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1. P118 Increased atherothrombotic risk in SLE patients: the role of oxidative stress in fibrinogen structural and functional modifications

Author: Augusto Vaglio, Giacomo Emmi, Domenico Prisco, Alessandra Bettiol, Elena Silvestri, Federica Bello, Claudia Fiorillo, Matteo Becatti, Irene Mattioli, Amanda Mannucci, Flavia Rita Argento, Eleonora Fini, Maria Nicastro, and Niccolò Taddei
Subjects: Immunologic diseases. Allergy, RC581-607
Published: 2024
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2. SIRT1 and thrombosis

Author: Alessandra Bettiol, Maria Letizia Urban, Giacomo Emmi, Silvia Galora, Flavia Rita Argento, Eleonora Fini, Serena Borghi, Giacomo Bagni, Irene Mattioli, Domenico Prisco, Claudia Fiorillo, and Matteo Becatti
Subjects: SIRT1, thrombosis, oxidative stress, atherosclerosis, sirtuins, Biology (General), QH301-705.5
Abstract: Thrombosis is a major cause of morbidity and mortality worldwide, with a complex and multifactorial pathogenesis. Recent studies have shown that SIRT1, a member of the sirtuin family of NAD + -dependent deacetylases, plays a crucial role in regulating thrombosis, modulating key pathways including endothelial activation, platelet aggregation, and coagulation. Furthermore, SIRT1 displays anti-inflammatory activity both in vitro, in vivo and in clinical studies, particularly via the reduction of oxidative stress. On these bases, several studies have investigated the therapeutic potential of targeting SIRT1 for the prevention of thrombosis. This review provides a comprehensive and critical overview of the main preclinical and clinical studies and of the current understanding of the role of SIRT1 in thrombosis.
Published: 2024
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3. The new era of anticoagulation: factor XI and XII inhibitors

Author: Domenico Prisco, Irene Mattioli, Raffaele De Caterina, and Alessandra Bettiol
Subjects: Anticoagulation, bleeding, factor XI, factor XII, thrombosis, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: The two last decades have witnessed a revolution in the field of anticoagulation, mainly due to the advent of direct anticoagulant with targeted action against single coagulation proteins. However, the residual risk of cardio- and cerebrovascular events, particularly in some critical settings, and the risk of major bleeding still represent unmet medical needs. Preclinical studies and experience from families with genetic deficiencies of factor XI or XII (FXI and FXII) allowed to identify these factors involved in the contact pathway of coagulation as potential targets for new anticoagulant approaches. To date, several pharmacological classes of FXI and FXII inhibitors have been developed, including antisense oligonucleotides, monoclonal antibodies, small molecules, natural inhibitors, and aptamers, and various molecules are currently under phase 2 or 3 clinical investigation. Particularly, promising results have been obtained in patients undergoing major orthopedic surgery, in those with end-stage kidney disease, atrial fibrillation and acute coronary syndrome. This review summarizes current knowledge on FXI and FXII inhibitors, with a particular focus on their pharmacological properties and potential clinical indications.
Published: 2023
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4. Serum Interleukin-36 α as a Candidate Biomarker to Distinguish Behçet’s Syndrome and Psoriatic Arthritis

Author: Alessandra Bettiol, Filippo Fagni, Irene Mattioli, Giacomo Bagni, Gianfranco Vitiello, Alessia Grassi, Chiara Della Bella, Marisa Benagiano, Arianna Troilo, Katarzyna Stella Holownia, David Simon, Flavia Rita Argento, Jurgen Sota, Claudia Fabiani, Matteo Becatti, Claudia Fiorillo, Georg Schett, Giuseppe Lopalco, Luca Cantarini, Domenico Prisco, Elena Silvestri, Giacomo Emmi, and Mario Milco D’Elios
Subjects: Behçet disease, biomarkers, cytokines, interleukin 36, vasculitis, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract: Behçet’s syndrome (BS) is a rare systemic vasculitis characterized by different clinical manifestations. As no specific laboratory tests exist, the diagnosis relies on clinical criteria, and the differential diagnosis with other inflammatory diseases can be challenging. Indeed, in a relatively small proportion of patients, BS symptoms include only mucocutaneous, articular, gastrointestinal, and non-typical ocular manifestations, which are frequently found also in psoriatic arthritis (PsA). We investigate the ability of serum interleukin (IL)-36α—a pro-inflammatory cytokine involved in cutaneous and articular inflammatory diseases—to differentiate BS from PsA. A cross-sectional study was performed on 90 patients with BS, 80 with PsA and 80 healthy controls. Significantly lower IL-36α concentrations were found in patients with BS as compared to PsA, although in both groups IL-36α was significantly increased compared to healthy controls. An empirical cut-off of 420.6 pg/mL displayed a specificity of 0.93, with a sensitivity of 0.70 (AUC 0.82) in discriminating PsA from BS. This cut-off displayed a good diagnostic performance also in BS patients lacking highly specific BS manifestations. Our results indicate that IL-36α might be involved in the pathogenesis of both BS and PsA, and might be a candidate biomarker to support the differential diagnosis of BS.
Published: 2023
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5. Management of ongoing direct anticoagulant treatment in patients with hip fracture

Author: Carlo Rostagno, Alessandro Cartei, Gianluca Polidori, Roberto Civinini, Alice Ceccofiglio, Gaia Rubbieri, Massimo Curcio, Alberto Boccaccini, Adriano Peris, and Domenico Prisco
Subjects: Medicine, Science
Abstract: Abstract Aim of the present study was to investigate the effects of ongoing treatment with DOACs on time from trauma to surgery and on in-hospital clinical outcomes (blood losses, need for transfusion, mortality) in patients with hip fracture. Moreover we evaluated the adherence to current guidelines regarding the time from last drug intake and surgery. In this observational retrospective study clinical records of patients admitted for hip fracture from January 2016 to January 2019 were reviewed. 74 patients were in treatment with DOACs at hospital admission. Demographic data, comorbidities and functional status before trauma were retrieved. As control group we evaluated 206 patients not on anticoagulants matched for age, gender, type of fracture and ASA score. Time to surgery was significantly longer in patients treated with DOACs (3.6 + 2.7 vs. 2.15 ± 1.07 days, p
Published: 2021
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6. Circulating miRNome profiling data in Behçet's syndrome

Author: Giacomo Bagni, Giacomo Emmi, Elena Lastraioli, Francesca Di Patti, Elena Silvestri, Angela Guerriero, Serena Pillozzi, Elena Niccolai, Amedeo Amedei, Lorenzo Emmi, Domenico Prisco, and Annarosa Arcangeli
Subjects: microRNA, Circulating miRNAs, Behçet, Microarray, Biomarker, Computer applications to medicine. Medical informatics, R858-859.7, Science (General), Q1-390
Abstract: We conducted a screening analysis to assess the presence of a characteristic extracellular circulating microRNAs (ci-miRNAs) profile in Behçet's syndrome (BS).Total RNA was extracted from platelets-free plasma (PFP) samples obtained from 16 BS patients and 18 healthy controls. Ci-miRNAs profiling was conducted by using dedicated Agilent microarray hybridization and data extraction technology. Statistical analysis of data extracted from microarray scanning revealed the deregulation of 36 ci-miRNAs, which turned out be differentially expressed between BS patients and healthy controls. Detailed experimental methods and data analysis were described here.The raw and normalized microarray data were deposited into Gene Expression Omnibus (GEO) under accession number GSE145191.
Published: 2021
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7. Gut Microbiota and Associated Mucosal Immune Response in Eosinophilic Granulomatosis with Polyangiitis (EGPA)

Author: Elena Niccolai, Alessandra Bettiol, Simone Baldi, Elena Silvestri, Leandro Di Gloria, Federica Bello, Giulia Nannini, Federica Ricci, Maria Nicastro, Matteo Ramazzotti, Augusto Vaglio, Gianluca Bartolucci, Giacomo Emmi, Amedeo Amedei, and Domenico Prisco
Subjects: eosinophilic granulomatosis with polyangiitis, ANCA-associated vasculitis, microbiota, T lymphocytes, short-chain fatty acids, Biology (General), QH301-705.5
Abstract: Eosinophilic granulomatosis with polyangiitis (EGPA) is an anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. A genome-wide association study showed a correlation between ANCA-negative EGPA and variants of genes encoding proteins with intestinal barrier functions, suggesting that modifications of the mucosal layer and consequent gut dysbiosis might be involved in EGPA pathogenesis. Here, we characterized the gut microbiota (GM) composition and the intestinal immune response in a cohort of EGPA patients. Faeces from 29 patients and 9 unrelated healthy cohabitants were collected, and GM and derived metabolites’ composition were compared. Seven intestinal biopsies from EGPA patients with gastrointestinal manifestations were analysed to assess the T-cell distribution and its correlation with GM and EGPA clinical and laboratory features. No significant differences in GM composition, nor in the total amount of faecal metabolites, emerged between patients and controls. Nevertheless, differences in bacterial taxa abundances and compositional GM-derived metabolites profile were observed. Notably, an enrichment of potential pathobionts (Enterobacteriacee and Streptococcaceae) was found in EGPA, particularly in patients with active disease, while lower levels were found in patients on immunosuppression, compared with non-immunosuppressed ones. Significantly lower amounts of hexanoic acid were found in patients, compared to controls. The analysis of the immune response in the gut mucosa revealed a high frequency of IFN-γ/IL-17-producing T lymphocytes, and a positive correlation between EGPA disease activity and intestinal T-cell levels. Our data suggest that an enrichment in potential intestinal pathobionts might drive an imbalanced inflammatory response in EGPA.
Published: 2022
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8. 36-month clinical outcomes of patients with venous thromboembolism

Author: Alexander G.G. Turpie, Alfredo E. Farjat, Sylvia Haas, Walter Ageno, Jeffrey I. Weitz, Samuel Z. Goldhaber, Shinya Goto, Pantep Angchaisuksiri, Gloria Kayani, Renato D. Lopes, Chern-En Chiang, Harry Gibbs, Eric Tse, Peter Verhamme, Hugo ten Cate, Juan Muntaner, Sebastian Schellong, Henri Bounameaux, Paolo Prandoni, Uma Maheshwari, Ajay K. Kakkar, Ab Loualidi, Abdurrahim Colak, Abraham Bezuidenhout, Abu Abdool-Carrim, Addala Azeddine, Adriaan Beyers, Adriaan Dees, Ahmed Mohamed, Ahmet Aksoy, Akihiko Abiko, Akinori Watanabe, Alan Krichell, Alberto Alfredo Fernandez, Alberto Tosetto, Alexey Khotuntsov, Alisha Oropallo, Alison Slocombe, Allan Kelly, Amanda Clark, Amr Gad, Amy Arouni, Andor Schmidt, Andrea Berni, Andres Javier Kleiban, Andrew Machowski, Andrey Kazakov, Angel Galvez, Ann Lockman, Anna Falanga, Anoop Chauhan, Antoni Riera-Mestre, Antonino Mazzone, Armando D'Angelo, Artur Herdy, Atsushi Kato, Ayman Abd Elhamid Ebrahim Mahmoud Salem, Azlan Husin, Barbara Erdelyi, Barry Jacobson, Beatrice Amann-Vesti, Bektas Battaloglu, Benedicte Wilson, Benilde Cosmi, Bergmann Jean Francois, Berremeli Toufek, Beverley Hunt, Bhavesh Natha, Bisher Mustafa, Bonnie Chi Shan Kho, Boulon Carine, Brian Zidel, Brisot Dominique, Brousse Christophe, Bruno Trimarco, Canhua Luo, Carlos Alberto Cuneo, Carlos Jerjes Sanchez Diaz, Carsten Schwencke, Cas Cader, Celal Yavuz, Cesar Javier Zaidman, Charles Lunn, Chau-Chung Wu, Cheng Hock Toh, Chevrier Elisa, Chien-Hsun Hsia, Chien-Lung Huang, Chi-Hang Kevin Kwok, Chih-Cheng Wu, Chi-Hung Huang, Chris Ward, Christian Opitz, Christina Jeanneret-Gris, Chung Yin Ha, Chun-Yao Huang, Claude Luyeye Bidi, Clifford Smith, Cornelia Brauer, Corrado Lodigiani, Couturaud Francis, Cynthia Wu, Daniel Staub, Daniel Theodoro, Daniela Poli, David - Riesco Acevedo, David Adler, David Jimenez, David Keeling, David Scott, Davide Imberti, Desmond Creagh, Desmurs-Clavel Helene, Dirk Hagemann, Dirk Le Roux, Dirk Skowasch, Dmitry Belenky, Dmitry Dorokhov, Dmitry Petrov, Dmitry Zateyshchikov, Domenico Prisco, Dorthe Møller, Dusan Kucera, Ehab M. Esheiba, Elizaveta Panchenko, Elkouri Dominique, Emre Dogan, Emre Kubat, Enrique Diaz Diaz, Eric Wai Choi Tse, Erik Yeo, Erman Hashas, Ernst Grochenig, Eros Tiraferri, Erwin Blessing, Escande Orthlieb Michèle, Esther Usandizaga, Ettore Porreca, Fabian Ferroni, Falvo Nicolas, Félix Ayala-Paredes, Firas Koura, Fitjerald Henry, Franco Cosmi, Frans Erdkamp, Gadel Kamalov, Garcia-Bragado Dalmau, Garrigues Damien, Garry Klein, Gaurand Shah, Geert Hollanders, Geno Merli, Georg Plassmann, George Platt, Germain Poirier, German Sokurenko, Ghassan Haddad, Gholam Ali, Giancarlo Agnelli, Gin Gin Gan, Grace Kaye-Eddie, Gregoire Le Gal, Gregory Allen, Guillermo Antonio Llamas Esperón, Guillot Jean-Paul, Hagen Gerofke, Hallah Elali, Hana Burianova, Hans-Juergen Ohler, Haofu Wang, Harald Darius, Harinder S. Gogia, Harry Striekwold, Hatice Hasanoglu, Hatice Turker, Hendrik Franow, Herbert De Raedt, Herman Schroe, Hesham Salah ElDin, Hesham Zidan, Hiroaki Nakamura, Ho Young Kim, Holger Lawall, Hong Zhu, Hongyan Tian, Ho-Young Yhim, Hun Gyu Hwang, Hyeok Shim, Igor Kim, Igor Libov, Igor Sonkin, Igor Suchkov, Ik-Chan Song, Ilker Kiris, Ilya Staroverov, Irene Looi, Isabel M. De La Azuela Tenorio, Ismail Savas, Ivan Gordeev, Ivo Podpera, Jae Hoon Lee, Jameela Sathar, James Welker, Jan Beyer-Westendorf, Jan Kvasnicka, Jan Vanwelden, JangYong Kim, Jaromira Svobodova, Jaspal Gujral, Javier Marino, Javier Tristan Galvar, Jeannine Kassis, Jen-Yuan Kuo, Jhih-Yuan Shih, JiHyun Kwon, Jin Hyun Joh, Jin Hyun Park, Jin Seok Kim, Jinghua Yang, Jiri Krupicka, Jiri Lastuvka, Jiri Pumprla, Jiri Vesely, Joan Carlos Souto, João Antônio Correa, Johan Duchateau, John Perry Fletcher, Jorge del Toro, Jorge Guillermo Chavez Paez, Jørn Nielsen, Jose Dalmo Araujo Filho, Jose Saraiva, Jose Antonio Diaz Peromingo, Jose Gomez Lara, Jose Luis Fedele, Jose Maria Surinach, Joseph Chacko, Juan Antonio Muntaner, Juan Carlos Álvarez Benitez, Juan Moreno Hoyos Abril, Julian Humphrey, Julio Bono, Junji Kanda, Juree Boondumrongsagoon, Kai Hang Yiu, Kanchana Chansung, Karin Boomars, Kate Burbury, Katsuhiro Kondo, Kemal Karaarslan, Kensuke Takeuchi, Knut Kroeger, Konstantin Zrazhevskiy, Koscál Svatopluk, Kou-Gi Shyu, Kristel Vandenbosch, Kuan-Cheng Chang, Kuan-Ming Chiu, Kubina Jean-Manuel, Kwan Jing Wern, Kwo-Chang Ueng, Lalita Norasetthada, Laure Binet, Lee Ping Chew, Lei Zhang, Leone Maria Cristina, Lidwine Tick, Lilia Beatriz Schiavi, Lily Lee Lee Wong, Lohana Borges, Louis Botha, Luc Capiau, Luc Timmermans, Luciano Eduardo López, Luigi Ria, Luis Manuel Hernandez Blasco, Luis Alberto Guzman, Luis Flota Cervera, Mahe Isabelle, Manuel Monreal Bosch, Manuel de los Rios Ibarra, Manuel Núñez Fernandez, Marc Carrier, Marcelo Raul Barrionuevo, Marco Antonio Alcocer Gamba, Marco Cattaneo, Marco Moia, Margaret Bowers, Mariam Chetanachan, Mario Alberto Berli, Mark Fixley, Markus Faghih, Markus Stuecker, Marlin Schul, Martin Banyai, Martin Koretzky, Martin Myriam, Mary Elizabeth Gaffney, Masao Hirano, Masashi Kanemoto, Mashio Nakamura, Mersel Tahar, Messas Emmanuel, Michael Kovacs, Michael Leahy, Michael Levy, Michael Munch, Michael Olsen, Michel De Pauw, Michel Gustin, Michiel Van Betsbrugge, Mikhail Boyarkin, Miroslav Homza, Modise Koto, Mohamed Abdool-Gaffar, Mohamed Ayman Fakhry Nagib, Mohamed El-Dessoki, Mohamed Khan, Monniaty Mohamed, Moo Hyun Kim, Moon-Hee Lee, Mosaad Soliman, Mostafa Shawky Ahmed, Mostafa Soliman Abd el Bary, Moustafa A. Moustafa, Muhammad Hameed, Muhip Kanko, Mujibur Majumder, Nadezhda Zubareva, Nicola Mumoli, Nik Azim Nik Abdullah, Nisa Makruasi, Nishen Paruk, Nonglak Kanitsap, Norberto Duda, Nordiana Nordin, Ole Nyvad, Olga Barbarash, Orcun Gurbuz, Oscar Gomez Vilamajo, Oscar Nandayapa Flores, Ozcan Gur, Oztekin Oto, Pablo Javier Marchena, Patrick Carroll, Pavel Lang, Peter MacCallum, Peter Baron von Bilderling, Peter Blombery, Petr Jansky, Peuch Bernadette, Philippe De Vleeschauwer, Philippe Hainaut, Piera Maria Ferrini, Piriyaporn Iamsai, Ponchaux Christian, Pongtep Viboonjuntra, Ponlapat Rojnuckarin, Prahlad Ho, Pramook Mutirangura, Rachel Wells, Rafael Martinez, Raimundo Tirado Miranda, Ralf Kroening, Rapule Ratsela, Raquel Lopez Reyes, Raul Franco Diaz de Leon, Raymond Siu Ming Wong, Raz Alikhan, Reinhold Jerwan-Keim, Remedios Otero, Renate Murena-Schmidt, Reto Canevascini, Richard Ferkl, Richard White, Rika Van Herreweghe, Rita Santoro, Robert Klamroth, Robert Mendes, Robert Prosecky, Roberto Cappelli, Rudolf Spacek, Rupesh Singh, Sam Griffin, Sang Hoon Na, Sanjeev Chunilal, Saskia Middeldorp, Satoshi Nakazawa, See Guan Toh, Seinturier Christophe, Selim Isbir, Selma Raymundo, Seng Kiat Ting, Serge Motte, Serir Ozkan Aktogu, Servaas Donders, Seung Ick Cha, Seung-Hyun Nam, Sevestre-Pietri Marie-Antoinette, Shaun Maasdorp, Shenghua Sun, Shenming Wang, Sherif Mohamed Essameldin, Sherif Mohamed Sholkamy, Shintaro Kuki, Shuichi Yoshida, Shunzo Matsuoka, Simon McRae, Simon Watt, Siriwimon Patanasing, Siwe-Nana Jean-Léopold, Somchai Wongkhantee, Soo-Mee Bang, Sophie Testa, Stanislav Zemek, Steffen Behrens, Stephan Dominique, Stuart Mellor, Suaran Singh Gurcharan Singh, Sudip Datta, Sunee Chayangsu, Susan Solymoss, Tamara Everington, Tarek Ahmed Adel Abdel-Azim, Tawatchai Suwanban, Taylan Adademir, Terence Hart, Terriat Béatrice, Thifhelimbilu Luvhengo, Thomas Horacek, Thomas Zeller, Tim Boussy, Tim Reynolds, Tina Biss, Ting-Hsing Chao, Tomas Smith Casabella, Tomoya Onodera, Tontanai Numbenjapon, Victor Gerdes, Vladimir Cech, Vladimir Krasavin, Vladimir Tolstikhin, W.A. Bax, Wagih Fawzy Abdel Malek, Wai Khoon Ho, Walter Pharr, Weihong Jiang, Wei-Hsiang Lin, Weihua Zhang, Wei-Kung Tseng, Wen-Ter Lai, Wilfried De Backer, Wilhelm Haverkamp, Winston Yoshida, Wolfgang Korte, Won Il Choi, Yang-Ki Kim, Yasuhiro Tanabe, Yasushi Ohnuma, Yeung-Chul Mun, Yohan Balthazar, Yong Park, Yoshisato Shibata, Yuriy Burov, Yuriy Subbotin, Zdenek Coufal, Zhenwen Yang, Zhicheng Jing, Zhongqi Yang, Pulmonary Medicine, Clinical Genetics, Internal Medicine, Vascular Medicine, ACS - Pulmonary hypertension & thrombosis, ARD - Amsterdam Reproduction and Development, ACS - Diabetes & metabolism, VU University medical center, Interne Geneeskunde, MUMC+: MA Alg Interne Geneeskunde (9), and RS: Carim - B04 Clinical thrombosis and Haemostasis
Subjects: History, Anticoagulation, Registry, Polymers and Plastics, SDG 3 - Good Health and Well-being, Deep vein thrombosis, Pulmonary embolism, Hematology, Business and International Management, Industrial and Manufacturing Engineering, Venous thromboembolism
Abstract: BACKGROUND: Venous thromboembolism (VTE), encompassing both deep vein thrombosis (DVT) and pulmonary embolism (PE), is a leading cause of morbidity and mortality worldwide. METHODS: GARFIELD-VTE is a prospective, non-interventional observational study of real-world treatment practices. We aimed to capture the 36-month clinical outcomes of 10,679 patients with objectively confirmed VTE enrolled between May 2014 and January 2017 from 415 sites in 28 countries. FINDINGS: A total of 6582 (61.6 %) patients had DVT alone, 4097 (38.4 %) had PE ± DVT. At baseline, 98.1 % of patients received anticoagulation (AC) with or without other modalities of therapy. The proportion of patients on AC therapy decreased over time: 87.6 % at 3 months, 73.0 % at 6 months, 54.2 % at 12 months and 42.0 % at 36 months. At 12-months follow-up, the incidences (95 % confidence interval [CI]) of all-cause mortality, recurrent VTE and major bleeding were 6.5 (7.0-8.1), 5.4 (4.9-5.9) and 2.7 (2.4-3.0) per 100 person-years, respectively. At 36-months, these decreased to 4.4 (4.2-4.7), 3.5 (3.2-2.7) and 1.4 (1.3-1.6) per 100 person-years, respectively. Over 36-months, the rate of all-cause mortality and major bleeds were highest in patients treated with parenteral therapy (PAR) versus oral anti-coagulants (OAC) and no OAC, and the rate of recurrent VTE was highest in patients on no OAC versus those on PAR and OAC. The most frequent cause of death after 36-month follow-up was cancer (n = 565, 48.6 %), followed by cardiac (n = 94, 8.1 %), and VTE (n = 38, 3.2 %). Most recurrent VTE events were DVT alone (n = 564, 63.3 %), with the remainder PE, (n = 236, 27.3 %), or PE in combination with DVT (n = 63, 7.3 %). INTERPRETATION: GARFIELD-VTE provides a global perspective of anticoagulation patterns and highlights the accumulation of events within the first 12 months after diagnosis. These findings may help identify treatment gaps for subsequent interventions to improve patient outcomes in this patient population. ispartof: THROMBOSIS RESEARCH vol:222 pages:31-39 ispartof: location:United States status: published
Published: 2023

9. Significant and Conflicting Correlation of IL-9 With Prevotella and Bacteroides in Human Colorectal Cancer

Author: Elena Niccolai, Edda Russo, Simone Baldi, Federica Ricci, Giulia Nannini, Matteo Pedone, Francesco Claudio Stingo, Antonio Taddei, Maria Novella Ringressi, Paolo Bechi, Alessio Mengoni, Renato Fani, Giovanni Bacci, Camilla Fagorzi, Carolina Chiellini, Domenico Prisco, Matteo Ramazzotti, and Amedeo Amedei
Subjects: cytokines, colorectal cancer, T cells, immune response, gut microbiota, Immunologic diseases. Allergy, RC581-607
Abstract: Background and aimGut microbiota (GM) can support colorectal cancer (CRC) progression by modulating immune responses through the production of both immunostimulatory and/or immunosuppressive cytokines. The role of IL-9 is paradigmatic because it can either promote tumor progression in hematological malignancies or inhibit tumorigenesis in solid cancers. Therefore, we investigate the microbiota–immunity axis in healthy and tumor mucosa, focusing on the correlation between cytokine profile and GM signature.MethodsIn this observational study, we collected tumor (CRC) and healthy (CRC-S) mucosa samples from 45 CRC patients, who were undergoing surgery in 2018 at the Careggi University Hospital (Florence, Italy). First, we characterized the tissue infiltrating lymphocyte subset profile and the GM composition. Subsequently, we evaluated the CRC and CRC-S molecular inflammatory response and correlated this profile with GM composition, using Dirichlet multinomial regression.ResultsCRC samples displayed higher percentages of Th17, Th2, and Tregs. Moreover, CRC tissues showed significantly higher levels of MIP-1α, IL-1α, IL-1β, IL-2, IP-10, IL-6, IL-8, IL-17A, IFN-γ, TNF-α, MCP-1, P-selectin, and IL-9. Compared to CRC-S, CRC samples also showed significantly higher levels of the following genera: Fusobacteria, Proteobacteria, Fusobacterium, Ruminococcus2, and Ruminococcus. Finally, the abundance of Prevotella spp. in CRC samples negatively correlated with IL-17A and positively with IL-9. On the contrary, Bacteroides spp. presence negatively correlated with IL-9.ConclusionsOur data consolidate antitumor immunity impairment and the presence of a distinct microbiota profile in the tumor microenvironment compared with the healthy mucosa counterpart. Relating the CRC cytokine profile with GM composition, we confirm the presence of bidirectional crosstalk between the immune response and the host’s commensal microorganisms. Indeed, we document, for the first time, that Prevotella spp. and Bacteroides spp. are, respectively, positively and negatively correlated with IL-9, whose role in CRC development is still under debate.
Published: 2021
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10. Incidence of deep vein thrombosis through an ultrasound surveillance protocol in patients with COVID-19 pneumonia in non-ICU setting: A multicenter prospective study.

