. RESULTS: Of 1298 records identified, after valuating article titles and abstracts, 97 (7.5%) records underwent full-text evaluation and 38 records met the inclusion criteria. Two rapid World Health Organization (WHO)-endorsed tests are available: Xpert MTB/XDR and GenoType MTBDRsl (VER1.0 and VER 2.0). Both tests had similar performance, slightly favouring Xpert, although only 2 studies were available (sensitivity 91.4-94; specificity 98.5-99; accuracy 97.2-97.7; PPV 88.9-99.1; NPV 95.8-98.9). CONCLUSIONS: Xpert MTB/XDR could be suggested at near-point-of-care settings to be used primarily as a follow-on test for laboratory-confirmed TB, complementing existing rapid tests detecting at least rifampicin-resistance. Both Xpert MTB/XDR and GenoType MTBDRsl are presently diagnosing what WHO defined, in 2021, as pre-XDR-TB.

Published
2022

13. Wideband acoustic immittance in superior semicircular canal dehiscence

Author

Hendriena Pieterse, Leigh Biagio-De Jager, Louis M. Hofmeyr, and Bart H.M.E. Vinck

Subjects
Semicircular Canal Dehiscence, Acoustic Impedance Tests, Otorhinolaryngology, Ear, Middle, Humans, Surgery, Acoustics, General Medicine, Cochlea
Abstract

The apparent effect of superior semicircular canal dehiscence (SSCD) on middle ear- and cochlear impedance has led researchers to investigate the use of wideband acoustic immittance as a screening tool when SSCD is suspected. The purpose of the study was to describe the absorbance characteristics and tympanometric values of ears with confirmed SSCD measured at tympanometric peak pressure (TPP) and at ambient pressure.Wideband Acoustic Immittance was performed at ambient pressure and at TPP on ten participants (12 ears) with confirmed SSCD, as well as on an age- and gender matched control group (12 ears). Inferential statistics were used to determine whether statistical differences existed for the absorbance values at each of the averaged frequencies, the resonance frequency (RF) and tympanometric data between the SSCD and control groups.The mean absorbance of the SSCD group reached a maximum at 890.9 Hz and a minimum at 6349.6 Hz. When testing absorbance at TPP, a statistically significant increase/peak in the absorbance values of the SSCD group (compared to those of the control group) was found from 630 to 890.9 Hz and a decrease from 4489.8 to 6349.6 Hz. Similar patterns were observed for absorbance at ambient pressure. A lower mean RF for ears with SSCD as well as an increased mean admittance magnitude (AM) value at RF was found compared to those of the control group.The use of SSCD as a screening tool when SSCD is suspected was strengthened by results similar to those of previous studies. As a result of the significant difference in RF of SSCD ears compared to the RF of the control group, the potential value of measuring the RF of the middle ear to differentiate between mass-and stiffness dominated pathologies, was also illustrated.

Published
2022

14. Metabolic syndrome and body weight in people living with HIV infection: analysis of differences observed in three different cohort studies over a decade

Author

Taramasso L., Bonfanti P., Ricci E., Maggi P., Orofino G., Squillace N., Menzaghi B., Madeddu G., Molteni C., Vichi F., Riguccini E., Saracino A., Santoro C., Guastavigna M., Francisci D., Di Biagio A., De Socio G. V., Sarchi E., Chichino G., Bolla C., Bellacosa C., Angarano G., Calza L., Farinazzo M., Angioni G., Gussio M., Celesia B. M., Falasca K., Mastroianni A., Guadagnino G., Salomoni E., Martinelli C., Dentone C., Bassetti M., Cenderello G., Pellicano G. F., Nunnari G., Valsecchi L., Cordier L., Parisini S., Rizzardini G., Rusconi S., Conti F., Bandera A., Gori A., Motta D., Puoti M., Migliorino G. M., Martini S., Cascio A., Trizzino M., Gulminetti R., Nofri M., Cibelli D., Parruti G., Mameli M. S., Taramasso L., Bonfanti P., Ricci E., Maggi P., Orofino G., Squillace N., Menzaghi B., Madeddu G., Molteni C., Vichi F., Riguccini E., Saracino A., Santoro C., Guastavigna M., Francisci D., Di Biagio A., De Socio G.V., Sarchi E., Chichino G., Bolla C., Bellacosa C., Angarano G., Calza L., Farinazzo M., Angioni G., Gussio M., Celesia B.M., Falasca K., Mastroianni A., Guadagnino G., Salomoni E., Martinelli C., Dentone C., Bassetti M., Cenderello G., Pellicano G.F., Nunnari G., Valsecchi L., Cordier L., Parisini S., Rizzardini G., Rusconi S., Conti F., Bandera A., Gori A., Motta D., Puoti M., Migliorino G.M., Martini S., Cascio A., Trizzino M., Gulminetti R., Nofri M., Cibelli D., Parruti G., Mameli M.S., Taramasso, L, Bonfanti, P, Ricci, E, Maggi, P, Orofino, G, Squillace, N, Menzaghi, B, Madeddu, G, Molteni, C, Vichi, F, Riguccini, E, Saracino, A, Santoro, C, Guastavigna, M, Francisci, D, Di Biagio, A, De Socio, G, Taramasso, Lucia, Bonfanti, Paolo, Ricci, Elena, Maggi, Paolo, Orofino, Giancarlo, Squillace, Nicola, Menzaghi, Barbara, Madeddu, Giordano, Molteni, Chiara, Vichi, Francesca, Riguccini, Erika, Saracino, Annalisa, Santoro, Carmen, Guastavigna, Marta, Francisci, Daniela, Di Biagio, Antonio, and De Socio, Giuseppe Vittorio

Subjects
Adult, Male, dyslipidaemia, antiretroviral therapy, HIV Infections, Overweight, Logistic regression, Body Mass Index, Cohort Studies, Prevalence, medicine, overweight, Humans, Pharmacology (medical), Metabolic Syndrome, business.industry, Health Policy, Incidence (epidemiology), Body Weight, HIV, weight gain, Odds ratio, Middle Aged, medicine.disease, Confidence interval, metabolic syndrome, Cross-Sectional Studies, Infectious Diseases, Metabolic syndrome, medicine.symptom, business, Weight gain, Demography, Cohort study
Abstract

Objectives: The aim of this study was to assess the incidence of being overweight and metabolic syndrome (MS) among people living with HIV (PHIV) in three different cross-sectional studies conducted over three different periods: 2005, 2011 and 2015. Methods: This was a multi-centre, nationwide study. Data were collected in three studies from the CISAI group - SIMOne, HIV-HY and STOPSHIV - and included a total of 3014 PHIV. Logistic regression [odds ratio (OR), 95% confidence interval (CI)] was used to account for age and gender difference among three groups when comparing MS prevalence and being overweight; potential confounders were accounted for by including them in the regression equation. Results: Overall, the mean age was 46.9±10.2years, and men comprised 73.3% of participants. Comparing 2005, 2011 and 2015, MS was present in 34.5%, 33.0% and 29.3% of PHIV, respectively. Adjusted OR for MS was 0.64 (95% CI: 0.52-0.78) in 2011 and 0.56 (95% CI: 0.46-0.69) in 2015 compared with 2005, while BMI (kg/m2 ) increased from 23.6 in 2005, 24.5 in 2011 and 24.5 in 2015, with a concomitant increase of being overweight from 29.4% to 39.5% to 39.6% (p&nbsp

Published
2021

15. Risk for non-AIDS-defining and AIDS-defining cancer of early versus delayed initiation of antiretroviral therapy

Author

Chammartin, F., Lodi, S., Logan, R., Ryom, L., Mocroft, A., Kirk, O., D'Arminio Monforte, A., Reiss, P., Phillips, A., El-Sadr, W., Hatleberg, C. I., Pradier, C., Bonnet, F., Law, M., De Wit, S., Sabin, C., Lundgren, J. D., Bucher, H. C., Calvo, G., Dabis, F., Morfeldt, L., Weber, R., Lind-Thomsen, A., Salbol Brandt, R., Hillebreght, M., Zaheri, S., Wit, F. W. N. M., Scherrer, A., Schoni-Affolter, F., Rickenbach, M., Tavelli, A., Fanti, I., Leleux, O., Mourali, J., Le Marec, F., Boerg, E., Thulin, E., Sundstrom, A., Bartsch, G., Thompsen, G., Necsoi, C., Delforge, M., Fontas, E., Caissotti, C., Dollet, K., Mateu, S., Torres, F., Petoumenos, K., Blance, A., Huang, R., Puhr, R., Gronborg Laut, K., Kristensen, D., Kamara, D. A., Smith, C. J., Raben, D., Matthews, C., Bojesen, A., Grevsen, A. L., Powderly, B., Shortman, N., Moecklinghoff, C., Reilly, G., Smit, C., Ross, M., Fux, C. A., Morlat, P., Friis-Moller, N., Kowalska, J., Bohlius, J., Bower, M., Fatkenheuer, G., Grulich, A., Sjol, A., Meidahl, P., Iversen, J. S., Hillebregt, M., Prins, J. M., Kuijpers, T. W., Scherpbier, H. J., Van Der Meer, J. T. M., Godfried, M. H., Van Der Poll, T., Nellen, F. J. B., Geerlings, S. E., Van Vugt, M., Pajkrt, D., Bos, J. C., Wiersinga, W. J., Van Der Valk, M., Goorhuis, A., Hovius, J. W., Van Eden, J., Henderiks, A., Van Hes, A. M. H., Mutschelknauss, M., Nobel, H. E., Pijnappel, F. J. J., Jurriaans, S., Back, N. K. T., Zaaijer, H. L., Berkhout, B., Cornelissen, M. T. E., Schinkel, C. J., Thomas, X. V., Van Den Berge, M., Stegeman, A., Baas, S., Hage De Looff, L., Versteeg, D., Pronk, M. J. H., Ammerlaan, H. S. M., de Munnik, E. S., Jansz, A. R., Tjhie, J., Wegdam, M. C. A., Deiman, B., Scharnhorst, V., Van Der Plas, A., Weijsenfeld, A. M., Van Der Ende, M. E., de Vries-Sluijs, T. E. M. S., van Gorp, E. C. M., Schurink, C. A. M., Nouwen, J. L., Verbon, A., Rijnders, B. J. A., Bax, H. I., Van Der Feltz, M., Bassant, N., Van Beek, J. E. A., Vriesde, M., Van Zonneveld, L. M., De Oude-Lubbers, A., Van Den Berg-Cameron, H. J., Bruinsma-Broekman, F. B., de Groot, J., De Zeeuw-De Man, M., Boucher, C. A. B., Koopmans, M. P. G., van Kampen, J. J. A., Pas, S. D., Driessen, G. J. A., van Rossum, A. M. C., Van Der Knaap, L. C., Visser, E., Branger, J., Rijkeboer-Mes, A., Duijf-Van De Ven, C. J. H. M., Schippers, E. F., van Nieuwkoop, C., van IJperen, J. M., Geilings, J., van der Hut, G., Franck, P. F. H., Van Eeden, A., Brokking, W., Groot, M., Elsenburg, L. J. M., Damen, M., Kwa, I. S., Groeneveld, P. H. P., Bouwhuis, J. W., Van Den Berg, J. F., Van Hulzen, A. G. W., Van Der Bliek, G. L., Bor, P. C. J., Bloembergen, P., Wolfhagen, M. J. H. M., Ruijs, G. J. H. M., Kroon, F. P., De Boer, M. G. J., Bauer, M. P., Jolink, H., Vollaard, A. M., Dorama, W., Van Holten, N., Claas, E. C. J., Wessels, E., Den Hollander, J. G., Pogany, K., Roukens, A., Kastelijns, M., Smit, J. V., Smit, E., Struik-Kalkman, D., Tearno, C., Bezemer, M., van Niekerk, T., Pontesilli, O., Lowe, S. H., Oude Lashof, A. M. L., Posthouwer, D., Ackens, R. P., Schippers, J., Vergoossen, R., Weijenberg-Maes, B., van Loo, I. H. M., Havenith, T. R. A., Leyten, E. M. S., Gelinck, L. B. S., van Hartingsveld, A., Meerkerk, C., Wildenbeest, G. S., Mutsaers, J. A. E. M., Jansen, C. L., Mulder, J. W., Vrouenraets, S. M. E., Lauw, F. N., van Broekhuizen, M. C., Paap, H., Vlasblom, D. J., Smits, P. H. M., Weijer, S., El Moussaoui, R., Bosma, A. S., van Vonderen, M. G. A., van Houte, D. P. F., Kampschreur, L. M., Dijkstra, K., Faber, S., Weel, J., Kootstra, G. J., Delsing, C. E., van der Burg-Van de Plas, M., Heins, H., Lucas, E., Kortmann, W., van Twillert, G., Cohen Stuart, J. W. T., Diederen, B. M. W., van Truijen-Oud, F. A., van der Reijden, W. A., Jansen, R., Brinkman, K., van den Berk, G. E. L., Blok, W. L., Frissen, P. H. J., Lettinga, K. D., Schouten, W. E. M., Veenstra, J., Brouwer, J. C., Geerders, F. G., Hoeksema, K., Kleene, J. M., van der Meche, B. I., Spelbrink, M., Sulman, H., Toonen, A. J. M., Wijnands, S., Kwa, D., Witte, E., Koopmans, P. P., Keuter, M., van der Ven, A. J. A. M., ter Hofstede, H. J. M., Dofferhoff, A. S. M., van Crevel, R., Albers, M., Bosch, M. E. W., Grintjes-Huisman, K. J. T., Zomer, J. B., Stelma, F. F., Rahamat-Langendoen, J., Burger, D., Richter, C., Gisolf, H. E., Hassing, J. R., ter Beest, G., van Bentum, P. H. M., Langebeek, N., Tiemessen, R., Swanink, C. M. A., van Lelyveld, S. F. L., Soetekouw, R., Hulshoff, N., van der Prijt, L. M. M., van der Swaluw, J., Bermon, N., Herpers, B. L., Veenendaal, D., Verhagen, W. D. M., van Wijk, M., van Kasteren, M. E. E., Brouwer, E. A., de Kruijf-Van de Wiel, B. A. F. M., Kuipers, M., Santegoets, R. M. W. J., van der Ven, B., Marcelis, H. J., Buiting, A. G. M., Kabel, J. P., Bierman, W. F. W., Scholvinck, H., Wilting, R. K., Stienstra, Y., de Groot-De Jonge, H., van der Meulen, A. P., de Weerd, A. D., Ludwig-Roukema, J., Niesters, H. G. M., Riezebos-Brilman, A., van Leer-Buter, C. C., Knoester, M., Hoepelman, A. I. M., Mudrikova, T., Ellerbroek, M. P., Oosterheert, J. J., Arends, E. J., Barth, E. R., Wassenberg, M. W. M., Schadd, M. E., van Elst-Laurijssen, D. H. M., van Oers-Hazelzet, B. E., Vervoort, S., van Berkel, M., Schuurman, R., Verduyn-Lunel, F., Wensing, A. M. J., Peters, E. J. G., van Agtmael, A. M., Bomers, M., de Vocht, J., Heitmuller, M., Laan, M. L., Pettersson, M. A., Vandenbroucke-Grauls, C. M. J. E., Ang, W. C., Geelen, S. P. M., Wolfs, T. F. W., Bont, J. L., Nauta, N., Bezemer, O. D., van Sighem, I. A., Boender, S. T., de Jong, A., Bergsma, D., Hoekstra, P., de Lang, A., Grivell, S., Jansen, A., Rademaker, J. M., Raethke, M., Meijering, R., Schnorr, S., de Groot, L., van den Akker, M., Bakker, Y., Claessen, E., El Berkaoui, A., Koops, J., Kruijne, E., Lodewijk, C., Munjishvili, L., Peeck, B., Ree, C., Regtop, R., Ruijs, Y., Rutkens, T., van de Sande, L., Schoorl, M., Timmerman, A., Tuijn, E., Veenenberg, L., van der Vliet, S., Wisse, A., Woudstra, T., Tuk, B., Dupon, M., Gaborieau, V., Lacoste, D., Malvy, D., Mercie, P., Neau, D., Pellegrin, L. J., Tchamgoue, S., Lazaro, E., Cazanave, C., Vandenhende, M., Vareil, O. M., Gerard, Y., Blanco, P., Bouchet, S., Breilh, D., Fleury, H., Pellegrin, I., Chene, G., Thiebaut, R., Wittkop, L., Lawson-Ayayi, S., Gimbert, A., Desjardin, S., Lacaze-Buzy, L., Petrov-Sanchez, V., Andre, N., Bernard, K., Caubet, O., Caunegre, L., Chossat, I., Courtault, C., Dauchy, A. 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P., Kuznetsova A., Kyselyova G., Sluzhynska M., Johnson A.M., Simons E., Orkin C., Weber J., Scullard G., Clarke A., Leen C., Thulin G., Akerlund B., Koppel K., Karlsson A., Hakangard C., Castelli F., Cauda R., Di Perri G., Iardino R., Ippolito G., Marchetti C.G., Perno F.C., von Schloesser F., Viale P., Ceccherini-Silberstein F., Girardi E., Lo Caputo S., Puoti M., Andreoni M., Ammassari A., Balotta C., Bandera A., Bonfanti P., Bonora S., Borderi M., Calcagno A., Calza L., Capobianchi R.M., Cingolani A., Cinque P., De Luca A., Di Biagio A., Gori A., Guaraldi G., Lapadula G., Madeddu G., Maggiolo F., Marcotullio S., Monno L., Nozza S., Quiros Roldan E., Rossotti R., Rusconi S., Santoro M.M., Saracino A., Galli L., Lorenzini P., Rodano A., Shanyinde M., Carletti F., Carrara S., Di Caro A., Graziano S., Petrone F., Prota G., Quartu S., Truffa S., Giacometti A., Costantini A., Barocci V., Angarano G., Santoro C., Suardi C., Donati V., Verucchi G., Minardi C., Quirino T., Abeli C., Manconi E.P., Piano P., Cacopardo B., Celesia B., Vecchiet J., Falasca K., Pan A., Lorenzotti S., Sighinolfi L., Segala D., Vichi F., Cassola G., Viscoli C., Alessandrini A., Bobbio N., Mazzarello G., Mastroianni C., Belvisi V., Caramma I., Chiodera A., Milini P., Rizzardini G., Moioli C.M., Piolini R., Ridolfo L.A., Salpietro S., Tincati C., Puzzolante C., Abrescia N., Chirianni A., Borgia G., Orlando R., Bonadies G., Di Martino F., Gentile I., Maddaloni L., Cattelan M.A., Marinello S., Cascio A., Colomba C., Baldelli F., Schiaroli E., Parruti G., Sozio F., Magnani G., Ursitti A.M., Cristaudo A., Baldin G., Capozzi M., Cicalini S., Fontanelli Sulekova L., Iaiani G., Latini A., Mastrorosa I., Savinelli S., Vergori A., Cecchetto M., Viviani F., Bagella P., Rossetti B., Franco A., Fontana Del Vecchio R., Francisci D., Di Giuli C., Caramello P., Orofino C.G., Sciandra M., Bassetti M., Londero A., Pellizzer G., Manfrin V., Starnini G., Ialungo A., Dellamonica P., Bernard E., Courjon J., Cua E., De Salvador-Guillouet F., Durant J., Etienne C., Ferrando S., Mondain-Miton V., Naqvi A., Perbost I., Pillet S., Prouvost-Keller B., Pugliese P., Rio V., Risso K., Roger M.P., Aubert V., Bernasconi E., Ciuffi A., Dollenmaier G., Egger M., Elzi L., Fehr J., Fellay J., Gunthard F.H., Haerry D., Hasse B., Hirsch H.H., Hoffmann M., Hosli I., Kahlert C., Kaiser L., Keiser O., Klimkait T., Kouyos D.R., Kovari H., Ledergerber B., Martinetti G., Martinez de Tejada B., Marzolini C., Metzner J.K., Muller N., Nicca D., Pantaleo G., Paioni P., Rauch A., Rudin C., Speck R., Stockle M., Tarr P., Trkola A., Vernazza P., Wandeler G., Yerly S., Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Internal Medicine, Medical Microbiology & Infectious Diseases, Virology, Pediatric Surgery, Pediatrics, Chammartin, F, Lodi, S, Logan, R, Ryom, L, Mocroft, A, Kirk, O, D'Arminio Monforte, A, Reiss, P, Phillips, A, El-Sadr, W, Hatleberg, C, Pradier, C, Bonnet, F, Law, M, De Wit, S, Sabin, C, Lundgren, J, Bucher, H, Calvo, G, Dabis, F, Morfeldt, L, Weber, R, Lind-Thomsen, A, Salbol Brandt, R, Hillebreght, M, Zaheri, S, Wit, F, Scherrer, A, Schoni-Affolter, F, Rickenbach, M, Tavelli, A, Fanti, I, Leleux, O, Mourali, J, Le Marec, F, Boerg, E, Thulin, E, Sundstrom, A, Bartsch, G, Thompsen, G, Necsoi, C, Delforge, M, Fontas, E, Caissotti, C, Dollet, K, Mateu, S, Torres, F, Petoumenos, K, Blance, A, Huang, R, Puhr, R, Gronborg Laut, K, Kristensen, D, Kamara, D, Smith, C, Raben, D, Matthews, C, Bojesen, A, Grevsen, A, Powderly, B, Shortman, N, Moecklinghoff, C, Reilly, G, Smit, C, Ross, M, Fux, C, Morlat, P, Friis-Moller, N, Kowalska, J, Bohlius, J, Bower, M, Fatkenheuer, G, Grulich, A, Sjol, A, Meidahl, P, Iversen, J, Hillebregt, M, Prins, J, Kuijpers, T, Scherpbier, H, Van Der Meer, J, Godfried, M, Van Der Poll, T, Nellen, F, Geerlings, S, Van Vugt, M, 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M, Elsenburg, L, Damen, M, Kwa, I, Groeneveld, P, Bouwhuis, J, Van Den Berg, J, Van Hulzen, A, Van Der Bliek, G, Bor, P, Bloembergen, P, Wolfhagen, M, Ruijs, G, Kroon, F, De Boer, M, Bauer, M, Jolink, H, Vollaard, A, Dorama, W, Van Holten, N, Claas, E, Wessels, E, Den Hollander, J, Pogany, K, Roukens, A, Kastelijns, M, Smit, J, Smit, E, Struik-Kalkman, D, Tearno, C, Bezemer, M, van Niekerk, T, Pontesilli, O, Lowe, S, Oude Lashof, A, Posthouwer, D, Ackens, R, Schippers, J, Vergoossen, R, Weijenberg-Maes, B, van Loo, I, Havenith, T, Leyten, E, Gelinck, L, van Hartingsveld, A, Meerkerk, C, Wildenbeest, G, Mutsaers, J, Jansen, C, Mulder, J, Vrouenraets, S, Lauw, F, van Broekhuizen, M, Paap, H, Vlasblom, D, Smits, P, Weijer, S, El Moussaoui, R, Bosma, A, van Vonderen, M, van Houte, D, Kampschreur, L, Dijkstra, K, Faber, S, Weel, J, Kootstra, G, Delsing, C, van der Burg-Van de Plas, M, Heins, H, Lucas, E, Kortmann, W, van Twillert, G, Cohen Stuart, J, Diederen, B, van Truijen-Oud, F, van der Reijden, W, Jansen, R, Brinkman, K, van den Berk, G, Blok, W, Frissen, P, Lettinga, K, Schouten, W, Veenstra, J, Brouwer, J, Geerders, F, Hoeksema, K, Kleene, J, van der Meche, B, Spelbrink, M, Sulman, H, Toonen, A, Wijnands, S, Kwa, D, Witte, E, Koopmans, P, Keuter, M, van der Ven, A, ter Hofstede, H, Dofferhoff, A, van Crevel, R, Albers, M, Bosch, M, Grintjes-Huisman, K, Zomer, J, Stelma, F, Rahamat-Langendoen, J, Burger, D, Richter, C, Gisolf, H, Hassing, J, ter Beest, G, van Bentum, P, Langebeek, N, Tiemessen, R, Swanink, C, van Lelyveld, S, Soetekouw, R, Hulshoff, N, van der Prijt, L, van der Swaluw, J, Bermon, N, Herpers, B, Veenendaal, D, Verhagen, W, van Wijk, M, van Kasteren, M, Brouwer, E, de Kruijf-Van de Wiel, B, Kuipers, M, Santegoets, R, van der Ven, B, Marcelis, H, Buiting, A, Kabel, J, Bierman, W, Scholvinck, H, Wilting, R, Stienstra, Y, de Groot-De Jonge, H, van der Meulen, A, de Weerd, A, Ludwig-Roukema, J, Niesters, H, Riezebos-Brilman, A, van Leer-Buter, C, Knoester, M, Hoepelman, A, Mudrikova, T, Ellerbroek, M, Oosterheert, J, Arends, E, Barth, E, Wassenberg, M, Schadd, M, van Elst-Laurijssen, D, van Oers-Hazelzet, B, Vervoort, S, van Berkel, M, Schuurman, R, Verduyn-Lunel, F, Wensing, A, Peters, E, van Agtmael, A, Bomers, M, de Vocht, J, Heitmuller, M, Laan, M, Pettersson, M, Vandenbroucke-Grauls, C, Ang, W, Geelen, S, Wolfs, T, Bont, J, Nauta, N, Bezemer, O, van Sighem, I, Boender, S, de Jong, A, Bergsma, D, Hoekstra, P, de Lang, A, Grivell, S, Jansen, A, Rademaker, J, Raethke, M, Meijering, R, Schnorr, S, de Groot, L, van den Akker, M, Bakker, Y, Claessen, E, El Berkaoui, A, Koops, J, Kruijne, E, Lodewijk, C, Munjishvili, L, Peeck, B, Ree, C, Regtop, R, Ruijs, Y, Rutkens, T, van de Sande, L, Schoorl, M, Timmerman, A, Tuijn, E, Veenenberg, L, van der Vliet, S, Wisse, A, Woudstra, T, Tuk, B, Dupon, M, Gaborieau, V, Lacoste, D, Malvy, D, Mercie, P, Neau, D, Pellegrin, L, Tchamgoue, S, Lazaro, E, Cazanave, C, Vandenhende, M, Vareil, O, Gerard, Y, Blanco, P, Bouchet, S, Breilh, D, Fleury, H, Pellegrin, I, Chene, G, Thiebaut, R, Wittkop, L, Lawson-Ayayi, S, Gimbert, A, Desjardin, S, Lacaze-Buzy, L, Petrov-Sanchez, V, Andre, N, Bernard, K, Caubet, O, Caunegre, L, Chossat, I, Courtault, C, Dauchy, A, Dondia, D, Duffau, P, Dutronc, H, Farbos, S, Faure, I, Ferrand, H, Greib, C, Hessamfar, M, Imbert, Y, Lataste, P, Marie, J, Mechain, M, Monlun, E, Ochoa, A, Pistone, T, Raymond, I, Receveur, C, Rispal, P, Sorin, L, Valette, C, Viallard, J, Wille, H, Wirth, G, Lafon, M, Trimoulet, P, Bellecave, P, Tumiotto, C, Haramburu, F, Miremeont-Salame, G, Blaizeau, J, Decoin, M, Hannapier, C, Lenaud, E, Pougetoux, A, Delveaux, S, D'Ivernois, C, Diarra, F, Uwamaliya-Nziyumvira, B, Palmer, G, Conte, V, Sapparrart, V, Moore, R, Edwards, S, Hoy, J, Watson, K, Roth, N, Lau, H, Bloch, M, Baker, D, Carr, A, Cooper, D, O'Sullivan, M, Nolan, D, Guelfi, G, Domingo, P, Sambeat, A, Gatell, J, Del Cacho, E, Cadafalch, J, Fuster, M, Codina, C, Sirera, G, Vaque, A, Clumeck, N, Gennotte, F, Gerard, M, Kabeya, K, Konopnicki, D, Libois, A, Martin, C, Payen, C, Semaille, P, Van Laethem, Y, Neaton, J, El-Sadr, M, Krum, E, Thompson, G, Wentworth, D, Luskin-Hawk, R, Telzak, E, Abrams, I, Cohn, D, Markowitz, N, Arduino, R, Mushatt, D, Friedland, G, Perez, G, Tedaldi, E, Fisher, E, Gordin, F, Crane, R, Sampson, J, Baxter, J, Gazzard, B, Horban, A, Karpov, I, Pedersen, C, Ristola, M, Rockstroh, J, Peters, L, Fischer, H, Larsen, F, Podlekareva, D, Cozzi-Lepri, A, Shepherd, L, Schultze, A, Amele, S, Losso, M, Kundro, M, Schmied, B, Zangerle, R, Vassilenko, A, Mitsura, M, Paduto, D, Florence, E, Vandekerckhove, L, Hadziosmanovic, V, Begovac, J, Machala, L, Jilich, D, Sedlacek, D, Kronborg, G, Benfield, T, Gerstoft, J, Katzenstein, T, Moller, F, Ostergaard, L, Wiese, L, Nielsen, N, Zilmer, K, Smidt, J, Aho, I, Viard, J, Girard, P, Duvivier, C, Schmidt, R, Degen, O, Stellbrink, J, Stefan, C, Bogner, J, Chkhartishvili, N, Gargalianos, P, Xylomenos, G, Armenis, K, Sambatakou, H, Szlavik, J, Gottfredsson, M, Mulcahy, F, Yust, I, Turner, D, Burke, M, Shahar, E, Hassoun, G, Elinav, H, Haouzi, M, Elbirt, D, Sthoeger, M, Esposito, R, Mazeu, I, Mussini, C, Mazzotta, F, Gabbuti, A, Vullo, V, Lichtner, M, Zaccarelli, M, Antinori, A, Acinapura, R, Plazzi, M, Lazzarin, A, Castagna, A, Gianotti, N, Galli, M, Ridolfo, A, Rozentale, B, Uzdaviniene, V, Matulionyte, R, Staub, T, Hemmer, R, Ormaasen, V, Maeland, A, Bruun, J, Knysz, B, Gasiorowski, J, Inglot, M, Bakowska, E, Flisiak, R, Grzeszczuk, A, Parczewski, M, Maciejewska, K, Aksak-Was, B, Beniowski, M, Mularska, E, Smiatacz, T, Gensing, M, Jablonowska, E, Malolepsza, E, Wojcik, K, Mozer-Lisewska, I, Caldeira, L, Mansinho, K, Maltez, F, Radoi, R, Oprea, C, Panteleev, A, Panteleev, O, Yakovlev, A, Trofimora, T, Khromova, I, Kuzovatova, E, Borodulina, E, Vdoushkina, E, Jevtovic, D, Tomazic, J, Miro, M, Moreno, S, Rodriguez, J, Clotet, B, Jou, A, Paredes, R, Tural, C, Puig, J, Bravo, I, Gutierrez, M, Mateo, G, Laporte, M, Falconer, K, Thalme, A, Sonnerborg, A, Blaxhult, A, Flamholc, L, Cavassini, M, Calmy, A, Furrer, H, Battegay, M, Schmid, P, Kuznetsova, A, Kyselyova, G, Sluzhynska, M, Johnson, A, Simons, E, Orkin, C, Weber, J, Scullard, G, Clarke, A, Leen, C, Thulin, G, Akerlund, B, Koppel, K, Karlsson, A, Hakangard, C, Castelli, F, Cauda, R, Di Perri, G, Iardino, R, Ippolito, G, Marchetti, C, Perno, F, von Schloesser, F, Viale, P, Ceccherini-Silberstein, F, Girardi, E, Lo Caputo, S, Puoti, M, Andreoni, M, Ammassari, A, Balotta, C, Bandera, A, Bonfanti, P, Bonora, S, Borderi, M, Calcagno, A, Calza, L, Capobianchi, R, Cingolani, A, Cinque, P, De Luca, A, Di Biagio, A, Gori, A, Guaraldi, G, Lapadula, G, Madeddu, G, Maggiolo, F, Marcotullio, S, Monno, L, Nozza, S, Quiros Roldan, E, Rossotti, R, Rusconi, S, Santoro, M, Saracino, A, Galli, L, Lorenzini, P, Rodano, A, Shanyinde, M, Carletti, F, Carrara, S, Di Caro, A, Graziano, S, Petrone, F, Prota, G, Quartu, S, Truffa, S, Giacometti, A, Costantini, A, Barocci, V, Angarano, G, Santoro, C, Suardi, C, Donati, V, Verucchi, G, Minardi, C, Quirino, T, Abeli, C, Manconi, E, Piano, P, Cacopardo, B, Celesia, B, Vecchiet, J, Falasca, K, Pan, A, Lorenzotti, S, Sighinolfi, L, Segala, D, Vichi, F, Cassola, G, Viscoli, C, Alessandrini, A, Bobbio, N, Mazzarello, G, Mastroianni, C, Belvisi, V, Caramma, I, Chiodera, A, Milini, P, Rizzardini, G, Moioli, C, Piolini, R, Ridolfo, L, Salpietro, S, Tincati, C, Puzzolante, C, Abrescia, N, Chirianni, A, Borgia, G, Orlando, R, Bonadies, G, Di Martino, F, Gentile, I, Maddaloni, L, Cattelan, M, Marinello, S, Cascio, A, Colomba, C, Baldelli, F, Schiaroli, E, Parruti, G, Sozio, F, Magnani, G, Ursitti, A, Cristaudo, A, Baldin, G, Capozzi, M, Cicalini, S, Fontanelli Sulekova, L, Iaiani, G, Latini, A, Mastrorosa, I, Savinelli, S, Vergori, A, Cecchetto, M, Viviani, F, Bagella, P, Rossetti, B, Franco, A, Fontana Del Vecchio, R, Francisci, D, Di Giuli, C, Caramello, P, Orofino, C, Sciandra, M, Bassetti, M, Londero, A, Pellizzer, G, Manfrin, V, Starnini, G, Ialungo, A, Dellamonica, P, Bernard, E, Courjon, J, Cua, E, De Salvador-Guillouet, F, Durant, J, Etienne, C, Ferrando, S, Mondain-Miton, V, Naqvi, A, Perbost, I, Pillet, S, Prouvost-Keller, B, Pugliese, P, Rio, V, Risso, K, Roger, M, Aubert, V, Bernasconi, E, Ciuffi, A, Dollenmaier, G, Egger, M, Elzi, L, Fehr, J, Fellay, J, Gunthard, F, Haerry, D, Hasse, B, Hirsch, H, Hoffmann, M, Hosli, I, Kahlert, C, Kaiser, L, Keiser, O, Klimkait, T, Kouyos, D, Kovari, H, Ledergerber, B, Martinetti, G, Martinez de Tejada, B, Marzolini, C, Metzner, J, Muller, N, Nicca, D, Pantaleo, G, Paioni, P, Rauch, A, Rudin, C, Speck, R, Stockle, M, Tarr, P, Trkola, A, Vernazza, P, Wandeler, G, Yerly, S, Internal medicine, Pediatric surgery, Medical Microbiology and Infection Prevention, Amsterdam Gastroenterology Endocrinology Metabolism, Faculteit Medische Wetenschappen/UMCG, Microbes in Health and Disease (MHD), and Molecular Pharmacology

Subjects
Male, HIV AIDS, HIV Infections, 0302 clinical medicine, Interquartile range, Risk Factors, Neoplasms, Medicine, 030212 general & internal medicine, Prospective Studies, Prospective cohort study, 0303 health sciences, Incidence, Absolute risk reduction, Drugs, General Medicine, Middle Aged, Viral Load, Antiretroviral therapy, 3. Good health, AIDS, Cancer treatment, Prevention policy and public health, Cohort, Infectious diseases, Cohort studies, Female, Viral load, Adult, medicine.medical_specialty, Anti-HIV Agents, HIV Infections/drug therapy, Socio-culturale, Time-to-Treatment, 03 medical and health sciences, Acquired immunodeficiency syndrome (AIDS), SDG 3 - Good Health and Well-being, Internal medicine, Internal Medicine, Humans, Adverse effect, 030306 microbiology, business.industry, HIV, Cancer, medicine.disease, CD4 Lymphocyte Count, Anti-HIV Agents/therapeutic use, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Neoplasms/epidemiology
Abstract

BACKGROUND: Immediate initiation of antiretroviral therapy (ART) regardless of CD4 cell count reduces risk for AIDS and non-AIDS-related events in asymptomatic, HIV-positive persons and is the standard of care. However, most HIV-positive persons initiate ART when their CD4 count decreases below 500 × 10 9 cells/L. Consequences of delayed ART on risk for non-AIDS-defining and AIDS-defining cancer, one of the most common reasons for death in HIV, are unclear. OBJECTIVE: To estimate the long-term risk difference for cancer with the immediate ART strategy.DESIGN: Multinational prospective cohort study.SETTING: The D:A:D (Data collection on Adverse events of anti-HIV Drugs) study, which included HIV-positive persons from Europe, Australia, and the United States.PARTICIPANTS: 8318 HIV-positive persons with at least 1 measurement each of CD4 cell count and viral load while ART-naive (study period, 2006 to 2016).MEASUREMENTS: The parametric g-formula was used, with adjustment for baseline and time-dependent confounders (CD4 cell count and viral load), to assess the 10-year risk for non-AIDS-defining and AIDS-defining cancer of immediate versus deferred (at CD4 counts RESULTS: During 64 021 person-years of follow-up, 231 cases of non-AIDS-defining cancer and 272 of AIDS-defining cancer occurred among HIV-positive persons with a median age of 36 years (interquartile range, 29 to 43 years). With immediate ART, the 10-year risk for non-AIDS-defining cancer was 2.97% (95% CI, 2.37% to 3.50%) and that for AIDS-defining cancer was 2.50% (CI, 2.37% to 3.38%). Compared with immediate ART initiation, the 10-year absolute risk differences when deferring ART to CD4 counts less than 500 × 10 9 cells/L and less than 350 × 10 9 cells/L were 0.12 percentage point (CI, -0.01 to 0.26 percentage point) and 0.29 percentage point (CI, -0.03 to 0.73 percentage point), respectively, for non-AIDS-defining cancer and 0.32 percentage point (CI, 0.21 to 0.44 percentage point) and 1.00 percentage point (CI, 0.67 to 1.44 percentage points), respectively, for AIDS-defining cancer. LIMITATION: Potential residual confounding due to observational study design.CONCLUSION: In this young cohort, effects of immediate ART on 10-year risk for cancer were small, and further supportive data are needed for non-AIDS-defining cancer.PRIMARY FUNDING SOURCE: Highly Active Antiretroviral Therapy Oversight Committee.

Published
2021

16. Treatment strategies for neuroendocrine liver metastases: a systematic review

Author

Edoardo M. Muttillo, Gennaro Mazzarella, Biagio Picardi, Stefano Rossi, Lorenzo Cinelli, Michele Diana, Andrea Baiocchini, Eric Felli, Patrick Pessaux, Emanuele Felli, and Irnerio A. Muttillo

Subjects
Hepatology, Liver Neoplasms, Gastroenterology, liver, Liver Transplantation, Pancreatic Neoplasms, neuroendocrine liver metastases, surgery, Neuroendocrine Tumors, Intestinal Neoplasms, Humans, 610 Medicine & health, liver metastases
Abstract

BACKGROUND Gastroenteropancreatic neuroendocrine tumors are often diagnosed when metastatic. The liver is the main site of metastases. Unfortunately, optimal management of neuroendocrine liver metastases remains a topic of debate. The aim of this study was to make a systematic review of the current literature about the results of the different treatments of neuroendocrine liver metastases. METHODS A systematic review was conducted for English language publications from 1995 to 2021. Outcomes were analyzed according to survival, disease-free survival, and in the case of systemic therapies, progression-free survival. RESULTS 5509 patients were analyzed in the review. 67% of patients underwent surgery achieving 5 years overall survival despite only 30% percent without a recurrence. 60% of patients that had received a transplant reached 5 years survival with a low disease-free survival rate (20%). Five-year survival rate was 36.2% for patients undergoing loco-regional therapies. CONCLUSION Surgical resection is the best treatment when metastases are resectable, with the highest rate of survival, although liver transplantation shows good results for patients not eligible for surgery. Loco-regional therapies may be useful when surgical resection is contraindicated, or selectively used as a bridge to surgery or transplantation. Systemic therapies are indicated in patients for whom curative treatment cannot be obtained.

Published
2022

17. Intrapartum use of zidovudine in a large cohort of pregnant women living with HIV in Italy

Author

Lucia Taramasso, Francesca Bovis, Antonio Di Biagio, Federica Mignone, Carlo Giaquinto, Claudia Tagliabue, Vania Giacomet, Orazio Genovese, Elena Chiappini, Serena Salomè, Raffaele Badolato, Ines Carloni, Monica Cellini, Icilio Dodi, Grazia Bossi, Alessandra Allodi, Stefania Bernardi, Rita Consolini, Maurizio Dedoni, Giuseppe Banderali, Antonio Mazza, Giulia Pruccoli, Osvalda Rampon, Paola Erba, Giada Di Pietro, Carlotta Montagnani, Letizia Capasso, Laura Dotta, Federica Zallocco, Maurizio De Martino, Catiuscia Lisi, Pier Angelo Tovo, Matteo Bassetti, Clara Gabiano, and Luisa Galli

Subjects
U=U, Microbiology (medical), Anti-HIV Agents, Infant, Newborn, HIV, HIV Infections, peripartum, vertical transmission, zidovudine, Infectious Diseases, Pregnancy, Humans, Female, Pregnant Women, Pregnancy Complications, Infectious, Child, Zidovudine
Abstract

Intravenous administration of zidovudine (ZDV) during labour is a key step for vertical HIV transmission (VT) prevention, but there is no evidence of benefit when maternal HIV-RNA at delivery is50 copies/mL. The aim of this study is evaluating the appropriateness of intrapartum ZDV use in Italy.Observational study including mother-infant pairs with perinatal HIV exposure during 2002-2019, enrolled in the Italian Register for HIV Infection in Children. Univariable and multivariable logistic regression were used to evaluate factors associated with VT.A total of 3,861 infants, born from 3,791 pregnancies were included. The frequency of ZDV use was 79.9%, 92.1%, 93.7% and 92.8% when HIV-RNA was not available, ≥400 copies, between 50 and 399 copies, and50 copies/mL. Thirty-three out of 3861 (0.85%) infants were subsequently diagnosed with HIV, 25/3861 (0.6%) of them born to mothers receiving intrapartum ZDV, and 31 (93.9%) to mothers with HIV-RNA ≥50 copies/mL or not available. In women with HIV-RNA50 copies/mL, ART discontinuation during pregnancy was the strongest risk factor for VT (odds ratio, OR, 23.1, 95%CI 2.4-219.3), while a higher gestational age (OR 0.6, 95%CI 0.4-0.8) and PEP administration to the newborn (aOR 0.004, 95%CI0.0001-0.4) were protective factors. Intrapartum ZDV administration did not influence the final outcome in this group.In ART era, more transmission events may occur in utero, limiting value of intrapartum ZDV, particularly for women with suppressed HIV-RNA load. More attention to the HIV-RNA testing of mothers before delivery may avoid unnecessary ZDV use.