Author: Filippo Pieralli, Fulvio Pomero, Margherita Giampieri, Rossella Marcucci, Domenico Prisco, Fabio Luise, Antonio Mancini, Alessandro Milia, Lucia Sammicheli, Irene Tassinari, Francesca Caldi, Francesca Innocenti, Antonio Faraone, Chiara Beltrame, Riccardo Pini, Andrea Ungar, and Alberto Fortini
Subjects: Medicine, Science
Abstract: ObjectiveThe aim of this study was to assess the incidence of deep vein thrombosis (DVT) of the lower limbs, using serial compression ultrasound (CUS) surveillance, in acutely ill patients with COVID-19 pneumonia admitted to a non-ICU setting.MethodsMulticenter, prospective study of patients with COVID-19 pneumonia admitted to Internal Medicine units. All patients were screened for DVT of the lower limbs with serial CUS. Anticoagulation was defined as: low dose (enoxaparin 20-40 mg/day or fondaparinux 1.5-2.5 mg/day); intermediate dose (enoxaparin 60-80 mg/day); high dose (enoxaparin 120-160 mg or fondaparinux 5-10 mg/day or oral anticoagulation). The primary end-point of the study was the diagnosis of DVT by CUS.ResultsOver a two-month period, 227 consecutive patients with moderate-severe COVID-19 pneumonia were enrolled. The incidence of DVT was 13.7% (6.2% proximal, 7.5% distal), mostly asymptomatic. All patients received anticoagulation (enoxaparin 95.6%) at the following doses: low 57.3%, intermediate 22.9%, high 19.8%. Patients with and without DVT had similar characteristics, and no difference in anticoagulant regimen was observed. DVT patients were older (mean 77±9.6 vs 71±13.1 years; p = 0.042) and had higher peak D-dimer levels (5403 vs 1723 ng/mL; p = 0.004). At ROC analysis peak D-dimer level >2000 ng/mL (AUC 0.703; 95% CI 0.572-0.834; p = 0.004) was the most accurate cut-off value able to predict DVT (RR 3.74; 95%CI 1.27-10, p = 0.016).ConclusionsThe incidence of DVT in acutely ill patients with COVID-19 pneumonia is relevant. A surveillance protocol by serial CUS of the lower limbs is useful to timely identify DVT that would go otherwise largely undetected.
Published: 2021
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11. Interleukin-17/Interleukin-21 and Interferon-γ producing T cells specific for β2 Glycoprotein I in atherosclerosis inflammation of systemic lupus erythematosus patients with antiphospholipid syndrome

Author: Marisa Benagiano, Maria Orietta Borghi, Jacopo Romagnoli, Michael Mahler, Chiara Della Bella, Alessia Grassi, Nagaja Capitani, Giacomo Emmi, Arianna Troilo, Elena Silvestri, Lorenzo Emmi, Heba Alnwaisri, Jacopo Bitetti, Simona Tapinassi, Domenico Prisco, Cosima Tatiana Baldari, Pier Luigi Meroni, and Mario Milco D’Elios
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Abstract: Systemic lupus erythematosus is frequently associated with antiphospholipid syndrome. Patients with lupus-antiphospholipid syndrome are characterized by recurrent arterial/venous thrombosis, miscarriages, and persistent presence of autoantibodies against phospholipid-binding proteins, such as β2-Glycoprotein I. We investigated the cytokine production induced by β2-Glycoprotein I in activated T cells that infiltrate in vivo atherosclerotic lesions of lupus-antiphospholipid syndrome patients. We examined the helper function of β2-Glycoprotein I-specific T cells for tissue factor production, as well as their cytolytic potential and their helper function for antibody production. Lupus-antiphospholipid syndrome patients harbor in vivo activated CD4+ T cells that recognize β2-Glycoprotein I in atherosclerotic lesions. β2-Glycoprotein I induces T-cell proliferation and expression of both Interleukin-17/Interleukin-21 and Interferon-γ in plaque-derived T-cell clones. β2-Glycoprotein I-specific T cells display strong help for monocyte tissue factor production, and promote antibody production in autologous B cells. Moreover, plaque-derived β2-Glycoprotein I-specific CD4+ T lymphocytes express both perforin-mediated and Fas/FasLigand-mediated-cytotoxicity. Altogether, our results indicate that β2-Glycoprotein I is able to elicit a local Interleukin-17/Interleukin-21 and Interferon-γ inflammation in lupus-antiphospholipid syndrome patients that might lead, if unabated, to plaque instability and subsequent arterial thrombosis, suggesting that the T helper 17/T helper 1 pathway may represent a novel target for the prevention and treatment of the disease.
Published: 2019
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12. Stem-Cell-Derived Circulating Progenitors Dysfunction in Behçet's Syndrome Patients Correlates With Oxidative Stress

Author: Giacomo Emmi, Amanda Mannucci, Flavia Rita Argento, Elena Silvestri, Augusto Vaglio, Alessandra Bettiol, Alessandra Fanelli, Laura Stefani, Niccolò Taddei, Domenico Prisco, Claudia Fiorillo, and Matteo Becatti
Subjects: Behçet's syndrome, thrombosis, circulating progenitor cells, oxidation, apoptosis, Immunologic diseases. Allergy, RC581-607
Abstract: Behçet's syndrome (BS) is a systemic vasculitis considered as the prototype of a systemic inflammation-induced thrombotic condition whose pathogenesis cannot be explained just by coagulation abnormalities. Circulating hematopoietic progenitor cells (CPC), a population of rare, pre-differentiated adult stem cells originating in the bone marrow and capable of both self-renewal and multi-lineage differentiation, are mobilized in response to vascular injury and play a key role in tissue repair. In cardiovascular and thrombotic diseases, low circulating CPC number and reduced CPC function have been observed. Oxidative stress may be one of the relevant culprits that account for the dysfunctional and numerically reduced CPC in these conditions. However, the detailed mechanisms underlying CPC number reduction are unknown. On this background, the present study was designed to evaluate for the first time the possible relationship between CPC dysfunction and oxidative stress in BS patients. In BS patients, we found signs of plasma oxidative stress and significantly lower CD34+/CD45−/dim and CD34+/CD45−/dim/CD133+ CPC levels. Importantly, in all the considered CPC subsets, significantly higher ROS levels with respect to controls were observed. Higher levels of caspase-3 activity in all the considered CPC population and a strong reduction in GSH content in CPC subpopulation from BS patients with respect to controls were also observed. Interestingly, in BS patients, ROS significantly correlated with CPC number and CPC caspase-3 activity and CPC GSH content significantly correlated with CPC number, in all CPC subsets. Collectively, these data demonstrate for the first time that CPC from BS patients show signs of oxidative stress and apoptosis and that a reduced CPC number is present in BS patients with respect to controls. Interestingly, we observed an inverse correlation between circulating CPC number and CPC ROS production, suggesting a possible toxic ROS effect on CPC in BS patients. The significant correlations between ROS production/GSH content and caspase-3 activity point out that oxidative stress can represent a determinant in the onset of apoptosis in CPC. These data support the hypothesis that oxidative-stress-mediated CPC dysfunctioning may counteract their vascular repair actions, thereby contributing to the pathogenesis and the progression of vascular disease in BS.
Published: 2019
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13. Treating the Different Phenotypes of Behçet's Syndrome

Author: Alessandra Bettiol, Gulen Hatemi, Lorenzo Vannozzi, Alessandro Barilaro, Domenico Prisco, and Giacomo Emmi
Subjects: Behçet's syndrome, phenotypes, cluster analysis, anti-TNF-α, DMARDs, Immunologic diseases. Allergy, RC581-607
Abstract: Behçet's syndrome (BS) is a multisystemic vasculitis, characterized by different clinical involvements, including mucocutaneous, ocular, vascular, neurological, and gastrointestinal manifestations. Based on this heterogeneity, BS can be hardly considered as a single clinical entity. Growing evidence supports that, within BS, different phenotypes, characterized by clusters of co-existing involvements, can be distinguished. Namely, three major BS phenotypes have been reported: (a) the mucocutaneous and articular phenotype, (b) the extra-parenchymal neurological and peripheral vascular phenotype, and (c) the parenchymal neurological and ocular phenotype. To date, guidelines for the management of BS have been focused on the pharmacological treatment of each specific BS manifestation. However, tailoring the treatments on patient's specific phenotype, rather than on single disease manifestation, could represent a valid strategy for a personalized therapeutic approach to BS. In the present literature review, we summarize current evidence on the pharmacological treatments for the first-, second-, and third-line treatment of the major BS phenotypes.
Published: 2019
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14. Impact of cardiovascular and immunologic variables on subclinical carotid atherosclerosis in subjects with anti-phospholipid antibodies

Author: Matteo Nicola Dario Di Minno, Giacomo Emmi, Pasquale Ambrosino, Antonella Scalera, Antonella Tufano, Giovanni Cafaro, Rosario Peluso, Alessandra Bettiol, Gerardo Di Scala, Elena Silvestri, and Domenico Prisco
Subjects: Computer applications to medicine. Medical informatics, R858-859.7, Science (General), Q1-390
Abstract: Whereas some previous data on carriers with isolated antiphospholipid antibodies positivity (APP) suggested an increased risk of arterial events in this clinical setting, no data are available on subclinical atherosclerosis in this clinical setting. This article reports data on intima-media thickness of the common carotid artery (CCA-IMT) and of the Bulb (Bulb-IMT) and on the prevalence of carotid plaques in APP carriers and in subjects with antiphospholipid syndrome (APS) specifically stratifying for the presence of thrombotic manifestations, cardiovascular risk factors, antibody isotype and concomitant Systemic Lupus Erythematosus (SLE) or other autoimmune diseases.
Published: 2018
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15. Factor XI inhibitors: cardiovascular perspectives

Author: Raffaele De Caterina, Domenico Prisco, and John W Eikelboom
Subjects: Cardiology and Cardiovascular Medicine
Abstract: Anticoagulants are the cornerstone for prevention and treatment of thrombosis but are not completely effective, and concerns about the risk of bleeding continue to limit their uptake. Animal studies and experience from patients with genetic coagulation factor XI deficiency suggesting that this factor is more important for thrombosis than for haemostasis raises the potential for drugs that target factor XI to provide safer anticoagulation. Multiple factor XI inhibitors are currently under evaluation in clinical trials, including parenterally administered antisense oligonucleotides, monoclonal antibodies, and orally active small-molecule inhibitors. Promising results of phase 2 trials in patients undergoing major orthopaedic surgery, and in those with end-stage kidney disease, atrial fibrillation and acute coronary syndromes have led to large phase 3 trials that are currently ongoing. We here review premises for the use of these agents, results so far accrued, ongoing studies, and perspectives for future patient care.
Published: 2022

16. Serum Interleukin-36 α as a Candidate Biomarker to Distinguish Behçet’s Syndrome and Psoriatic Arthritis

Author: D’Elios, Alessandra Bettiol, Filippo Fagni, Irene Mattioli, Giacomo Bagni, Gianfranco Vitiello, Alessia Grassi, Chiara Della Bella, Marisa Benagiano, Arianna Troilo, Katarzyna Stella Holownia, David Simon, Flavia Rita Argento, Jurgen Sota, Claudia Fabiani, Matteo Becatti, Claudia Fiorillo, Georg Schett, Giuseppe Lopalco, Luca Cantarini, Domenico Prisco, Elena Silvestri, Giacomo Emmi, and Mario Milco
Subjects: Behçet disease, biomarkers, cytokines, interleukin 36, vasculitis
Abstract: Behçet’s syndrome (BS) is a rare systemic vasculitis characterized by different clinical manifestations. As no specific laboratory tests exist, the diagnosis relies on clinical criteria, and the differential diagnosis with other inflammatory diseases can be challenging. Indeed, in a relatively small proportion of patients, BS symptoms include only mucocutaneous, articular, gastrointestinal, and non-typical ocular manifestations, which are frequently found also in psoriatic arthritis (PsA). We investigate the ability of serum interleukin (IL)-36α—a pro-inflammatory cytokine involved in cutaneous and articular inflammatory diseases—to differentiate BS from PsA. A cross-sectional study was performed on 90 patients with BS, 80 with PsA and 80 healthy controls. Significantly lower IL-36α concentrations were found in patients with BS as compared to PsA, although in both groups IL-36α was significantly increased compared to healthy controls. An empirical cut-off of 420.6 pg/mL displayed a specificity of 0.93, with a sensitivity of 0.70 (AUC 0.82) in discriminating PsA from BS. This cut-off displayed a good diagnostic performance also in BS patients lacking highly specific BS manifestations. Our results indicate that IL-36α might be involved in the pathogenesis of both BS and PsA, and might be a candidate biomarker to support the differential diagnosis of BS.
Published: 2023
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17. An Insight into Giant Cell Arteritis Pathogenesis: Evidence for Oxidative Stress and SIRT1 Downregulation

Author: Alessandro Ianni, Poonam Kumari, Shahriar Tarighi, Flavia Rita Argento, Eleonora Fini, Giacomo Emmi, Alessandra Bettiol, Thomas Braun, Domenico Prisco, Claudia Fiorillo, and Matteo Becatti
Subjects: giant cell arteritis (GCA), oxidative stress, SIRT1, Therapeutics. Pharmacology, RM1-950
Abstract: Giant cell arteritis (GCA), medium and large vessel granulomatous vasculitis affecting the elderly, is characterized by a multitude of vascular complications, including venous thrombosis, myocardial infraction and stroke. The formation of granulomatous infiltrates and the enhanced accumulation of proinflammatory cytokines are typical features of this condition. The GCA pathogenesis remains largely unknown, but recent studies have suggested the involvement of oxidative stress, mainly sustained by an enhanced reactive oxygen species (ROS) production by immature neutrophils. On this basis, in the present study, we intended to evaluate, in GCA patients, the presence of systemic oxidative stress and possible alterations in the expression level of nuclear sirtuins, enzymes involved in the inhibition of inflammation and oxidative stress. Thirty GCA patients were included in the study and compared to 30 healthy controls in terms of leukocyte ROS production, oxidative stress and SIRT1 expression. Our results clearly indicated a significant increase (p < 0.05) both in the ROS levels in the leukocyte fractions and plasma oxidative stress markers (lipid peroxidation and total antioxidant capacity) in the GCA patients compared to the healthy controls. In PBMCs from the GCA patients, a significant decrease in SIRT1 expression (p < 0.05) but not in SIRT6 and SIRT7 expression was found. Taken together, our preliminary findings indicate that, in GCA patients, plasma oxidative stress is paralleled by a reduced SIRT1 expression in PBMC. Further studies are needed to highlight if and how these alterations contribute to GCA pathogenesis.
Published: 2021
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18. Evidence of subclinical atherosclerosis in eosinophilic granulomatosis with polyangiitis

Author: Federica Bello, Alessandra Bettiol, Elena Silvestri, Irene Mattioli, Maria Letizia Urban, Adalgisa Palermo, Matteo Mazzetti, Danilo Malandrino, Ilenia Calcaterra, Augusto Vaglio, Matteo Nicola Dario Di Minno, Giacomo Emmi, and Domenico Prisco
Subjects: Rheumatology, Pharmacology (medical)
Abstract: Objectives Patients affected by eosinophilic granulomatosis with polyangiitis (EGPA) display an increased risk of atherothrombotic events compared with the general population. An increased frequency of subclinical markers of atherosclerosis has been observed in other ANCA-associated vasculitis, but no specific study focused on EGPA. We therefore evaluated subclinical atherosclerosis in EGPA patients and in a control population. Methods Forty EGPA patients and 80 controls matched by age, sex and traditional cardiovascular risk factors underwent sonographic assessment of common carotid artery (CCA) intima–media thickness (IMT). The presence of plaques of the CCA was also investigated. The correlation between CCA-IMT and clinical and laboratory features was also assessed. Results Median CCA-IMT was significantly higher in EGPA patients compared with controls (P = 0.002). Also, the proportion of subjects with increased CCA-IMT and with presence of plaques was significantly higher among EGPA patients (P Conclusion Ultrasound markers of subclinical atherosclerosis are increased in EGPA patients as compared with controls, independently of traditional cardiovascular risk factors.
Published: 2022

19. Behçet syndrome in children and adults: discovering similarities and differences by a comparative study

Author: Maria Vincenza Mastrolia, Alessandra Bettiol, Edoardo Marrani, Ilaria Maccora, Emilia Taddei, Ilaria Pagnini, Maria Canfora, Giacomo Emmi, Elena Silvestri, Domenico Prisco, and Gabriele Simonini
Subjects: Rheumatology, Pharmacology (medical)
Abstract: Objective Behçet’s syndrome (BS) is a rare disorder with a relapsing-remitting course. Clinical variance across geographical regions and different age groups has been observed. This study matched the demographic, clinical and treatment features of adult- and juvenile-onset BS in the Italian population. Methods Two clinical databases of BS patients were compared. The paediatric BS database was collected at the Meyer Children’s Hospital, Florence, while the adult BS database was collected at the Careggi University Hospital, Florence. Results A familiar predisposition for BS was significantly more frequent in the paediatric cohort (3/33 vs 1/165, P = 0.015). No difference emerged in terms of prevalence of HLA-B51 positivity. The proportion of patients meeting the revised ICBD and/or the ISG criteria at BS diagnosis was comparable in the two cohorts. No significant difference emerged between the two cohorts in terms of muco-cutaneous, ocular and neurological involvement, and gastrointestinal symptoms. Articular manifestations resulted as more common in the paediatric cohort, whereas venous vascular events were more frequent in the adult cohort. Regarding treatment strategy, paediatric patients more frequently received no treatment or corticosteroid monotherapy. Conversely, the use of DMARDs, both traditional and biologic, was significantly higher in the adult cohort. Conclusion Remarkable differences between juvenile-onset and adult-onset BS, both in terms of gender, familiar predisposition and clinical manifestations have been observed and a different therapeutic approach in the real clinical practice of the two settings emerged. Prospective, comparison studies with a longer follow-up are encouraged to provide further data about the disease course for juvenile- and adult-onset BS.
Published: 2022

20. Management of antithrombotic treatment and bleeding disorders in patients requiring venous access devices: A systematic review and a GAVeCeLT consensus statement

Author: Maria Giuseppina Annetta, Sergio Bertoglio, Roberto Biffi, Fabrizio Brescia, Igor Giarretta, Antonio La Greca, Nicola Panocchia, Giovanna Passaro, Francesco Perna, Fulvio Pinelli, Mauro Pittiruti, Domenico Prisco, Tommaso Sanna, and Giancarlo Scoppettuolo
Subjects: Plasma, Fibrinolytic Agents, Nephrology, Anticoagulants, Humans, Blood Component Transfusion, Hemorrhage, Surgery
Abstract: Insertion of venous access devices (VAD) is usually considered a procedure with low risk of bleeding. Nonetheless, insertion of some devices is invasive enough to be associated with bleeding, especially in patients with previous coagulopathy or in treatment with antithrombotic drugs for cardiovascular disease. The current practices of platelet/plasma transfusion in coagulopathic patients and of temporary suspension of the antithrombotic treatment before VAD insertion are based on local policies and are often inadequately supported by evidence, since many of the clinical studies on this topic are not recent and are not of high quality. Furthermore, the protocols of antithrombotic treatment have changed during the last decade, after the introduction of new oral anticoagulant drugs. Though some guidelines address some of these issues in relation with specific procedures (port insertion, etc.), no evidence-based document covering all the aspects of this clinical problem is currently available. Thus, the Italian Group of Venous Access Devices (GAVeCeLT) has decided to develop a consensus on the management of antithrombotic treatment and bleeding disorders in patients requiring VADs. After a systematic review of the available evidence, the panel of the consensus (which included vascular access specialists, surgeons, intensivists, anesthetists, cardiologists, vascular medicine experts, nephrologists, infective disease specialists, and thrombotic disease specialists) has structured the final recommendations as detailed answers to three sets of questions: (1) which is an appropriate classification of VAD-related procedures based on the specific bleeding risk? (2) Which is the appropriate management of the patient with bleeding disorders candidate to VAD insertion/removal? (3) Which is the appropriate management of the patient on antithrombotic treatment candidate to VAD insertion/removal? Only statements reaching a complete agreement were included in the final recommendations, and all recommendations were offered in a clear and synthetic list, so to be easily translated into clinical practice.
Published: 2022

21. Behçet's Syndrome as a Model of Thrombo-Inflammation: The Role of Neutrophils

Author: Giacomo Emmi, Matteo Becatti, Alessandra Bettiol, Gülen Hatemi, Domenico Prisco, and Claudia Fiorillo
Subjects: Behçet's syndrome, thrombosis, neutrophils, oxidative stress, fibrinogen, Immunologic diseases. Allergy, RC581-607
Abstract: Behçet's syndrome (BS) is a systemic vasculitis, clinically characterized by different organ involvement and often complicated by thrombosis which occurs in vessels of all sizes. Thrombosis is more frequent in male patients with active disease and represents an important cause of morbidity and mortality. Neutrophil involvement in BS has been repeatedly suggested in the last few years. Indeed, neutrophils have been shown to be hyperactivated in BS patients, probably with a HLAB51 related contribution, and represent the main cells infiltrating not only oral and genital ulcers or erythema nodosum, but also other sites. Besides being deputed to host defense against micro-organisms, neutrophils display fundamental roles both in inflammation and tissue damage becoming inappropriately activated by cytokines, chemokines and autoantibodies and subsequently producing large amounts of superoxide anion (O2.) via NADPH oxidase (NOX2). The strict relationship between inflammation and hemostasis has been already demonstrated. Indeed, inflammation and immune-mediated disorders increase the risk of thrombosis, but the pathways that link these processes have not been completely elucidated. In this regard, we recently demonstrated, in a large population of BS patients, a new neutrophil-dependent pathogenetic mechanism of thrombosis. In particular, it was shown that neutrophils, mainly through NADPH oxidase, produce excessive amounts of reactive oxygen species (ROS), which are able to markedly modify the secondary structure of fibrinogen and hence the overall architecture of the fibrin clot that becomes less susceptible to plasmin-induced lysis. These data point out that BS represents “per se” a model of inflammation-induced thrombosis and suggest that neutrophils specifically contribute to thrombo-inflammation in this rare disease. In particular, it is suggested that an alteration in fibrinogen structure and function are associated with enhanced ROS production via neutrophil NADPH oxidase. Altogether, these findings improve our understanding of the intricate pathogenetic mechanisms of thrombo-inflammation and may indicate potential new therapeutic targets.
Published: 2019
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22. Adalimumab Accounts for Long-Term Control of Noninfectious Uveitis Also in the Absence of Concomitant DMARD Treatment: A Multicenter Retrospective Study

Author: Alice Bitossi, Alessandra Bettiol, Elena Silvestri, Gerardo Di Scala, Daniela Bacherini, Giuseppe Lopalco, Vincenzo Venerito, Florenzo Iannone, Antonio Vitale, Gian Marco Tosi, Domenico Prisco, Stanislao Rizzo, Claudia Fabiani, Luca Cantarini, Gianni Virgili, Lorenzo Vannozzi, and Giacomo Emmi
Subjects: Pathology, RB1-214
Abstract: Objective. This study was aimed at assessing the long-term ocular control of adalimumab (ADA) in a large real-world population with noninfectious primary or secondary uveitis, focusing on the steroid-sparing effect and on disease-modifying antirheumatic drug (DMARD) cotreatment. Methods. In this retrospective, multicenter study, the efficacy of ADA was evaluated in terms of ocular control, changes in best-corrected visual acuity (BCVA), corticosteroid-sparing effect, and drug retention rate, overall and stratified according to DMARD cotreatment. Results. 106 patients were included. 88.7% had an associated systemic disease. After 6 and 12 months, proportions of patients with effective ocular control were 83.7% and 83.3%, respectively. At last the follow-up, 94.6% of patients had satisfactory ocular control. No difference in terms of ocular control at all time points emerged among patients starting ADA for ocular vs. systemic involvements. Patients with poor baseline BCVA remained stable or improved, while those with good BCVA hardly worsened. At 6 and 12 months, the median dose of prednisone significantly reduced to 5 mg/day (0-5) and 2.5 mg/day (0-5) (p
Published: 2019
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23. Prevalence and clinical associations of ultrasound-confirmed enthesitis in systemic lupus erythematosus

Author: Filippo Fagni, Alessandra Bettiol, Elena Silvestri, Roberto Fedi, Adalgisa Palermo, Maria Letizia Urban, Ruggero Mazzotta, Danilo Malandrino, Federica Bello, Irene Mattioli, David Simon, Gerardo Di Scala, Georg Schett, Domenico Prisco, and Giacomo Emmi
Subjects: Rheumatology, Pharmacology (medical)
Abstract: Objectives To assess the prevalence of US-confirmed enthesitis in a cohort of patients with SLE and to analyse the clinical associations to enthesitis during the course of SLE. Methods In a retrospective analysis of the SLE cohort of the Lupus Unit of the Careggi University Hospital, US examinations of SLE patients presenting with tender and/or swollen joints were retrieved to assess the presence of enthesitis. Patients with US-proven enthesitis were compared with SLE controls with tender and/or swollen joints who showed no US evidence of enthesitis. Clinical and laboratory features were compared at disease onset and during follow-up. Results A total of 400 patients fulfilling EULAR/ACR classification criteria for SLE were assessed. Of these, 106 underwent articular US examination. Evidence of enthesitis was found in 31/106 (29.2%) patients. Seventy-one patients without US-enthesitis were included as controls; four were excluded due to lack of follow-up data. Laboratory and clinical features were comparable between cases and controls at disease onset. Throughout a median follow-up of 10.0 (interquartile range [IQR] 8.3–23.3) years for cases and 12.4 (IQR 7.2–13.3) years for controls, patients with enthesitis were less likely to develop renal involvement (22.6% vs 46.5%, P = 0.028) and failed B cell depletion more frequently (75.0% vs 0%). Conclusion In SLE patients with clinically active joints, US-proven enthesitis is a fairly common finding. Enthesitis in SLE could be the hallmark of a distinct disease phenotype with less renal involvement, more arthritis and low response to anti-CD 20 therapy, potentially requiring a tailored treatment.
Published: 2023

24. Post-Stroke Detection of Subclinical Paroxysmal Atrial Fibrillation in Patients With Embolic Stroke of Undetermined Source in the Real World Practice

Author: Elisa, Grifoni, Giulia, Baldini, Mariella, Baldini, Gabriele, Pinto, Irene, Micheletti, Elisa M, Madonia, Eleonora, Cosentino, Maria L, Bartolozzi, Elisabetta, Bertini, Alessandro, Dei, Ira, Signorini, Sara, Giannoni, Attilio, Del Rosso, Domenico, Prisco, Leonello, Guidi, and Luca, Masotti
Subjects: Stroke, Embolic Stroke, Risk Factors, Atrial Fibrillation, Hypertension, Humans, Female, General Medicine, Aged, Retrospective Studies
Abstract: Subclinical paroxysmal atrial fibrillation (AF) is one of the main occult causative mechanisms of embolic stroke of undetermined source (ESUS). Aim of this study was to identify AF predictors, and to develop a score to predict the probability of AF detection in ESUS.We retrospectively analyzed ESUS patients undergoing 2-week external electrocardiographic monitoring. Patients with and without AF detection were compared. On the basis of multivariate analysis, predictors of AF were identified and used to develop a predictive score, which was then compared with other existing literature scores.Eighty-two patients, 48 females, mean age±SD 72±10 years, were included. In 36 patients (43.9%) AF was detected. The frequency of age 75 years or above and arterial hypertension, and the median CHA 2 DS 2 -VASc score were significantly higher in patients with AF compared with those without. National Institutes of Health Stroke Scale (NIHSS) score ≥8 was the only independent variable associated with AF detection. We derived the Empoli ESUS-AF (E 2 AF) score (NIHSS ≥8 5 points, arterial hypertension 3 points, age 75 years or above 2 points, age 65 to 74 years 1 point, history of coronary/peripheral artery disease 1 point, left atrial enlargement 1 point, posterior lesion 1 point, cortical or cortical-subcortical lesion 1 point), whose predictive power in detecting AF was good (area under the curve: 0.746, 95% confidence interval: 0.638-0.836) and higher than that of CHA 2 DS 2 -VASc and other scores.In our study NIHSS score ≥8 was the only independent predictor of post-ESUS-AF detection. The E 2 AF score appears to have a good predictive power for detecting AF. External validations are required.
Published: 2022

25. Impact of Rotational Thromboelastometry (ROTEM) on Clinical Course and Outcomes of COVID -19 Critically Ill Patients: A Retrospective Single Center Observational Study

Author: Maddalena Pazzi, Duccio Conti, Lorenzo Tofani, Lucantonio Zanfino, Eleonora Gemmi, Filippo Pasquinelli, Francesca Covani Frigieri, Angelica Venni, Lara Gianesello, Roberto Carpi, Domenico Prisco, Rossella Marcucci, and Vittorio Pavoni
Abstract: BACKGROUND The severity of coagulation derangement correlates with poor prognosis in COVID-19 patients. However, the clinical impact of coagulation alterations detected with rotational thromboelastometry (ROTEM) in intensive care unit (ICU) COVID-19 patients is not completely defined. The study aimed to identify the correlation between ROTEM parameters and adverse ICU outcomes. The relationship between COVID-19 associated coagulopathy (CAC) and ROTEM alterations and possible risk factors for ICU mortality were also investigated. METHODS COVID-19 patients admitted to ICU between October 1, 2020 and May 31, 2021, were retrospectively enrolled. The sample was subsequently divided into subgroups (survivors vs. non-survivors, mechanical ventilation (MV) vs. non-invasive ventilation (NIV), venous thromboembolism (VTE) vs. NO-VTE, CAC vs. NO-CAC) among which ROTEM parameters and standard coagulation tests were compared. RESULTS One hundred ICU patients were enrolled. High D-dimer (DD) (5089 ± 1035 ng/ml) and fibrinogen levels (640 ± 112 mg/dl) and an increase in maximum clot firmness (MCF) were revealed. The non-survivors (n=50, 50%) had higher DD levels and lower platelet counts as well as lower clot lysis rates than survivors. EXTEM maximum lysis (ML) resulted lower in the MV subgroup than in NIV treated patients. Patients with thrombotic complications had higher DD levels than patients without VTE whereas ROTEM parameters were not different. Similarly no coagulation or ROTEM differences were identified in the subgroup of CAC patients (n=29, 29%). Reduced ML values in EXTEM and INTEM resulted as possible risk factors for ICU mortality. CONCLUSIONS In critically ill COVID-19 patients, hypofibrinolysis and not hypercoagulability seems to be correlated with unfavourable ICU prognosis.
Published: 2023

26. Etiopathogenesis of Behçet’s syndrome: The role of infectious, genetic, and immunological environmental factors

Author: Alessandra Bettiol, Giacomo Emmi, Irene Mattioli, and Domenico Prisco
Published: 2023

27. Contributors

Author: Mostafa A. Abdel-Maksoud, Maryam Akhtari, Ayda AlHammadi, Amer Ali Almohssen, Amedeo Amedei, Kosar Asnaashari, Raul Aviles, Samar Freschi de Barros, İlke Coşkun Benlidayı, Alessandra Bettiol, Nicola Bizzaro, Carlos Eduardo Branco, Femke Broere, Luigi Cinquanta, Maria do Carmo Pereira Nunes, Ana Caroline Melo dos Santos, Bárbara Rayssa Correia dos Santos, Jean Carlos Vencioneck Dutra, Willem van Eden, Giacomo Emmi, Mickael Essouma, Elham Farhadi, Jean Moisés Ferreira, Michael Frech, Vadim Gorodetskiy, Luiza Guilherme, Agnès Hamzaoui, Kamel Hamzaoui, Gunnar Houen, Janaki Iyer, Hongxing Jia, Jorge Kalil, Parisa Khayambashi, Dominika Kwiatkowska, Jacob M. van Laar, José Luiz de Lima Filho, Mahdi Mahmoudi, Anselm Mak, Irene Mattioli, Edilson Leite de Moura, Elena Niccolai, Sean O’Neill, Yasunori Omata, Win Min Oo, Martin E. Perry, Domenico Prisco, Silvia Bellando Randone, Adam Reich, Nima Rezaei, Lazaros I. Sakkas, Blake Savage, Georg Schett, Syahrul Sazliyana Shaharir, Theodora Simopoulou, Nicole Marie Smith, Elaine Virgínia Martins de Souza Figueiredo, Arie J. Stoppelenburg, Rossella Talotta, Ithallo Sathio Bessoni Tanabe, Sakae Tanaka, Antonio Lucio Teixeira, Renato Tozzoli, Simon D. Tran, Nicole Hartwig Trier, Katie S. Turnbull, Luiz Paulo Bastos Vasconcelos, Marcelle Cristina Vasconcelos, H. John Visser, Asrul Abdul Wahab, Joshua Wolfe, Niloufar Yazdanpanah, Mario M. Zaiss, and Peipei Zhang
Published: 2023

28. Clinical features and outcomes of elderly hospitalised patients with chronic obstructive pulmonary disease, heart failure or both

Author: Crisafulli, Ernesto, Sartori, Giulia, Vianello, Alice, Busti, Fabiana, Nobili, Alessandro, Mannucci, Pier Mannuccio, Girelli, Domenico Investigators—Domenico Prisco, Elena, Silvestri, Giacomo, Emmi, Alessandra, Bettiol, Irene Mattioli (Azienda Ospedaliero Universitaria Careggi Firenze, SOD Medicina Interna Interdisciplinare), Gianni, Biolo, Michela, Zanetti, Giacomo, Bartelloni, Michele, Zaccari, Massi- miliano Chiuch (Azienda Sanitaria Universitaria Integrata di Trieste, Clinica Medica Generale, e Terapia Medica), Massimo, Vanoli, Giulia, Grignani, Edoardo Alessandro Pulixi (Azienda Ospedaliera della Pro- vincia di Lecco, Ospedale di Merate, Lecco, Medicina, Interna), Matteo, Pirro, Graziana, Lupattelli, Vanessa, Bianconi, Riccardo, Alcidi, Alessia, Giotta, Mannarino (Azienda Ospedaliera Santa Maria della Misericordia, Massimo R., Perugia, Medicina, Interna, Angiologia Malattie da Arteriosclerosi), Domenico, Girelli, Fabiana, Busti, Giacomo Marchi (Azienda Ospedaliera Universitaria Integrata di Verona, Verona, Medicina Generale e Malattie Aterotrombotiche, e Degenerative), Mario, Barbagallo, Ligia, Dominguez, Vincenza, Beneduce, Federica Cacioppo (Azienda Ospedaliera Universitaria Policlinico Giaccone Policlinico di Palermo, Palermo, Unità Operativa di Geriatria, e Lun- godegenza), Salvatore, Corrao, Giuseppe, Natoli, Salvatore, Mularo, Massimo, Raspanti, Christiano, Argano, Civico, Federica Cavallaro (A. R. N. A. S., Cristina, Di, Benfratelli, Palermo, UOC Medicina Interna ad Indirizzo Geriatrico- Riabilitativo), Marco, Zoli, Maria Laura Mata- cena, Giuseppe, Orio, Eleonora, Magnolfi, Giovanni, Serafini, Angelo, Simili, Mattia, Brunori, Ilaria, Lazzari, Orsola-Malpighi, Angelo Simili (Azienda Ospe- daliera Universitaria Policlinico S., Bologna, Unità Operativa di Medicina Interna Zoli), Maria Domenica Cappellini, Gio- vanna Fabio, Margherita Migone De Amicis, Giacomo De Luca, Nata- lia Scaramellini, Valeria Di Stefano, Simona, Leoni, Sonia, Seghezzi, Alessandra Danuto Di Mauro, Diletta, Maira, Marta Mancarella (Fon- dazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milano, Unità Operativa Medicina Interna IA), Tiziano, Lucchi, Paolo Dionigi Rossi, Marta, Clerici, Alessandra Danuta Di Mauro, Giulia, Bonini, Federica, Conti, Silvia, Prolo, Maddalena, Fabrizi, Miriana, Martelengo, Giulia, Vigani, Paola Nicolini (Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milano, Geriatria), Antonio Di Sabatino, Emanuela, Miceli, Marco Vincenzo Lenti, Martina, Pisati, Lavinia, Pitotti, Donatella, Padula, Valentina, Antoci, Ginevra Cambiè (IRCCS Policlinico San Matteo di Pavia, Pavia, Clinica Medica, I, Reparto, 11), Roberto, Pontremoli, Valentina, Beccati, Giulia, Nobili, Giovanna, Leoncini, Jacopo, Alberto, Federico Cattaneo (IRCCS Azienda Ospedaliera Universitaria San Martino-IST di Genova, Gen-, Ova, Clinica di Medicina Interna 2), Luigi, Anastasio, Lucia, Sofia, Maria Carbone (Ospedale Civile Jazzolino di Vibo Valentia, Vibo Val- entia, Medicina, Generale), Francesco, Cipollone, Maria Teresa Guag- nano, Ilaria, Rossi, Emanuele, Valeriani, Damiani, D’Ardes, Lucia, Esposito, Simona, Sestili, Annunziata, Ermanno Angelucci (Ospedale Clinicizzato SS., Chieti, Clinica, Medica), Gerardo, Mancuso, Daniela, Calipari, Mosè Bartone (Ospedale Giovanni Paolo II Lamezia Terme, Catanzaro, Unità Operativa Complessa Medicina Interna), Giuseppe, Delitala, Maria, Berria, Alessandro Delitala (Azienda ospedaliera- universitaria di Sassari, Maurizio, Muscaritoli, Ales- sio Molfino, Enrico, Petrillo, Antonella, Giorgi, Christian, Gracin, Gio- vanni Imbimbo (Policlinico Umberto, I, Sapienza Università di Roma, Medicina Interna, e Nutrizione Clinica Policlinico Umberto I), Giuseppe, Zuccalà, Gemelli, Gabriella D’Aurizio (Policlinico Universitario A., Roma, Roma, Unità Operativa Complessa Medicina d'Urgenza, e Pronto Soccorso)Giuseppe Romanelli, Alessandra, Marengoni, Andrea, Volpini, Daniela, Lucente, Francesca, Manzoni, Annalisa, Pirozzi, Alberto Zucchelli (Unità Operativa Complessa di Medicina I, a indirizzo geriatrico, Spedali, Civili, Montichiari, Brescia), Antonio, Picardi, Umberto Vespasiani Gentilucci, Paolo, Gallo, Chiara Dell’Unto (Università Campus Bio- Medico, Roma, Medicina Clinica-Epatolo- gia), Giuseppe, Bellelli, Maurizio, Corsi, Cesare, Antonucci, Chiara, Sidoli, Giulia, Principato, Alessandra, Bonfanti, Hajnalka, Szabo, Paolo, Mazzola, Andrea, Piazzoli, Gerardo, Maurizio Corsi (Università degli studi di Milano-Bicocca Ospedale S., Monza, Unità Operativa di Geri- atria), Franco, Arturi, Elena, Succurro, Bruno, Tassone, Federica Giofrè (Università degli Studi Magna Grecia, Policlinico Mater Domini, Cat-, Anzaro, Unità Operativa Complessa di Medicina Interna), Maria Grazia Serra, Maria Antonietta Bleve (Azienda Ospedaliera, Lecce, Unità Operativa Complessa Medicina), Antonio, Brucato, Teresa De Falco, Enrica, Negro, Martino, Brenna, Lucia, Trotta, Giovanni Lorenzo Squintani (ASST FatebenefratelliSacco, Maria Luisa Randi, Fabrizio, Fabris, Irene, Bertozzi, Giulia, Bogoni, Maria Victoria Rabuini, Tancredi, Prandini, Francesco, Ratti, Chiara, Zurlo, Lorenzo, Cerruti, Elisabetta Cosi (Azienda Ospe- daliera Università di Padova, Padova, Clinica Medica I), Roberto Man- fredini, Benedetta, Boari, Alfredo De Giorgi, Ruana, Tiseo, Giulia Marta Viglione, Caterina Savriè (Azienda OspedalieraUniversitaria Sant'Anna, Ferrara, Unità Operativa Clinica Medica), Giuseppe, Paolisso, Maria Rosaria Rizzo, Claudia, Catalano, Irene Di Meo (Azienda Ospedaliera Universitaria della Seconda Università degli Studi di Napoli, Napoli, VI Divisione di Medicina Interna, e Malattie Nutrizionali dell'Invecchiamento), Claudio, Borghi, Enrico, Strocchi, Eugenia, Ianniello, Mario, Soldati, Silvia, Schiavone, Alessio, Bragagni, 13 Francesca Giulia Leoni, Valeria De Sando, Sara, Scarduelli, Michela, Cammarosano, Orsola-Malpighi, Ilenia Pareo (Azienda Ospedaliera Universitaria Poli- clinico S., Unità Operativa di Medicina Interna Borghi), Carlo, Sabbà, Francesco Saverio Vella, Patrizia Sup- pressa, Giovanni Michele De Vincenzo, Alessio, Comitangelo, Ema- nuele Amoruso, Carlo, Custodero, Giuseppe, Re, Andrea, Schilardi, Francesca Loparco (Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari, Bari, Frugoni), Medicina Interna Universitaria C., Luigi, Fenoglio, Andrea, Falcetta, Alessia Valentina Giraudo, Salvatore D’Aniano (Azienda Sanitaria Ospedaliera Santa Croce, e Carle di Cuneo, Cuneo, Ademe, Medicina Interna), S. C., Fracanzani, Anna L., Silvia, Tiraboschi, Annalisa, Cespiati, Giovanna, Oberti, Giordano, Sigon, Felice Cinque (Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, UOC Medicina Generale ad Indirizzo Metabolico), Flora, Peyvandi, Raffaella, Rossio, Colombo, Giulia, Pasquale, Agosti, Erica, Pagliaro, Eleonora Semproni (Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Medicina Interna, 2, Emato- logia non tumorale, e Coagulopatie), Canetta, Ciro, Valter, Monzani, Valeria, Savojardo, Giuliana, Ceriani, Christian Folli (Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Medicina Interna Alta Intensità di Cure), Francesco, Salerno, Giada Pallini (IRCCS Policlinico San Donato, e Università di Milano, San Donato Milanese, Fabrizio, Montecucco, Luciano, Ottonello, Lara, Caserza, Giulia, Vischi, Salam, Kassem, Luca Liberale (IRCCS Ospedale Policlinico San Martino, e Università di Genova, Genova, Clinica Medica, 1, Medicina Interna, e Specialità Mediche), Nicola Lucio Liberato, Tiziana Tognin (ASST di Pavia, UOSD Medicina Interna, Ospedale di Casorate Primo, Pavia), Francesco, Purrello, Antonino Di Pino, Salvatore Piro (Ospedale Garibaldi Nesima, Catania, Giorgia, Renzo, Rozzini, Lina, Falanga, Maria Stella Pisciotta, Francesco Baffa Bellucci, Stefano Buf- felli, Camillo, Ferrandina, Francesca, Mazzeo, Elena, Spazzini, Giulia, Cono, Giulia Cesaroni (Ospedale Poliambulanza, Brescia, Medicina Interna, e Geriatria), Giuseppe, Montrucchio, Paolo, Peasso, Edoardo, Favale, Cesare, Poletto, Carl, Margaria, Maura Sanino (Dipartimento di Scienze Mediche, Università di Torino, Città della Scienza, e della Salute, Torino, Medicina Interna, 2 Unità Indirizzo d'Urgenza), Franc- esco Violi, Ludovica Perri (Policlinico Umberto, I, Prima Clinica Medica), Guasti, Luigina, Rotunno, Francesca, Castiglioni, Luana, Maresca, ANDREA MARIA, Squizzato, Alessandro, Campiotti, Leonardo, Ales- sandra Grossi, Diprizio, ROBERTO DAVIDE, Francesco Dentali (Università degli Studi dell'Insubria, Ospedale di Circolo, e Fondazione Macchi, Varese, Elena, Medicina, e Geriatria), Marco, Bertolotti, Chiara, Mussi, Giulia, Lancellotti, Maria Vittoria Libbra, Matteo, Galassi, Yasmine, Grassi, Alessio, Greco, Elena, Bigi, Elisa, Pellegrini, Laura, Orlandi, Giulia, Dondi, Lucia Carulli (Università di Modena, e Reggio Emilia, Azienda Ospedaliero-Universitaria di Modena, Ospedale Civile di Baggiovara, Unità Operativa di Geriatria), Angela, Sciacqua, Maria, Perticone, Rosa, Battaglia, Raffaele, Maio, Aleandra, Scozzafava, Valentino, Condoleo, Tania, Falbo, Lidia, Colangelo, Marco Filice, Elvira Clausi (Università Geriatriche), Vincenzo, Stanghellini, Eugenio, Ruggeri, Sara del Vec- chio, Ilaria Benzoni (Dipartimento di Scienze Mediche, e Chirurgiche, Unità Operativa di Medicina Interna, Orsola-Malpighi, Università degli Studi di Bologna/ Azienda Ospedaliero- Universitaria S., Bologna), Andrea, Salvi, Roberto, Leonardi, Giampaolo Damiani (Spedali Civili di Brescia, Medicina Generale), U. O. 3a., Gianluca, Moroncini, William, Capeci, Massimo, Mattioli, Giuseppe Pio Martino, Lorenzo, Biondi, Pietro, Pettinari, Monica, Ormas, Emanuele, Filippini, Devis, Benfaremo, Roberto Romiti (Clinica Medica, Azienda Ospedaliera Universitaria- Ospedali Riuniti di Ancona), Riccardo, Ghio, Anna Dal Col (Azienda Ospedaliera Università San Martino, Medicina, III), Salvatore, Minisola, Luciano, Colangelo, Mirella, Cilli, Giancarlo Labbadia (Poli- clinico Umberto, I, SMSC03Medicina Interna F, e Malattie Meta- boliche dell'osso), Antonella, Afeltra, Benedetta, Marigliano, Maria Elena Pipita (Policlinico Campus Biomedico Roma, Medicina, Clinica), Pietro, Castellino, Luca, Zanoli, Alfio, Gennaro, Agostino, Gaudio, Emanuele, Samuele Pignataro (Azienda Ospedaliera Universitaria Poli- clinico – V., Catania, Dipartimento di Medicina), Francesca, Mete, Miriam Gino (Ospedale degli Infermi di Rivoli, Medicina Interna)Guido Moreo, Gloria Pina (Clinica San Carlo Casa di Cura Polispecialistica, Paderno, Dugnano, Unità Operativa di Medicina Generale Emilio Bernardelli), Alberto Balle- strero, Fabio, Ferrando, Roberta, Gonella, Domenico, Cerminara, Paolo, Setti, Chiara, Traversa, Camilla Scarsi (Clinica Di Medicina Interna ad Indirizzo Oncologico, Azienda Ospedaliera Università San Martino di Genova), Bruno, Graziella, Stefano, Baldassarre, Salvatore, Fragapani, Gabriella Gruden (Medicina Interna III, Giovanni Battista Molinette, Ospedale S., Torino), Franco, Berti, Giuseppe, Famularo, Patrizia Tarsitani (Azienda Ospedaliera San Camillo Forlanini, Medicina Interna II), Roberto, Castello, Michela Pasino (Ospedale Civile Maggiore Borgo Trento, Medicina Generale, e Sezione di Decisione Cli- nica), Marcello Giuseppe Maggio Gian Paolo Ceda, Simonetta Mor- ganti, Andrea, Artoni, Margherita Grossi (Azienda Ospedaliero Uni- versitaria di Parma, Clinica Geriatrica), U. O. C., Stefano Del Giacco, Davide, Firinu, Giulia, Costanzo, Giacomo, Argiolas, Giovanni, Paoletti, Francesca Losa (Policlinico Universitario Duilio Casula, Azienda Ospedaliero-Universitaria di Cagliari, Cagliari, Allergologia ed Immunologia Clinica), Giuseppe, Montalto, Anna, Licata, Filippo Alessandro Montalto, Angelo Rizzo (Azienda Ospe- daliera Universitaria Policlinico Paolo Giaccone, UOC di Medicina Interna), Francesco, Corica, Giorgio, Basile, Antonino Cata- lano, Federica, Bellone, Martino, Concetto Principato (Azienda Ospedaliera Universitaria Policlinico G., Messina, Lorenzo, Malatino, Benedetta, Stancanelli, Valentina, Terranova, Salvatore Di Marca, Rosario Di Quattro, Lara La Malfa, Rossella Caruso (Azienda Ospedaliera per l'Emergenza Cannizzaro, Clinica Medica Università di Catania), Patrizia, Mecocci, Carmelinda, Ruggiero, della Misericordia, Virginia Boccardi (Università degli Studi di Perugia-Azienda Ospedaliera S. M., Struttura Complessa di Geriatria), Tiziana, Meschi, Andrea, Ticinesi, Antonio Nouvenne (Azienda Ospedaliera Universitaria di Parma, Medicina Interna e Lungodegenza Critica), U. O., Pietro, Minuz, Luigi, Fondrieschi, Giandomen- ico Nigro Imperiale, Sarah Morellini (Azienda Ospedaliera Universi- taria Verona, Policlinico GB Rossi, Medicina Generale per lo Studio ed il Trattamento dell’Ipertensione Arteriosa), Mario, Pirisi, Gian Paolo Fra, Daniele, Sola, Mattia Bellan (Azienda Ospedaliera Universitaria Maggiore della Carità, Medicina Interna 1), Roberto, Quadri, Erica, Larovere, Marco Novelli (Ospedale di Ciriè, Asl, To4, Emilio, Simeone, Rosa, Scurti, Fabio Tolloso (Ospedale Spirito Santo di Pescara, Geriatria), Roberto Tar- quini, Alice, Valoriani, Silvia, Dolenti, Giulia Vannini (Ospedale San Giuseppe, Empoli, USL Toscana Centro, Firenze, Medicina Interna I), Riccardo, Volpi, Pietro, Bocchi, Alessandro Vignali (Azienda Ospe- daliera Universitaria di Parma, Clinica, e Terapia Medica), Sergio, Harari, Chiara, Lonati, Federico, Napoli, Italia Aiello (Divisione di Medicina Interna, Multimedica, Ircss, Milano), Antonino Di Pino (Ospedale GaribaldiNesima, – Catania, Medicina Interna), U. O. C., Teresa, Salvatore, Lucio, Monaco, Vanvitelli, Carmen Ricozzi (Policlinico Università della Campania L., UOC Medicina Interna), Alberto, Pilotto, Ilaria, Indiano, Federica Gandolfo (Ente Ospe- daliero Ospedali Galliera Genova, SC Geriatria Dipartimento Cure Geriatriche, Ortogeriatria, e Riabilitazione)Franco Laghi Pasini, Pier Leopoldo Capecchi (Azienda Ospedaliera Universitaria Senese, Siena, Unità Operativa Complessa Medicina 2), Ranuccio, Nuti, Roberto Val- enti, Martina, Ruvio, Silvia, Cappelli, Alberto Palazzuoli (Azienda Ospedaliera Università Senese, Mauro Ber- nardi, Silvia Li Bassi, Luca, Santi, Giacomo Zaccherini (Azienda Ospe- daliera Policlinico Sant’Orsola-Malpighi, Semeiotica Medica Bernardi), Vittorio, Durante, Daniela, Tirotta, Giovanna Eusebi (Ospedale di Cattolica, Rimini, Marco, Cattaneo, Maria Valentina Amoruso, Paola, Fracasso, Cristina Fasolino (Azienda ospedaliera San Paolo, Moreno, Tresoldi, Enrica 13 Internal and Emergency Medicine Internal and Emergency Medicine Bozzolo, Sarah Damanti (IRCCS Ospedale San Raffaele, – Milano, Medicina Generale, e delle Cure Avanzate), Massimo, Porta, Miriam Gino (AOU Città della Salute e della Scienza di Torino, – Torino, and Medicina Interna, 1U).
Subjects: Hospital cure, Chronic obstructive pulmonary disease, Heart failure, Mortality, Multimorbidity, Prognosis
Published: 2023