Published
2022

18. Genomic Landscapes and Hallmarks of Mutant RAS in Human Cancers

Author

Robert B. Scharpf, Archana Balan, Biagio Ricciuti, Jacob Fiksel, Christopher Cherry, Chenguang Wang, Michele L. Lenoue-Newton, Hira A. Rizvi, James R. White, Alexander S. Baras, Jordan Anaya, Blair V. Landon, Marta Majcherska-Agrawal, Paola Ghanem, Jocelyn Lee, Leon Raskin, Andrew S. Park, Huakang Tu, Hil Hsu, Kathryn C. Arbour, Mark M. Awad, Gregory J. Riely, Christine M. Lovly, and Valsamo Anagnostou

Subjects
Proto-Oncogene Proteins p21(ras), Cancer Research, Lung Neoplasms, Oncology, Carcinoma, Non-Small-Cell Lung, Mutation, Tumor Microenvironment, Humans, Bayes Theorem, Genomics, Article
Abstract

The RAS family of small GTPases represents the most commonly activated oncogenes in human cancers. To better understand the prevalence of somatic RAS mutations and the compendium of genes that are coaltered in RAS-mutant tumors, we analyzed targeted next-generation sequencing data of 607,863 mutations from 66,372 tumors in 51 cancer types in the AACR Project GENIE Registry. Bayesian hierarchical models were implemented to estimate the cancer-specific prevalence of RAS and non-RAS somatic mutations, to evaluate co-occurrence and mutual exclusivity, and to model the effects of tumor mutation burden and mutational signatures on comutation patterns. These analyses revealed differential RAS prevalence and comutations with non-RAS genes in a cancer lineage-dependent and context-dependent manner, with differences across age, sex, and ethnic groups. Allele-specific RAS co-mutational patterns included an enrichment in NTRK3 and chromatin-regulating gene mutations in KRAS G12C-mutant non–small cell lung cancer. Integrated multiomic analyses of 10,217 tumors from The Cancer Genome Atlas (TCGA) revealed distinct genotype-driven gene expression programs pointing to differential recruitment of cancer hallmarks as well as phenotypic differences and immune surveillance states in the tumor microenvironment of RAS-mutant tumors. The distinct genomic tracks discovered in RAS-mutant tumors reflected differential clinical outcomes in TCGA cohort and in an independent cohort of patients with KRAS G12C-mutant non–small cell lung cancer that received immunotherapy-containing regimens. The RAS genetic architecture points to cancer lineage–specific therapeutic vulnerabilities that can be leveraged for rationally combining RAS-mutant allele-directed therapies with targeted therapies and immunotherapy. Significance: The complex genomic landscape of RAS-mutant tumors is reflective of selection processes in a cancer lineage–specific and context-dependent manner, highlighting differential therapeutic vulnerabilities that can be clinically translated.

Published
2022

19. Non-motor symptoms burden in motor-fluctuating patients with Parkinson’s disease may be alleviated by safinamide: the VALE-SAFI study

Author

Claudia De Masi, Claudio Liguori, Matteo Spanetta, Mariana Fernandes, Rocco Cerroni, Elena Garasto, Mariangela Pierantozzi, Nicola Biagio Mercuri, and Alessandro Stefani

Subjects
Male, Benzylamines, Psychiatry and Mental health, Alanine, Neurology, Quality of Life, Humans, Pain, Female, Parkinson Disease, Neurology (clinical), Fatigue, Biological Psychiatry
Abstract

Parkinson’s disease (PD) is characterized by motor symptoms often experienced in concomitance with non-motor symptoms (NMS), such as depression, apathy, pain, sleep disorders, and urinary dysfunction. The present study aimed to explore the effect of safinamide treatment on NMS and quality of life in motor-fluctuating PD patients. VALE-SAFI is an observational single-centre study performed in fluctuating PD patients starting safinamide treatment and followed for 6 months. The effects of safinamide on NMS, sleep, fatigue, depression and pain were assessed through validated sales. Changes in the scales from baseline to the 6-month follow-up visit were analysed. 60 PD patients (66.67% males) were enrolled at baseline, and 45 patients completed the 6-month follow-up. PD patients improved motor symptoms at follow-up, with the significant reduction of motor fluctuations. The global score of the NMS Scale significantly decreased between baseline and the follow-up. Regarding pain domains, patients reported a significant improvement in discolouration and oedema/swelling. Further, a significant improvement was observed from baseline to follow-up in sleep quality measured through the Pittsburgh Sleep Quality Index, while no changes were documented in daytime sleepiness. No differences were found in depression and fatigue between baseline and follow-up. Finally, the patient’s perception of the impact of PD on functioning and well-being decreased from baseline to follow-up. The present findings confirmed the beneficial effect of safinamide on both motor and non-motor symptoms, also improving the quality of life of PD patients. Furthermore, these data support the positive effects of safinamide on pain and mood, as well as on sleep quality and continuity.

Published
2022

20. Constipation distinguishes different clinical-biochemical patterns in de novo Parkinson's disease

Author

Piergiorgio Grillo, Giulia Maria Sancesario, Davide Mascioli, Lorenza Geusa, Henri Zenuni, Emilia Giannella, David Della Morte, Nicola Biagio Mercuri, and Tommaso Schirinzi

Subjects
Parkinson Disease, Settore MED/26, Levodopa, Cerebrospinal fluid, Neurology, Lactates, alpha-Synuclein, Humans, Neurology (clinical), Geriatrics and Gerontology, Constipation, Biomarkers, Serum Albumin, Blood-brain barrier
Abstract

Prodromal constipation (PC) at Parkinson's disease (PD) onset may mark a distinct neurodegenerative trajectory; accordingly, presenting phenotype, biochemical signature, and progression of PD patients with PC (PD + PC) might differ from those without (PDwoPC). We compared the clinical-biochemical profile of de novo PD patients with and without PC, and the respective mid-term progression, to establish the grouping effect of PC.Motor and non-motor scores were collected at diagnosis in n = 57 PD + PC patients and n = 73 PDwoPC. Paired CSF biomarkers (α-synuclein, amyloid and tau peptides, lactate, CSF/serum albumin ratio or AR) were assessed into a smaller sample and n = 46 controls. Clinical progression was estimated as Hoehn and Yahr stage (HY) and levodopa equivalent daily dose (LEDD) change 2.06 ± 1.35 years after diagnosis.At onset, PD + PC patients had higher HY and MDS-UPDRS-part III scores, and higher CSF AR. PDwoPC had higher Non-Motor Symptoms Scale domain-2 score, and lower CSF α-synuclein level. At follow-up, PD + PC had greater LEDD.PC identifies a group of de novo patients with more severe motor impairment, possible blood brain barrier disruption, and greater dopaminergic requirement at mid-term; conversely, de novo PDwoPC patients had prominent fatigue, and pronounced central synucleinopathy.

Published
2022

21. Off-label use of combined antiretroviral therapy, analysis of data collected by the Italian Register for HIV-1 infection in paediatrics in a large cohort of children

Author

Chiappini, E., Lisi, C., Giacomet, V., Erba, P., Bernardi, S., Zangari, P., Di Biagio, A., Taramasso, L., Giaquinto, C., Rampon, O., Gabiano, C., Garazzino, S., Tagliabue, C., Esposito, S., Bruzzese, E., Badolato, R., Zanaboni, D., Cellini, M., Dedoni, M., Mazza, A., Pession, A., Giannini, A. M., Salvini, F., Dodi, I., Carloni, I., Cazzato, S., Tovo, P. A., de Martino, M., Galli, L., Parigi, S., Orlandi, F., de Martino, A., Pinzani, R., Abbagnato, L., Ruggeri, M., Baldi, F., Faldella, G., Chiriaco, P., Dessi, C., Panto, M. G., Anastasio, E., Govoni, M. R., Bigi, M., Bondi, E., Borea, R., Cenderello, G., Tommasi, D., Nogare, E. R. D., Saitta, M., Felici, L., Consolini, R., Antonellini, A., Anzidei, G., Genovese, O., Catania, S., Natale, F., Olmeo, P., Cristiano, L., Portelli, V., Rabusin, M., Di Pietro, G. M., Fabrizio, L., Chiappini, Elena, Lisi, Catiuscia, Giacomet, Vania, Erba, Paola, Bernardi, Stefania, Zangari, Paola, Di Biagio, Antonio, Taramasso, Lucia, Giaquinto, Carlo, Rampon, Osvalda, Gabiano, Clara, Garazzino, Silvia, Tagliabue, Claudia, Esposito, Susanna, Bruzzese, Eugenia, Badolato, Raffaele, Zanaboni, Domenico, Cellini, Monica, Dedoni, Maurizio, Mazza, Antonio, Pession, Andrea, Giannini, Anna Maria, Salvini, Filippo, Dodi, Icilio, Carloni, Ine, Cazzato, Salvatore, Tovo, Pier Angelo, de Martino, Maurizio, and Galli, Luisa

Subjects
Register (sociolinguistics), Pediatrics, medicine.medical_specialty, HAART, Adolescent, Anti-HIV Agents, Off-label therapy, Human immunodeficiency virus (HIV), HIV Infections, Infectious and parasitic diseases, RC109-216, HIV-1 infection, medicine.disease_cause, Off-label use, Retrospective Studie, Antiretroviral Therapy, Highly Active, medicine, Humans, Highly Active, HIV Infection, Child, Children, Antiretroviral therapy, CD4 Lymphocyte Count, Off-Label Use, Retrospective Studies, Viral Load, HIV-1, business.industry, Research, Anti-HIV Agent, virus diseases, Large cohort, Infectious Diseases, business, Human
Abstract

Background Early start of highly active antiretroviral therapy (HAART) in perinatally HIV-1 infected children is the optimal strategy to prevent immunological and clinical deterioration. To date, according to EMA, only 35% of antiretroviral drugs are licenced in children Methods An observational retrospective study investigating the rate and the outcomes of off-label prescription of HAART was conducted on 225 perinatally HIV-1 infected children enrolled in the Italian Register for HIV Infection in Children and followed-up from 2001 to 2018. Results 22.2% (50/225) of included children were receiving an off-label HAART regimen at last check. Only 26% (13/50) of off-label children had an undetectable viral load (VL) before the commencing of the regimen and the 52.0% (26/50) had a CD4 + T lymphocyte percentage > 25%. At last check, during the off label regimen, the 80% (40/50) of patients had an undetectable VL, and 90% (45/50) of them displayed CD4 + T lymphocyte percentage > 25%. The most widely used off-label drugs were: dolutegravir/abacavir/lamivudine (16%; 8/50), emtricitbine/tenofovir disoproxil (22%; 11/50), lopinavir/ritonavir (20%; 10/50) and elvitegravir/cobicistat/emtricitabine/ tenofovir alafenamide (10%; 10/50). At logistic regression analysis, detectable VL before starting the current HAART regimen was a risk factor for receiving an off-label therapy (OR: 2.41; 95% CI 1.13–5.19; p = 0.024). Moreover, children Conclusion The prescription of an off-label HAART regimen in perinatally HIV-1 infected children was common, in particular in children with detectable VL despite previous HAART and in younger children, especially those receiving their first regimen. Our data suggest similar proportions of virological and immunological successes at last check among children receiving off-label or on-label HAART. Larger studies are needed to better clarify efficacy and safety of off-label HAART regimens in children, in order to allow the enlargement of on-label prescription in children.

Published
2022

22. Nasal Microbiome in COVID-19: A Potential Role of Corynebacterium in Anosmia

Author

Carmela, Nardelli, Giovanni Luca, Scaglione, Domenico, Testa, Mario, Setaro, Filippo, Russo, Carmela, Di Domenico, Lidia, Atripaldi, Massimo, Zollo, Federica, Corrado, Paola, Salvatore, Biagio, Pinchera, Ivan, Gentile, Ettore, Capoluongo, Nardelli, Carmela, Scaglione, Giovanni Luca, Testa, Domenico, Setaro, Mario, Russo, Filippo, Di Domenico, Carmela, Atripaldi, Lidia, Zollo, Massimo, Corrado, Federica, Salvatore, Paola, Pinchera, Biagio, Gentile, Ivan, and Capoluongo, Ettore

Subjects
Actinobacteria, Bacteria, SARS-CoV-2, Anosmia, RNA, Ribosomal, 16S, Microbiota, Humans, COVID-19, General Medicine, Corynebacterium, Applied Microbiology and Biotechnology, Microbiology
Abstract

The evolution and the development of the symptoms of Coronavirus disease 19 (COVID-19) are due to different factors, where the microbiome plays a relevant role. The possible relationships between the gut, lung, nasopharyngeal, and oral microbiome with COVID-19 have been investigated. We analyzed the nasal microbiome of both positive and negative SARS-CoV-2 individuals, showing differences in terms of bacterial composition in this niche of respiratory tract. The microbiota solution A (Arrow Diagnostics) was used to cover the hypervariable V1–V3 regions of the bacterial 16S rRNA gene. MicrobAT Suite and MicrobiomeAnalyst program were used to identify the operational taxonomic units (OTUs) and to perform the statistical analysis, respectively. The main taxa identified in nasal microbiome of COVID-19 patients and in Healthy Control subjects belonged to three distinct phyla: Proteobacteria (HC = 14%, Cov19 = 35.8%), Firmicutes (HC = 28.8%, Cov19 = 30.6%), and Actinobacteria (HC = 56.7%, Cov19 = 14.4%) with a relative abundance > 1% in all groups. A significant reduction of Actinobacteria in Cov19 group compared to controls (P P Corynebacterium was found in the patients compared to healthy controls (P = 0.001). Reduced abundance of Corynebacterium has been widely associated with anosmia, a common symptom of COVID-19 as suffered from our patients. Contrastingly, the Corynebacterium genus was highly represented in the nasal mucosa of healthy subjects. Further investigations on larger cohorts are necessary to establish functional relationships between nasal microbiota content and clinical features of COVID-19.

Published
2022

23. How Long Can a Dead Body Remain Infectious?

Author

Francesco, Ventura, Martina, Drommi, Rosario, Barranco, Arianna, Balbo, Stefano, Errico, Manuela, Mangioni, Giulia, Molinari, Antonio, Di Biagio, Vanessa, De Pace, Alessia, Lai, and Bianca, Bruzzone

Subjects
Male, SARS-CoV-2, Nasopharynx, Cadaver, COVID-19, Humans, Autopsy, United States, Aged, Body Remains, Pathology and Forensic Medicine
Abstract

The SARS-CoV-2 pandemic involved several changes and difficulties in the work of forensic pathologists. Postmortem nasopharyngeal swabs for the diagnosis of the SARS-CoV-2 infection are recommended before an autopsy examination by the Centers for Disease Control and Prevention.Autopsy examinations must not be performed for SARS-CoV-2 infection cases when airborne infection isolation rooms or other suitable spaces are unavailable. However, it has not yet been reported whether the presence of SARS-CoV-2 at a low viral load may be enough to infect and disseminate the contagion.Here, we report the case of a 67-year-old man found dead at home on November 9, 2020, and transferred immediately after to the Genova District Mortuary. As the first postmortem molecular nasopharyngeal swab resulted positive, a weekly sampling was carried until February 4, 2021. All the molecular tests were positive for SARS-CoV-2, including the last swab performed 87 days after the arrival of the corpse at the morgue. Virus isolation conducted on VERO E6 cells revealed no cytopathic effect indicating no viral replication as early as 18 days after the corpse's arrival at the morgue and until January 2021.Our findings suggest that the presence of the genome of SARS-CoV-2 at low viral load should not be considered a sign of an active infection but a trace of a remaining viral genome from a previous infection. Then, if the virus shows no replication activity, its molecular detection should not constitute a threat to public health. Further studies are required to establish the infection's potential and its correlation with viral load.

Published
2022

24. Apremilast retention rate in clinical practice: observations from an Italian multi-center study

Author

Alarico Ariani, Simone Parisi, Patrizia Del Medico, Antonella Farina, Elisa Visalli, Aldo Biagio Molica Colella, Federica Lumetti, Rosalba Caccavale, Palma Scolieri, Romina Andracco, Francesco Girelli, Elena Bravi, Matteo Colina, Alessandro Volpe, Aurora Ianniello, Veronica Franchina, Ilaria Platè, Eleonora Di Donato, Giorgio Amato, Carlo Salvarani, Gianluca Lucchini, Francesco De Lucia, Francesco Molica Colella, Daniele Santilli, Giulio Ferrero, Antonio Marchetta, Eugenio Arrigoni, Flavio Mozzani, Rosario Foti, Gilda Sandri, Vincenzo Bruzzese, Marino Paroli, Enrico Fusaro, and Andrea Becciolini

Subjects
psoriatic arthritis, Male, Anti-Inflammatory Agents, Non-Steroidal, Arthritis, Psoriatic, apremilast, General Medicine, Thalidomide, Treatment Outcome, Apremilast retention rates, Rheumatology, drug retention rate, Antirheumatic Agents, Humans, Apremilast, Drug retention rate, Psoriatic arthritis, Retrospective Studies
Abstract

There are few real-world setting studies focused on apremilast effectiveness (i.e., retention rate) in psoriatic arthritis (PsA). The main aim of this retrospective observational study is the assessment of apremilast 3-year retention rate in real-world PsA patients. Moreover, the secondary objective is to report the reasons of apremilast discontinuation and the factors related to treatment persistence.In fifteen Italian rheumatological referral centers, all PsA consecutive patients who received apremilast were enrolled. Anamnestic data, treatment history, and PsA disease activity (DAPSA) at baseline were recorded. The Kaplan-Meier curve and the Cox analysis computed the apremilast retention rate and treatment persistence-related risk factors. A p-value 0.05 was considered statistically significant.The 356 enrolled patients (median age 60 [interquartile range IQR 52-67] yrs; male prevalence 42.7%) median observation period was 17 [IQR 7-34] months (7218 patients-months). The apremilast retention rate at 12, 24, and 36 months was, respectively, 85.6%, 73.6%, and 61.8%. The main discontinuation reasons were secondary inefficacy (34% of interruptions), gastro-intestinal intolerance (24%), and primary inefficacy (19%). Age and oligo-articular phenotype were related to treatment persistence (respectively hazard ratio 0.98 IQR 0.96-0.99; p = 0.048 and 0.54 IQR 0.31-0.95; p = 0.03).Almost three-fifths of PsA patients receiving apremilast were still in treatment after 3 years. This study confirmed its effectiveness and safety profile. Apremilast appears as a good treatment choice in all oligo-articular PsA patients and in those ones burdened by relevant comorbidities. Key Points • Apremilast retention rates in this real-life cohort and trials are comparable. • The oligo-articular phenotype is associated with long-lasting treatment (i.e., 3 years). • No different or more prevalent adverse events were observed.

Published
2022

25. Total embedding of spermatic cord and hilar soft tissue in orchiectomy for seminoma: does the extensive sampling improve pathologic risk factors?

Author

Maurizio Colecchia, Biagio Paolini, Giacomo Maria Pini, Laura Carpenito, Beatrice Maghini, Barbara Avuzzi, Anna Maria Paganoni, and Nicola Nicolai

Subjects
Male, Spermatic Cord, Testicular Neoplasms, Risk Factors, Humans, Neoplasm Invasiveness, Cell Biology, General Medicine, Orchiectomy, Molecular Biology, Seminoma, Neoplasm Staging, Pathology and Forensic Medicine
Abstract

Pure seminomas represent the majority of testicular germ cell tumors and accurate diagnosis and staging require an accurate sampling of radical orchiectomy specimens. The aim of our study is to find the most informative gross sampling method for orchiectomy specimens. We performed the extensive sampling of 88 radical orchiectomy specimens embedding in their entirety testicular hilum, rete testis, hilar soft tissue, and spermatic cord. We examined the impact of this procedure on tumor stage, prognostic parameters (lymphovascular invasion and infiltration of rete testis, epididymis, tunica vaginalis, and spermatic cord), and their relationship with recurrence. Eighty-eight seminomas from 88 radical orchiectomies were sampled. Seventy-seven cases (87.5%) presented as clinical stage I and 11 cases (12.5%) as clinical stage II. The follow-up period range was 18-54 months and 82 patients (93.2%) had a minimum of 2-year follow-up. Tumor size ranged from 0.4 to 16 cm (mean 3.6) requiring a mean of 7.1 sections for entire tumoral sampling. Epididymis required 2 to 8 sections (mean 3.3), and hilum and hilar soft tissues 2 to 9 sections (mean 3.4). Epididymal infiltration and lymphovascular invasion resulted significant at multivariate analysis generating a receiver operating characteristic (ROC) curve with area under curve of 0.778. All the other parameters (except for pagetoid rete testis infiltration) were significant to predict metastasis only at univariate analysis. Extensive sampling of radical orchiectomy specimens does not improve the accuracy of staging in pure seminomas. Lymphovascular invasion and epididymal infiltration are useful to predict metastasis.