29. Vascular Behçet syndrome: from pathogenesis to treatment

Author: Alessandra Bettiol, Fatma Alibaz-Oner, Haner Direskeneli, Gulen Hatemi, David Saadoun, Emire Seyahi, Domenico Prisco, Giacomo Emmi, and Bettiol A., ALİBAZ ÖNER F., DİRESKENELİ R. H., HATEMİ G., Saadoun D., SEYAHİ E., Prisco D., Emmi G.
Subjects: Internal Diseases, RHEUMATOLOGY, Internal Medicine Sciences, Klinik Tıp, Dahili Tıp Bilimleri, CLINICAL MEDICINE, Sağlık Bilimleri, İmmünoloji ve Romatoloji, İç Hastalıkları, Clinical Medicine (MED), Tıp, Immunology and Rheumatology, Health Sciences, Medicine, Klinik Tıp (MED), Romatoloji, ROMATOLOJİ
Abstract: © 2022, Springer Nature Limited.Behçet syndrome is a rare, chronic inflammatory disease of unknown aetiopathogenesis, most commonly presenting with mucocutaneous and ocular manifestations. Vascular involvement, most frequently superficial vein and deep vein thrombosis, can occur in up to 50% of patients with Behçet syndrome. Venous thrombosis at atypical sites (inferior and superior vena cava, suprahepatic veins with Budd–Chiari syndrome, portal vein, cerebral sinuses and right atrium and/or ventricle) and arterial involvement (mostly in situ thrombosis and aneurysms of the pulmonary arteries, as well as aneurysms of the abdominal aorta, and peripheral and visceral arteries) are also unique features of Behçet syndrome. Behçet syndrome is considered a natural model of inflammation-induced thrombosis in humans, with an impaired immune-inflammatory response rather than traditional cardiovascular risk factors contributing to thrombogenesis. Specifically, neutrophil hyperactivation and neutrophil-mediated mechanisms of damage directly promote endothelial dysfunction, platelet activation and thrombogenesis in Behçet syndrome. This unusual pathogenesis directly determines the treatment approach, which relies mostly on immunosuppressants rather than anticoagulants for treatment of thrombosis and for secondary prevention. This Review discusses the main histopathological, pathogenetic and clinical aspects of vascular Behçet syndrome, addressing their implications for therapeutic management. Future perspectives in terms of pathogenetic studies, disease monitoring and treatment strategies are also discussed.
Published: 2022

30. The Different Functional Distribution of 'Not Effector' T Cells (Treg/Tnull) in Colorectal Cancer

Author: Elena Niccolai, Federica Ricci, Edda Russo, Giulia Nannini, Giacomo Emmi, Antonio Taddei, Maria Novella Ringressi, Filippo Melli, Manouela Miloeva, Fabio Cianchi, Paolo Bechi, Domenico Prisco, and Amedeo Amedei
Subjects: colorectal cancer, tumor-infiltrating lymphocytes, regulatory T cells, not effector T cells, T helper, tumor microenvironment, Immunologic diseases. Allergy, RC581-607
Abstract: Colorectal cancer (CRC) is the third most common cancer worldwide, ranking as high as the second leading cause of cancer-related deaths in industrialized countries. Consistent with immunosurveillance theory, the immune system is crucial to protect the host from developing tumors, and the major players in tumoral immunity are effector T cells. Anyway, cancer cells develop strategies of immunoevasion influencing the cancer-specific lymphocyte priming, activation, and effector function. Therefore, the T cell subsets that mature during the stages of tumor growth, differently contribute to disease progression and/or regression. In our study, we analyzed the intra-tumoral and peripheral T cell subsets’ distribution in 30 patients with CRC, in order to clarify their functional role toward cancer. We found that percentage of infiltrating effector T cells decreased in cancer tissue than in healthy mucosa and that the tumor microenvironment negatively influences the cytolytic activity of T lymphocytes reactive to cancer cells. Moreover, we found that the tumor tissue was infiltrated by a large amount of “not effector” T (neT) cells with a regulatory or an anergic profile, which are unable to kill cancer cells, may be contributing to the CRC promotion. The presence of neT cells was investigated also in the peripheral blood of CRC patients, demonstrating that the peripheral T regulatory cells can inhibit the proliferation of effector T cells, confirming their immunosuppressive properties. Finally, monitoring the changes in circulating neT cells’ frequencies after the tumor removal, we confirmed the role of cancer in the modulation of immune system, in particular, in supporting a Tregs-mediated immunosuppression.
Published: 2017
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31. Neutrophil-mediated mechanisms of damage and in-vitro protective effect of colchicine in non-vascular Behçet's syndrome

Author: Adalgisa Palermo, Giacomo Emmi, Matteo Becatti, Niccolò Taddei, Alessandra Bettiol, Silvia Galora, Irene Mattioli, Maria Letizia Urban, Amanda Mannucci, Domenico Prisco, Flavia Rita Argento, Eleonora Fini, Claudia Fiorillo, Elena Silvestri, and Danilo Malandrino
Subjects: Adult, Male, Neutrophils, Immunology, Anti-Inflammatory Agents, Inflammation/Inflammatory Disease, Pharmacology, medicine.disease_cause, Extracellular Traps, vasculitis, Antioxidants, Autoimmunity, Pathogenesis, chemistry.chemical_compound, medicine, Humans, Immunology and Allergy, Colchicine, human, Retrospective Studies, reactive oxygen species, chemistry.chemical_classification, Reactive oxygen species, business.industry, Behcet Syndrome, autoimmunity, Neutrophil extracellular traps, Middle Aged, medicine.disease, Oxidative Stress, chemistry, Apoptosis, Case-Control Studies, Original Article, Female, ORIGINAL ARTICLES, business, Intracellular, Systemic vasculitis
Abstract: Behçet’s syndrome (BS) is a systemic vasculitis with several clinical manifestations. Neutrophil hyperactivation mediates vascular BS pathogenesis, via both a massive reactive oxygen species (ROS) production and neutrophil extracellular traps (NETs) release. Here, we investigated neutrophil‐mediated mechanisms of damage in non‐vascular BS manifestations and explored the in‐vitro effects of colchicine in counteracting these mechanisms. NETs and intracellular ROS production was assessed in blood samples from 80 BS patients (46 with active non‐vascular BS, 34 with inactive disease) and 80 healthy controls. Moreover, isolated neutrophils were incubated for 1 h with an oxidating agent [2,2′‐azobis (2‐amidinopropane) dihydrochloride; 250 nM] and the ability of pure colchicine pretreatment (100 ng/ml) to counteract oxidation‐induced damage was assessed. Patients with active non‐vascular BS showed remarkably increased NET levels [21.2, interquartile range (IQR) = 18.3–25.9 mU/ml] compared to patients with inactive disease (16.8, IQR = 13.3–20.2 mU/ml) and to controls (7.1, IQR = 5.1–8.7 mU/ml, p, Neutrophil‐mediated mechanisms of damage might be directly involved in non‐vascular Behçet's syndrome. Neutrophil extracellular traps (NETs), more than an impaired redox status, might play a central role in the pathogenesis of mucosal, articular and intestinal BS manifestations. Colchicine might be effective to counteract neutrophils‐mediated damage in Behçet's syndrome, via the inhibition of NETs release.
Published: 2021

32. Questions about COVID-19 associated coagulopathy: possible answers from the viscoelastic tests

Author: Domenico Prisco, Pietro Dattolo, Maddalena Pazzi, Vittorio Pavoni, and Lara Gianesello
Subjects: medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Health Informatics, Critical Care and Intensive Care Medicine, Coagulopathy, Anesthesiology, medicine, Humans, In patient, Intensive care medicine, Hemostasis, Review Paper, Thromboembolic events, Viscoelastic tests, medicine.diagnostic_test, SARS-CoV-2, business.industry, fungi, COVID-19, Blood Coagulation Disorders, medicine.disease, Clot formation, Thromboelastography, Thrombelastography, Thromboelastometry, Anesthesiology and Pain Medicine, business
Abstract: Abnormal coagulation parameters are often observed in patients with coronavirus disease 2019 (COVID-19) and the severity of derangement has been associated with a poor prognosis. The COVID-19 associated coagulopathy (CAC) displays unique features that include a high risk of developing thromboembolic complications. Viscoelastic tests (VETs), such as thromboelastometry (ROTEM), thromboelastography (TEG) and Quantra Hemostasis Analyzer (Quantra), provide “dynamic” data on clot formation and dissolution; they are used in different critical care settings, both in hemorrhagic and in thrombotic conditions. In patients with severe COVID-19 infection VETs can supply to clinicians more information about the CAC, identifying the presence of hypercoagulable and hypofibrinolysis states. In the last year, many studies have proposed to explain the underlying characteristics of CAC; however, there remain many unanswered questions. We tried to address some of the important queries about CAC through VETs analysis.
Published: 2021

33. Hyperglycemia at admission, comorbidities, and in-hospital mortality in elderly patients hospitalized in internal medicine wards: data from the RePoSI Registry

Author: Salvatore, Corrao, Alessandro, Nobili, Giuseppe, Natoli, Pier Mannuccio Mannucci, Francesco, Perticone, Antonello, Pietrangelo, Christiano, Argano, Giuseppe, Licata, Francesco, Violi, Gino Roberto Corazza, Alessandra, Marengoni, Francesco, Salerno, Matteo, Cesari, Mauro, Tettamanti, Luca, Pasina, Carlotta, Franchi, Laura, Cortesi, Gabriella, Miglio, Ilaria, Ardoino, Alessio, Novella, Domenico, Prisco, Elena, Silvestri, Giacomo, Emmi, Alessandra, Bettiol, Cenci, Caterina, Gianni, Biolo, Michela, Zanetti, Martina, Guadagni, Michele, Zaccari, Massimiliano, Chiuch, Massimo, Vanoli, Giulia, Grignani, Edoardo Alessandro Pulixi, Mauro, Bernardi, Silvia Li Bassi, Luca, Santi, Giacomo, Zaccherini, Graziana, Lupattelli, Elmo, Mannarino, Vanessa, Bianconi, Francesco, Paciullo, Riccardo, Alcidi, Ranuccio, Nuti, Roberto, Valenti, Martina, Ruvio, Silvia, Cappelli, Alberto, Palazzuoli, Domenico, Girelli, Fabiana, Busti, Giacomo, Marchi, Mario, Barbagallo, Ligia, Dominguez, Floriana, Cocita, Vincenza, Beneduce, Lidia, Plances, Salvatore, Mularo, Massimo, Raspanti, Marco, Zoli, Ilaria, Lazzari, Mattia, Brunori, Elisa, Fabbri, Donatella, Magalotti, Raffaella, Arnò, Franco Laghi Pasini, Pier Leopoldo Capecchi, Giuseppe, Palasciano, Maria Ester Modeo, Carla Di Gennaro, Maria Domenica Cappellini, Diletta, Maira, Valeria Di Stefano, Giovanna, Fabio, Sonia, Seghezzi, Marta, Mancarella, Margherita Migone De Amicis, Giacomo De Luca, Natalia, Scaramellini, Paolo Dionigi Rossi, Sarah, Damanti, Marta, Clerici, Federica, Conti, Giulia, Bonini, Barbara Brignolo Ottolini, Antonio Di Sabatino, Emanuela, Miceli, Marco Vincenzo Lenti, Martina, Pisati, Costanza Caccia Dominioni, Giovanni, Murialdo, Alessio, Marra, Federico, Cattaneo, Roberto, Pontremoli, Valentina, Beccati, Giulia, Nobili, Maria Beatrice Secchi, Davide, Ghelfi, Luigi, Anastasio, Lucia, Sofia, Maria, Carbone, Francesco, Cipollone, Maria Teresa Guagnano, Emanuele, Valeriani, Ilaria, Rossi, Gerardo, Mancuso, Daniela, Calipari, Mosè, Bartone, Giuseppe, Delitala, Maria, Berria, Chiara, Pes, Alessandro, Delitala, Maurizio, Muscaritoli, Alessio, Molfino, Enrico, Petrillo, Giuseppe, Zuccalà, Gabriella, D'Aurizio, Giuseppe, Romanelli, Alberto, Zucchelli, Francesca, Manzoni, Andrea, Volpini, Antonio, Picardi, Umberto Vespasiani Gentilucci, Paolo, Gallo, Chiara, Dell'Unto, Giorgio, Annoni, Maurizio, Corsi, Giuseppe, Bellelli, Sara, Zazzetta, Paolo, Mazzola, Hajnalka, Szabo, Alessandra, Bonfanti, Franco, Arturi, Elena, Succurro, Mariangela, Rubino, Bruno, Tassone, Giorgio, Sesti, Maria Grazia Serra, Maria Antonietta Bleve, Laura, Gasbarrone, Maria Rosaria Sajeva, Antonio, Brucato, Silvia, Ghidoni, Fabrizio, Fabris, Irene, Bertozzi, Giulia, Bogoni, Maria Victoria Rabuini, Elisabetta, Cosi, Paolo, Scarinzi, Annalisa, Amabile, Elisabetta, Omenetto, Tancredi, Prandini, Manfredini, Roberto, Fabbian, Fabio, Boari, Benedetta, DE GIORGI, Alfredo, Tiseo, Ruana, DE GIORGIO, Roberto, Giuseppe, Paolisso, Maria Rosaria Rizzo, Claudio, Borghi, Enrico, Strocchi, Eugenia, Ianniello, Mario, Soldati, Carlo, Sabbà, Francesco Saverio Vella, Patrizia, Suppressa, Andrea, Schilardi, Francesca, Loparco, Giovanni Michele De Vincenzo, Alessio, Comitangelo, Emanuele, Amoruso, Luigi, Fenoglio, Andrea, Falcetta, Christian, Bracco, Anna, L Fracanzani Silvia Fargion, Silvia, Tiraboschi, Annalisa, Cespiati, Giovanna, Oberti, Giordano, Sigon, Flora, Peyvandi, Raffaella, Rossio, Barbara, Ferrari, Giulia, Colombo, Pasquale, Agosti, Valter, Monzani, Valeria, Savojardo, Christian, Folli, Giuliana, Ceriani, Giada, Pallini, Franco, Dallegri, Luciano, Ottonello, Luca, Liberale, Lara, Caserza, Kassem, Salam, Nicola Lucio Liberato, Tiziana, Tognin, Giovanni Battista Bianchi, Sabrina, Giaquinto, Francesco, Purrello, Antonino Di Pino, Salvatore, Piro, Renzo, Rozzini, Lina, Falanga, Elena, Spazzini, Camillo, Ferrandina, Giuseppe, Montrucchio, Paolo, Petitti, Paolo, Peasso, Edoardo, Favale, Cesare, Poletto, Raffaella, Salmi, Piergiorgio, 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Filippo Alessandro Montalto, Antonino, Lasco, Giorgio, Basile, Antonino, Catalano, Lorenzo, Malatino, Benedetta, Stancanelli, Valentina, Terranova, Salvatore Di Marca, Rosario Di Quattro, Lara La Malfa, Rossella, Caruso, Patrizia, Mecocci, Carmelinda, Ruggiero, Virginia, Boccardi, Tiziana, Meschi, Fulvio, Lauretani, Andrea, Ticinesi, Antonio, Nouvenne, Pietro, Minuz, Luigi, Fondrieschi, Mario, Pirisi, Gian Paolo Fra, Daniele, Sola, Massimo, Porta, Piero, Riva, Roberto, Quadri, Erica, Larovere, Marco, Novelli, Giorgio, Scanzi, Caterina, Mengoli, Stella, Provini, Laura, Ricevuti, Emilio, Simeone, Rosa, Scurti, Fabio, Tolloso, Roberto, Tarquini, Alice, Valoriani, Silvia, Dolenti, Giulia, Vannini, Alberto, Tedeschi, Lucia, Trotta, Riccardo, Volpi, Pietro, Bocchi, Alessandro, Vignali, Sergio, Harari, Chiara, Lonati, Mara, Cattaneo, Federico, Napoli., Corrao S, Nobili A, Natoli G, Mannucci PM, Perticone F, Pietrangelo A, Argano C, REPOSI Investigator, Borghi C, Corrao S., Nobili A., Natoli G., Mannucci P.M., Perticone F., Pietrangelo A., Argano C., Licata G., Violi F., Corazza G.R., Marengoni A., Salerno F., Cesari M., Tettamanti M., Pasina L., Franchi C., Cortesi L., Miglio G., Ardoino I., Novella A., Prisco D., Silvestri E., Emmi G., Bettiol A., Caterina C., Biolo G., Zanetti M., Guadagni M., Zaccari M., Chiuch M., Vanoli M., Grignani G., Pulixi E.A., Bernardi M., Bassi S.L., Santi L., Zaccherini G., Lupattelli G., Mannarino E., Bianconi V., Paciullo F., Alcidi R., Nuti R., Valenti R., Ruvio M., Cappelli S., Palazzuoli A., Girelli D., Busti F., Marchi G., Barbagallo M., Dominguez L., Cocita F., Beneduce V., Plances L., Mularo S., Raspanti M., Zoli M., Lazzari I., Brunori M., Fabbri E., Magalotti D., Arno R., Pasini F.L., Capecchi P.L., Palasciano G., Modeo M.E., Di Gennaro C., Cappellini M.D., Maira D., Di Stefano V., Fabio G., Seghezzi S., Mancarella M., De Amicis M.M., De Luca G., Scaramellini N., Rossi P.D., Damanti S., Clerici M., Conti F., Bonini G., Ottolini B.B., Di Sabatino A., Miceli E., Lenti M.V., Pisati M., Dominioni C.C., Murialdo G., Marra A., Cattaneo F., Pontremoli R., Beccati V., Nobili G., Secchi M.B., Ghelfi D., Anastasio L., Sofia L., Carbone M., Cipollone F., Guagnano M.T., Valeriani E., Rossi I., Mancuso G., Calipari D., Bartone M., Delitala G., Berria M., Pes C., Delitala A., Muscaritoli M., Molfino A., Petrillo E., Zuccala G., D'Aurizio G., Romanelli G., Zucchelli A., Manzoni F., Volpini A., Picardi A., Gentilucci U.V., Gallo P., Dell'Unto C., Annoni G., Corsi M., Bellelli G., Zazzetta S., Mazzola P., Szabo H., Bonfanti A., Arturi F., Succurro E., Rubino M., Tassone B., Sesti G., Serra M.G., Bleve M.A., Gasbarrone L., Sajeva M.R., Brucato A., Ghidoni S., Fabris F., Bertozzi I., Bogoni G., Rabuini M.V., Cosi E., Scarinzi P., Amabile A., Omenetto E., Prandini T., Manfredini R., Fabbian F., Boari B., De Giorgi A., Tiseo R., De Giorgio R., Paolisso G., Rizzo M.R., Borghi C., Strocchi E., Ianniello E., Soldati M., Sabba C., Vella F.S., Suppressa P., Schilardi A., Loparco F., De Vincenzo G.M., Comitangelo A., Amoruso E., Fenoglio L., Falcetta A., Bracco C., Fargion A.L.F.S., Tiraboschi S., Cespiati A., Oberti G., Sigon G., Peyvandi F., Rossio R., Ferrari B., Colombo G., Agosti P., Monzani V., Savojardo V., Folli C., Ceriani G., Pallini G., Dallegri F., Ottonello L., Liberale L., Caserza L., Salam K., Liberato N.L., Tognin T., Bianchi G.B., Giaquinto S., Purrello F., Di Pino A., Piro S., Rozzini R., Falanga L., Spazzini E., Ferrandina C., Montrucchio G., Petitti P., Peasso P., Favale E., Poletto C., Salmi R., Gaudenzi P., Perri L., Landolfi R., Montalto M., Mirijello A., Guasti L., Castiglioni L., Maresca A., Squizzato A., Campiotti L., Grossi A., Bertolotti M., Mussi C., Lancellotti G., Libbra M.V., Dondi G., Pellegrini E., Carulli L., Galassi M., Grassi Y., Perticone M., Battaglia R., FIlice M., Maio R., Stanghellini V., Ruggeri E., del Vecchio S., Salvi A., Leonardi R., Damiani G., Capeci W., Gabrielli A., Mattioli M., Martino G.P., Biondi L., Pettinari P., Ghio R., Col A.D., Minisola S., Colangelo L., Cilli M., Labbadia G., Afeltra A., Marigliano B., Pipita M.E., Castellino P., Zanoli L., Pignataro S., Gennaro A., Blanco J., Saracco V., Fogliati M., Bussolino C., Mete F., Gino M., Cittadini A., Vigorito C., Arcopinto M., Salzano A., Bobbio E., Marra A.M., Sirico D., Moreo G., Gasparini F., Prolo S., Pina G., Ballestrero A., Ferrando F., Berra S., Dassi S., Nava M.C., Graziella B., Baldassarre S., Fragapani S., Gruden G., Galanti G., Mascherini G., Petri C., Stefani L., Girino M., Piccinelli V., Nasso F., Gioffre V., Pasquale M., Scattolin G., Martinelli S., Turrin M., Sechi L., Catena C., Colussi G., Passariello N., Rinaldi L., Berti F., Famularo G., Tarsitani P., Castello R., Pasino M., Ceda G.P., Maggio M.G., Morganti S., Artoni A., Del Giacco S., Firinu D., Losa F., Paoletti G., Costanzo G., Montalto G., Licata A., Malerba V., Montalto F.A., Lasco A., Basile G., Catalano A., Malatino L., Stancanelli B., Terranova V., Di Marca S., Di Quattro R., La Malfa L., Caruso R., Mecocci P., Ruggiero C., Boccardi V., Meschi T., Lauretani F., Ticinesi A., Nouvenne A., Minuz P., Fondrieschi L., Pirisi M., Fra G.P., Sola D., Porta M., Riva P., Quadri R., Larovere E., Novelli M., Scanzi G., Mengoli C., Provini S., Ricevuti L., Simeone E., Scurti R., Tolloso F., Tarquini R., Valoriani A., Dolenti S., Vannini G., Tedeschi A., Trotta L., Volpi R., Bocchi P., Vignali A., Harari S., Lonati C., Cattaneo M., Napoli F., Corrao, S., Nobili, A., Natoli, G., Mannucci, P. M., Perticone, F., Pietrangelo, A., Argano, C., Licata, G., Violi, F., Corazza, G. R., Marengoni, A., Salerno, F., Cesari, M., Tettamanti, M., Pasina, L., Franchi, C., Cortesi, L., Miglio, G., Ardoino, I., Novella, A., Prisco, D., Silvestri, E., Emmi, G., Bettiol, A., Caterina, C., Biolo, G., Zanetti, M., Guadagni, M., Zaccari, M., Chiuch, M., Vanoli, M., Grignani, G., Pulixi, E. A., Bernardi, M., Bassi, S. L., Santi, L., Zaccherini, G., Lupattelli, G., Mannarino, E., Bianconi, V., Paciullo, F., Alcidi, R., Nuti, R., Valenti, R., Ruvio, M., Cappelli, S., Palazzuoli, A., Girelli, D., Busti, F., Marchi, G., Barbagallo, M., Dominguez, L., Cocita, F., Beneduce, V., Plances, L., Mularo, S., Raspanti, M., Zoli, M., Lazzari, I., Brunori, M., Fabbri, E., Magalotti, D., Arno, R., Pasini, F. L., Capecchi, P. L., Palasciano, G., Modeo, M. E., Di Gennaro, C., Cappellini, M. D., Maira, D., Di Stefano, V., Fabio, G., Seghezzi, S., Mancarella, M., De Amicis, M. M., De Luca, G., Scaramellini, N., Rossi, P. D., Damanti, S., Clerici, M., Conti, F., Bonini, G., Ottolini, B. B., Di Sabatino, A., Miceli, E., Lenti, M. V., Pisati, M., Dominioni, C. C., Murialdo, G., Marra, A., Cattaneo, F., Pontremoli, R., Beccati, V., Nobili, G., Secchi, M. B., Ghelfi, D., Anastasio, L., Sofia, L., Carbone, M., Cipollone, F., Guagnano, M. T., Valeriani, E., Rossi, I., Mancuso, G., Calipari, D., Bartone, M., Delitala, G., Berria, M., Pes, C., Delitala, A., Muscaritoli, M., Molfino, A., Petrillo, E., Zuccala, G., D'Aurizio, G., Romanelli, G., Zucchelli, A., Manzoni, F., Volpini, A., Picardi, A., Gentilucci, U. V., Gallo, P., Dell'Unto, C., Annoni, G., Corsi, M., Bellelli, G., Zazzetta, S., Mazzola, P., Szabo, H., Bonfanti, A., Arturi, F., Succurro, E., Rubino, M., Tassone, B., Sesti, G., Serra, M. G., Bleve, M. A., Gasbarrone, L., Sajeva, M. R., Brucato, A., Ghidoni, S., Fabris, F., Bertozzi, I., Bogoni, G., Rabuini, M. V., Cosi, E., Scarinzi, P., Amabile, A., Omenetto, E., Prandini, T., Manfredini, R., Fabbian, F., Boari, B., De Giorgi, A., Tiseo, R., De Giorgio, R., Paolisso, G., Rizzo, M. R., Borghi, C., Strocchi, E., Ianniello, E., Soldati, M., Sabba, C., Vella, F. S., Suppressa, P., Schilardi, A., Loparco, F., De Vincenzo, G. M., Comitangelo, A., Amoruso, E., Fenoglio, L., Falcetta, A., Bracco, C., Fargion, A. L. F. S., Tiraboschi, S., Cespiati, A., Oberti, G., Sigon, G., Peyvandi, F., Rossio, R., Ferrari, B., Colombo, G., Agosti, P., Monzani, V., Savojardo, V., Folli, C., Ceriani, G., Pallini, G., Dallegri, F., Ottonello, L., Liberale, L., Caserza, L., Salam, K., Liberato, N. L., Tognin, T., Bianchi, G. B., Giaquinto, S., Purrello, F., Di Pino, A., Piro, S., Rozzini, R., Falanga, L., Spazzini, E., Ferrandina, C., Montrucchio, G., Petitti, P., Peasso, P., Favale, E., Poletto, C., Salmi, R., Gaudenzi, P., Perri, L., Landolfi, R., Montalto, M., Mirijello, A., Guasti, L., Castiglioni, L., Maresca, A., Squizzato, A., Campiotti, L., Grossi, A., Bertolotti, M., Mussi, C., Lancellotti, G., Libbra, M. V., Dondi, G., Pellegrini, E., Carulli, L., Galassi, M., Grassi, Y., Perticone, M., Battaglia, R., Filice, M., Maio, R., Stanghellini, V., Ruggeri, E., del Vecchio, S., Salvi, A., Leonardi, R., Damiani, G., Capeci, W., Gabrielli, A., Mattioli, M., Martino, G. P., Biondi, L., Pettinari, P., Ghio, R., Col, A. D., Minisola, S., Colangelo, L., Cilli, M., Labbadia, G., Afeltra, A., Marigliano, B., Pipita, M. E., Castellino, P., Zanoli, L., Pignataro, S., Gennaro, A., Blanco, J., Saracco, V., Fogliati, M., Bussolino, C., Mete, F., Gino, M., Cittadini, A., Vigorito, C., Arcopinto, M., Salzano, A., Bobbio, E., Marra, A. M., Sirico, D., Moreo, G., Gasparini, F., Prolo, S., Pina, G., Ballestrero, A., Ferrando, F., Berra, S., Dassi, S., Nava, M. C., Graziella, B., Baldassarre, S., Fragapani, S., Gruden, G., Galanti, G., Mascherini, G., Petri, C., Stefani, L., Girino, M., Piccinelli, V., Nasso, F., Gioffre, V., Pasquale, M., Scattolin, G., Martinelli, S., Turrin, M., Sechi, L., Catena, C., Colussi, G., Passariello, N., Rinaldi, L., Berti, F., Famularo, G., Tarsitani, P., Castello, R., Pasino, M., Ceda, G. P., Maggio, M. G., Morganti, S., Artoni, A., Del Giacco, S., Firinu, D., Losa, F., Paoletti, G., Costanzo, G., Montalto, G., Licata, A., Malerba, V., Montalto, F. A., Lasco, A., Basile, G., Catalano, A., Malatino, L., Stancanelli, B., Terranova, V., Di Marca, S., Di Quattro, R., La Malfa, L., Caruso, R., Mecocci, P., Ruggiero, C., Boccardi, V., Meschi, T., Lauretani, F., Ticinesi, A., Nouvenne, A., Minuz, P., Fondrieschi, L., Pirisi, M., Fra, G. P., Sola, D., Porta, M., Riva, P., Quadri, R., Larovere, E., Novelli, M., Scanzi, G., Mengoli, C., Provini, S., Ricevuti, L., Simeone, E., Scurti, R., Tolloso, F., Tarquini, R., Valoriani, A., Dolenti, S., Vannini, G., Tedeschi, A., Trotta, L., Volpi, R., Bocchi, P., Vignali, A., Harari, S., Lonati, C., Cattaneo, M., Napoli, F., Corrao, S, Nobili, A, Natoli, G, Mannucci, P, Perticone, F, Pietrangelo, A, Argano, C, Licata, G, Violi, F, Corazza, G, Marengoni, A, Salerno, F, Cesari, M, Tettamanti, M, Pasina, L, Franchi, C, Cortesi, L, Miglio, G, Ardoino, I, Novella, A, Prisco, D, Silvestri, E, Emmi, G, Bettiol, A, Caterina, C, Biolo, G, Zanetti, M, Guadagni, M, Zaccari, M, Chiuch, M, Vanoli, M, Grignani, G, Pulixi, E, Bernardi, M, Bassi, S, Santi, L, Zaccherini, G, Lupattelli, G, Mannarino, E, Bianconi, V, Paciullo, F, Alcidi, R, Nuti, R, Valenti, R, Ruvio, M, Cappelli, S, Palazzuoli, A, Girelli, D, Busti, F, Marchi, G, Barbagallo, M, Dominguez, L, Cocita, F, Beneduce, V, Plances, L, Mularo, S, Raspanti, M, Zoli, M, Lazzari, I, Brunori, M, Fabbri, E, Magalotti, D, Arno, R, Pasini, F, Capecchi, P, Palasciano, G, Modeo, M, Di Gennaro, C, Cappellini, M, Maira, D, Di Stefano, V, Fabio, G, Seghezzi, S, Mancarella, M, De Amicis, M, De Luca, G, Scaramellini, N, Rossi, P, Damanti, S, Clerici, M, Conti, F, Bonini, G, Ottolini, B, Di Sabatino, A, Miceli, E, Lenti, M, Pisati, M, Dominioni, C, Murialdo, G, Marra, A, Cattaneo, F, Pontremoli, R, Beccati, V, Nobili, G, Secchi, M, Ghelfi, D, Anastasio, L, Sofia, L, Carbone, M, Cipollone, F, Guagnano, M, Valeriani, E, Rossi, I, Mancuso, G, Calipari, D, Bartone, M, Delitala, G, Berria, M, Pes, C, Delitala, A, Muscaritoli, M, Molfino, A, Petrillo, E, Zuccala, G, D'Aurizio, G, Romanelli, G, Zucchelli, A, Manzoni, F, Volpini, A, Picardi, A, Gentilucci, U, Gallo, P, Dell'Unto, C, Annoni, G, Corsi, M, Bellelli, G, Zazzetta, S, Mazzola, P, Szabo, H, Bonfanti, A, Arturi, F, Succurro, E, Rubino, M, Tassone, B, Sesti, G, Serra, M, Bleve, M, Gasbarrone, L, Sajeva, M, Brucato, A, Ghidoni, S, Fabris, F, Bertozzi, I, Bogoni, G, Rabuini, M, Cosi, E, Scarinzi, P, Amabile, A, Omenetto, E, Prandini, T, Manfredini, R, Fabbian, F, Boari, B, De Giorgi, A, Tiseo, R, De Giorgio, R, Paolisso, G, Rizzo, M, Borghi, C, Strocchi, E, Ianniello, E, Soldati, M, Sabba, C, Vella, F, Suppressa, P, Schilardi, A, Loparco, F, De Vincenzo, G, Comitangelo, A, Amoruso, E, Fenoglio, L, Falcetta, A, Bracco, C, Fargion, A, Tiraboschi, S, Cespiati, A, Oberti, G, Sigon, G, Peyvandi, F, Rossio, R, Ferrari, B, Colombo, G, Agosti, P, Monzani, V, Savojardo, V, Folli, C, Ceriani, G, Pallini, G, Dallegri, F, Ottonello, L, Liberale, L, Caserza, L, Salam, K, Liberato, N, Tognin, T, Bianchi, G, Giaquinto, S, Purrello, F, Di Pino, A, Piro, S, Rozzini, R, Falanga, L, Spazzini, E, Ferrandina, C, Montrucchio, G, Petitti, P, Peasso, P, Favale, E, Poletto, C, Salmi, R, Gaudenzi, P, Perri, L, Landolfi, R, Montalto, M, Mirijello, A, Guasti, L, Castiglioni, L, Maresca, A, Squizzato, A, Campiotti, L, Grossi, A, Bertolotti, M, Mussi, C, Lancellotti, G, Libbra, M, Dondi, G, Pellegrini, E, Carulli, L, Galassi, M, Grassi, Y, Perticone, M, Battaglia, R, Filice, M, Maio, R, Stanghellini, V, Ruggeri, E, del Vecchio, S, Salvi, A, Leonardi, R, Damiani, G, Capeci, W, Gabrielli, A, Mattioli, M, Martino, G, Biondi, L, Pettinari, P, Ghio, R, Col, A, Minisola, S, Colangelo, L, Cilli, M, Labbadia, G, Afeltra, A, Marigliano, B, Pipita, M, Castellino, P, Zanoli, L, Pignataro, S, Gennaro, A, Blanco, J, Saracco, V, Fogliati, M, Bussolino, C, Mete, F, Gino, M, Cittadini, A, Vigorito, C, Arcopinto, M, Salzano, A, Bobbio, E, Sirico, D, Moreo, G, Gasparini, F, Prolo, S, Pina, G, Ballestrero, A, Ferrando, F, Berra, S, Dassi, S, Nava, M, Graziella, B, Baldassarre, S, Fragapani, S, Gruden, G, Galanti, G, Mascherini, G, Petri, C, Stefani, L, Girino, M, Piccinelli, V, Nasso, F, Gioffre, V, Pasquale, M, Scattolin, G, Martinelli, S, Turrin, M, Sechi, L, Catena, C, Colussi, G, Passariello, N, Rinaldi, L, Berti, F, Famularo, G, Tarsitani, P, Castello, R, Pasino, M, Ceda, G, Maggio, M, Morganti, S, Artoni, A, Del Giacco, S, Firinu, D, Losa, F, Paoletti, G, Costanzo, G, Montalto, G, Licata, A, Malerba, V, Montalto, F, Lasco, A, Basile, G, Catalano, A, Malatino, L, Stancanelli, B, Terranova, V, Di Marca, S, Di Quattro, R, La Malfa, L, Caruso, R, Mecocci, P, Ruggiero, C, Boccardi, V, Meschi, T, Lauretani, F, Ticinesi, A, Nouvenne, A, Minuz, P, Fondrieschi, L, Pirisi, M, Fra, G, Sola, D, Porta, M, Riva, P, Quadri, R, Larovere, E, Novelli, M, Scanzi, G, Mengoli, C, Provini, S, Ricevuti, L, Simeone, E, Scurti, R, Tolloso, F, Tarquini, R, Valoriani, A, Dolenti, S, Vannini, G, Tedeschi, A, Trotta, L, Volpi, R, Bocchi, P, Vignali, A, Harari, S, Lonati, C, Cattaneo, M, and Napoli, F
Subjects: Registrie, Male, Comorbidity, Diabetes, Disability, Elderly, Hyperglycemia, Mortality, Aged, Aged, 80 and over, Female, Hospital Mortality, Hospitals, Humans, Internal Medicine, Registries, Hospitalization, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Socio-culturale, Renal function, 030204 cardiovascular system & hematology, Diabete, Hospital, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Rating scale, Internal medicine, Diabetes mellitus, 80 and over, medicine, LS4_4, 030212 general & internal medicine, Class III obesity, business.industry, Mortality rate, Comorbidity, Diabetes, Disability, Elderly, Hyperglycemia, Mortality, General Medicine, medicine.disease, Mood disorders, Geriatric Depression Scale, Original Article, business, Human
Abstract: Aims The association between hyperglycemia at hospital admission and relevant short- and long-term outcomes in elderly population is known. We assessed the effects on mortality of hyperglycemia, disability, and multimorbidity at admission in internal medicine ward in patients aged ≥ 65 years. Methods Data were collected from an active register of 102 internal medicine and geriatric wards in Italy (RePoSi project). Patients were recruited during four index weeks of a year. Socio-demographic data, reason for hospitalization, diagnoses, treatment, severity and comorbidity indexes (Cumulative Illness rating Scale CIRS-SI and CIRS-CI), renal function, functional (Barthel Index), and cognitive status (Short Blessed Test) and mood disorders (Geriatric Depression Scale) were recorded. Mortality rates were assessed in hospital 3 and 12 months after discharge. Results Of the 4714 elderly patients hospitalized, 361 had a glycemia level ≥ 250 mg/dL at admission. Compared to subjects with lower glycemia level, patients with glycemia ≥ 250 mg/dL showed higher rates of male sex, smoke and class III obesity. These patients had a significantly lower Barthel Index (p = 0.0249), higher CIRS-SI and CIRS-CI scores (p = 0.0025 and p = 0.0013, respectively), and took more drugs. In-hospital mortality rate was 9.2% and 5.1% in subjects with glycemia ≥ 250 and p = 0.0010). Regression analysis showed a strong association between in-hospital death and glycemia ≥ 250 mg/dL (OR 2.07; [95% CI 1.34–3.19]), Barthel Index ≤ 40 (3.28[2.44–4.42]), CIRS-SI (1.87[1.27–2.77]), and male sex (1.54[1.16–2.03]). Conclusions The stronger predictors of in-hospital mortality for older patients admitted in general wards were glycemia level ≥ 250 mg/dL, Barthel Index ≤ 40, CIRS-SI, and male sex.
Published: 2021

34. Cardiac involvement in eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss syndrome): Prospective evaluation at a tertiary referral centre