Published
2022

26. Differential prognostic effect of systemic inflammation in patients with non–small cell lung cancer treated with immunotherapy or chemotherapy: A post hoc analysis of the phase 3 <scp>OAK</scp> trial

Author

Alessio Cortellini, Biagio Ricciuti, Hossein Borghaei, Abdul Rafeh Naqash, Antonio D'Alessio, Claudia A. M. Fulgenzi, Alfredo Addeo, Giuseppe L. Banna, and David James Pinato

Subjects
Inflammation, Male, Cancer Research, Kelch-Like ECH-Associated Protein 1, Lung Neoplasms, NF-E2-Related Factor 2, DNA Helicases, Nuclear Proteins, Docetaxel, Prognosis, B7-H1 Antigen, ErbB Receptors, Proto-Oncogene Proteins p21(ras), Oncology, Carcinoma, Non-Small-Cell Lung, Humans, Immunologic Factors, Immunotherapy, Cell-Free Nucleic Acids, Transcription Factors
Abstract

A proinflammatory diathesis, as measured by the neutrophil to lymphocyte ratio (NLR), heralds an adverse disease course for non-small cell lung cancer (NSCLC).This post hoc analysis used data from the phase 3 OAK trial (NCT02008227), which randomized previously treated patients with NSCLC to atezolizumab or docetaxel. The main objective was assessing the differential impact of the pretreatment NLR on overall survival according to the treatment modality. In addition, patients' genomic characteristics were assessed according to their inflammatory status with a circulating free DNA (cfDNA) next-generation sequencing (NGS) analysis.In all, 600 and 575 patients with NLR data were included in the atezolizumab and docetaxel cohorts, respectively, with a median NLR of 4 (interquartile range, 2.6-6.7) for the pooled population. An NLR ≥4 was associated with a positive smoking status (88.6% vs. 78.1%; p .01), male sex (66.4% vs. 57.6%; p = .01), a worse performance status (71.3% vs. 55.2%; p .01), a higher number of metastatic sites (63.2% vs. 51.6%; p = .01), squamous histology (32.1% vs. 21.4%; p .01), and tissue KRAS mutations (30% vs. 18.7%; p = .02) but not with programmed death ligand 1 (PD-L1) expression or the tissue epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK) status. A pretreatment NLR ≥4 was more strongly associated with mortality after atezolizumab (adjusted hazard ratio [HR], 1.64; 95% confidence interval [CI], 1.35-2.01) versus docetaxel (HR, 1.32; 95% CI, 1.08-1.60; multivariable [MVA] interaction p = .08). The HR for an increased risk of death for PD-L1-negative/NLR ≥4 patients (compared with PD-L1-positive/NLR 4 patients) was significantly higher in the atezolizumab cohort (MVA interaction p = .01). The exclusion of EGFR/ALK-positive patients further increased the prognostic ability of the baseline NLR in favor of atezolizumab (MVA interaction p = .02). Pretreatment cfDNA data from NGS showed that patients with a high blood tumor mutation burden (cutoff, 16 mut/Mb) had a higher median NLR (4.6 vs. 3.7; p = .01). After adjustments for multiple comparisons, none of the selected variants of interest (EGFR, KRAS, TP53, KEAP1, STK11, SMARCA4, ARID1A, and targeted DNA damage response and repair genes) were significantly associated with the NLR.A low baseline NLR identified patients with NSCLC who derived a greater survival benefit from atezolizumab in comparison with those identified in the docetaxel cohort. The NLR could complement PD-L1 expression in tailoring treatment in this setting.

Published
2022

27. Predictors of Virological Failure Among People Living with HIV Switching from an Effective First-Line Antiretroviral Regimen

Author

Laura Magnasco, Rachele Pincino, Giuseppe Pasculli, Yagai Bouba, Francesco Saladini, Davide Fiore Bavaro, Andrea De Vito, Rossana Lattanzio, Romina Corsini, Maurizio Zazzi, Francesca Incardona, Barbara Rossetti, Antonia Bezenchek, Vanni Borghi, and Antonio Di Biagio

Subjects
Adult, Male, resistance-associated mutations, Anti-HIV Agents, Immunology, HIV Infections, Viral Load, Cohort Studies, optimization, second-line antiretroviral therapy, Infectious Diseases, Anti-Retroviral Agents, Virology, Humans, Female, Protease Inhibitors, AIDS HIV VF ART
Abstract

Aim of this study was to assess the predictors of virological failure (VF) among patients living with HIV (PLWHIV) switching from an effective first-line antiretroviral therapy (ART) regimen, and to evaluate the emergence of resistance-associated mutations. All adult patients enrolled in the Antiviral Response Cohort Analysis cohort who started ART after 2010, with at least 6 months of virological suppression (VS) before ART switch and with an available genotypic resistance test (GRT) at baseline were included. Thirty-two patients out of the 607 PLWHIV included (5.3%) experienced VF after a median of 11 months from ART switch. Younger age (adjusted Hazard Ratio [aHR] 0.96, 95% confidence interval [CI] 0.92-0.99

Published
2022

28. Reversibility of Central Nervous System Adverse Events in Course of Art

Author

Lucia Taramasso, Giancarlo Orofino, Elena Ricci, Barbara Menzaghi, Giuseppe Vittorio De Socio, Nicola Squillace, Giordano Madeddu, Francesca Vichi, Benedetto Maurizio Celesia, Chiara Molteni, Federico Conti, Filippo Del Puente, Eleonora Sarchi, Goffredo Angioni, Antonio Cascio, Carmela Grosso, Giustino Parruti, Antonio Di Biagio, Paolo Bonfanti, Taramasso, Lucia, Orofino, Giancarlo, Ricci, Elena, Menzaghi, Barbara, De Socio, Giuseppe Vittorio, Squillace, Nicola, Madeddu, Giordano, Vichi, Francesca, Celesia, Benedetto Maurizio, Molteni, Chiara, Conti, Federico, Del Puente, Filippo, Sarchi, Eleonora, Angioni, Goffredo, Cascio, Antonio, Grosso, Carmela, Parruti, Giustino, Di Biagio, Antonio, Bonfanti, Paolo, Taramasso, L, Orofino, G, Ricci, E, Menzaghi, B, De Socio, G, Squillace, N, Madeddu, G, Vichi, F, Celesia, B, Molteni, C, Conti, F, Del Puente, F, Sarchi, E, Angioni, G, Cascio, A, Grosso, C, Parruti, G, Di Biagio, A, and Bonfanti, P

Subjects
Central Nervous System, Anti-HIV Agents, adverse event, HIV, Anti-HIV Agent, HIV Infections, dolutegravir, CD4 Lymphocyte Count, Prospective Studie, Infectious Diseases, psychiatric, reversibility, Virology, neurocognitive, Humans, Prospective Studies, CNS, adverse events, Human
Abstract

The purpose of this study is to evaluate the frequency of central nervous system adverse events (CNS-AE) on dolutegravir (DTG) and non-DTG containing ART, and their reversibility, in the observational prospective SCOLTA cohort. Factors associated with CNS-AE were estimated using a Cox proportional-hazards model. 4939 people living with HIV (PLWH) were enrolled in DTG (n = 1179) and non-DTG (n = 3760) cohorts. Sixty-six SNC-AE leading to ART discontinuation were reported, 39/1179 (3.3%) in DTG and 27/3760 (0.7%) in non-DTG cohort. PLWH naïve to ART, with higher CD4 + T count and with psychiatric disorders were more likely to develop a CNS-AE. The risk was lower in non-DTG than DTG-cohort (aHR 0.33, 95% CI 0.19–0.55, p < 0.0001). One-year follow-up was available for 63/66 PLWH with CNS-AE. AE resolution was reported in 35/39 and 23/24 cases in DTG and non-DTG cohorts, respectively. The probability of AE reversibility was not different based on ART class, sex, ethnicity, CDC stage, or baseline psychiatric disorder. At the same time, a lower rate of event resolution was found in PLWH older than 50 years (p = 0.017). In conclusion, CNS-AE leading to ART discontinuation was more frequent in DTG than non-DTG treated PLWH. Most CNS-AE resolved after ART switch, similarly in both DTG and non-DTG cohorts.

Published
2022
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29. Characteristics and Subjective Evaluation of an Intelligent Empowering Agent for Health Person Empowerment

Author

Marco Alfano, John Kellett, Biagio Lenzitti, Markus Helfert, Blobel, B, Yang, B, Giacomini, M, Alfano, Marco, Kellett, John, Lenzitti, Biagio, and Helfert, Markus

Subjects
Patient Empowerment, Settore ING-INF/05 - Sistemi Di Elaborazione Delle Informazioni, Settore INF/01 - Informatica, Artificial Intelligence, Communication, Surveys and Questionnaires, Digital Health, Humans, Empowerment, Tailored Health Information, Patient Participation, Intelligent Agent, Language
Abstract

Empowerment is a process through which people acquire the necessary knowledge and self-awareness to understand their health conditions and treatment options, self-manage them, and make informed choices. Currently, few stand-alone applications for patient empowerment exist and people/patients often go on the Web to search for health information. Such information is mainly obtained through generic search engines and it is often overwhelming, too generic, and of poor quality. Intelligent Empowering Agents (IEA) can filter such information and assist the user in the understanding of health information about specific complaints or health in general. We have designed and developed a first prototype of an IEA that dialogues with the user in simple language, collects health information from the Web, and provides tailored, easily understood, and trusted information. It empowers users to create their own comprehensive and objective opinion on health matters that concern them. The paper describes the IEA main characteristics and presents the results of subjective tests carried out to assess the effectiveness of the IEA. Twenty-eight Master students in Digital Health filled an online survey presenting questions on usability, user experience and perceived value. Most respondents found the IEA easy to use and helpful. They also felt that it would improve communication with their doctors.