Author: Elena Silvestri, Matteo Beltrami, Domenico Prisco, Mattia Zampieri, Carlo Fumagalli, Silvia Pradella, Maria Letizia Urban, Lorenzo-Lupo Dei, Augusto Vaglio, Alessandra Bettiol, Alberto Marchi, Katia Baldini, Giacomo Emmi, Martina Berteotti, Iacopo Olivotto, Niccolò Marchionni, and Alessia Tomberli
Subjects: medicine.medical_specialty, Myocarditis, Population, Churg-Strauss Syndrome, 030204 cardiovascular system & hematology, Tertiary Care Centers, Angina, 03 medical and health sciences, Pericarditis, 0302 clinical medicine, Internal medicine, Eosinophilic, Internal Medicine, medicine, Humans, Prospective Studies, 030212 general & internal medicine, education, education.field_of_study, business.industry, Granulomatosis with Polyangiitis, Heart, Middle Aged, medicine.disease, 3. Good health, Granulomatosis with polyangiitis, business, Vasculitis, Systemic vasculitis
Abstract: Background Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic vasculitis. Cardiac specific involvement (CSI) is caused by coronary artery vasculitis, but also by myocardial eosinophilic infiltration. To date, the prevalence of CSI associated with EGPA is unresolved. Aim of this study was to systematically assess the prevalence and clinical impact of CSI in a consecutive outpatient EGPA population. Methods Between October 2018 and July 2019, we prospectively enrolled 52 consecutive EGPA patients. All underwent comprehensive evaluation including a standardized questionnaire, physical examination, 12-lead-ECG, echocardiography. Cardiac magnetic resonance and 24 h-Holter were performed as deemed clinically appropriate. Cardiac abnormalities were defined as CSI based on the likelihood of their relation to EGPA vasculitis, after exclusion of alternative diagnoses. Results 52 enrolled patients, mean age 59±1 years. Thirteen of the 52 patients (25%) were classified as CSI+. CSI was characterized by myocarditis in four patients, non-scar-related regional wall motions abnormalities (RWMA) in three, apical thrombosis in two (one also had RWMA), pericarditis in three and non-atherosclerotic coronary disease (Prinzmetal angina and coronaritis) in 2. Five (38%) of the 13 CSI+ patients, presented an apical aneurysm. Peak eosinophil count at diagnosis was higher in CSI+: 8000 /μl vs CSI-: 3000 /μl, p = 0.017. Overall, 2 patients had severe LV dysfunction, 5 required urgent hospitalization and 8 required long-term cardioactive therapy. Conclusions CSI was present in one-quarter of patients, often associated with high peak eosinophils. Myocarditis, RWMA and apical aneurysms were the most common manifestations. Although rarely severe and life-threatening, CSI often required long-term cardioactive treatment.
Published: 2021

35. Direct oral anticoagulants for secondary prevention in patients with non-valvular atrial fibrillation

Author: Luca Masotti, Mario Di Napoli, Walter Ageno, Davide Imberti, Cecilia Becattini, Maurizio Paciaroni, Daniel Augustin Godoy, Roberto Cappelli, Giancarlo Landini, Grazia Panigada, Ido Iori, Domenico Prisco, and Giancarlo Agnelli
Subjects: atrial fibrillation, warfarin, stroke, prophylaxis, dabigatran, rivaroxaban, apixaban., Medicine
Abstract: The patients with non-valvular atrial fibrillation (NVAF), both permanent and paroxysmal, and history of previous transient ischemic attack (TIA) or stroke represent a category of patients at high risk of new embolic events, independently of the presence of other risk factors. In these patients, national and international guidelines recommend oral anticoagulants as first choice for antithrombotic prevention. Direct oral anticoagulants (DOACs) have been demonstrated to be not inferior to warfarin for many end points in NVAF patients in terms of efficacy and safety. The post hoc analysis in selected subgroups of patients enrolled in the three mega trials of phase III comparing DOACs (RE-LY, ROCKET-AF and ARISTOTLE) with warfarin help to evaluate whether superiority and non-inferiority persist in these subgroups. Here, patients with NVAF and history of previous TIA/stroke receiving DOACs as secondary prevention are compared with patients with the same characteristics receiving warfarin. An analysis of these patients has been recently published (separately for each of three DOACs). This analysis shows that DOACs maintain their non-inferiority when compared with warfarin in secondary prevention, representing a real alternative in this context of patients at high risk for ischemic and bleeding events.
Published: 2013
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36. International Consensus on Antineutrophil Cytoplasm Antibodies Testing in Eosinophilic Granulomatosis with Polyangiitis

Author: Sergey Moiseev, Xavier Bossuyt, Yoshihiro Arimura, Daniel Blockmans, Elena Csernok, Jan Damoiseaux, Giacomo Emmi, Luis Felipe Flores-Suárez, Bernhard Hellmich, David Jayne, J. Charles Jennette, Mark A. Little, Aladdin J. Mohammad, Frank Moosig, Pavel Novikov, Christian Pagnoux, Antonella Radice, Ken-ei Sada, Mårten Segelmark, Yehuda Shoenfeld, Renato A. Sinico, Ulrich Specks, Benjamin Terrier, Athanasios G. Tzioufas, Augusto Vaglio, Ming-Hui Zhao, Jan Willem Cohen Tervaert, Fabian Arndt, Allyson Egan, Jean-Emmanuel Kahn, Anna Kernder, Alfred Mahr, Julian Mahrhold, Chiara Marvisi, Thomas Neumann, Domenico Prisco, Carlo Salvarani, Franco Schiavon, Arianna Troilo, Maria L. Urban, Nils Venhoff, Faculteit FHML Centraal, MUMC+: DA CDL Algemeen (9), and RS: MHeNs - R3 - Neuroscience
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, Cyclophosphamide, SYSTEMIC VASCULITIS, urologic and male genital diseases, Critical Care and Intensive Care Medicine, Gastroenterology, vasculitis, 03 medical and health sciences, 0302 clinical medicine, immune system diseases, Internal medicine, Eosinophilic, CYCLOPHOSPHAMIDE, medicine, cardiovascular diseases, 030212 general & internal medicine, RITUXIMAB, skin and connective tissue diseases, TERM-FOLLOW-UP, business.industry, ANCA, MYELOPEROXIDASE, CARDIAC INVOLVEMENT, medicine.disease, EGPA, respiratory tract diseases, eosinophilic granulomatosis with polyangiitis, CHURG-STRAUSS-SYNDROME, 030228 respiratory system, consensus, Rituximab, AUTOANTIBODIES, business, Granulomatosis with polyangiitis, Vasculitis, Mepolizumab, Polyneuropathy, medicine.drug, Kidney disease
Abstract: An international consensus on antineutrophil cytoplasm antibodies (ANCA) testing in eosinophilic granulomatosis with polyangiitis (EGPA) is presented. ANCA, specific for myeloperoxidase (MPO), can be detected in 30-35% of patients with EGPA. MPO-ANCA should be tested with antigen-specific immunoassays in any patient with eosinophilic asthma and clinical features suggesting EGPA, including constitutional symptoms; purpura; polyneuropathy; unexplained heart, gastrointestinal, or kidney disease; and/or pulmonary infiltrates or hemorrhage. A positive MPO-ANCA result contributes to the diagnostic workup for EGPA. Patients with MPO-ANCA-associated EGPA have vasculitis features, such as glomerulonephritis, neuropathy, and skin manifestations, more frequently than patients with ANCA-negative EGPA. However, the presence of MPO-ANCA is neither sensitive nor specific enough to identify whether a patient should be subclassified as having "vasculitic" or eosinophilic" EGPA. At present, ANCA status cannot guide treatment decisions, that is, whether cyclophosphamide, rituximab, or mepolizumab should be added to conventional glucocorticoid treatment. In EGPA, monitoring of ANCA is only useful when MPO-ANCA was tested positive at disease onset.
Published: 2020

37. Hospitalisations related to benzodiazepine, Z-drug, and opioid treatment in Italy: a claim on the risks associated with inappropriate use

Author: Irene, Mattioli, Alessandra, Bettiol, Giada, Crescioli, Roberto, Bonaiuti, Domenico, Prisco, Guido, Mannaioni, Niccolò, Lombardi, and Alfredo, Vannacci
Subjects: Analgesics, Opioid, Hospitalization, Benzodiazepines, Substance-Related Disorders, Humans, Female, Emergency Service, Hospital
Abstract: Benzodiazepines (BZD), Z-drugs (ZD), and opioids share a high risk of abuse. This study assessed and characterised adverse events (AEs) related to BDZ, ZD, and opioids leading to emergency department (ED) visits in the Italian setting.ED accesses related to BDZ, ZD, and/or opioids were analysed from the MEREAFaPS database. Information on AEs, suspected and concomitant medications was retrieved. Multivariate logistic regression was used to estimate the reporting odds ratios (RORs) of hospitalisation according to the different treatments.A total of 5,970 pharmacovigilance reports involving BZD/ZD (n = 3,106), opioids (n = 2,767), or their combination (n = 97) were analysed. Compared to opioids, patients with BZD/ZD-related AEs were often younger (51 vs 64 years), more frequently presented 2+ suspected medications (13 vs 3%), and often had a history of abuse (4%). Twenty-three percent of BZD/ZD-related AEs were related to drug abuse (vs 2% of opioid-related ones) and frequently required patient hospitalisation (52% vs 24%), despite the significantly lower clinical complexity of these patients as compared to those on opioids. An increased risk of hospitalisation was found for flurazepam (ROR 1.62; 95% CI, 1.18-2.22), prazepam (2.66; 1.05-6.70), lorazepam (1.26; 1.07-1.49), and morphine (1.76; 1.11-2.79).These results indicate that, in Italy, the inappropriate use of BZD/ZD is a relevant heath issue, often leading to serious AEs requiring patients' ED visits and hospitalisation, especially in young women and patients with a history of substance abuse.
Published: 2022

38. Apolipoprotein(a) Kringle-IV Type 2 Copy Number Variation Is Associated with Venous Thromboembolism.

Author: Elena Sticchi, Alberto Magi, Pia R Kamstrup, Rossella Marcucci, Domenico Prisco, Ida Martinelli, Pier Mannuccio Mannucci, Rosanna Abbate, and Betti Giusti
Subjects: Medicine, Science
Abstract: In addition to the established association between high lipoprotein(a) [Lp(a)] concentrations and coronary artery disease, an association between Lp(a) and venous thromboembolism (VTE) has also been described. Lp(a) is controlled by genetic variants in LPA gene, coding for apolipoprotein(a), including the kringle-IV type 2 (KIV-2) size polymorphism. Aim of the study was to investigate the role of LPA gene KIV-2 size polymorphism and single nucleotide polymorphisms (SNPs) (rs1853021, rs1800769, rs3798220, rs10455872) in modulating VTE susceptibility. Five hundred and sixteen patients with VTE without hereditary and acquired thrombophilia and 1117 healthy control subjects, comparable for age and sex, were investigated. LPA KIV-2 polymorphism, rs3798220 and rs10455872 SNPs were genotyped by TaqMan technology. Concerning rs1853021 and rs1800769 SNPs, PCR-RFLP assay was used. LPA KIV-2 repeat number was significantly lower in patients than in controls [median (interquartile range) 11(6-17) vs 15(9-25), p
Published: 2016
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39. 'COVID-19: diagnosis, management and prognosis': a new topical collection of Internal and Emergency Medicine

Author: Riccardo Polosa, Domenico Prisco, and Michele Spinicci
Subjects: 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), business.industry, SARS-CoV-2, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Pneumonia, Viral, MEDLINE, COVID-19, medicine.disease, Prognosis, Betacoronavirus, Diagnosis management, medicine, Emergency Medicine, Internal Medicine, Viral therapy, Humans, Medical emergency, business, Coronavirus Infections, Pandemics, Editor's Page
Abstract: At the dawn of 2020, the planet woke up with an unexpected shocking public health threat. A novel zoonotic coronavirus, later named severe acute respiratory syndrome 2 (SARS-CoV-2), genetically close to SARS-CoV responsible for the outbreak in 2003, emerged as causative agent of a multifaceted syndrome, known as coronavirus disease 2019 (COVID-19) [1]. The outbreak rapidly spread from the Wuhan City, Hubei Province, China, where the first cases of SARS-CoV-2 infection occurred in early December 2019, toward western countries, resulting in an unprecedented challenge for the health systems worldwide. On 11th March 2020, the World Health Organization declared the outbreak of SARS-CoV-2 a pandemic. As of the 8th of July 2020 globally more than 11 million cases of SARS-CoV-2 infections had been confirmed, and 545,398 COVID-19 related fatalities had occurred globally [2]. The body of knowledge about biologic SARS-CoV-2 and clinical features of COVID-19 has been increasing exponentially. Nonetheless, conflicting opinions and confusing issues still dominate the scientific debate. The topical collection ofInternal and Emergency Medicine, titled “COVID-19: diagnosis, management and prognosis” was launched to better inform researchers, academics, physicians and healthcare professionals about the evolving understanding of the topic. Ethical issues are at the forefront of the debate, as it deserves for an event of such magnitude, to whom healthcare workers (HCWs) paid a heavy price. In their fascinating letter, Lippi et al. offered a historical perspective of doctors’ role in the past epidemics, stuck between professional duties, based on the Hippocratic Oath, and the need to protect themselves, through adequate measures and equipment [3]. More to the point, Arora et al. identified ethics key issues in the COVID-19 era, such as the long-term implications of non-urgent care cancelled, how to make priority decisions on patients’ treatment escalation and how clinicians should act when adequate personal protective equipment (PPE) is not available [4]. Indeed, as highlighted by Russo et al., the pandemic storm has been not only a clinical challenge but also an organizational crisis for our health systems [5]. Shortage of PPE for frontline HCWs was one of the more worrisome aspects of the early pandemic. Tsilingiris et al. went into the debate on the appropriate use of medical masks and respirators for HCWs and revised available evidence on the topic [6]. The theme of COVID-19 as diversion and deterrent from the care of patients with chronic conditions, causing possible negative consequences in the near future, returned in the point of view by Viganò et al.: in their Emergency Department, the admissions dropped in March and April 2020 by 53% and 63%, respectively, with respect to the period December 2019–February 2020 [7]. Two nice papers rose concern on how pandemic can represent an additional complication for the management of cardiac emergencies, both inside and outside the hospitals [8,9]. The experience of the first 5weeks of COVID-19 epidemic in a referral centre in the epicentre of the Italian epidemic represented an effective strategy of Emergency Medicine network, able to manage an increased amount of calls and requests, by integrating “out-of-hospital” and “hospital” efforts [10]. Within the hospitals, physicians from disparate specialities were called to change their habits, when their facilities and wards were converted to COVID-19 areas, in response to an overwhelming flow of affected patients. At best, it was an occasion to put in place an unexpected teamwork cooperation and to share different skills and experiences [11]. The correct identification of COVID-19 cases remains the cornerstone for the control of the epidemic, allowing to confine infected patients and prevent SARS-CoV-2 spread. At the hospital level, an effective triage strategy is of paramount importance to avoid nosocomial outbreaks amongst HCWs and patients with other diseases than COVID-19. Poggiali et al. described their flowchart, applied in the heart of the Italian epidemic storm [12]. Polymerase chain reaction (PCR) testing on respiratory samples, i.e., nasopharyngeal swab, sputum or bronchoalveolar lavage, is the gold standard for a confirmed diagnosis of SARS-CoV-2 infection. However, physicians soon learned that in some cases, a typical clinical and radiological picture should drive the diagnosis, regardless of a negative microbiological result. As an example, in the case report by Song et al. a patient with fever, respiratory symptoms and evocative mixed ground-glass opacity at the computed tomography (CT), had negative PCR on seven consecutive sputum sample, before achieving the diagnosis of SARS-CoV-2 infection on the eighth sample [13]. Typical and atypical clinical features of COVID-19 patients, as well as risk factors with possible impact on COVID-19 outcome, are outlined in several papers of this Topical Collection. Bertolino et al. tried to summarize the evidences on key clinical features to differentiate COVID-19 case from upper respiratory and/or influenza-like illnesses of other aetiology, providing a practical guide for internists [14]. According to data collected by Lapostolle et al. among 1487 outpatients diagnosed with COVID-19 in the Greater Paris region, dry cough and fever were the most frequent symptoms reported (more than 90% of cases), in association with general symptoms, such as body aches/myalgia, headache, and asthenia, and a considerable quote of anosmia and ageusia [15]. Nevertheless, the clinical presentation can be sometimes atypical, respiratory symptoms can be less pronounced, and other sites targeted, such as the digestive tract, the cardiovascular system and central nervous system. For instance, a number of neurologic manifestation, from unspecific symptoms such as headache, altered mental status, and anosmia, up to cerebrovascular accidents and Guillain–Barré syndrome have occurred in many patients with Covid-19 [16,17]. Morjaria et al. described two cases of unusual neurological complications, i.e. bilateral lower limbs weakness, possibly related to cerebrovascular accidents, in critically ill patients with prolonged hospital stays [18]. Great interest exists on whether patients presenting with atypical symptoms are at increased risk to evolve toward severe forms of COVID-19. Henry et al. revised the available literature about common gastrointestinal symptoms and found that abdominal pain, nausea and vomiting, but not diarrhoea, were significantly associated with an increased odds of severe COVID-19 [19]. Moreover, myocardial injury was often observed in SARS-CoV-2 patients, especially those with severe to critical disease, in need of intensive care treatment. Preliminary data by Violi et al. on a limited sample of patients suggested that patients who show troponin elevation may be at higher risk of mortality [20]. As for other predictors of outcome in COVID-19 patients, Sciacqua et al. explored the potential causative factors of poor outcome in elderly people, such as immunosenescence, reduced resilience and the coexistence of multiple comorbidities, and focused on impaired nutritional status and sarcopenia, commonly due to inadequate food and calorie intake and an unmet increased protein demand [21]. Pantanetti et al. reviewed the pathophysiologic basis related to an excess of disease severity in diabetic patients and suggested a possible use of dipeptidyl peptidase-4 inhibitors as immunomodulatory drugs in COVID-19 [22]. Surprisingly, a systematic review by Farsalinos et al. found that smoking had a protective effect against COVID-19, based on an unexpected low prevalence of current smokers among Chinese patients hospitalized with COVID-19 [23]. Despite confidence issues on the accuracy about data collection methods for reporting smoking status, similar findings have been reported from other countries, allowing to speculate on pharmaceutical nicotine as a potential treatment option in COVID-19 [24]. To date, there is no established treatment for COVID-19. In recent days, remdesivir was the first antiviral drug approved by U.S. Food and Drug Administration (FDA) and European Medicine Agency (EMA) for the treatment of hospitalized adults with evidence of SARS-CoV-2 lower respiratory tract involvement, in virtue of the positive results obtained in a double-blind, randomized, placebo-controlled trial [25]. So far, remdesivir has been available only for compassionate use or within the randomized clinical trial and therapeutic strategies have largely relied on off-label use of old drugs, such as antimalarial drugs chloroquine (CQ) and hydroxychloroquine (HCQ) and antiretroviral lopinavir/ritonavir and darunavir/cobicistat [26]. Unfortunately, conclusive data about the real impact of these compounds on the outcome on Covid-19 patients are still lacking, albeit a constant flow of published data from clinical experiences, mostly biased by methodological flaws. Fanin et al. analysed ins and outs of a well-known open-label non-randomized clinical trial by Gautret et al. on the efficacy of the combination use of hydroxychloroquine and azithromycin, which had great resonance and influenced treatment strategies worldwide, despite important limitations [27,28]. Depfenhart et al. revised pharmacodynamics basis of antiviral drugs available so far, and suggested bromhexine, an FDA-approved ingredient in mucolytic cough suppressants, as a potential new option, due to its TMPRSS2 inhibitor activity [29]. However, overall management of Covid-19 patients exceeds the administration of antiviral drugs. Immune-modulant drugs and anti-thrombotic prophylaxis are pillars of the treatment of severe forms. Both arterial and venous thrombotic events frequently complicated the course of patients with COVID-19, especially in those critically ill, leading to the definition of Coronavirus-associated coagulopathy (CAC) by the International Society on Thrombosis and Haemostasis [30,31]. An interesting Spanish case series of non-ICU hospitalized COVID-19 patients diagnosed with pulmonary embolism, without evidence of concomitant deep–vein thrombosis of the lower limbs, suggested a predominance of small-vessel thrombosis secondary to inflammatory and immune responses [32]. Understanding mechanism underlying CAC is crucial to put in place appropriate therapeutic measures: observed hemostatic alternations—increasedD-dimer, normal or slightly deranged prothrombin time and within range platelets count—differ from those usually observed during the disseminated intravascular coagulopathy. Bazzan et al. found reduced levels of ADAMTS-13 and higher levels of von Willebrand factor in a cohort of COVID-19 patients, in comparison with healthy controls, and also in fatal COVID-19 cases, when compared to patients with the non-fatal outcome. These alterations, similar to those observed in patients with thrombotic thrombocytopenic purpura, may lean more to a thrombotic microangiopathy origin of CAC, rather than a consumption coagulopathy [33]. Moreover, the infusion of hyperimmune plasma from donors recovered from SARS-CoV-2 infection emerged as an attractive option. Perotti et al. presented the COVID-19 PLASMA trial, the first proof-of-concept interventional trial using hyperimmune plasma with a high titre of specific neutralizing antibodies for treating critical patients with COVID-19 [34]. Supportive care includes supplemental oxygen and ventilatory management of patients with respiratory distress. Privitera et al. proposed a flowchart for non-invasive ventilation support in COVID-19 patients, as a first approach in the Emergency Department [35]. Management of chronic therapies was also challenging. The role of ACE-2 receptor in SARS-CoV-2 cell entry process produced a lively debate on the potential impact of angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin II receptor blockers (ARBs), extensively used for the treatment of hypertension and other cardiovascular diseases, on the natural history of SARS-Cov-2 infection. Two papers of the Topical Collection explored the potential implication of ACE-Is and ARBs use in Covid-19 patients [36,37]. Finally, Testa et al. addressed the management of Covid-19 patients on oral anticoagulant drugs, and the high risk of over/under treatment due to the multiple pharmacological interactions, and the possible necessity of mechanical ventilation, and suggested replacing oral anticoagulant therapies with parenteral low-molecular-weight heparin or unfractionated heparin [38]. On the other hand, a paper by Poli et al. provided some advice aimed at improving the outpatient management of people on anticoagulant treatment during COVID-19 pandemic, with particular regard to the lockdown and reopening periods [39]. In the authors’ view, this new Topical Collection will contribute significantly to stimulate the scientific debate and to advance the current body of knowledge of the medical community about the pandemic and its ethical, organizational, and clinical challenges. Given the importance of the topic to the active role that internists and general physicians play in assisting the many patients directly or indirectly affected by COVID-19,Internal and Emergency Medicineremains committed to further expanding the current knowledge base and advancing the scientific debate about the impact of SARS-CoV-2 on human health worldwide.
Published: 2020

40. Postoperative atrial fibrillation is related to a worse outcome in patients undergoing surgery for hip fracture

Author: Carlo Rostagno, Roberto Civinini, Domenico Prisco, Alice Ceccofiglio, Gianluca Polidori, Massimo Curcio, Gaia Rubbieri, and Alessandro Cartei
Subjects: Male, medicine.medical_specialty, Hip fracture surgery, 030204 cardiovascular system & hematology, Asymptomatic, 03 medical and health sciences, Postoperative Complications, 0302 clinical medicine, Atrial Fibrillation, Internal Medicine, medicine, Humans, Sinus rhythm, In patient, 030212 general & internal medicine, Aged, 80 and over, Hip surgery, Hip fracture, Hip Fractures, business.industry, Incidence (epidemiology), Atrial fibrillation, Length of Stay, Prognosis, medicine.disease, Surgery, Case-Control Studies, Emergency Medicine, Female, medicine.symptom, business
Abstract: Few information exist about incidence and prognostic significance of postoperative atrial fibrillation (POAF) in patients undergoing hip fracture surgery. In the period comprised between January 2012 and December 2016, we evaluated 3129 patients referred for hip fracture. At hospital admission 277 were in permanent atrial fibrillation and were excluded from the study. POAF was defined as symptomatic or asymptomatic AF of duration > 10 min occurring during hospitalization after hip surgery. In-hospital and 1-year outcomes of POAF patients were compared to that of an age- and sex-matched hip fracture control group. Survival rates were estimated by Kaplan–Meier curves and differences between groups compared by log-rank test. One hundred and four patients (mean age 83.7 years, men 27%) developed POAF (3.6%). Time of onset after surgery was on average 2 days after surgery. Eight POAF patients died during hospitalization. 81.7% were discharged in sinus rhythm. Patients with POAF had a longer time to surgery (3.8 ± 3.3 vs. 2.4 ± 1.6 days, p = 0.0007) and length of hospital stay (19.7 ± 10.4 vs. 14.4 ± 5.1 days p
Published: 2020