Published
2022

30. Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy

Author

Rottoli, Matteo, Gori, Alice, Pellino, Gianluca, Flacco, Maria Elena, Martellucci, Cecilia, Spinelli, Antonino, Poggioli, Gilberto, Romano, Angela, Belvedere, Angela, Lanci Lanci, Antonio, Parlanti, Daniele, Vago, Gabriele, Pezzuto, Paola, Canavese, Anna, Dajti, Gerti, Cardelli, Stefano, Catalioto, Caterina, Russo, Iris S, Violante, Tommaso, Morezzi, Daniele, Maurino, Ludovica, Filippone, Eleonora, Cuicchi, Dajana, Bernante, Paolo, Jovine, Elio, Lombardi, Raffaele, Masetti, Michele, Cipressi, Chiara, Offi, Maria F, Larotonda, Cristina, Puglisi, Silvana B, Barbosa, Augusto, Vaiana, Roberto, Bianchi, Paolo M, Tonti, Carlo, Codignola, Claudio, Zorcolo, Luigi, Restivo, Angelo, Deidda, Simona, Marchetti, Marcello E, Ippolito, Luca, Spolverato, Gaya, Pucciarelli, Salvatore, Marchegiani, Francesco, Ghio, Giacomo, Zagolin, Gaya, Glavas, Dajana, Tomassi, Monica, Rosati, Riccardo, Elmore, Ugo, Gozzini, Lorenzo, Calef, Riccardo, Puccetti, Francesco, Cossu, Andrea, Vignali, Andrea, Morino, Mario, Allaix, Marco E, Cannata, Gaspare, Lombardi, Erica, Ammirati, Carlo A, Piceni, Chiara, Buccianti, Piero, Balestri, Riccardo, Puccini, Marco, Pezzati, Daniele, d'Ischia, Roberto, Asta, Vito F, Sargenti, Benedetta, Taddei, Giacomo, Bonari, Federica, Boni, Giulia, Ferrero, Alessandro, Mineccia, Michela, Gonella, Federica, Palisi, Marco, Danese, Francesco, Cherubini, Valeria, Perotti, Serena, Carvello, Michele, Carbone, Fabio, Luberto, Antonio, Calafiore, Eleonora, De Lucia, Francesca, Sacchi, Matteo, Sasia, Diego, Giuffrida, Maria C, Ballauri, Edoardo, Cardile, Mathieu, Armentano, Serena, Beltrami, Elsa, Preve, Gabriele, Vercellone, Barbara, Mozzon, Marta, Folliero, Cristina, Lirusso, Chiara, Vecchiato, Massimo, Ziccarelli, Antonio, Gattesco, Davide, Moretti, Luisa, Crestale, Sara, Banchini, Filippo, Capelli, Patrizio, Romboli, Andrea, Palmieri, Gerardo, Conti, Luigi, Rizzi, Nicholas, Bonfili, Deborah, de Manzini, Nicolò, Germani, Paola, Osenda, Edoardo, Cortinovis, Sara, Giunta, Carlotta, Fracon, Stefano, Abdallah, Hussein, Bogoni, Selene, Portolani, Nazario, Nascimbeni, Riccardo, Molfino, Sarah, Tiberio, Guido A M, Garosio, Ilenia, Lamperti, Giulia, Rigosa, Diego, Ercolani, Giorgio, Solaini, Leonardo, Cavaliere, Davide, Avanzolini, Andrea, D'Acapito, Fabrizio, Chiarella, Leonardo L, Di Pietrantonio, Daniela, Annunziata, Domenico, Piccolo, Roberta, Sorrentino, Mario, Pansini, Mauro, Cojutti, Alessandro, Graziano, Michele, Callegari, Francesco, Balzarotti, Laura, Dameno, Vitale R, Cattaneo, Antonio, Santolamazza, Giuliano, Altieri, Caterina, Magarini, Riccardo, Pietrabissa, Andrea, Dominioni, Tommaso, Pugliese, Luigi, Peri, Andrea, Botti, Marta, Salvetti, Francesco, Cassinotti, Elisa, Baldari, Ludovica, Boni, Luigi, Messina, Valentina, D'Abrosca, Vera, Cianci, Pasquale, Tumolo, Rocco, Gattulli, Domenico, Restini, Enrico, Minafra, Marina, Sederino, Maria G, Bottalico, Bernardino, Pilati, Pierluigi, Franzato, Boris, Mattara, Genny, De Simoni, Ottavia, Barina, Andrea, Tonello, Marco, Muratore, Andrea, Calabrò, Marcello, Federico Pipitone, Nicoletta S, Cuzzola, Bruno, Herranz van Nood, Elena, Passuello, Nicola, Frasson, Alvise, Mammano, Enzo, Faccio, Luca, Vittadello, Fabrizio, Bressan, Alice, Sarzo, Giacomo, Tamini, Nicolò, Oldani, Massimo, Cigagna, Luca, Carissimi, Francesca, De Carlo, Giulia, Baccalini, Edoardo, Nespoli, Luca, Giordano, Alessio, Cantafio, Stefano, Grifoni, Lucrezia, Matani, Davide, Livi, Serena, Delogu, Daniele, Scognamillo, Fabrizio, Marrosu, Antonio, Guerrini, Luca, Ugolini, Giampaolo, Ghignone, Federico, Frascaroli, Giacomo, Albertini, Nicola, Zattoni, Davide, Taffurelli, Giovanni, Montroni, Isacco, Colombo, Francesco, Danelli, Piergiorgio, Bondurri, Andrea, Maffioli, Anna, Bonomi, Alessandro, Pezzoli, Isabella, Cammarata, Francesco, Goletti, Orlando, Molteni, Mattia, Assisi, Alberto, Quartierini, Giorgio, Da Lio, Corrado, Verdi, Daunia, Mondi, Isabella, Peluso, Claudia, Macchi, Lorenzo, Tanzanu, Marta, Zanzi, Federico, Pellegrini, Sara, Andreuccetti, Jacopo, D'Alessio, Rossella, Pignata, Giusto, De Capua, Michele, Canfora, Ilaria, Ottaviani, Luca, Lepiane, Pasquale, Balla, Andrea, De Carlo, Antonio, Saraceno, Federica, Scaramuzzo, Rosa, Guida, Anna, Aguzzi, Daniele, Bellora, Paolo, Gentilli, Sergio, Monni, Manuela, Nikaj, Herald, Cillara, Nicola, Cannavera, Alessandro, Deserra, Antonello, Margiani, Carla, Cabula, Roberta, Dettori, Manuela, Gramignano, Giulia, Lezoche, Giovanni, Ortenzi, Monica, Orlandoni, Elena S, Curzi, Federica, Vitali, Francesca, Capomagi, Perla, Palmieri, Miriam, Giuffrida, Mario, Del Rio, Paolo, Bonati, Elena, Loderer, Tommaso, Cozzani, Federico, Rossini, Matteo, Agnesi, Stefano, Capolupo, Gabriella T, Caricato, Marco, Carannante, Filippo, Mascianà, Gianluca, Marrelli, Martina, Miacci, Valentina, Lauricella, Sara, Tonini, Valeria, Cervellera, Maurizio, Pisconti, Salvatore, Lozito, Concetta, Shahu, Juliana, Mongelli, Claudia, Morelli, Giulia, Sartarelli, Lodovico, Sica, Giuseppe S, Siragusa, Leandro, Bagaglini, Giulia, Sensi, Bruno, Guida, Andrea M, Franceschilli, Marzia, Vinci, Danilo, Taddei, Antonio, Risaliti, Matteo, Bartolini, Ilenia, Ringressi, Maria N, Tirloni, Luca, Laface, Letizia, Abate, Emmanuele, Casati, Massimiliano, Gobbi, Pietro, Opocher, Enrico, Mariani, Nicolò M, Pisani Ceretti, Andrea, Giovenzana, Marco, Giuliani, Beatrice, Sironi, Martina, Grossi, Ugo, Zanus, Giacomo, Aniello Santoro, Giulio, Brizzolari, Marco, De Leo, Eugenio, Novello, Simone, Aquilino, Krizia, Milardi, Francesco, Olmi, Stefano, Uccelli, Matteo, Bonaldi, Marta, Cesana, Giovanni C, Bindi, Marco, Galleano, Raffaele, Langone, Antonio, Botto, Massimiliano, Franceschi, Angelo, Gambino, Elena, Ronconi, Maurizio, Casiraghi, Silvia, Casole, Giovanni, Ciulla, Salvatore L, Terrosu, Giovanni, Calandra, Sergio, Scarpa, Edoardo, Cherchi, Vittorio, Calini, Giacomo, Martinuzzo, Lisa, Clocchiatti, Lucrezia, Muschitiello, Davide, Romanzi, Andrea, Vignati, Barbara, Vannelli, Alberto, Scolaro, Roberta, Milanesi, Maria, Rossi, Fabrizio, Canonico, Giuseppe, Anastasi, Alessandro, Nelli, Tommaso, Barlettai, Marco, Fratarcangeli, Riccardo, Di Martino, Carmela, Damigella, Andrea, Adinolfi, Elvira, Birindelli, Arianna, Taglietti, Lucio, Dester, Sara E, Fleres, Francesco, Cucinotta, Eugenio, Viscosi, Francesca, Biondo Santino, Antonio, Badessi, Giorgio, Catarsini, Nivia, Mazzeo, Carmelo, Rega, Daniela, Delrio, Paolo, Cervone, Carmela, Aversano, Alessia, De Franciscis, Silvia, Di Marzo, Massimiliano, Marra, Bruno, Pace, Ugo, Amato, Antonio, Batistotti, Paola, Mina, Elisa, Serventi, Alberto, Lapolla, Pierfrancesco, Mingoli, Andrea, Sapienza, Paolo, Brachini, Gioia, Cirillo, Bruno, Fiori, Enrico, Crocetti, Daniele, Clementi, Ilaria, Martines, Gennaro, Picciariello, Arcangelo, Tomasicchio, Giovanni, Dibra, Rigers, Trigiante, Giuseppe, Rinaldi, Marcella, Lantone, Giuliano, Porcu, Alberto, Perra, Teresa, Scanu, Antonio M, Feo, Claudio F, Fancellu, Alessandro, Cossu, Maria L, Ginesu, Giorgio C, Patriti, Alberto, Coletta, Diego, Petrelli, Filippo, Greco, Paola A, Spadoni, Claudia, Cassiani, Giovanna, Bianchini, Federica, Arganini, Marco, Bianchini, Matteo, Perotti, Bruno, Palmeri, Matteo, Scabini, Stefano, Deiana, Selene, Carganico, Giacomo, Pertile, Davide, Soriero, Domenico, Fioravanti, Emanuela, Sperotto, Beatrice, Nardo, Bruno, Paglione, Daniele, Crocco, Veronica, Doni, Marco, Osso, Mariasara, Perri, Roberto, Sampietro, Gianluca M, Corbellini, Carlo, Lorusso, Leonardo, Manzo, Carlo A, Cigognini, Maria, Baldi, Caterina, Palomba, Giuseppe, Aprea, Giovanni, Capuano, Marianna, Basile, Raffaele, Tutino, Roberta, Massani, Marco, Marinelli, Laura, Canitano, Nicola, Pilia, Tiziana, Podda, Mauro, Pisanu, Adolfo, Murzi, Valentina, Incani, Silvia, Frongia, Federica, Esposito, Giuseppe, Luglio, Gaetano, Tropeano, Francesca P, Pagano, Gianluca, Spina, Eduardo, De Simone, Giuseppe, Cricrì, Michele, Catena, Fausto, Vallicelli, Carlo, Zanini, Nicola, Ronconi, Diana, Favi, Francesco, Mazzucchelli, Carlo, Convertini, Girolamo, Vincenti, Leonardo, Andriola, Valeria, Bizzoca, Cinzia, Feo, Carlo V, Fabbri, Nicolò, Fazzin, Marta, Pesce, Antonio, Gennari, Silvia, Torchiaro, Marco, Severi, Silvia, Frontali, Alice, Bracchetti, Greta, Granieri, Stefano, Cotsoglou, Christian, Carlini, Massimo, Lisi, Giorgio, Spoletini, Domenico, Mastrangeli, Maria R, Campanelli, Michela, Manigrasso, Michele, Milone, Marco, De Palma, Giovanni D, Vertaldi, Sara, Chini, Alessia, Maione, Francesco, Marello, Alessandra, Selvaggi, Francesco, Sciaudone, Guido, Selvaggi, Lucio, Menegon Tasselli, Francesco, Fuschillo, Giacomo, Oddis, Lidia, Grande, Simona, Grande, Michele, Ascanelli, Simona, Chimisso, Laura, Aisoni, Filippo, Rossin, Eleonora, Pepe, Francesco, Marchetti, Francesco, Picardi, Biagio, Rossi, Stefano, Rossi Del Monte, Simone, Picarelli, Matteo, Muttillo, Irnerio A, Ratto, Carlo, Marra, Angelo A, Parello, Angelo, Litta, Francesco, Campennì, Paola, De Simone, Veronica, Pata, Francesco, Riboni, Cristiana, Rausa, Emanuele, Celentano, Valerio, Institut Català de la Salut, [Rottoli M, Gori A, Pellino G] Surgery of the Alimentary Tract, IRCCS Azienda Ospedaliero–Universitaria di Bologna, Bologna, Italy. Surgery of the Alimentary Tract, IRCCS Azienda Ospedaliero–Universitaria di Bologna, Bologna, Italy. [Pellino G] Department of Advanced Medical and Surgical Sciences, Università degli Studi della Campania Luigi Vanvitelli, Naples, Italy. Unitat de Cirurgia de Còlon i Recte, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Flacco ME, Martellucci C] Department of Environmental and Preventive Sciences, University of Ferrara, Ferrara, Italy. [Spinelli A] Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy. Colorectal Surgery, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy, Vall d'Hebron Barcelona Hospital Campus, Rottoli, Matteo, Gori, Alice, Pellino, Gianluca, Flacco, Maria Elena, Martellucci, Cecilia, Spinelli, Antonino, Poggioli, Gilberto, Romano, Angela, Belvedere, Angela, Lanci Lanci, Antonio, Parlanti, Daniele, Vago, Gabriele, Pezzuto, Paola, Canavese, Anna, Dajti, Gerti, Cardelli, Stefano, Catalioto, Caterina, Russo, Iris S, Violante, Tommaso, Morezzi, Daniele, Maurino, Ludovica, Filippone, Eleonora, Cuicchi, Dajana, Bernante, Paolo, Jovine, Elio, Lombardi, Raffaele, Masetti, Michele, Cipressi, Chiara, Offi, Maria F, Larotonda, Cristina, Puglisi, Silvana B, Barbosa, Augusto, Vaiana, Roberto, Bianchi, Paolo M, Tonti, Carlo, Codignola, Claudio, Zorcolo, Luigi, Restivo, Angelo, Deidda, Simona, Marchetti, Marcello E, Ippolito, Luca, Spolverato, Gaya, Pucciarelli, Salvatore, Marchegiani, Francesco, Ghio, Giacomo, Zagolin, Gaya, Glavas, Dajana, Tomassi, Monica, Rosati, Riccardo, Elmore, Ugo, Gozzini, Lorenzo, Calef, Riccardo, Puccetti, Francesco, Cossu, Andrea, Vignali, Andrea, Morino, Mario, Allaix, Marco E, Cannata, Gaspare, Lombardi, Erica, Ammirati, Carlo A, Piceni, Chiara, Buccianti, Piero, Balestri, Riccardo, Puccini, Marco, Pezzati, Daniele, d'Ischia, Roberto, Asta, Vito F, Sargenti, Benedetta, Taddei, Giacomo, Bonari, Federica, Boni, Giulia, Ferrero, Alessandro, Mineccia, Michela, Gonella, Federica, Palisi, Marco, Danese, Francesco, Cherubini, Valeria, Perotti, Serena, Carvello, Michele, Carbone, Fabio, Luberto, Antonio, Calafiore, Eleonora, De Lucia, Francesca, Sacchi, Matteo, Sasia, Diego, Giuffrida, Maria C, Ballauri, Edoardo, Cardile, Mathieu, Armentano, Serena, Beltrami, Elsa, Preve, Gabriele, Vercellone, Barbara, Mozzon, Marta, Folliero, Cristina, Lirusso, Chiara, Vecchiato, Massimo, Ziccarelli, Antonio, Gattesco, Davide, Moretti, Luisa, Crestale, Sara, Banchini, Filippo, Capelli, Patrizio, Romboli, Andrea, Palmieri, Gerardo, Conti, Luigi, Rizzi, Nichola, Bonfili, Deborah, de Manzini, Nicolò, Germani, Paola, Osenda, Edoardo, Cortinovis, Sara, Giunta, Carlotta, Fracon, Stefano, Abdallah, Hussein, Bogoni, Selene, Portolani, Nazario, Nascimbeni, Riccardo, Molfino, Sarah, Tiberio, Guido A M, Garosio, Ilenia, Lamperti, Giulia, Rigosa, Diego, Ercolani, Giorgio, Solaini, Leonardo, Cavaliere, Davide, Avanzolini, Andrea, D'Acapito, Fabrizio, Chiarella, Leonardo L, Di Pietrantonio, Daniela, Annunziata, Domenico, Piccolo, Roberta, Sorrentino, Mario, Pansini, Mauro, Cojutti, Alessandro, Graziano, Michele, Callegari, Francesco, Balzarotti, Laura, Dameno, Vitale R, Cattaneo, Antonio, Santolamazza, Giuliano, Altieri, Caterina, Magarini, Riccardo, Pietrabissa, Andrea, Dominioni, Tommaso, Pugliese, Luigi, Peri, Andrea, Botti, Marta, Salvetti, Francesco, Cassinotti, Elisa, Baldari, Ludovica, Boni, Luigi, Messina, Valentina, D'Abrosca, Vera, Cianci, Pasquale, Tumolo, Rocco, Gattulli, Domenico, Restini, Enrico, Minafra, Marina, Sederino, Maria G, Bottalico, Bernardino, Pilati, Pierluigi, Franzato, Bori, Mattara, Genny, De Simoni, Ottavia, Barina, Andrea, Tonello, Marco, Muratore, Andrea, Calabrò, Marcello, Federico Pipitone, Nicoletta S, Cuzzola, Bruno, Herranz van Nood, Elena, Passuello, Nicola, Frasson, Alvise, Mammano, Enzo, Faccio, Luca, Vittadello, Fabrizio, Bressan, Alice, Sarzo, Giacomo, Tamini, Nicolò, Oldani, Massimo, Cigagna, Luca, Carissimi, Francesca, De Carlo, Giulia, Baccalini, Edoardo, Nespoli, Luca, Giordano, Alessio, Cantafio, Stefano, Grifoni, Lucrezia, Matani, Davide, Livi, Serena, Delogu, Daniele, Scognamillo, Fabrizio, Marrosu, Antonio, Guerrini, Luca, Ugolini, Giampaolo, Ghignone, Federico, Frascaroli, Giacomo, Albertini, Nicola, Zattoni, Davide, Taffurelli, Giovanni, Montroni, Isacco, Colombo, Francesco, Danelli, Piergiorgio, Bondurri, Andrea, Maffioli, Anna, Bonomi, Alessandro, Pezzoli, Isabella, Cammarata, Francesco, Goletti, Orlando, Molteni, Mattia, Assisi, Alberto, Quartierini, Giorgio, Da Lio, Corrado, Verdi, Daunia, Mondi, Isabella, Peluso, Claudia, Macchi, Lorenzo, Tanzanu, Marta, Zanzi, Federico, Pellegrini, Sara, Andreuccetti, Jacopo, D'Alessio, Rossella, Pignata, Giusto, De Capua, Michele, Canfora, Ilaria, Ottaviani, Luca, Lepiane, Pasquale, Balla, Andrea, De Carlo, Antonio, Saraceno, Federica, Scaramuzzo, Rosa, Guida, Anna, Aguzzi, Daniele, Bellora, Paolo, Gentilli, Sergio, Monni, Manuela, Nikaj, Herald, Cillara, Nicola, Cannavera, Alessandro, Deserra, Antonello, Margiani, Carla, Cabula, Roberta, Dettori, Manuela, Gramignano, Giulia, Lezoche, Giovanni, Ortenzi, Monica, Orlandoni, Elena S, Curzi, Federica, Vitali, Francesca, Capomagi, Perla, Palmieri, Miriam, Giuffrida, Mario, Del Rio, Paolo, Bonati, Elena, Loderer, Tommaso, Cozzani, Federico, Rossini, Matteo, Agnesi, Stefano, Capolupo, Gabriella T, Caricato, Marco, Carannante, Filippo, Mascianà, Gianluca, Marrelli, Martina, Miacci, Valentina, Lauricella, Sara, Tonini, Valeria, Cervellera, Maurizio, Pisconti, Salvatore, Lozito, Concetta, Shahu, Juliana, Mongelli, Claudia, Morelli, Giulia, Sartarelli, Lodovico, Sica, Giuseppe S, Siragusa, Leandro, Bagaglini, Giulia, Sensi, Bruno, Guida, Andrea M, Franceschilli, Marzia, Vinci, Danilo, Taddei, Antonio, Risaliti, Matteo, Bartolini, Ilenia, Ringressi, Maria N, Tirloni, Luca, Laface, Letizia, Abate, Emmanuele, Casati, Massimiliano, Gobbi, Pietro, Opocher, Enrico, Mariani, Nicolò M, Pisani Ceretti, Andrea, Giovenzana, Marco, Giuliani, Beatrice, Sironi, Martina, Grossi, Ugo, Zanus, Giacomo, Aniello Santoro, Giulio, Brizzolari, Marco, De Leo, Eugenio, Novello, Simone, Aquilino, Krizia, Milardi, Francesco, Olmi, Stefano, Uccelli, Matteo, Bonaldi, Marta, Cesana, Giovanni C, Bindi, Marco, Galleano, Raffaele, Langone, Antonio, Botto, Massimiliano, Franceschi, Angelo, Gambino, Elena, Ronconi, Maurizio, Casiraghi, Silvia, Casole, Giovanni, Ciulla, Salvatore L, Terrosu, Giovanni, Calandra, Sergio, Scarpa, Edoardo, Cherchi, Vittorio, Calini, Giacomo, Martinuzzo, Lisa, Clocchiatti, Lucrezia, Muschitiello, Davide, Romanzi, Andrea, Vignati, Barbara, Vannelli, Alberto, Scolaro, Roberta, Milanesi, Maria, Rossi, Fabrizio, Canonico, Giuseppe, Anastasi, Alessandro, Nelli, Tommaso, Barlettai, Marco, Fratarcangeli, Riccardo, Di Martino, Carmela, Damigella, Andrea, Adinolfi, Elvira, Birindelli, Arianna, Taglietti, Lucio, Dester, Sara E, Fleres, Francesco, Cucinotta, Eugenio, Viscosi, Francesca, Biondo Santino, Antonio, Badessi, Giorgio, Catarsini, Nivia, Mazzeo, Carmelo, Rega, Daniela, Delrio, Paolo, Cervone, Carmela, Aversano, Alessia, De Franciscis, Silvia, Di Marzo, Massimiliano, Marra, Bruno, Pace, Ugo, Amato, Antonio, Batistotti, Paola, Mina, Elisa, Serventi, Alberto, Lapolla, Pierfrancesco, Mingoli, Andrea, Sapienza, Paolo, Brachini, Gioia, Cirillo, Bruno, Fiori, Enrico, Crocetti, Daniele, Clementi, Ilaria, Martines, Gennaro, Picciariello, Arcangelo, Tomasicchio, Giovanni, Dibra, Riger, Trigiante, Giuseppe, Rinaldi, Marcella, Lantone, Giuliano, Porcu, Alberto, Perra, Teresa, Scanu, Antonio M, Feo, Claudio F, Fancellu, Alessandro, Cossu, Maria L, Ginesu, Giorgio C, Patriti, Alberto, Coletta, Diego, Petrelli, Filippo, Greco, Paola A, Spadoni, Claudia, Cassiani, Giovanna, Bianchini, Federica, Arganini, Marco, Bianchini, Matteo, Perotti, Bruno, Palmeri, Matteo, Scabini, Stefano, Deiana, Selene, Carganico, Giacomo, Pertile, Davide, Soriero, Domenico, Fioravanti, Emanuela, Sperotto, Beatrice, Nardo, Bruno, Paglione, Daniele, Crocco, Veronica, Doni, Marco, Osso, Mariasara, Perri, Roberto, Sampietro, Gianluca M, Corbellini, Carlo, Lorusso, Leonardo, Manzo, Carlo A, Cigognini, Maria, Baldi, Caterina, Palomba, Giuseppe, Aprea, Giovanni, Capuano, Marianna, Basile, Raffaele, Tutino, Roberta, Massani, Marco, Marinelli, Laura, Canitano, Nicola, Pilia, Tiziana, Podda, Mauro, Pisanu, Adolfo, Murzi, Valentina, Incani, Silvia, Frongia, Federica, Esposito, Giuseppe, Luglio, Gaetano, Tropeano, Francesca P, Pagano, Gianluca, Spina, Eduardo, De Simone, Giuseppe, Cricrì, Michele, Catena, Fausto, Vallicelli, Carlo, Zanini, Nicola, Ronconi, Diana, Favi, Francesco, Mazzucchelli, Carlo, Convertini, Girolamo, Vincenti, Leonardo, Andriola, Valeria, Bizzoca, Cinzia, Feo, Carlo V, Fabbri, Nicolò, Fazzin, Marta, Pesce, Antonio, Gennari, Silvia, Torchiaro, Marco, Severi, Silvia, Frontali, Alice, Bracchetti, Greta, Granieri, Stefano, Cotsoglou, Christian, Carlini, Massimo, Lisi, Giorgio, Spoletini, Domenico, Mastrangeli, Maria R, Campanelli, Michela, Manigrasso, Michele, Milone, Marco, De Palma, Giovanni D, Vertaldi, Sara, Chini, Alessia, Maione, Francesco, Marello, Alessandra, Selvaggi, Francesco, Sciaudone, Guido, Selvaggi, Lucio, Menegon Tasselli, Francesco, Fuschillo, Giacomo, Oddis, Lidia, Grande, Simona, Grande, Michele, Ascanelli, Simona, Chimisso, Laura, Aisoni, Filippo, Rossin, Eleonora, Pepe, Francesco, Marchetti, Francesco, Picardi, Biagio, Rossi, Stefano, Rossi Del Monte, Simone, Picarelli, Matteo, Muttillo, Irnerio A, Ratto, Carlo, Marra, Angelo A, Parello, Angelo, Litta, Francesco, Campennì, Paola, De Simone, Veronica, Pata, Francesco, Riboni, Cristiana, Rausa, Emanuele, and Celentano, Valerio

Subjects
Adult, Male, Settore MED/18 - CHIRURGIA GENERALE, Otros calificadores::/diagnóstico [Otros calificadores], Hospitals, Community, colorectal cancer, Community, advanced stage, COVID-19 (Malaltia), Cohort Studies, Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms [DISEASES], Retrospective Studie, Other subheadings::/diagnosis [Other subheadings], virosis::infecciones por virus ARN::infecciones por Nidovirales::infecciones por Coronaviridae::infecciones por Coronavirus [ENFERMEDADES], Humans, Pandemics, Aged, Retrospective Studies, Pandemic, SARS-CoV-2, COVID-19, Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections [DISEASES], General Medicine, neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias gastrointestinales::neoplasias intestinales::neoplasias colorrectales [ENFERMEDADES], Hospitals, Recte - Càncer - Diagnòstic, Settore MED/18, Italy, Còlon - Càncer - Diagnòstic, Cohort Studie, Colorectal Neoplasms, Human
Abstract

ImportanceDelays in screening programs and the reluctance of patients to seek medical attention because of the outbreak of SARS-CoV-2 could be associated with the risk of more advanced colorectal cancers at diagnosis.ObjectiveTo evaluate whether the SARS-CoV-2 pandemic was associated with more advanced oncologic stage and change in clinical presentation for patients with colorectal cancer.Design, Setting, and ParticipantsThis retrospective, multicenter cohort study included all 17 938 adult patients who underwent surgery for colorectal cancer from March 1, 2020, to December 31, 2021 (pandemic period), and from January 1, 2018, to February 29, 2020 (prepandemic period), in 81 participating centers in Italy, including tertiary centers and community hospitals. Follow-up was 30 days from surgery.ExposuresAny type of surgical procedure for colorectal cancer, including explorative surgery, palliative procedures, and atypical or segmental resections.Main Outcomes and MeasuresThe primary outcome was advanced stage of colorectal cancer at diagnosis. Secondary outcomes were distant metastasis, T4 stage, aggressive biology (defined as cancer with at least 1 of the following characteristics: signet ring cells, mucinous tumor, budding, lymphovascular invasion, perineural invasion, and lymphangitis), stenotic lesion, emergency surgery, and palliative surgery. The independent association between the pandemic period and the outcomes was assessed using multivariate random-effects logistic regression, with hospital as the cluster variable.ResultsA total of 17 938 patients (10 007 men [55.8%]; mean [SD] age, 70.6 [12.2] years) underwent surgery for colorectal cancer: 7796 (43.5%) during the pandemic period and 10 142 (56.5%) during the prepandemic period. Logistic regression indicated that the pandemic period was significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio [OR], 1.07; 95% CI, 1.01-1.13; P = .03), aggressive biology (OR, 1.32; 95% CI, 1.15-1.53; P P = .03).Conclusions and RelevanceThis cohort study suggests a significant association between the SARS-CoV-2 pandemic and the risk of a more advanced oncologic stage at diagnosis among patients undergoing surgery for colorectal cancer and might indicate a potential reduction of survival for these patients.

Published
2022

31. Digital Health Care, Telemedicine, and Medicolegal Issues in Orthopedics: A Review

Author

Davide Ferorelli, Lorenzo Moretti, Marcello Benevento, Maurizio Mastrapasqua, Michele Telegrafo, Biagio Solarino, Alessandro Dell’Erba, Davide Bizzoca, and Biagio Moretti

Subjects
Orthopedics, Health, Toxicology and Mutagenesis, Public Health, Environmental and Occupational Health, Humans, COVID-19, Pandemics, Delivery of Health Care, Telemedicine
Abstract

The use of technologies in medicine has great potential to reduce the costs of health care services by making appropriate decisions that provide timely patient care. The evolution of telemedicine poses a series of clinical and medicolegal considerations. However, only a few articles have dealt with telemedicine and orthopedics. This review assesses the ethical and medicolegal issues related to tele-orthopedics. A systematic review was performed including papers published between 2017 and 2021 focusing on the main medicolegal and clinical-governance aspects of tele-orthopedics. Most of the articles were published during the COVID-19 pandemic, confirming the impetus that the pandemic has also given to the spread of telemedicine in the orthopedic field. The areas of interest dealt with in the scientific evidence, almost exclusively produced in the USA, Europe, the UK, and Canada, are quality, patient satisfaction, and safety. The impact of telemedicine in orthopedics has not yet been fully evaluated and studied in terms of the potential medicolegal concerns. Most of the authors performed qualitative studies with poor consistency. Authorizations and accreditations, protection of patient confidentiality, and professional responsibility are issues that will certainly soon emerge.

Published
2022

32. Microbiota and HPV: The role of viral infection on vaginal microbiota

Author

Biagio Santella, Maria T. Schettino, Gianluigi Franci, Pasquale De Franciscis, Nicola Colacurci, Antonio Schiattarella, Massimiliano Galdiero, Santella, B., Schettino, M. T., Franci, G., De Franciscis, P., Colacurci, N., Schiattarella, A., and Galdiero, M.

Subjects
Bacteria, Microbiota, Papillomavirus Infections, Uterine Cervical Neoplasms, Cervix Uteri, Infectious Diseases, RNA, Ribosomal, 16S, Virology, uterine cervical neoplasm, Vagina, Humans, Female, Papillomavirus Infection, Human
Abstract

The World Health Organization (WHO) estimates that the prevalence of human papillomaviruses (HPV) infection is between 9% and 13% of the world population and only in the United States, more than 6.2 million are positive every year. There are more than 100 types of HPV, among them, two serotypes (16 and 18) are related to 70% of cervical cancers and precancerous cervical lesions. The vaginal microbiota could play a considerable role in HPV infection and the genesis of cervical tumors caused by HPV. Moreover, bacteria are strongly associated with vaginal inflammation and oncogenic mutations in human cells. We aim to investigate whether HPV infection could influence the bacterial microbiota composition in the uterine cervix. A total of 31 women were enrolled in this study. The vaginal swabs were collected; the HPV-DNA was extracted with QIAamp DNA Microbiome. The V3–V4–V6 region of the 16S rDNA gene was amplified by polymerase chain reaction (PCR) followed by sequencing with MiSeq Illumina. The main phylum identified in the vaginal microbiota were Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria. The phylum of Actinobacteria, Proteobacteria, and Bacteroides was more represented in HPV-positive patients. Lactobacilli represented the dominant genus, with a high percentage of Lactobacilli iners, Lactobacilli jensenii, and Lactobacilli crispatus as species. Gardnerella vaginalis, Enterococcus spp., Staphylococcus spp., Proteus spp., and Atopobium were the most represented in HPV-positive patients. An altered vaginal microbiota might play a functional role in HPV cervical infection, progression, and clearance. The relationship between infection and microbiota could spur the development of new probiotics. However, further studies are needed to clarify the role of the vaginal microbiota in HPV infection.

Published
2022

33. Minimally invasive simple prostatectomy: Robotic-assisted versus laparoscopy. A comparative study

Author

Michele Amenta, Francesco Oliva, Biagio Barone, Alfio Corsaro, Davide Arcaniolo, Antonio Scarpato, Gennaro Mattiello, Lorenzo Romano, Carmine Sciorio, Tommaso Silvestri, Giovanni Costa, Felice Crocetto, Antonio Celia, Amenta, M., Oliva, F., Barone, B., Corsaro, A., Arcaniolo, D., Scarpato, A., Mattiello, G., Romano, L., Sciorio, C., Silvestri, T., Costa, G., Crocetto, F., and Celia, A.

Subjects
Robotic-assisted surgery, Male, Prostatectomy, Benign prostatic hyperplasia, Robotic Surgical Procedures, Retrospective Studie, Urology, Prostatic Hyperplasia, Humans, Laparoscopy, Minimally invasive simple prostatectomy, Retrospective Studies, Human
Abstract

Purpose: Robotic-assisted simple prostatectomy (RASP) is a novel surgical procedure for the management of obstructive symptoms caused by enlarged prostate glands. Before the introduction of minimally invasive techniques, the standard approach was the open simple prostatectomy (OSP). The aim of our study was to compare intraoperative and perioperative outcomes of robotic (RASP) and laparoscopic (LSP) simple prostatectomy. Methods: We retrospectively analyzed data from patients who underwent minimally invasive simple prostatectomy at the Urological Department of Portogruaro Hospital, Portogruaro, and at the Urological Department of “San Bassiano” Hospital, in Bassano del Grappa, from March 2015 to December 2020. Data collected from medical records included age, body mass index, prostate volume, operative time, preoperative International Prostatic Symptoms Score (IPSS), postoperative IPSS, time with drainage, blood transfusion, intraoperative complications, perioperative complications and length of hospital stay. Results: Robotic-assisted (n = 25) and laparoscopic simple prostatectomy (n = 25) were performed with a transvesical approach. No significant differences were observed regarding baseline characteristics, body mass index, prostate volume and IPSS. Operative time was lower in the laparoscopic group (122 min vs 139 min) (p = 0.024), while hospital stay was lower in the robotic group (4 days vs 6 days) (p = 0.047). Conclusions: Robotic-assisted simple prostatectomy is a safe technique with results comparable to laparoscopic simple prostatectomy, encompassing the advantage of a shorter hospitalization. Considering the costs and the limited availability of robotic-assisted simple prostatectomy, laparoscopic simple prostatectomy is a valid and safe alternative for experienced surgeons.

Published
2022

34. Pharmacokinetic determinants for the right dose of antiarrhythmic drugs

Author

Roberta Bottino, Andreina Carbone, Antonello D’Andrea, Biagio Liccardo, Giovanni Cimmino, Egidio Imbalzano, Vincenzo Russo, Bottino, R., Carbone, A., D'Andrea, A., Liccardo, B., Cimmino, G., Imbalzano, E., and Russo, V.

Subjects
Pharmacology, Antiarrhythmic drug, pharmacogenomic, therapeutic drug monitoring, Humans, Arrhythmias, Cardiac, General Medicine, pharmacokinetic, arrhythmia, Toxicology, Anti-Arrhythmia Agents, Aged
Abstract

Introduction: Antiarrhythmic drugs (AADs) show a narrow therapeutic range and marked intersubject variability in pharmacokinetics (PK), which may lead to inappropriate dosing and drug toxicity. Areas covered: The aim of the present review is to describe PK properties of AADs, discussing the main changes in different clinical scenarios, such as the elderly and patients with obese, chronic kidney, liver, and cardiac disease, in order to guide their right prescription in clinical practice. Expert opinion: There are few data about PK properties of AADs in a special population or challenging clinical setting. The use and dose of AADs is commonly based on physicians’ clinical experience observing the clinical effects rather than being personalized on the individual patients PK profiles. More and updated studies are needed to validate a patient centered approach in the pharmacological treatment of arrhythmias based on patients’ clinical features, including pharmacogenomics, and AAD pharmacokinetics.

Published
2022

35. Off-Label Use of Cardiovascular Drugs in the Home Therapy of Children With Congenital or Acquired Heart Disease

Author

Giovanni Meliota, Maristella Lombardi, Marcello Benevento, Valentina Console, Marco Matteo Ciccone, Biagio Solarino, and Ugo Vairo

Subjects
Heart Defects, Congenital, Heart Failure, Humans, Cardiovascular Agents, Off-Label Use, Child, Hospitals, Pediatric, Cardiology and Cardiovascular Medicine
Abstract

Most medications are not labeled for use in the pediatric population because they have not been formally studied in children. Data on off-label use of cardiovascular (CV) drugs in the home therapy of children with CV disease are scanty. The study included 325 pediatric patients with CV disease and on ≥1 CV medication who underwent ≥1 visit during 2019 at the Pediatric Cardiology outpatient clinic of Giovanni XXIII Pediatric Hospital in Bari, Italy. A total of 287 patients (88.3%) received ≥1 off-label medication, whereas 113 patients (34.7%) received ≥2 off-label medications, and 22 patients (6.7%) ≥3 off-label medications. In CV medications (n = 27) 85% were used off-label in all cases, and 92.5% were used off-label in ≥50% of patients. Adverse events occurred in 8 patients, leading to drug discontinuation in 2 of them. In all 8 cases, medications were used off-label. In multivariate analysis, congenital heart disease patients with single-ventricle physiology (odds ratio 8.4, 95% confidence interval 2.25 to 54.4) and those with heart failure (odds ratio 2.0, 95% confidence interval 1.1 to 3.6) were at higher risk for receiving ≥2 off-label drugs. The off-label use of CV drugs in the home therapy of children with congenital or acquired heart disease is common and adverse events may occur. Patients with congenital heart disease with single-ventricle physiology and those with heart failure have a higher probability to receive ≥2 off-label medications. This study highlights the need for larger safety and efficacy trials in this specific cohort of pediatric patients.

Published
2022

36. Growing old with antiretroviral therapy or elderly people in antiretroviral therapy: two different profiles of comorbidity?

Author

Paolo Maggi, Giuseppe Vittorio De Socio, Barbara Menzaghi, Chiara Molteni, Nicola Squillace, Lucia Taramasso, Marta Guastavigna, Giulia Gamboni, Giordano Madeddu, Francesca Vichi, Antonio Cascio, Eleonora Sarchi, Giovanni Pellicanò, Canio Vito Martinelli, Benedetto Maurizio Celesia, Laura Valsecchi, Roberto Gulminetti, Giovanni Cenderello, Andrea Parisini, Leonardo Calza, Katia Falasca, Giancarlo Orofino, Elena Ricci, Antonio Di Biagio, Paolo Bonfanti, Maggi, Paolo, De Socio, Giuseppe Vittorio, Menzaghi, Barbara, Molteni, Chiara, Squillace, Nicola, Taramasso, Lucia, Guastavigna, Marta, Gamboni, Giulia, Madeddu, Giordano, Vichi, Francesca, Cascio, Antonio, Sarchi, Eleonora, Pellicanò, Giovanni, Martinelli, Canio Vito, Celesia, Benedetto Maurizio, Valsecchi, Laura, Gulminetti, Roberto, Cenderello, Giovanni, Parisini, Andrea, Calza, Leonardo, Falasca, Katia, Orofino, Giancarlo, Ricci, Elena, Di Biagio, Antonio, Bonfanti, Paolo, Maggi, P, De Socio, G, Menzaghi, B, Molteni, C, Squillace, N, Taramasso, L, Guastavigna, M, Gamboni, G, Madeddu, G, Vichi, F, Cascio, A, Sarchi, E, Pellicanò, G, Martinelli, C, Celesia, B, Valsecchi, L, Gulminetti, R, Cenderello, G, Parisini, A, Calza, L, Falasca, K, Orofino, G, Ricci, E, Di Biagio, A, Bonfanti, P, and Maggi P, De Socio GV, Menzaghi B, Molteni C, Squillace N, Taramasso L, Guastavigna M, Gamboni G, Madeddu G, Vichi F, Cascio A, Sarchi E, Pellicanò G, Martinelli CV, Celesia BM, Valsecchi L, Gulminetti R, Cenderello G, Parisini A, Calza L, Falasca K, Orofino G, Ricci E, Di Biagio A, Bonfanti P.

Subjects
Cross-Sectional Studie, Male, ART exposure, HIV, Multimorbidity, HIV Infections, Comorbidity, Osteoporosis, Noncommunicable Disease, Bone Diseases, Metabolic, Cross-Sectional Studies, Infectious Diseases, Age, Anti-Retroviral Agents, Hypertension, Humans, Anti-Retroviral Agent, Female, HIV Infection, Noncommunicable Diseases, Aged, Human
Abstract

Background In persons living with HIV (PLWH), the burden of non-communicable chronic diseases increased over time, because of aging associated with chronic inflammation, systemic immune activation, and long-term exposure to the combination antiretroviral therapy (ART). Methods To explore the association of chronological age, age at first ART, and exposure to ART with non-communicable chronic diseases, we performed a cross-sectional analysis to evaluate the prevalence of comorbidities in patients enrolled in the SCOLTA Project, stratified by groups of chronological age (50–59 and 60–69 years) and by years of antiretroviral treatment (ART, ≤ 3 or > 3 years). Results In 1394 subjects (23.8% women), mean age at enrollment was 57.4 (SD 6.5) years, and at first ART 45.3 (SD 10.7). Men were older than women both at enrollment (57.6 vs 56.8, p = 0.06) and at first ART (45.8 vs 43.6, p = 0.0009). ART duration was longer in women (13.1 vs 11.7 years, p = 0.01). The age- and sex-adjusted rate ratios (aRRs, and 95% confidence interval, CI) showed that longer ART exposure was associated with dyslipidemia (aRR 1.35, 95% CI 1.20–1.52), hypertension (aRR 1.52, 95% CI 1.22–1.89), liver disease (aRR 1.78, 95% CI 1.32–2.41), osteopenia/osteoporosis (aRR 2.88, 95% CI 1.65–5.03) and multimorbidity (aRR 1.36, 95% CI 1.21–1.54). These findings were confirmed in strata of age, adjusting for sex. Conclusions Our data suggest that longer ART exposure was associated with increased risk of dyslipidemia, hypertension, and osteopenia/osteoporosis, hence the presence of multimorbidity, possibly due to the exposition to more toxic antiretrovirals. We observed different comorbidities, according to ART exposure and age.

Published
2022

37. Natural history of type 1 diabetes on an immunodysregulatory background with genetic alteration in B-cell activating factor receptor: A case report

Author

Biagio Di Lorenzo, Lucia Pacillo, Giulia Milardi, Tatiana Jofra, Silvia Di Cesare, Jolanda Gerosa, Ilaria Marzinotto, Ettore Zapparoli, Beatrice Rivalta, Cristina Cifaldi, Federica Barzaghi, Carmela Giancotta, Paola Zangari, Novella Rapini, Annalisa Deodati, Giada Amodio, Laura Passerini, Paola Carrera, Silvia Gregori, Paolo Palma, Andrea Finocchi, Vito Lampasona, Maria Pia Cicalese, Riccardo Schiaffini, Gigliola Di Matteo, Ivan Merelli, Matteo Barcella, Alessandro Aiuti, Lorenzo Piemonti, Caterina Cancrini, Georgia Fousteri, Di Lorenzo, Biagio, Pacillo, Lucia, Milardi, Giulia, Jofra, Tatiana, Di Cesare, Silvia, Gerosa, Jolanda, Marzinotto, Ilaria, Zapparoli, Ettore, Rivalta, Beatrice, Cifaldi, Cristina, Barzaghi, Federica, Giancotta, Carmela, Zangari, Paola, Rapini, Novella, Deodati, Annalisa, Amodio, Giada, Passerini, Laura, Carrera, Paola, Gregori, Silvia, Palma, Paolo, Finocchi, Andrea, Lampasona, Vito, Cicalese, Maria Pia, Schiaffini, Riccardo, Di Matteo, Gigliola, Merelli, Ivan, Barcella, Matteo, Aiuti, Alessandro, Piemonti, Lorenzo, Cancrini, Caterina, and Fousteri, Georgia

Subjects
Adolescent, Immunology, type 1 diabetes (T1D), BAFFR mutation, Diabetes Mellitus, Type 1, Settore MED/02, B-Cell Activating Factor, Mutation, circulating T follicular helper cells (cTfh), Humans, Insulin, Immunology and Allergy, common variable immunodeficiency (CVID), islet autoimmunity, Autoantibodies
Abstract

The immunological events leading to type 1 diabetes (T1D) are complex and heterogeneous, underscoring the necessity to study rare cases to improve our understanding. Here, we report the case of a 16-year-old patient who showed glycosuria during a regular checkup. Upon further evaluation, stage 2 T1D, autoimmune thrombocytopenic purpura (AITP), and common variable immunodeficiency (CVID) were diagnosed. The patient underwent low carb diet, losing > 8 kg, and was placed on Ig replacement therapy. Anti-CD20 monoclonal antibody (Rituximab, RTX) was administered 2 years after diagnosis to treat peripheral polyneuropathy, whereas an atypical mycobacteriosis manifested 4 years after diagnosis and was managed with prolonged antibiotic treatment. In the fifth year of monitoring, the patient progressed to insulin dependency despite ZnT8A autoantibody resolution and IA-2A and GADA autoantibody decline. The patient had low T1D genetic risk score (GRS = 0.22817) and absence of human leukocyte antigen (HLA) DR3/DR4-DQ8. Genetic analysis identified the monoallelic mutation H159Y in TNFRSF13C, a gene encoding B-cell activating factor receptor (BAFFR). Significant reduced blood B-cell numbers and BAFFR levels were observed in line with a dysregulation in BAFF–BAFFR signaling. The elevated frequency of PD-1+ dysfunctional Tfh cells composed predominantly by Th1 phenotype was observed at disease onset and during follow-up. This case report describes a patient progressing to T1D on a BAFFR-mediated immunodysregulatory background, suggesting a role of BAFF–BAFFR signaling in islet-specific tolerance and T1D progression.

Published
2022

38. From Small Peptides to Large Proteins against Alzheimer'sDisease

Author

Pasquale Picone, Tiziana Sanfilippo, Sonya Vasto, Sara Baldassano, Rossella Guggino, Domenico Nuzzo, Donatella Bulone, Pier Luigi San Biagio, Emanuela Muscolino, Roberto Monastero, Clelia Dispenza, Daniela Giacomazza, Picone, Pasquale, Sanfilippo, Tiziana, Vasto, Sonya, Baldassano, Sara, Guggino, Rossella, Nuzzo, Domenico, Bulone, Donatella, San Biagio, Pier Luigi, Muscolino, Emanuela, Monastero, Roberto, Dispenza, Clelia, and Giacomazza, Daniela

Subjects
Neurons, Amyloid beta-Peptides, amyloid-beta protein: amyloid fibrillation, Alzheimer Disease, Tau protein, Humans, tau Proteins, Plaque, Amyloid, Neurofibrillary Tangles, Molecular Biology, Biochemistry, Alzheimer’s disease, Aged
Abstract

Alzheimer’s disease (AD) is the most common neurodegenerative disorder in the elderly. The two cardinal neuropathological hallmarks of AD are the senile plaques, which are extracellular deposits mainly constituted by beta-amyloids, and neurofibrillary tangles formed by abnormally phosphorylated Tau (p-Tau) located in the cytoplasm of neurons. Although the research has made relevant progress in the management of the disease, the treatment is still lacking. Only symptomatic medications exist for the disease, and, in the meantime, laboratories worldwide are investigating disease-modifying treatments for AD. In the present review, results centered on the use of peptides of different sizes involved in AD are presented.

Published
2022

39. The relationship between obstructive sleep apnoea and erectile dysfunction: An underdiagnosed link? A prospective cross-sectional study

Author

Elena Cantone, Matteo Massanova, Felice Crocetto, Biagio Barone, Fabio Esposito, Davide Arcaniolo, Fabrizio Corlianò, Luigi Romano, Gaetano Motta, Antonio Celia, Cantone, E., Massanova, M., Crocetto, F., Barone, B., Esposito, F., Arcaniolo, D., Corliano, F., Romano, L., Motta, G., Celia, A., Cantone, Elena, Massanova, Matteo, Crocetto, Felice, Barone, Biagio, Esposito, Fabio, Arcaniolo, Davide, Corlianò, Fabrizio, Romano, Luigi, Motta, Gaetano, and Celia, Antonio

Subjects
Male, Sleep Apnea, Obstructive, Sleepiness, Urology, General Medicine, ED, SatO2, OSA, Oxygen, Endocrinology, Cross-Sectional Studies, Erectile Dysfunction, Obstructive sleep apnoea, Risk Factors, Humans, Prospective Studies
Abstract

This cross-sectional study aimed to investigate the prevalence and clinical characteristics of erectile dysfunction in patients with obstructive sleep apnoea. We enrolled 133 male patients with suspected obstructive sleep apnoea. Ear, nose and throat evaluation, laboratory tests, body mass index, Epworth sleepiness scale, 5-international index of erectile function, overnight ambulatory polygraphy and drug-induced sleep endoscopy patterns were assessed. Eighty patients reported obstructive sleep apnoea. 60% (n=48) reported erectile dysfunction. Statistically significant correlations were found between 5-International Index of Erectile Function and age, hypertension, diabetes, Epworth sleepiness scale, apnoea-hypopnea index score, O2 saturation-nadir, and oxygen desaturation index. Age, diabetes and O2 saturation-nadir were independent predictors of erectile function. Epworth sleepiness scale, apnoea-hypopnea index score, O2 saturation-nadir, oxygen desaturation index and albumin were higher compared to patients without erectile dysfunction. No statistically significant differences were reported for drug-induced sleep endoscopy patterns and erectile dysfunction. Patients with obstructive sleep apnoea were at significant risk of having erectile dysfunction. Males with obstructive sleep apnoea should be investigated for erectile dysfunction.

Published
2022

40. Subjective perception of spinal deformity after selective versus non-selective fusion of Lenke 1C curves

Author

Davide Bizzoca, Andrea Piazzolla, Giuseppe Solarino, Lorenzo Moretti, and Biagio Moretti

Subjects
Spinal Fusion, Adolescent, Scoliosis, Body Image, Quality of Life, Humans, Female, Orthopedics and Sports Medicine, Kyphosis
Abstract

Purpose To assess the self-image perception and the Quality-of-Life (QoL) in female adolescents, with Lenke 1C scoliosis curves, treated with selective versus non-selective posterior spinal instrumentation and fusion (PSF). Methods Patients undergoing PSF for idiopathic adolescent scoliosis (AIS) were recruited and divided into two groups: patients managed with selective thoracic fusion (STF) were included in Group A, whereas patients treated with non-selective fusion (N-STF) in Group B. Each patient completed the Italian version of the Scoliosis Research Society-22R questionnaire (SRS-22R), the Quality-of-Life Profile for Spinal Deformities questionnaire (QLPSD) and the Spinal Appearance Questionnaire (SAQ), before surgery and at 24-month follow-up. Results One hundred and fifty seven female patients (mean age 16.38) were included in this study. 80 patients underwent STF, while 77 patients received N-STF. At 24-month follow-up, patients managed with N-STF showed better SRS-22R self-image mean score (p = .012), SRS-22R satisfaction mean score (p = .033), QLPSD body image mean score (p = .005), but worse SRS-22 function mean score (p = .006) and QLPSD back flexibility mean score (p = .007), compared with patients who underwent STF. In terms of self-image perception, patients undergoing STF showed significantly worse SAQ total mean score (p = .002), SAQ appearance mean score (p = .001) and SAQ expectation (p = .001). We found a significant correlation between SAQ appearance mean score and SRS-22R self-image (R = − 0.721), SRS-22 mental health (R = − 0.8), QLPSD psychosocial functioning (R = 0.7) and QLPSD back flexibility (R = 0.8). Conclusion Although the STF of Lenke 1C curves provides better functional outcomes, in the present study, female patients receiving STF revealed a worse perceived body image, compared with patients treated with N-STF, at 24-month follow-up. Particular attention should be addressed to the preoperative patient’s mental health and body image perception, when choosing between STF and N-STF.