41. Obstetric antiphospholipid syndrome is not associated with an increased risk of subclinical atherosclerosis

Author: Giacomo Emmi, Antonella Scalera, Alfredo Vannacci, Matteo Nicola Dario Di Minno, Maria Letizia Urban, Elena Silvestri, Alessandra Bettiol, Roberta Lupoli, Irene Mattioli, Martina Finocchi, Domenico Prisco, Bettiol, A., Emmi, G., Finocchi, M., Silvestri, E., Urban, M. L., Mattioli, I., Scalera, A., Lupoli, R., Vannacci, A., Di Minno, M. N. D., and Prisco, D.
Subjects: Adult, Male, medicine.medical_specialty, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Pregnancy, Antiphospholipid syndrome, Carotid Intima-Media Thickne, Internal medicine, medicine.artery, medicine, Pharmacology (medical), Common carotid artery, Thrombus, 030203 arthritis & rheumatology, Lupus anticoagulant, business.industry, Thrombosis, Middle Aged, Antiphospholipid Syndrome, medicine.disease, Pregnancy Complication, Increased risk, Atherosclerosi, Subclinical atherosclerosis, Thrombosi, Cardiology, Female, Case-Control Studie, business, Human
Abstract: Objectives The persistent positivity of aPLs, either isolated or associated with thrombotic and/or obstetric events (APS), has been associated with the increase of intima-media thickness (IMT) and carotid plaques. Despite the fact that aPLs can promote both thrombotic and obstetric complications, some pathogenic differences have been documented between the two entities. This study aimed to evaluate whether the atherosclerotic risk differs between subjects with obstetric and thrombotic APS. Methods A total of 167 APS women (36 obstetric and 131 thrombotic) were compared with 250 aPLs negative controls. IMT of the common carotid artery (CCA) and of the bulb and the prevalence of carotid plaques were assessed. Results CCA- and bulb-IMT were significantly higher in women with thrombotic APS, while being similar between the obstetric APS and the controls [CCA-IMT: mean (s.d.) 0.97 (0.49), 0.78 (0.22) and 0.81 (0.12) mm for the thrombotic, obstetric and control groups, respectively, P < 0.001 between thrombotic and controls, P = 0.002 between thrombotic and obstetric; bulb-IMT: mean (s.d.) 1.38 (0.79), 0.96 (0.27) and 0.96 (0.51) mm for the thrombotic, obstetric and control groups, P < 0.001]. Women with thrombotic APS had significantly increased risk of presenting carotid plaques. This risk was significantly lower in obstetric APS. Conclusion Unlike thrombotic APS, obstetric APS is not associated with an increase of markers of subclinical atherosclerosis. If confirmed on wider populations, these results could suggest different pathogenetic role of aPLs in promoting atherosclerosis in vascular and obstetric APS, and raise questions on the risk–benefit profile of thromboprophylaxis in obstetric APS outside pregnancy periods.
Published: 2020

42. Design and rationale of a randomized, placebo-controlled trial on the efficacy and safety of sulodexide for extended treatment in elderly patients after a first venous thromboembolism

Author: Alberto Tosetto, Lorenza Bertù, Angelo A. Bignamini, Gualtiero Palareti, Corrado Lodigiani, Serena Zorzi, Domenico Prisco, Emilia Antonucci, Cristina Legnani, Sophie Testa, Vittorio Pengo, Daniela Poli, Walter Ageno, and Paolo Prandoni
Subjects: Male, medicine.medical_specialty, Population, Placebo-controlled study, 030204 cardiovascular system & hematology, Placebo, Placebos, 03 medical and health sciences, Sulodexide, 0302 clinical medicine, Elderly, Double-Blind Method, Informed consent, Extension, Recurrence, Internal medicine, Internal Medicine, Secondary Prevention, Medicine, Humans, 030212 general & internal medicine, education, Stroke, Aged, Glycosaminoglycans, Randomized Controlled Trials as Topic, education.field_of_study, business.industry, Anticoagulants, Venous Thromboembolism, medicine.disease, Im - Original, Research Design, Emergency Medicine, Female, Venous thromboembolism, business, Major bleeding
Abstract: How to prevent recurrences after a first venous thromboembolic (VTE) event in elderly patients is still an open issue, especially because of the high bleeding risk of anticoagulation in these patients. The placebo-controlled “Jason” study aims at assessing the efficacy and safety for secondary VTE prevention in elderly patients of oral Sulodexide (Vessel®) administration, a mixture of glycosaminoglycans (Alfasigma, Bologna, Italy) which proved effective against recurrences in a general population (SURVET study) without major bleeding (MB) complications. 1450 patients, aged ≥ 75 years, after at least 3 months of anticoagulation treatment for a first VTE episode, are double-blind randomized to receive for 12 months either sulodexide 500 lipasemic units (LSUs) twice daily, or sulodexide 250 LSU twice daily + indistinguishable placebo, or indistinguishable placebo. Primary outcomes for efficacy are the composite of death for VTE and recurrent VTE, and occurrence of MB for safety. Secondary outcomes include stroke, cardiovascular death and other thromboembolic events, and MB + clinically relevant non-MB. The first patient is scheduled to be randomized in May 2020. The study protocol has been approved by AIFA (Agenzia Italiana del Farmaco) and the Ethics Committee of the coordinating center. Written informed consent will be obtained from all patients prior to study participation. Jason study is an investigator-initiated trial, promoted by “Arianna Anticoagulazione” Foundation, Bologna, Italy, and supported by Alfasigma, Bologna, Italy. Study findings will be disseminated to participant centers, at research conferences and in peer-reviewed journals. Trial registration numbers NCT 04257487; EudraCT (2019–000570-33). Electronic supplementary material The online version of this article (10.1007/s11739-020-02381-5) contains supplementary material, which is available to authorized users.
Published: 2020

43. Adalimumab effectively controls both anterior and posterior noninfectious uveitis associated with systemic inflammatory diseases: focus on Behçet’s syndrome

Author: Daniela Bacherini, Alice Bitossi, Stanislao Rizzo, Gianni Virgili, Vincenzo Venerito, Irene Mattioli, Domenico Prisco, Lorenzo Vannozzi, Antonio Vitale, Elena Silvestri, Luca Cantarini, Florenzo Iannone, Maria Letizia Urban, Gian Marco Tosi, Claudia Fabiani, Giacomo Emmi, Giuseppe Lopalco, Alessandra Bettiol, and Gerardo Di Scala
Subjects: Adult, Male, 0301 basic medicine, medicine.medical_specialty, Adolescent, Immunology, Arthritis, Gastroenterology, Inflammatory bowel disease, Ocular relapses, Uveitis, Young Adult, 03 medical and health sciences, Psoriatic arthritis, 0302 clinical medicine, Adalimumab, Anterior uveitis, Behçet’s syndrome, Macular edema, Internal medicine, medicine, Humans, Pharmacology (medical), Retrospective Studies, Inflammation, Pharmacology, Ankylosing spondylitis, business.industry, Behcet Syndrome, medicine.disease, Arthritis, Juvenile, eye diseases, Posterior segment of eyeball, 030104 developmental biology, Female, business, 030217 neurology & neurosurgery, medicine.drug
Abstract: To compare the efficacy of Adalimumab (ADA) in noninfectious anterior uveitis (AU) and posterior segment (PS) involvement, associated with different conditions, with a focus on Behcet’s syndrome (BS). In this retrospective, multicenter post-hoc study, we evaluated the efficacy of ADA in terms of ocular control and relapses in 96 patients with AU and PS uveitis, either idiopathic (IU) or associated with BS or with other systemic disorders (OSD) (Juvenile Idiopathic Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis, Vogt-Koyanagi-Harada, Inflammatory Bowel Disease), followed in three tertiary referral centers. Ninety-six patients (45 AU; 51 PS uveitis) were included. Eleven had IU, 58 BS, and 27 OSD. All patients with AU achieved complete long-term ocular control. In PS uveitis, 89%, 67% and 100% of patients with BS, IU and OSD achieved ocular control at the last follow-up (> 12 months), respectively. The lowest ocular relapse rate occurred in patients with AU with BS (1/13) or IU (0/2). ADA accounted for long-term disease control, and no predictors of ocular control and relapse were identified; particularly, ocular relapses seemed not related to systemic ones. Macular edema resolved in 75% and 67% of PS uveitis with BS and IU, respectively. ADA controls both anterior and posterior uveitis, with an efficacy similar in IU, BS and OSD patients. In BS, the efficacy of ADA seems to be independent of demographic and clinical characteristics, and ocular relapses mostly occurred independently from systemic ones. Based on our results, ADA may represent a valid alternative in anterior refractory uveitis.
Published: 2020

44. nibizione della Interleuchina-1 nella pericardite ricorrente refrattaria

Author: Berkson Laeora, Emmi Giacomo, Carla Giustetto, Vassilopoulos Dimitrios, Lazaros George, Dagna Lorenzo, Marzia De Biasio, Allan L. Klein, Marcolongo Renzo, Brucato Antonio, Paul Cremer, Imazio Massimo, Gaetano M. De Ferrari, Vartan Mardigyan Domenico Prisco, Alessandro Andreis, Cantarini Luca, Lotan Dor, Andrea Cerne Cercek, Iannone Florenzo, Tousoulis Dimitrios, Lopalco Giuseppe, and Maestroni Silvia
Subjects: Marketing, medicine.medical_specialty, Anakinra, business.industry, Strategy and Management, Gastroenterology, chemistry.chemical_compound, Interleukin 1 receptor antagonist, chemistry, Internal medicine, Media Technology, medicine, Colchicine, General Materials Science, Recurrent pericarditis, business, medicine.drug
Published: 2020

45. Impact of Diabetes Mellitus and Its Comorbidities on Elderly Patients Hospitalized in Internal Medicine Wards: Data from the RePoSi Registry

Author: Christiano, Argano, Giuseppe, Natoli, Salvatore, Mularo, Alessandro, Nobili, Marika Lo Monaco, Pier Mannuccio Mannucci, Francesco, Perticone, Antonello, Pietrangelo, Salvatore, Corrao, Domenico, Prisco, Elena, Silvestri, Giacomo, Emmi, Alessandra, Bettiol, Irene, Mattioli, Gianni, Biolo, Michela, Zanetti, Giacomo, Bartelloni, Massimo, Vanoli, Giulia, Grignani, Edoardo Alessandro Pulixi, Graziana, Lupattelli, Vanessa, Bianconi, Riccardo, Alcidi, Domenico, Girelli, Fabiana, Busti, Giacomo, Marchi, Mario, Barbagallo, Ligia, Dominguez, Vincenza, Beneduce, Federica, Cacioppo, Massimo, Raspanti, Marco, Zoli, Maria Laura Matacena, Giuseppe, Orio, Eleonora, Magnolfi, Giovanni, Serafini, Angelo, Simili, Giuseppe, Palasciano, Maria Ester Modeo, Carla Di Gennaro, Maria Domenica Cappellini, Giovanna, Fabio, Margherita Migone De Amicis, Giacomo De Luca, Natalia, Scaramellini, Matteo, Cesari, Paolo Dionigi Rossi, Sarah, Damanti, Marta, Clerici, Simona, Leoni, Alessandra Danuta Di Mauro, Antonio Di Sabatino, Emanuela, Miceli, Marco Vincenzo Lenti, Martina, Pisati, Costanza Caccia Dominioni, Roberto, Pontremoli, Valentina, Beccati, Giulia, Nobili, Giovanna, Leoncini, Luigi, Anastasio, Maria, Carbone, Francesco, Cipollone, Maria Teresa Guagnano, Ilaria, Rossi, Gerardo, Mancuso, Daniela, Calipari, Mosè, Bartone, Giuseppe, Delitala, Maria, Berria, Alessandro, Delitala, Maurizio, Muscaritoli, Alessio, Molfino, Enrico, Petrillo, Antonella, Giorgi, Christian, Gracin, Giuseppe, Zuccalà, Gabriella, D’Aurizio, Giuseppe, Romanelli, Alessandra, Marengoni, Andrea, Volpini, Daniela, Lucente, Antonio, Picardi, Umberto Vespasiani Gentilucci, Paolo, Gallo, Giuseppe, Bellelli, Maurizio, Corsi, Cesare, Antonucci, Chiara, Sidoli, Giulia, Principato, Franco, Arturi, Elena, Succurro, Bruno, Tassone, Federica, Giofrè, Maria Grazia Serra, Maria Antonietta Bleve, Antonio, Brucato, Teresa De Falco, Fabrizio, Fabris, Irene, Bertozzi, Giulia, Bogoni, Maria Victoria Rabuini, Tancredi, Prandini, Manfredini, Roberto, Fabbian, Fabio, Benedetta, Boari, DE GIORGI, Alfredo, Ruana, Tiseo, Giuseppe, Paolisso, Maria Rosaria Rizzo, Claudia, Catalano, Claudio, Borghi, Enrico, Strocchi, Eugenia, Ianniello, Mario, Soldati, Silvia, Schiavone, Alessio, Bragagni, Carlo, Sabbà, Francesco Saverio Vella, Patrizia, Suppressa, Giovanni Michele De Vincenzo, Alessio, Comitangelo, Emanuele, Amoruso, Carlo, Custodero, Luigi, Fenoglio, Andrea, Falcetta, Fracanzani, Anna L., Silvia, Tiraboschi, Annalisa, Cespiati, Giovanna, Oberti, Giordano, Sigon, Flora, Peyvandi, Raffaella, Rossio, Giulia, Colombo, Pasquale, Agosti, Valter, Monzani, Valeria, Savojardo, Giuliana, Ceriani, Francesco, Salerno, Giada, Pallini, Fabrizio, Montecucco, Luciano, Ottonello, Lara, Caserza, Giulia, Vischi, Nicola Lucio Liberato, Tiziana, Tognin, Francesco, Purrello, Antonino Di Pino, Salvatore, Piro, Renzo, Rozzini, Lina, Falanga, Maria Stella Pisciotta, Francesco Baffa Bellucci, Stefano, Buffelli, Giuseppe, Montrucchio, Paolo, Peasso, Edoardo, Favale, Cesare, Poletto, Carl, Margaria, Maura, Sanino, Francesco, Violi, Ludovica, Perri, Luigina, Guasti, Luana, Castiglioni, Andrea, Maresca, Alessandro, Squizzato, Leonardo, Campiotti, Alessandra, Grossi, Roberto Davide Diprizio, Marco, Bertolotti, Chiara, Mussi, Giulia, Lancellotti, Maria Vittoria Libbra, Matteo, Galassi, Yasmine, Grassi, Alessio, Greco, Angela, Sciacqua, Maria, Perticone, Rosa, Battaglia, Raffaele, Maio, Vincenzo, Stanghellini, Eugenio, Ruggeri, Sara del Vecchio, Andrea, Salvi, Roberto, Leonardi, Giampaolo, Damiani, William, Capeci, Massimo, Mattioli, Giuseppe Pio Martino, Lorenzo, Biondi, Pietro, Pettinari, Riccardo, Ghio, Anna Dal Col, Salvatore, Minisola, Luciano, Colangelo, Mirella, Cilli, Giancarlo, Labbadia, Antonella, Afeltra, Benedetta, Marigliano, Maria Elena Pipita, Pietro, Castellino, Luca, Zanoli, Alfio, Gennaro, Agostino, Gaudio, Valter, Saracco, Marisa, Fogliati, Carlo, Bussolino, Francesca, Mete, Miriam, Gino, Carlo, Vigorito, Antonio, Cittadini, Guido, Moreo, Silvia, Prolo, Gloria, Pina, Alberto, Ballestrero, Fabio, Ferrando, Roberta, Gonella, Domenico, Cerminara, Sergio, Berra, Simonetta, Dassi, Maria Cristina Nava, Bruno, Graziella, Stefano, Baldassarre, Salvatore, Fragapani, Gabriella, Gruden, Giorgio, Galanti, Gabriele, Mascherini, Cristian, Petri, Laura, Stefani, Margherita, Girino, Valeria, Piccinelli, Francesco, Nasso, Vincenza, Gioffrè, Maria, Pasquale, Leonardo, Sechi, Cristiana, Catena, Gianluca, Colussi, Alessandro, Cavarape, Andea Da Porto, Nicola, Passariello, Luca, Rinaldi, Franco, Berti, Giuseppe, Famularo, Patrizia, Tarsitani, Roberto, Castello, Michela, Pasino, Gian Paolo Ceda, Marcello Giuseppe Maggio, Simonetta, Morganti, Andrea, Artoni, Margherita, Grossi, Stefano Del Giacco, Davide, Firinu, Giulia, Costanzo, Giacomo, Argiolas, Giuseppe, Montalto, Anna, Licata, Filippo Alessandro Montalto, Francesco, Corica, Giorgio, Basile, Antonino, Catalano, Federica, Bellone, Concetto, Principato, Lorenzo, Malatino, Benedetta, Stancanelli, Valentina, Terranova, Salvatore Di Marca, Rosario Di Quattro, Lara La Malfa, Rossella, Caruso, Patrizia, Mecocci, Carmelinda, Ruggiero, Virginia, Boccardi, Tiziana, Meschi, Andrea, Ticinesi, Antonio, Nouvenne, Pietro, Minuz, Luigi, Fondrieschi, Giandomenico Nigro Imperiale, Mario, Pirisi, Gian Paolo Fra, Daniele, Sola, Mattia, Bellan, Massimo, Porta, Piero, Riva, Roberto, Quadri, Erica, Larovere, Marco, Novelli, Giorgio, Scanzi, Caterina, Mengoli, Stella, Provini, Laura, Ricevuti, Emilio, Simeone, Rosa, Scurti, Fabio, Tolloso, Roberto, Tarquini, Alice, Valoriani, Silvia, Dolenti, Giulia, Vannini, Riccardo, Volpi, Pietro, Bocchi, Alessandro, Vignali, Sergio, Harari, Chiara, Lonati, Federico, Napoli, Italia, Aiello, Raffaele, Landolfi, Massimo, Montalto, Antonio, Mirijello, Silvia, Ghidoni, Teresa, Salvatore, Lucio, Monaco, Carmen, Ricozzi, Alberto, Pilotto, Ilaria, Indiano, Federica, Gandolfo., Argano C., Natoli G., Mularo S., Nobili A., Lo Monaco M., Mannucci P.M., Perticone F., Pietrangelo A., and Corrao S.
Subjects: Leadership and Management, 1-year mortality, cancer, comorbidities, diabetes, heart rate, in-hospital mortality, male sex, Heart rate, Socio-culturale, Health Informatics, comorbidities, Article, Comorbidities, Health Information Management, diabetes, heart rate, cancer, male sex, in-hospital mortality, 1-year mortality, Cancer, Diabetes, In-hospital mortality, Male sex, LS4_4, Health Policy, Medicine, 1-year mortality, Cancer, Comorbidities, Diabetes, Heart rate, In-hospital mortality, Male
Abstract: Background: Currently, diabetes represents the seventh leading cause of death worldwide, with a significant economic burden. The number and severity of comorbidities increase with age, and are identified as important determinants that influence the prognosis. We aimed to investigate comorbidities and outcomes in a cohort of hospitalized elderly patients affected by diabetes. Methods: In this observational study, we retrospectively analyzed data collected from the REgistro dei pazienti per lo studio delle POlipatologie e politerapie in reparti della rete Simi (RePoSi) registry. Socio-demographic, clinical characteristics, and laboratory findings were considered. The association between variables and in-hospital and 1-year follow-up were analyzed. Results: Among 4708 in-patients, 1378 (29.3%) had a diagnosis of diabetes. Patients with diabetes had more previous hospitalization, a clinically significant disability, and more need for a urinary catheter in comparison with subjects without diabetes. Patients affected by diabetes took more drugs, both at admission, at in-hospital stay, at discharge, and at 1-year follow-up. Thirty-five comorbidities were more frequent in patients with diabetes, and the first five were hypertension (57.1%), ischemic heart disease (31.4%), chronic renal failure (28.8%), atrial fibrillation (25.6%), and chronic obstructive pulmonary disease (22.7%). Heart rate was an independent predictor of in-hospital mortality. At 1-year follow-up, cancer and male sex were strongly independently associated with mortality. Conclusions: Our findings showed the severity of the impact of diabetes and its comorbidities in the real life of internal medicine and geriatric wards, and provide data to be used for a better tailored management of elderly in-patients with diabetes.
Published: 2022

46. Relation between drug therapy-based comorbidity indices, Charlson's comorbidity index, polypharmacy and mortality in three samples of older adults