Published
2022

41. Understanding and managing the impact of the COVID-19 pandemic and lockdown on patients with epilepsy

Author

Giovanni Assenza, Lorenzo Ricci, Jacopo Lanzone, Marilisa Boscarino, Carlo Vico, Flavia Narducci, Biagio Sancetta, Vincenzo Di Lazzaro, and Mario Tombini

Subjects
Epilepsy, SARS-CoV-2, General Neuroscience, Communicable Disease Control, COVID-19, Humans, Pharmacology (medical), Neurology (clinical), Pandemics
Abstract

The coronavirus disease 2019 (COVID-19) pandemic represented a relevant issue for people with epilepsy (PwE). Medical care and social restrictions exposed PwE to a high risk of seizure worsening. Medical institutions answered to the pandemic assuring only emergency care and implementing a remote assistance that highlighted the technological obsolescence of the medical care paradigms for PwE.We reviewed the literature on the COVID-19-related factors influencing the epilepsy course, from the evidence of seizure risk in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infected PwE to anti-Sars-Cov-2 drugs interactions with antiseizure medications and the perceived changes of seizures in PwE.COVID-19 pandemic was a problematic experience for PwE. We must make treasure of the lessons learned during this period of social restrictions and employ the recent technological advances to improve PwE assistance, in particular telemedicine and electronic media for patients' education.

Published
2022

42. Olfactory impairment in autoimmune encephalitis: another piece of the puzzle

Author

Alessandra Morano, Emanuele Cerulli Irelli, Martina Fanella, Biagio Orlando, Enrico Michele Salamone, Emanuele Tinelli, Gabriele Ruffolo, Luigi Zuliani, Jinane Fattouch, Mario Manfredi, Anna Teresa Giallonardo, and Carlo Di Bonaventura

Subjects
Adult, Male, Anosmia, Autoimmune encephalitis, Limbic system, Neuroinflammation, Smell impairment, Hashimoto Disease, Middle Aged, Smell, Short Commentary, Olfaction Disorders, Neurology, Encephalitis, Humans, Female, Neurology (clinical)
Abstract

Background Despite being long neglected, olfaction has recently become a focus of intense research in neuroscience, as smell impairment has been consistently documented in both neurodegenerative and neuroinflammatory diseases. Considering the close anatomo-functional correlations between the limbic system and the central olfactory structures, we investigated olfaction in a population of patients with autoimmune encephalitis (AE). Methods Nineteen adult subjects (14 males, median age 64 years) diagnosed with definite (14/19) or possible (5/19) AE and followed for ≥ 6 months were enrolled. The Brief Smell Identification Test (B-SIT), a 12-item, forced-choice, scratch-and-sniff measure, was used to assess the patients’ olfactory function in comparison with a group of sex- and age-matched healthy controls (HC). According to the B-SIT score, subjects were classified as anosmic (

Published
2022

43. Validation of MiROvaR, a microRNA-based predictor of early relapse in early stage epithelial ovarian cancer as a new strategy to optimise patients' prognostic assessment

Author

Antonino Ditto, Loris De Cecco, Biagio Paolini, Paola Alberti, Fabio Martinelli, Umberto Leone Roberti Maggiore, Giorgio Bogani, Paolo Chiodini, Sandro Pignata, Antonella Tomassetti, Francesco Raspagliesi, Delia Mezzanzanica, Marina Bagnoli, Ditto, A., De Cecco, L., Paolini, B., Alberti, P., Martinelli, F., Leone Roberti Maggiore, U., Bogani, G., Chiodini, P., Pignata, S., Tomassetti, A., Raspagliesi, F., Mezzanzanica, D., and Bagnoli, M.

Subjects
Adult, Aged, 80 and over, Male, microRNA signature, Cancer Research, Carcinoma, Ovarian Epithelial, Middle Aged, Prognosis, Progression-Free Survival, MicroRNAs, Young Adult, Oncology, Early-stage ovarian cancer, Disease Progression, Humans, Female, Neoplasm Recurrence, Local, Aged, Neoplasm Staging, Retrospective Studies
Abstract

Aim: Early-stage epithelial ovarian cancer (eEOC) patients have a generally favorable prognosis but unpredictable recurrence. Accurate prediction of risk of relapse is still a major concern, essentially to avoid overtreatment. Our robust tissue-based miRNA signature named MiROvaR, predicting early EOC recurrence in mostly advanced-stage EOC patients, is here challenged in an independent cohort to extend its classifying ability in the early-stage EOC setting. Methods: We retrospectively selected patients who underwent comprehensive surgical staging at our institution including stages from IA to IIB. miRNA expression profile was analysed in 89 cases and MiROvaR algorithm was applied using the previously validated cut-off for patients' classification. The primary endpoint was progression-free survival (PFS) at 5 years. Complete follow-up time (median = 112 months) was also considered as secondary analysis. Results: MiROvaR was assessable on 87 cases (19 events of disease progression) and classified 68 (78%) low-risk and 19 (22%) high-risk patients. Recurrence rate at primary end-point was 39% for high-risk patients as compared to 9.5% for low-risk ones. Accordingly, their Kaplan–Meier PFS curves were significantly different at both primary and secondary analysis (p = 0.0006 and p = 0.03, respectively). While none of the prominent clinical variables had prognostic relevance, MiROvaR significantly predicted disease recurrence at the 5-year assessment (primary endpoint analysis; HR:5.43, 95%CI:1.82–16.1, p = 0.0024; AUC = 0.78, 95%CI:0.53–0.82) and at complete follow-up time (HR:2.67, 95%CI:1.04–6.8, p = 0.041; AUC:0.68, 95%CI:0.52–0.82). Conclusions: We validated MiROvaR performance in identifying at diagnosis eEOC patients' at higher risk of early relapse thus enabling selection of the most effective therapeutic approach.

Published
2022

44. PD‐1‐induced T cell exhaustion is controlled by a Drp1‐dependent mechanism

Author

Giuseppe Matarese, Biagio De Angelis, Valeria Cancila, Giorgia Scarpelli, Claudio Procaccini, Silvia Campello, Luca Simula, Claudio Tripodo, Alessandra Colamatteo, Simona Manni, Ylenia Antonucci, Concetta Quintarelli, Simula L., Antonucci Y., Scarpelli G., Cancila V., Colamatteo A., Manni S., De Angelis B., Quintarelli C., Procaccini C., Matarese G., Tripodo C., Campello S., Simula, L., Antonucci, Y., Scarpelli, G., Cancila, V., Colamatteo, A., Manni, S., De Angelis, B., Quintarelli, C., Procaccini, C., Matarese, G., Tripodo, C., and Campello, S.

Subjects
Dynamins, Cancer Research, endocrine system, Settore BIO/06, T cell, medicine.medical_treatment, Programmed Cell Death 1 Receptor, Drp1, CD8-Positive T-Lymphocytes, Settore MED/08 - Anatomia Patologica, Mitochondrial Dynamics, tumor‐infiltrating lymphocytes, Mice, Immune system, Downregulation and upregulation, Drp1, mitochondria, PD-1, T cell, tumor-infiltrating lymphocytes, PD-1, Genetics, medicine, Animals, Humans, Settore MED/05 - Patologia Clinica, Research Articles, PI3K/AKT/mTOR pathway, RC254-282, Tumor-infiltrating lymphocytes, Chemistry, PD‐1, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, General Medicine, Immunotherapy, Cell biology, mitochondria, medicine.anatomical_structure, Oncology, tumor-infiltrating lymphocytes, Molecular Medicine, Mitochondrial fission, CD8, Research Article
Abstract

Programmed cell death‐1 (PD‐1) signaling downregulates the T‐cell response, promoting an exhausted state in tumor‐infiltrating T cells, through mostly unveiled molecular mechanisms. Dynamin‐related protein‐1 (Drp1)‐dependent mitochondrial fission plays a crucial role in sustaining T‐cell motility, proliferation, survival, and glycolytic engagement. Interestingly, such processes are exactly those inhibited by PD‐1 in tumor‐infiltrating T cells. Here, we show that PD‐1pos CD8+ T cells infiltrating an MC38 (murine adenocarcinoma)‐derived murine tumor mass have a downregulated Drp1 activity and more elongated mitochondria compared with PD‐1neg counterparts. Also, PD‐1pos lymphocytic elements infiltrating a human colon cancer rarely express active Drp1. Mechanistically, PD‐1 signaling directly prevents mitochondrial fragmentation following T‐cell stimulation by downregulating Drp1 phosphorylation on Ser616, via regulation of the ERK1/2 and mTOR pathways. In addition, downregulation of Drp1 activity in tumor‐infiltrating PD‐1pos CD8+ T cells seems to be a mechanism exploited by PD‐1 signaling to reduce motility and proliferation of these cells. Overall, our data indicate that the modulation of Drp1 activity in tumor‐infiltrating T cells may become a valuable target to ameliorate the anticancer immune response in future immunotherapy approaches., PD‐1 signaling prevents TCR‐dependent Drp1 activation and subsequent mitochondrial fragmentation in T cells. In turn, this reduces both proliferation and migration of activated T cells. Cancer cells exploit this mechanism to downregulate T‐cell functionality within the tumor microenvironment, favoring tumor progression. These findings shed light on a new possible therapeutical approach for the treatment of solid cancers. (image made in BioRender).

Published
2022

45. Uterine serous carcinoma: role of surgery, risk factors and oncologic outcomes. Experience of a tertiary center

Author

Biagio Paolini, Valentina Chiappa, Monika Ducceschi, Mara Mantiero, Claudia Brusadelli, Giorgio Bogani, Mariateresa Evangelista, Antonino Ditto, Luigi Mariani, Salvatore Lopez, Mauro Signorelli, Fabio Martinelli, Salvatore Lo Vullo, Francesco Raspagliesi, and Umberto Maggiore

Subjects
Adult, medicine.medical_specialty, Neoplasm, Residual, Multivariate analysis, Uterus, Kaplan-Meier Estimate, Disease, Hysterectomy, Uterine serous carcinoma, Tertiary Care Centers, Positron Emission Tomography Computed Tomography, Cytology, Humans, Medicine, Neoplasm Invasiveness, Retroperitoneal Neoplasms, Stage (cooking), Peritoneal Neoplasms, Aged, Neoplasm Staging, Proportional Hazards Models, Sentinel Lymph Node Biopsy, business.industry, Carcinoma, Significant difference, Cytoreduction Surgical Procedures, General Medicine, Middle Aged, medicine.disease, Progression-Free Survival, Confidence interval, Endometrial Neoplasms, Surgery, medicine.anatomical_structure, Oncology, Myometrium, Lymph Node Excision, Female, Lymph Nodes, Neoplasms, Cystic, Mucinous, and Serous, business
Abstract

Objective To evaluate factors impacting survival outcomes in patients with uterine serous carcinoma (USC). Methods Data of consecutive patients diagnosed with USC undergoing surgery between 2000 and 2020 at Fondazione IRCCS Istituto Nazionale Tumori of Milan (Italy) were reviewed. Progression-free (PFS) and overall survival (OS) outcomes were evaluated using Kaplan-Meier and Cox proportional hazard models. Results Records of 147 consecutive patients meeting the inclusion criteria were analyzed. Stage distribution was: 67 (45.6%) patients with early-stage with uterine confined disease and 80 (54.4%) with advanced stages disease. Minimally invasive surgery was performed in 43 patients (29.5%). The median follow-up period was 78.6 months (IQ range = 35.7–117.3 months). The overall recurrence rate was 41% (60 patients): 19/67 patients (28.4%) with early-stage disease and 41/80 patients (51.3%) with advanced stage. The 5-year PFS rate was 35.0% (95% confidence interval [CI]: 27.5–44.7%). In multivariate analysis, age, BMI, depth of myometrial invasion, cytology, and optimal cytoreduction with postoperative residual tumor absent significantly impacted on PFS. The 5-year OS rates were 46.5% (95% CI: 38.1–56.8). The result of multivariate analysis showed that there was significant difference in OS based only on optimal cytoreduction and accuracy of retroperitoneal surgery. Conclusions In apparent early-stage USC, peritoneal and retroperitoneal staging allows to identify patients with disease harboring outside the uterus. Optimal cytoreduction is the most significant prognostic factor. Further collaborative studies are warranted in order to improve outcomes of USC patients.

Published
2022

46. High rates of early remission pattern in adult-onset compared with earlier-onset idiopathic generalized epilepsy: A long-term follow-up study

Author

Emanuele Cerulli Irelli, Biagio Orlando, Mario Manfredi, Carlo Di Bonaventura, Alessandra Morano, Martina Fanella, Giacomo Fisco, Enrico M Salamone, Anna Teresa Giallonardo, Francesca Barone, and Jinane Fattouch

Subjects
Adult, Pediatrics, medicine.medical_specialty, Antiseizure medication (ASM) withdrawal, prognostic patterns, Early remission, Late-onset, Electroencephalography, Immunoglobulin E, Idiopathic generalized epilepsy, Idiopathic generalized epilepsy (IGE), Long-term seizure outcome, prognostic factors, Age of Onset, Follow-Up Studies, Humans, Remission Induction, Retrospective Studies, Epilepsy, Absence, Epilepsy, Generalized, Epilepsy, Medicine, High rate, biology, medicine.diagnostic_test, Generalized, business.industry, Retrospective cohort study, General Medicine, medicine.disease, Absence, Neurology, biology.protein, Neurology (clinical), Juvenile myoclonic epilepsy, business
Abstract

Objective To investigate electroclinical characteristics and prognostic patterns of adult-onset vs. younger-onset idiopathic generalized epilepsy (IGE) patients during long-term follow-up. Methods In this single-center retrospective cohort comparative study, adult-onset IGE was defined as onset after 20 years of age. Patients with a follow-up duration between 10 and 30 years from epilepsy diagnosis were enrolled. Maximum follow-up duration was limited to 30 years to ensure a better comparison of prognostic data between adult-onset and younger-onset patients. The Benjamini-Hochberg false discovery rate (FDR) method was applied to obtain FDR-adjusted p-values. Results A total of 177 IGE patients were recruited and 27 adult-onset IGE patients were identified (15.3%). Follow-up duration was similar between younger- and adult-onset IGE patients and 74% of subjects performed at least one 24-hour EEG recording. Of adult-onset IGE patients, 8/27 were diagnosed with juvenile myoclonic epilepsy, while 19/27 were diagnosed with generalized tonic-clonic seizures (GTCS) only. EEG photosensitivity and absence seizures were significantly less frequent among adult-onset IGE patients as compared with younger subjects. When considering prognostic patterns, an early remission pattern was significantly higher among adult-onset IGE patients as compared with younger-onset IGE patients (55.6% vs. 24%, adjusted p value = 0.007). Antiseizure medication withdrawal was attempted in 3/27 adult-onset patients, and all had GTCS relapses. Conclusion Our study contributes to better defining the electroclinical characteristics and long-term follow-up of adult-onset IGE patients. A favorable long-term seizure outcome was found in adult-onset IGE patients, as evidenced by the high rates of early remission pattern when compared with younger onset patients.

Published
2022

47. Low in-hospital mortality rate in patients with COVID-19 receiving thromboprophylaxis: data from the multicentre observational START-COVID Register

Author

Rossella, Marcucci, Poli, Daniela, SOD Malattie Aterotrombotiche, Azienda Ospedaliero Universitaria-Careggi, Walter Ageno, Firenze., Giovanna, Colombo, UOSD Degenza Breve, e Internistica, Centro trombosi Ospedale di Circolo, Chiara Ambaglio, Varese., UOSD SIMT Servizio di Immunoematologia, e Medicina Trasfusionale, Ospedale di Treviglio, – Caravaggio, ASST Bergamo Ovest, Guido Arpaia, Bergamo., Giovanni Barillari, U. O. Medicina Interna Carate Brianza ASST-Vimercate., SOS di Dipartimento 'Malattie Emorragiche, e Trombotiche, Azienda Sanitaria Universitaria Friuli Centrale, Giuseppina Bitti, Presidio Ospedaliero Universitario 'Santa Maria della Misericordia'. Udine., Giuseppe Pio Martino Medicina Interna Ospedale Civile di Fermo, Eugenio Bucherini, Fermo (Ancona)., Antonio Chistolini, Monica Vastola— SS Az. le di Angiologia Faenza (RA) AUSL Romagna., Alessandra, Serrao, Dipartimento di Medicina Traslazionale, e di Precisione, Egidio De Gaudenzi, Sapienza Universita di Roma., Valeria De Micheli, SOC Medicina Interna Ospedale San Biagio – Domodossola., Anna Falanga, Ambulatorio Emostasi—Azienda Ospedaliera Di Lecco., Teresa, Lerede, Luca, Barcella, Laura, Russo, Usc, Simt, Centro Emostasi, e Trombosi, Ospedale Papa Giovanni XXIII, Vittorio Fregoni, Bergamo., Medicina Generale, U. O. C., Silvia Galliazzo, ASST Valtellina e Alto Lario Ospedale di Sondalo., UOC Medicina Generale, Ospedale San Valentino, Alberto Gandolfo, Montebelluna (TV)., Gianni, Biolo, Valentina, Trapletti, SC (UCO) Clinica Medica, Azienda sanitaria universitaria Giuliano Isontina (ASU GI)—Ospedale di Cattinara, Trieste, Ghigliotti, Giorgio, Elisa Grifoni, Clinica Delle Malattie Dell'apparato Cardiovascolare Policlinico San Martino Genova., Luca, Masotti, Medicina Interna, 2, Ospedale San Giuseppe, Egidio Imbalzano, Empoli (Fi)., UOC Medicina Interna, Gianfranco Lessiani, Policlinico di Messina., Unita, Angiologica, Dipartimento di Medicina, e Geriatria, Ospedale, Citta, Sant'Angelo, Niccolo Marchionni, Pescara., SOD Cardiologia Generale, Dipartimento, Cardiotoracovascolare, Aou, Careggi, Giuliana Martini, Firenze., Sara, Merelli, Nicola Portesi Centro Emostasi, Spedali Civili Di Brescia, Franco, Mastroianni, Giovanni, Larizza, Covid, Unit, Miulli, EE Ospedale Generale F., Carlo Nozzoli, Acquaviva delle Fonti (Ba)., SOD Medicina Interna, 1, Dipartimento di Emergenza AOU- Careggi, Serena Panarello, Firenze., Fioravanti, Chiara, SC Medicina Interna, Galliera, Eo, Simona Pedrini, Genova., Federica, Bertola, Servizio di Laboratorio, Istituto Ospedaliero Fondazione Poliambulanza, Raffaele Pesavento, Brescia., Filippo Pieralli, Davide Ceccato UO Clinica Medica 3 Azienda Ospedaliero Universitaria Padova., SOD Medicina Interna ad alta intensita, Dipartimento di Emergenza, AOU-, Careggi, Pasquale Pignatelli, Firenze., Daniele, Pastori, Centro, Trombosi, Clinica Medica, I, Paola Preti, Universita La Sapienza Roma., Centro Emostasi, e Trombosi Medicina Generale II, Matteo, IRCCS Fondazione Policlinico S., Elias Romano, Pavia., Alessandro, Morettini, Girolamo Sala, AOU-Careggi Firenze., Fabrizio, Foieni, Michela, Provisone, UOC Medicina II, Luca Sarti, Ospedale di Circolo Busto Arsizio (Va)., Antonella, Caronna, Struttura complessa di medicina interna ed area critica, Federico Simonetti, Ospedale di Baggiovara (Mo)., Ilaria, Bertaggia, Piera Sivera, UOC Ematologia Aziendale – Ospedale Versilia –Lido di Camaiore (Lucca)., Carmen, Fava, Ematologia e terapie cellulari, S. C. D. U., Viviana Scancassani, AO Ordine Mauriziano Umberto 1° Torino., Michele Spinicci, ASST Valtellina UOC di Medicina Sondrio., Alessio, Bartoloni, SOD Malattie Infettive, e Tropicali, Adriana Visona, Firenze., Beniamino, Zalunardo, Uoc, Angiologia, Ospedale San Giacomo Apostolo, Sabina Villalta, Castelfranco Veneto (Treviso)., and Castelfranco Veneto, (Treviso).

Subjects
Heparin, Anticoagulants, COVID-19, Antithrombotic, COVID-19 disease, Mortality, Hemorrhage, Venous Thromboembolism, Heparin, Low-Molecular-Weight, Im - Original, COVID-19 disease, Antithrombotic, Heparin, Mortality, Fibrinolytic Agents, Emergency Medicine, Internal Medicine, Humans, Hospital Mortality, Pulmonary Embolism, Retrospective Studies
Abstract

COVID-19 infection causes respiratory pathology with severe interstitial pneumonia and extra-pulmonary complications; in particular, it may predispose to thromboembolic disease. The current guidelines recommend the use of thromboprophylaxis in patients with COVID-19, however, the optimal heparin dosage treatment is not well-established. We conducted a multicentre, Italian, retrospective, observational study on COVID-19 patients admitted to ordinary wards, to describe clinical characteristic of patients at admission, bleeding and thrombotic events occurring during hospital stay. The strategies used for thromboprophylaxis and its role on patient outcome were, also, described. 1091 patients hospitalized were included in the START-COVID-19 Register. During hospital stay, 769 (70.7%) patients were treated with antithrombotic drugs: low molecular weight heparin (the great majority enoxaparin), fondaparinux, or unfractioned heparin. These patients were more frequently affected by comorbidities, such as hypertension, atrial fibrillation, previous thromboembolism, neurological disease, and cancer with respect to patients who did not receive thromboprophylaxis. During hospital stay, 1.2% patients had a major bleeding event. All patients were treated with antithrombotic drugs; 5.4%, had venous thromboembolism [30.5% deep vein thrombosis (DVT), 66.1% pulmonary embolism (PE), and 3.4% patients had DVT + PE]. In our cohort the mortality rate was 18.3%. Heparin use was independently associated with survival in patients aged ≥ 59 years at multivariable analysis. We confirmed the high mortality rate of COVID-19 in hospitalized patients in ordinary wards. Treatment with antithrombotic drugs is significantly associated with a reduction of mortality rates especially in patients older than 59 years.

Published
2022

48. Kidney failure prediction models

Author

Ramspek, Chava L, Evans, Marie, Wanner, Christoph, Drechsler, Christiane, Chesnaye, Nicholas C, Szymczak, Maciej, Krajewska, Magdalena, Torino, Claudia, Porto, Gaetana, Hayward, Samantha, Caskey, Fergus, Dekker, Friedo W, Jager, Kitty J, van Diepen, Merel, EQUAL Study Investigators: Adamasco Cupisti, Adelia Sagliocca, Alberto Ferraro, Aleksandra Musiała, Alessandra Mele, Alessandro Naticchia, Alex Còsaro, Alistair Woodman, Andrea Ranghino, Andrea Stucchi, Andreas Jonsson, Andreas Schneider, Angelo Pignataro, Anita Schrander, Anke Torp, Anna McKeever, Anna Szymczak, Anna-Lena Blom, Antonella De Blasio, Antonello Pani, Aris Tsalouichos, Asad Ullah, Barbara McLaren, Bastiaan van Dam, Beate Iwig, Bellasi Antonio, Biagio Raffaele Di Iorio, Björn Rogland, Boris Perras, Butti Alessandra, Camille Harron, Carin Wallquist, Carl Siegert, Carla Barrett, Carlo Gaillard, Carlo Garofalo, Cataldo Abaterusso, Charles Beerenhout, Charlotte O'Toole, Chiara Somma, Christian Marx, Christina Summersgill, Christof Blaser, Claudia D'alessandro, Claudia Emde, Claudia Zullo, Claudio Pozzi, Colin Geddes, Cornelis Verburgh, Daniela Bergamo, Daniele Ciurlino, Daria Motta, Deborah Glowski, Deborah McGlynn, Denes Vargas, Detlef Krieter, Domenico Russo, Dunja Fuchs, Dympna Sands, Ellen Hoogeveen, Ellen Irmler, Emöke Dimény, Enrico Favaro, Eva Platen, Ewelina Olczyk, Ewout Hoorn, Federica Vigotti, Ferruccio Ansali, Ferruccio Conte, Francesca Cianciotta, Francesca Giacchino, Francesco Cappellaio, Francesco Pizzarelli, Fredrik Sundelin, Fredrik Uhlin, Gaetano Greco, Geena Roy, Gaetana Porto, Giada Bigatti, Giancarlo Marinangeli, Gianfranca Cabiddu, Gillian Hirst, Giordano Fumagalli, Giorgia Caloro, Giorgina Piccoli, Giovanbattista Capasso, Giovanni Gambaro, Giuliana Tognarelli, Giuseppe Bonforte, Giuseppe Conte, Giuseppe Toscano, Goffredo Del Rosso, Gunilla Welander, Hanna Augustyniak-Bartosik, Hans Boots, Hans Schmidt-Gürtler, Hayley King, Helen McNally, Hendrik Schlee, Henk Boom, Holger Naujoks, Houda Masri-Senghor, Hugh Murtagh, Hugh Rayner, Ilona Miśkowiec-Wiśniewska, Ines Schlee, Irene Capizzi, Isabel Bascaran Hernandez, Ivano Baragetti, Jacek Manitius, Jane Turner, Jan-Willem Eijgenraam, Jeroen Kooman, Joachim Beige, Joanna Pondel, Joanne Wilcox, Jocelyn Berdeprado, Jochen Röthele, Jonathan Wong, Joris Rotmans, Joyce Banda, Justyna Mazur, Kai Hahn, Kamila Jędrzejak, Katarzyna Nowańska, Katja Blouin, Katrin Neumeier, Kirsteen Jones, Kirsten Anding-Rost, Knut-Christian Gröntoft, Lamberto Oldrizzi, Lesley Haydock, Liffert Vogt, Lily Wilkinson, Loreto Gesualdo, Lothar Schramm, Luigi Biancone, Łukasz Nowak, Maarten Raasveld, Magdalena Durlik, Manuela Magnano, Marc Vervloet, Marco Ricardi, Margaret Carmody, Maria Di Bari, Maria Laudato, Maria Luisa Sirico, Maria Stendahl, Maria Svensson, Maria Weetman, Marjolijn van Buren, Martin Joinson, Martina Ferraresi, Mary Dutton, Merel van Diepen, Michael Matthews, Michele Provenzano, Monika Hopf, Moreno Malaguti, Nadja Wuttke, Neal Morgan, Nicola Palmieri, Nikolaus Frischmuth, Nina Bleakley, Paola Murrone, Paul Cockwell, Paul Leurs, Paul Roderick, Pauline Voskamp, Pavlos Kashioulis, Pawlos Ichtiaris, Peter Blankestijn, Petra Kirste, Petra Schulz, Phil Mason, Philip Kalra, Pietro Cirillo, Pietro Dattolo, Pina Acampora, Rincy Sajith, Rita Nigro, Roberto Boero, Roberto Scarpioni, Rosa Sicoli, Rosella Malandra, Sabine Aign, Sabine Cäsar, Sadie van Esch, Sally Chapman, Sandra Biribauer, Santee Navjee, Sarah Crosbie, Sharon Brown, Sheila Tickle, Sherin Manan, Silke Röser, Silvana Savoldi, Silvio Bertoli, Silvio Borrelli, Siska Boorsma, Stefan Heidenreich, Stefan Melander, Stefania Maxia, Stefano Maffei, Stefano Mangano, Stephanie Palm, Stijn Konings, Suresh Mathavakkannan, Susanne Schwedler, Sylke Delrieux, Sylvia Renker, Sylvia Schättel, Szyszkowska Dorota, Teresa Cicchetti, Teresa Nieszporek, Theresa Stephan, Thomas Schmiedeke, Thomas Weinreich, Til Leimbach, Tiziana Rappa, Tora Almquist, Torsten Stövesand, Udo Bahner, Ulrika Jensen, Valentina Palazzo, Walter De Simone, Wolfgang Seeger, Ying Kuan, Zbigniew Heleniak, Zeynep Aydin, Internal Medicine, Chava L, Ramspek, Marie, Evan, Christoph, Wanner, Christiane, Drechsler, Nicholas C, Chesnaye, Maciej, Szymczak, Magdalena, Krajewska, Claudia, Torino, Gaetana, Porto, Samantha, Hayward, Fergus, Caskey, Friedo W, Dekker, Kitty J, Jager, Merel, van Diepen, Study Investigators: Adamasco Cupisti, Equal, Sagliocca, Adelia, Ferraro, Alberto, Musiała, Aleksandra, Mele, Alessandra, Naticchia, Alessandro, Còsaro, Alex, Woodman, Alistair, Ranghino, Andrea, Stucchi, Andrea, Jonsson, Andrea, Schneider, Andrea, Pignataro, Angelo, Schrander, Anita, Torp, Anke, Mckeever, Anna, Szymczak, Anna, Blom, Anna-Lena, De Blasio, Antonella, Pani, Antonello, Tsalouichos, Ari, Ullah, Asad, Mclaren, Barbara, van Dam, Bastiaan, Iwig, Beate, Antonio, Bellasi, Raffaele Di Iorio, Biagio, Rogland, Björn, Perras, Bori, Alessandra, Butti, Harron, Camille, Wallquist, Carin, Siegert, Carl, Barrett, Carla, Gaillard, Carlo, Garofalo, Carlo, Abaterusso, Cataldo, Beerenhout, Charle, O'Toole, Charlotte, Somma, Chiara, Marx, Christian, Summersgill, Christina, Blaser, Christof, D'Alessandro, Claudia, Emde, Claudia, Zullo, Claudia, Pozzi, Claudio, Geddes, Colin, Verburgh, Corneli, Bergamo, Daniela, Ciurlino, Daniele, Motta, Daria, Glowski, Deborah, Mcglynn, Deborah, Vargas, Dene, Krieter, Detlef, Russo, Domenico, Fuchs, Dunja, Sands, Dympna, Hoogeveen, Ellen, Irmler, Ellen, Dimény, Emöke, Favaro, Enrico, Platen, Eva, Olczyk, Ewelina, Hoorn, Ewout, Vigotti, Federica, Ansali, Ferruccio, Conte, Ferruccio, Cianciotta, Francesca, Giacchino, Francesca, Cappellaio, Francesco, Pizzarelli, Francesco, Sundelin, Fredrik, Uhlin, Fredrik, Greco, Gaetano, Roy, Geena, Porto, Gaetana, Bigatti, Giada, Marinangeli, Giancarlo, Cabiddu, Gianfranca, Hirst, Gillian, Fumagalli, Giordano, Caloro, Giorgia, Piccoli, Giorgina, Capasso, Giovanbattista, Gambaro, Giovanni, Tognarelli, Giuliana, Bonforte, Giuseppe, Conte, Giuseppe, Toscano, Giuseppe, Del Rosso, Goffredo, Welander, Gunilla, Augustyniak-Bartosik, Hanna, Boots, Han, Schmidt-Gürtler, Han, King, Hayley, Mcnally, Helen, Schlee, Hendrik, Boom, Henk, Naujoks, Holger, Masri-Senghor, Houda, Murtagh, Hugh, Rayner, Hugh, Miśkowiec-Wiśniewska, Ilona, Schlee, Ine, Capizzi, Irene, Bascaran Hernandez, Isabel, Baragetti, Ivano, Manitius, Jacek, Turner, Jane, Eijgenraam, Jan-Willem, Kooman, Jeroen, Beige, Joachim, Pondel, Joanna, Wilcox, Joanne, Berdeprado, Jocelyn, Röthele, Jochen, Wong, Jonathan, Rotmans, Jori, Banda, Joyce, Mazur, Justyna, Hahn, Kai, Jędrzejak, Kamila, Nowańska, Katarzyna, Blouin, Katja, Neumeier, Katrin, Jones, Kirsteen, Anding-Rost, Kirsten, Gröntoft, Knut-Christian, Oldrizzi, Lamberto, Haydock, Lesley, Vogt, Liffert, Wilkinson, Lily, Gesualdo, Loreto, Schramm, Lothar, Biancone, Luigi, Nowak, Łukasz, Raasveld, Maarten, Durlik, Magdalena, Magnano, Manuela, Vervloet, Marc, Ricardi, Marco, Carmody, Margaret, Di Bari, Maria, Laudato, Maria, Luisa Sirico, Maria, Stendahl, Maria, Svensson, Maria, Weetman, Maria, van Buren, Marjolijn, Joinson, Martin, Ferraresi, Martina, Dutton, Mary, van Diepen, Merel, Matthews, Michael, Provenzano, Michele, Hopf, Monika, Malaguti, Moreno, Wuttke, Nadja, Morgan, Neal, Palmieri, Nicola, Frischmuth, Nikolau, Bleakley, Nina, Murrone, Paola, Cockwell, Paul, Leurs, Paul, Roderick, Paul, Voskamp, Pauline, Kashioulis, Pavlo, Ichtiaris, Pawlo, Blankestijn, Peter, Kirste, Petra, Schulz, Petra, Mason, Phil, Kalra, Philip, Cirillo, Pietro, Dattolo, Pietro, Acampora, Pina, Sajith, Rincy, Nigro, Rita, Boero, Roberto, Scarpioni, Roberto, Sicoli, Rosa, Malandra, Rosella, Aign, Sabine, Cäsar, Sabine, van Esch, Sadie, Chapman, Sally, Biribauer, Sandra, Navjee, Santee, Crosbie, Sarah, Brown, Sharon, Tickle, Sheila, Manan, Sherin, Röser, Silke, Savoldi, Silvana, Bertoli, Silvio, Borrelli, Silvio, Boorsma, Siska, Heidenreich, Stefan, Melander, Stefan, Maxia, Stefania, Maffei, Stefano, Mangano, Stefano, Palm, Stephanie, Konings, Stijn, Mathavakkannan, Suresh, Schwedler, Susanne, Delrieux, Sylke, Renker, Sylvia, Schättel, Sylvia, Dorota, Szyszkowska, Cicchetti, Teresa, Nieszporek, Teresa, Stephan, Theresa, Schmiedeke, Thoma, Weinreich, Thoma, Leimbach, Til, Rappa, Tiziana, Almquist, Tora, Stövesand, Torsten, Bahner, Udo, Jensen, Ulrika, Palazzo, Valentina, De Simone, Walter, Seeger, Wolfgang, Kuan, Ying, Heleniak, Zbigniew, Aydin, Zeynep, Medical Informatics, ACS - Pulmonary hypertension & thrombosis, APH - Aging & Later Life, APH - Health Behaviors & Chronic Diseases, APH - Methodology, APH - Quality of Care, and APH - Global Health

Subjects
Male, progression of chronic renal failure, medicine.medical_specialty, Time Factors, epidemiology and outcome, 030232 urology & nephrology, Risk Assessment, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Older patients, external validation, Predictive Value of Tests, medicine, Humans, Failure risk, Clinical Epidemiology, In patient, comprehensive external validation, 030212 general & internal medicine, Statistic, Aged, Aged, 80 and over, Kidney, Models, Statistical, business.industry, External validation, General Medicine, prediction, kidney failure, Europe, prediction model, medicine.anatomical_structure, chronic kidney disease, epidemiology and outcomes, prognosis, Nephrology, Emergency medicine, Disease Progression, Kidney Failure, Chronic, Female, business, prognostic, Predictive modelling, prognosi, Cohort study
Abstract

Background Various prediction models have been developed to predict the risk of kidney failure in patients with CKD. However, guideline-recommended models have yet to be compared head to head, their validation in patients with advanced CKD is lacking, and most do not account for competing risks. Methods To externally validate 11 existing models of kidney failure, taking the competing risk of death into account, we included patients with advanced CKD from two large cohorts: the European Quality Study (EQUAL), an ongoing European prospective, multicenter cohort study of older patients with advanced CKD, and the Swedish Renal Registry (SRR), an ongoing registry of nephrology-referred patients with CKD in Sweden. The outcome of the models was kidney failure (defined as RRT-treated ESKD). We assessed model performance with discrimination and calibration. Results The study included 1580 patients from EQUAL and 13,489 patients from SRR. The average c statistic over the 11 validated models was 0.74 in EQUAL and 0.80 in SRR, compared with 0.89 in previous validations. Most models with longer prediction horizons overestimated the risk of kidney failure considerably. The 5-year Kidney Failure Risk Equation (KFRE) overpredicted risk by 10%-\18%. The four- and eight-variable 2-year KFRE and the 4-year Grams model showed excellent calibration and good discrimination in both cohorts. Conclusions Some existing models can accurately predict kidney failure in patients with advanced CKD. KFRE performed well for a shorter time frame (2 years), despite not accounting for competing events. Models predicting over a longer time frame (5 years) overestimated risk because of the competing risk of death. The Grams model, which accounts for the latter, is suitable for longer-term predictions (4 years).

Published
2021

49. HSP90 identified by a proteomic approach as druggable target to reverse platinum resistance in ovarian cancer

Author

Maria Rita Milone, Francesca Capone, Tania Moccia, Laura Addi, María Roca, Biagio Pucci, Elena Di Gennaro, Francesca Bruzzese, Maura Sonego, Alfredo Budillon, Alice Costa, Gustavo Baldassarre, Federica Iannelli, Rita Lombardi, Luigi Alfano, Lombardi, Rita, Sonego, Maura, Pucci, Biagio, Addi, Laura, Iannelli, Federica, Capone, Francesca, Alfano, Luigi, Roca, Maria Serena, Milone, Maria Rita, Moccia, Tania, Costa, Alice, Di Gennaro, Elena, Bruzzese, Francesca, Baldassarre, Gustavo, and Budillon, Alfredo

Subjects
0301 basic medicine, Cancer Research, Ganetespib, cisplatin, Mice, SCID, Carcinoma, Ovarian Epithelial, 0302 clinical medicine, Mice, Inbred NOD, Benzoquinones, Research Articles, Ovarian Neoplasms, biology, General Medicine, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Hsp90, female genital diseases and pregnancy complications, ovarian cancer, Oncology, 030220 oncology & carcinogenesis, Molecular Medicine, Female, Research Article, medicine.drug, DNA damage, Lactams, Macrocyclic, Mice, Nude, Antineoplastic Agents, lcsh:RC254-282, 03 medical and health sciences, proteomics, In vivo, Cell Line, Tumor, Genetics, medicine, Animals, Humans, HSP90, HSP90 Heat-Shock Proteins, Platinum, Cisplatin, drug resistance, business.industry, Triazoles, medicine.disease, Xenograft Model Antitumor Assays, 030104 developmental biology, Drug Resistance, Neoplasm, Apoptosis, biology.protein, Cancer research, business, Ovarian cancer, Ex vivo
Abstract

Acquired resistance to platinum (Pt)‐based therapies is an urgent unmet need in the management of epithelial ovarian cancer (EOC) patients. Here, we characterized by an unbiased proteomics method three isogenic EOC models of acquired Pt resistance (TOV‐112D, OVSAHO, and MDAH‐2774). Using this approach, we identified several differentially expressed proteins in Pt‐resistant (Pt‐res) compared to parental cells and the chaperone HSP90 as a central hub of these protein networks. Accordingly, up‐regulation of HSP90 was observed in all Pt‐res cells and heat‐shock protein 90 alpha isoform knockout resensitizes Pt‐res cells to cisplatin (CDDP) treatment. Moreover, pharmacological HSP90 inhibition using two different inhibitors [17‐(allylamino)‐17‐demethoxygeldanamycin (17AAG) and ganetespib] synergizes with CDDP in killing Pt‐res cells in all tested models. Mechanistically, genetic or pharmacological HSP90 inhibition plus CDDP ‐induced apoptosis and increased DNA damage, particularly in Pt‐res cells. Importantly, the antitumor activities of HSP90 inhibitors (HSP90i) were confirmed both ex vivo in primary cultures derived from Pt‐res EOC patients ascites and in vivo in a xenograft model. Collectively, our data suggest an innovative antitumor strategy, based on Pt compounds plus HSP90i, to rechallenge Pt‐res EOC patients that might warrant further clinical evaluation., By unbiased proteomics, we identified HSP90 as a central hub in platinum (Pt)‐resistant ovarian cancer models. Indeed, genetic and pharmacologial HSP90 inhibition sensitized resistant cells to CDDP treatment, potentiating DNA‐damage and apoptosis. Combined CDDP plus anti‐HSP90 therapy is effective also ex vivo on primary cultures from Pt‐resistant (Pt‐res) ovarian cancer patients and in vivo Pt‐res ovarian cancer xenograft mouse model.

Published
2021

50. New and Consolidated Therapeutic Options for Pubertal Induction in Hypogonadism: In-depth Review of the Literature

Author

Silvia Federici, Giovanni Goggi, Richard Quinton, Luca Giovanelli, Luca Persani, Biagio Cangiano, and Marco Bonomi

Subjects
Male, Puberty, Delayed, Endocrinology, Adolescent, Hypogonadism, Endocrinology, Diabetes and Metabolism, Puberty, Humans, Female, Testosterone, Child, Gonadotropins
Abstract

Delayed puberty (DP) defines a retardation of onset/progression of sexual maturation beyond the expected age from either a lack/delay of the hypothalamo-pituitary-gonadal axis activation or a gonadal failure. DP usually gives rise to concern and uncertainty in patients and their families, potentially affecting their immediate psychosocial well-being and also creating longer term psychosexual sequelae. The most frequent form of DP in younger teenagers is self-limiting and may not need any intervention. Conversely, DP from hypogonadism requires prompt and specific treatment that we summarize in this review. Hormone therapy primarily targets genital maturation, development of secondary sexual characteristics, and the achievement of target height in line with genetic potential, but other key standards of care include body composition and bone mass. Finally, pubertal induction should promote psychosexual development and mitigate both short- and long-term impairments comprising low self-esteem, social withdrawal, depression, and psychosexual difficulties. Different therapeutic options for pubertal induction have been described for both males and females, but we lack the necessary larger randomized trials to define the best approaches for both sexes. We provide an in-depth and updated literature review regarding therapeutic options for inducing puberty in males and females, particularly focusing on recent therapeutic refinements that better encompass the heterogeneity of this population, and underlining key differences in therapeutic timing and goals. We also highlight persistent shortcomings in clinical practice, wherein strategies directed at “the child with delayed puberty of uncertain etiology” risk being misapplied to older adolescents likely to have permanent hypogonadism.

Published
2021

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