Author: Alessio, Novella, Chiara, Elli, Mauro, Tettamanti, Alessandro, Nobili, Aladar, Ianes, Pier Mannuccio Mannucci, Luca, Pasina, Carlotta, Franchi, Gualberto, Gussoni, Stefano, Bonassi, Antonella, Valerio, Federica, Mammarella, Codjo Djignefa Djade, Raffaella, Rossio, Barbara, Ferrari, Daniela, Mari, Marco, Ferretti, Francesco, Salerno, Alessio, Conca, Antonino, Tuttolomondo, Anna, Cirrincione, Antonio, Pinto, Antonio, Cherubini, Giuseppina, Dell’Aquila, Roberto, Bernabei, Graziano, Onder, Michele, Ciaburri, Dario, Manfellotto, Irene, Caridi, Enzo, Lancia, Alessandra, Forgione, Concetta, Donato, Serra Maria Grazia, Luigi, Lusiani, Bullo, Cristina, Brocco, Stefano, Pedretti, Giovanni, Pattacini, Corrado, Francesco, Violi, Ludovica, Perri, Luigi Di Cioccio, Carlo Di Meo, Laura, Minchella, Moira, Ceci, Alberto, Ferrari, Salvatore, Foderaro, Antonio, Brucato, Anna, Valenti, Silvia, Ghidoni, Renzo, Rozzini, Lina, Falanga, Alessandra, Marengoni, Simona, Ghibelli, Chiara, Mussi, Maria Alice Ferri, Domenico, Prisco, Elena, Silvestri, Giacomo, Emmi, Alessandra, Bettiol, Irene, Mattioli, Gianni, Biolo, Michela, Zanetti, Giacomo, Bartelloni, Massimo, Vanoli, Giulia, Grignani, Edoardo Alessandro Pulixi, Graziana, Lupattelli, Vanessa, Bianconi, Riccardo, Alcidi, Domenico, Girelli, Fabiana, Busti, Giacomo, Marchi, Mario, Barbagallo, Ligia, Dominguez, Vincenza, Beneduce, Federica, Cacioppo, Salvatore, Corrao, Giuseppe, Natoli, Salvatore, Mularo, Massimo, Raspanti, Christiano, Argano, Marco, Zoli, Maria Laura Matacena, Giuseppe, Orio, Eleonora, Magnolfi, Giovanni, Serafini, Angelo, Simili, Giuseppe, Palasciano, Maria Ester Modeo, Carla Di Gennaro, Maria Domenica Cappellini, Giovanna, Fabio, Margherita Migone De Amicis, Giacomo De Luca, Natalia, Scaramellini, Matteo, Cesari, Paolo Dionigi Rossi, Sarah, Damanti, Marta, Clerici, Simona, Leoni, Alessandra Danuta Di Mauro, Antonio Di Sabatino, Emanuela, Miceli, Marco Vincenzo Lenti, Martina, Pisati, Costanza Caccia Dominioni, Roberto, Pontremoli, Valentina, Beccati, Giulia, Nobili, Giovanna, Leoncini, Luigi, Anastasio, Lucia, Sofia, Maria, Carbone, Francesco, Cipollone, Maria Teresa Guagnano, Ilaria, Rossi, Gerardo, Mancuso, Daniela, Calipari, Mosè, Bartone, Giuseppe, Delitala, Maria, Berria, Alessandro, Delitala, Maurizio, Muscaritoli, Alessio, Molfino, Enrico, Petrillo, Antonella, Giorgi, Christian, Gracin, Giuseppe, Zuccalà, Gabriella, D’Aurizio, Giuseppe, Romanelli, Andrea, Volpini, Daniela, Lucente, Antonio, Picardi, Umberto Vespasiani Gentilucci, Paolo, Gallo, Giuseppe, Bellelli, Maurizio, Corsi, Cesare, Antonucci, Chiara, Sidoli, Giulia, Principato, Franco, Arturi, Elena, Succurro, Bruno, Tassone, Federica, Giofrè, Maria Antonietta Bleve, Teresa De Falco, Fabrizio, Fabris, Irene, Bertozzi, Giulia, Bogoni, Maria Victoria Rabuini, Tancredi, Prandini, Manfredini, Roberto, Fabbian, Fabio, Benedetta, Boari, Alfredo De Giorgi, Ruana, Tiseo, Giuseppe, Paolisso, Maria Rosaria Rizzo, Claudia, Catalano, Claudio, Borghi, Enrico, Strocchi, Eugenia, Ianniello, Mario, Soldati, Silvia, Schiavone, Alessio, Bragagni, Carlo, Sabbà, Francesco Saverio Vella, Patrizia, Suppressa, Giovanni Michele De Vincenzo, Alessio, Comitangelo, Emanuele, Amoruso, Carlo, Custodero, Luigi, Fenoglio, Andrea, Falcetta, Fracanzani, Anna L., Silvia, Tiraboschi, Annalisa, Cespiati, Giovanna, Oberti, Giordano, Sigon, Flora, Peyvandi, Giulia, Colombo, Pasquale, Agosti, Valter, Monzani, Valeria, Savojardo, Giuliana, Ceriani, Giada, Pallini, Fabrizio, Montecucco, Luciano, Ottonello, Lara, Caserza, Giulia, Vischi, Nicola Lucio Liberato, Tiziana, Tognin, Francesco, Purrello, Antonino Di Pino, Salvatore, Piro, Maria Stella Pisciotta, Francesco Baffa Bellucci, Stefano, Buffelli, Giuseppe, Montrucchio, Paolo, Peasso, Edoardo, Favale, Cesare, Poletto, Carl, Margaria, Maura, Sanino, Luigina, Guasti, Luana, Castiglioni, Andrea, Maresca, Alessandro, Squizzato, Leonardo, Campiotti, Alessandra, Grossi, Roberto Davide Diprizio, Marco, Bertolotti, Giulia, Lancellotti, Maria Vittoria Libbra, Matteo, Galassi, Yasmine, Grassi, Alessio, Greco, Angela, Sciacqua, Maria, Perticone, Rosa, Battaglia, Raffaele, Maio, Vincenzo, Stanghellini, Eugenio, Ruggeri, Sara del Vecchio, Andrea, Salvi, Roberto, Leonardi, Giampaolo, Damiani, William, Capeci, Massimo, Mattioli, Giuseppe Pio Martino, Lorenzo, Biondi, Pietro, Pettinari, Riccardo, Ghio, Anna Dal Col, Salvatore, Minisola, Luciano, Colangelo, Mirella, Cilli, Giancarlo, Labbadia, Antonella, Afeltra, Benedetta, Marigliano, Maria Elena Pipita, Pietro, Castellino, Luca, Zanoli, Alfio, Gennaro, Agostino, Gaudio, Valter, Saracco, Marisa, Fogliati, Carlo, Bussolino, Francesca, Mete, Miriam, Gino, Carlo, Vigorito, Antonio, Cittadini, Guido, Moreo, Silvia, Prolo, Gloria, Pina, Alberto, Ballestrero, Fabio, Ferrando, Roberta, Gonella, Domenico, Cerminara, Sergio, Berra, Simonetta, Dassi, Maria Cristina Nava, Bruno, Graziella, Stefano, Baldassarre, Salvatore, Fragapani, Gabriella, Gruden, Giorgio, Galanti, Gabriele, Mascherini, Cristian, Petri, Laura, Stefani, Margherita, Girino, Valeria, Piccinelli, Francesco, Nasso, Vincenza, Gioffrè, Maria, Pasquale, Leonardo, Sechi, Cristiana, Catena, Gianluca, Colussi, Alessandro, Cavarape, Andea Da Porto, Nicola, Passariello, Luca, Rinaldi, Franco, Berti, Giuseppe, Famularo, Patrizia, Tarsitani, Roberto, Castello, Michela, Pasino, Gian Paolo Ceda, Marcello Giuseppe Maggio, Simonetta, Morganti, Andrea, Artoni, Margherita, Grossi, Stefano Del Giacco, Davide, Firinu, Giulia, Costanzo, Giacomo, Argiolas, Giuseppe, Montalto, Anna, Licata, Filippo Alessandro Montalto, Francesco, Corica, Giorgio, Basile, Antonino, Catalano, Federica, Bellone, Concetto, Principato, Lorenzo, Malatino, Benedetta, Stancanelli, Valentina, Terranova, Salvatore Di Marca, Rosario Di Quattro, Lara La Malfa, Rossella, Caruso, Patrizia, Mecocci, Carmelinda, Ruggiero, Virginia, Boccardi, Tiziana, Meschi, Andrea, Ticinesi, Antonio, Nouvenne, Pietro, Minuz, Luigi, Fondrieschi, Giandomenico Nigro Imperiale, Mario, Pirisi, Gian Paolo Fra, Daniele, Sola, Mattia, Bellan, Massimo, Porta, Piero, Riva, Roberto, Quadri, Erica, Larovere, Marco, Novelli, Giorgio, Scanzi, Caterina, Mengoli, Stella, Provini, Laura, Ricevuti, Emilio, Simeone, Rosa, Scurti, Fabio, Tolloso, Roberto, Tarquini, Alice, Valoriani, Silvia, Dolenti, Giulia, Vannini, Riccardo, Volpi, Pietro, Bocchi, Alessandro, Vignali, Sergio, Harari, Chiara, Lonati, Federico, Napoli, Italia, Aiello, Raffaele, Landolfi, Massimo, Montalto, Antonio, Mirijello, Teresa, Salvatore, Lucio, Monaco, Carmen, Ricozzi, Alberto, Pilotto, Ilaria, Indiano, and Federica, Gandolfo.
Subjects: Aging, Comorbidity indices, Health (social science), Socio-culturale, Multimorbidity, Comorbidity, Chronic disease, Hospitalization, Italy, Older adults, Chronic disease, Comorbidity indices, Excessive polypharmacy, Mortality, Multimorbidity, Older adults, Excessive polypharmacy, Polypharmacy, Humans, LS4_4, Geriatrics and Gerontology, Mortality, Gerontology, Aged
Abstract: Comorbidity indexes were designed in order to measure how the disease burden of a patient is related to different clinical outcomes such as mortality, especially in older and intensively treated people. Charlson's Comorbidity Index (CCI) is the most widely used rating system, based on diagnoses, but when this information is not available therapy-based comorbidity indices (TBCI) are an alternative: among them, Drug Derived Complexity Index (DDCI), Medicines Comorbidity Index (MCI), and Chronic Disease Score (CDS) are available.This study assessed the predictive power for 1-year mortality of these comorbidity indices and polypharmacy.Survival analysis and Receiver Operating Characteristic (ROC) analysis were conducted on three Italian cohorts: 2,389 nursing home residents (Korian), 4,765 and 633 older adults admitted acutely to geriatric or internal medicine wards (REPOSI and ELICADHE).Cox's regression indicated that the highest levels of the CCI are associated with an increment of 1-year mortality risk as compared to null score for all the three samples. DDCI and excessive polypharmacy gave similar results but MCI and CDS were not always statistically significant. The predictive power with the ROC curve of each comorbidity index was poor and similar in all settings.On the whole, comorbidity indices did not perform well in our three settings, although the highest level of each index was associated with higher mortality.
Published: 2022

47. Sequential rituximab and mepolizumab in eosinophilic granulomatosis with polyangiitis (EGPA): a European multicentre observational study

Author: Alessandra, Bettiol, Maria Letizia, Urban, Federica, Bello, Davide, Fiori, Irene, Mattioli, Giuseppe, Lopalco, Florenzo, Iannone, Allyson, Egan, Lorenzo, Dagna, Marco, Caminati, Simone, Negrini, Elena, Bargagli, Marco, Folci, Franco, Franceschini, Roberto, Padoan, Oliver, Flossmann, Roser, Solans, Jan, Schroeder, Marc, André, Laura, Moi, Paola, Parronchi, Dario, Roccatello, Savino, Sciascia, David, Jayne, Domenico, Prisco, Augusto, Vaglio, Giacomo, Emmi, and Paola, Toniati
Subjects: Biological Therapy, Rheumatology, Epidemiology, Immunology, Granulomatosis with Polyangiitis, Systemic vasculitis, Immunology and Allergy, Humans, Churg-Strauss Syndrome, Antibodies, Monoclonal, Humanized, Rituximab, General Biochemistry, Genetics and Molecular Biology
Published: 2022

48. Multiple Sclerosis: The Role of Cytokines in Pathogenesis and in Therapies

Author: Mario Milco D’Elios, Domenico Prisco, and Amedeo Amedei
Subjects: multiple sclerosis, cytokines, T helper cells (Th), Interleukin-17 (IL-17), Interferons (IFNs), Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract: Multiple sclerosis, the clinical features and pathological correlate for which were first described by Charcot, is a chronic neuroinflammatory disease with unknown etiology and variable clinical evolution. Although neuroinflammation is a descriptive denominator in multiple sclerosis based on histopathological observations, namely the penetration of leukocytes into the central nervous system, the clinical symptoms of relapses, remissions and progressive paralysis are the result of losses of myelin and neurons. In the absence of etiological factors as targets for prevention and therapy, the definition of molecular mechanisms that form the basis of inflammation, demyelination and toxicity for neurons have led to a number of treatments that slow down disease progression in specific patient cohorts, but that do not cure the disease. Current therapies are directed to block the immune processes, both innate and adaptive, that are associated with multiple sclerosis. In this review, we analyze the role of cytokines in the multiple sclerosis pathogenesis and current/future use of them in treatments of multiple sclerosis.
Published: 2012
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49. Sirt1 Protects against Oxidative Stress-Induced Apoptosis in Fibroblasts from Psoriatic Patients: A New Insight into the Pathogenetic Mechanisms of Psoriasis

Author: Matteo Becatti, Victoria Barygina, Amanda Mannucci, Giacomo Emmi, Domenico Prisco, Torello Lotti, Claudia Fiorillo, and Niccolò Taddei
Subjects: SIRT1, MAPK, oxidative stress, psoriasis, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract: Psoriasis, a multisystem chronic disease characterized by abnormal keratinocyte proliferation, has an unclear pathogenesis where systemic inflammation and oxidative stress play mutual roles. Dermal fibroblasts, which are known to provide a crucial microenvironment for epidermal keratinocyte function, represented the selected experimental model in our study which aimed to clarify the potential role of SIRT1 in the pathogenetic mechanisms of the disease. We firstly detected the presence of oxidative stress (lipid peroxidation and total antioxidant capacity), significantly reduced SIRT1 expression level and activity, mitochondrial damage and apoptosis (caspase-3, -8 and -9 activities) in psoriatic fibroblasts. Upon SIRT1 activation, redox balance was re-established, mitochondrial function was restored and apoptosis was no longer evident. Furthermore, we examined p38, ERK and JNK activation, which was strongly altered in psoriatic fibroblasts, in response to SIRT1 activation and we measured caspase-3 activity in the presence of specific MAPK inhibitors demonstrating the key role of the SIRT1 pathway against apoptotic cell death via MAPK modulation. Our results clearly demonstrate the involvement of SIRT1 in the protective mechanisms related to fibroblast injury in psoriasis. SIRT1 activation exerts an active role in restoring both mitochondrial function and redox balance via modulation of MAPK signaling. Hence, SIRT1 can be proposed as a specific tool for the treatment of psoriasis.
Published: 2018
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50. Kidney Disease Management in the Hospital Setting: A Focus on Inappropriate Drug Prescriptions in Older Patients

Author: Vincenzo, Arcoraci, Maria Antonietta Barbieri, Michelangelo, Rottura, Alessandro, Nobili, Giuseppe, Natoli, Christiano, Argano, Giovanni, Squadrito, Francesco, Squadrito, Salvatore, Corrao, Domenico, Prisco, Elena, Silvestri, Giacomo, Emmi, Alessandra, Bettiol, Irene, Mattioli, Gianni, Biolo, Michela, Zanetti, Giacomo, Bartelloni, Massimo, Vanoli, Giulia, Grignani, Edoardo Alessandro Pulixi, Graziana, Lupattelli, Vanessa, Bianconi, Riccardo, Alcidi, Domenico, Girelli, Fabiana, Busti, Giacomo, Marchi, Mario, Barbagallo, Ligia, Dominguez, Vincenza, Beneduce, Federica, Cacioppo, Massimo, Raspanti, Marco, Zoli, Maria Laura Matacena, Giuseppe, Orio, Eleonora, Magnolfi, Giovanni, Serafini, Angelo, Simili, Giuseppe, Palasciano, Maria Ester Modeo, Carla Di Gennaro, Maria Domenica Cappellini, Giovanna, Fabio, Margherita Migone De Amicis, Giacomo De Luca, Natalia, Scaramellini, Matteo, Cesari, Paolo Dionigi Rossi, Sarah, Damanti, Marta, Clerici, Simona, Leoni, Alessandra Danuta Di Mauro, Antonio Di Sabatino, Emanuela, Miceli, Marco Vincenzo Lenti, Martina, Pisati, Costanza Caccia Dominioni, Roberto, Pontremoli, Valentina, Beccati, Giulia, Nobili, Giovanna, Leoncini, Luigi, Anastasio, Maria, Carbone, Francesco, Cipollone, Maria Teresa Guagnano, Ilaria, Rossi, Gerardo, Mancuso, Daniela, Calipari, Mosè, Bartone, Giuseppe, Delitala, Maria, Berria, Alessandro, Delitala, Maurizio, Muscaritoli, Alessio, Molfino, Enrico, Petrillo, Antonella, Giorgi, Christian, Gracin, Giuseppe, Zuccalà, Gabriella, D’Aurizio, Giuseppe, Romanelli, Alessandra, Marengoni, Andrea, Volpini, Daniela, Lucente, Antonio, Picardi, Umberto Vespasiani Gentilucci, Paolo, Gallo, Giuseppe, Bellelli, Maurizio, Corsi, Cesare, Antonucci, Chiara, Sidoli, Giulia, Principato, Franco, Arturi, Elena, Succurro, Bruno, Tassone, Federica, Giofrè, Maria Grazia Serra, Maria Antonietta Bleve, Antonio, Brucato, Teresa De Falco, Fabrizio, Fabris, Irene, Bertozzi, Giulia, Bogoni, Maria Victoria Rabuini, Tancredi, Prandini, Manfredini, Roberto, Fabbian, Fabio, Benedetta, Boari, DE GIORGI, Alfredo, Ruana, Tiseo, Giuseppe, Paolisso, Maria Rosaria Rizzo, Claudia, Catalano, Claudio, Borghi, Enrico, Strocchi, Eugenia, Ianniello, Mario, Soldati, Silvia, Schiavone, Alessio, Bragagni, Carlo, Sabbà, Francesco Saverio Vella, Patrizia, Suppressa, Giovanni Michele De Vincenzo, Alessio, Comitangelo, Emanuele, Amoruso, Carlo, Custodero, Luigi, Fenoglio, Andrea, Falcetta, Fracanzani, Anna L., Silvia, Tiraboschi, Annalisa, Cespiati, Giovanna, Oberti, Giordano, Sigon, Flora, Peyvandi, Raffaella, Rossio, Giulia, Colombo, Pasquale, Agosti, Valter, Monzani, Valeria, Savojardo, Giuliana, Ceriani, Francesco, Salerno, Giada, Pallini, Fabrizio, Montecucco, Luciano, Ottonello, Lara, Caserza, Giulia, Vischi, Nicola Lucio Liberato, Tiziana, Tognin, Francesco, Purrello, Antonino Di Pino, Salvatore, Piro, Renzo, Rozzini, Lina, Falanga, Maria Stella Pisciotta, Francesco Baffa Bellucci, Stefano, Buffelli, Giuseppe, Montrucchio, Paolo, Peasso, Edoardo, Favale, Cesare, Poletto, Carl, Margaria, Maura, Sanino, Francesco, Violi, Ludovica, Perri, Luigina, Guasti, Luana, Castiglioni, Andrea, Maresca, Alessandro, Squizzato, Leonardo, Campiotti, Alessandra, Grossi, Roberto Davide Diprizio, Marco, Bertolotti, Chiara, Mussi, Giulia, Lancellotti, Maria Vittoria Libbra, Matteo, Galassi, Yasmine, Grassi, Alessio, Greco, Angela, Sciacqua, Maria, Perticone, Rosa, Battaglia, Raffaele, Maio, Vincenzo, Stanghellini, Eugenio, Ruggeri, Sara del Vecchio, Andrea, Salvi, Roberto, Leonardi, Giampaolo, Damiani, William, Capeci, Massimo, Mattioli, Giuseppe Pio Martino, Lorenzo, Biondi, Pietro, Pettinari, Riccardo, Ghio, Anna Dal Col, Salvatore, Minisola, Luciano, Colangelo, Mirella, Cilli, Giancarlo, Labbadia, Antonella, Afeltra, Benedetta, Marigliano, Maria Elena Pipita, Pietro, Castellino, Luca, Zanoli, Alfio, Gennaro, Agostino, Gaudio, Valter, Saracco, Marisa, Fogliati, Carlo, Bussolino, Francesca, Mete, Miriam, Gino, Carlo, Vigorito, Antonio, Cittadini, Guido, Moreo, Silvia, Prolo, Gloria, Pina, Alberto, Ballestrero, Fabio, Ferrando, Roberta, Gonella, Domenico, Cerminara, Sergio, Berra, Simonetta, Dassi, Maria Cristina Nava, Bruno, Graziella, Stefano, Baldassarre, Salvatore, Fragapani, Gabriella, Gruden, Giorgio, Galanti, Gabriele, Mascherini, Cristian, Petri, Laura, Stefani, Margherita, Girino, Valeria, Piccinelli, Francesco, Nasso, Vincenza, Gioffrè, Maria, Pasquale, Leonardo, Sechi, Cristiana, Catena, Gianluca, Colussi, Alessandro, Cavarape, Andea Da Porto, Nicola, Passariello, Luca, Rinaldi, Franco, Berti, Giuseppe, Famularo, Patrizia, Tarsitani, Roberto, Castello, Michela, Pasino, Gian Paolo Ceda, Marcello Giuseppe Maggio, Simonetta, Morganti, Andrea, Artoni, Margherita, Grossi, Stefano Del Giacco, Davide, Firinu, Giulia, Costanzo, Giacomo, Argiolas, Giuseppe, Montalto, Anna, Licata, Filippo Alessandro Montalto, Francesco, Corica, Giorgio, Basile, Antonino, Catalano, Federica, Bellone, Concetto, Principato, Lorenzo, Malatino, Benedetta, Stancanelli, Valentina, Terranova, Salvatore Di Marca, Rosario Di Quattro, Lara La Malfa, Rossella, Caruso, Patrizia, Mecocci, Carmelinda, Ruggiero, Virginia, Boccardi, Tiziana, Meschi, Andrea, Ticinesi, Antonio, Nouvenne, Pietro, Minuz, Luigi, Fondrieschi, Giandomenico Nigro Imperiale, Mario, Pirisi, Gian Paolo Fra, Daniele, Sola, Mattia, Bellan, Massimo, Porta, Piero, Riva, Roberto, Quadri, Erica, Larovere, Marco, Novelli, Giorgio, Scanzi, Caterina, Mengoli, Stella, Provini, Laura, Ricevuti, Emilio, Simeone, Rosa, Scurti, Fabio, Tolloso, Roberto, Tarquini, Alice, Valoriani, Silvia, Dolenti, Giulia, Vannini, Riccardo, Volpi, Pietro, Bocchi, Alessandro, Vignali, Sergio, Harari, Chiara, Lonati, Federico, Napoli, Italia, Aiello, Raffaele, Landolfi, Massimo, Montalto, Antonio, Mirijello, Silvia, Ghidoni, Teresa, Salvatore, Lucio, Monaco, Carmen, Ricozzi, Alberto, Pilotto, Ilaria, Indiano, Federica, Gandolfo., Arcoraci V., Barbieri M.A., Rottura M., Nobili A., Natoli G., Argano C., Squadrito G., Squadrito F., and Corrao S.
Subjects: medicine.medical_specialty, appropriateness of prescription, prescribing patterns, Renal function, Context (language use), RM1-950, Logistic regression, NO, chemistry.chemical_compound, older patient, Internal medicine, hospital setting, medicine, Pharmacology (medical), LS4_4, Medical prescription, prescribing pattern, appropriateness of prescriptions, chronic kidney disease, hospital setting, older patients, prescribing patterns, real-world data, Original Research, Pharmacology, Creatinine, real-world data, business.industry, Retrospective cohort study, medicine.disease, older patients, appropriateness of prescriptions, chronic kidney disease, chemistry, Observational study, Therapeutics. Pharmacology, business, Kidney disease
Abstract: Aging with multimorbidity and polytherapy are the most significant factors that could led to inappropriate prescribing of contraindicated medications in patients with chronic kidney disease (CKD). The aim of this study was to evaluate the prescriptions of contraindicated drugs in older adults in CKD and to identify their associated factors in a hospital context. An observational retrospective study was carried out considering all patients ≥65 years with at least one serum creatinine value recorded into the REPOSI register into 2010–2016 period. The estimated glomerular filtration rate (eGFR) was applied to identify CKD. A descriptive analysis was performed to compare demographic and clinical characteristics; logistic regression models were used to estimate factors of inappropriate and percentage changes of drug use during hospitalization. A total of 4,713 hospitalized patients were recorded, of which 49.8% had an eGFR 2; the 21.9% were in treatment with at least one inappropriate drug at the time of hospital admission with a decrease of 3.0% at discharge (p = 0.010). The probability of using at least one contraindicated drug was significantly higher in patients treated with more several drugs (OR 1.21, 95% CI 1.16–1.25, p p < 0.001; G5: 19.38, 11.51–32.64, p < 0.001). Low-dose acetylsalicylic acid was the contraindicated drug mainly used at the time of admission, reducing 1.2% at discharge. An overall increase in therapeutic appropriateness in hospitalized older patients with CKD was observed, despite a small percentage of therapeutic inappropriateness at discharge that underlines the need for a closer collaboration with the pharmacologist to improve the drug management.
Published: 2021

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