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1. Early anakinra treatment improves cardiac outcome of multisystem inflammatory syndrome in children, regardless of disease severity

Author

Taddio, A, Della Paolera, S, Abbagnato, L, Agrusti, A, Badolato, R, Biscaro, F, Caorsi, R, Consolaro, A, Dellepiane, Rm, Fabi, M, Floretta, I, Gattorno, M, Giangreco, M, La Torre, F, Maggio, Mc, Mambelli, L, Mauro, A, Mastrolia, Mv, Meneghel, A, Montin, D, Ricci, F, Simonini, G, Smarrazzo, A, Sottile, R, Stucchi, S, Tardi, M, Verdoni, L, Zuccotti, G, Zunica, F, Ravelli, A, Cattalini, M, Adamoli, P, Alberelli, Mc, Alessio, M, Alizzi, C, Barone, P, Baselli, La, Bennato, V, Boscarol, G, Bossi, G, Campana, A, Campus, S, Carone, M, Civino, A, Conti, G, Dei Rossi, E, Del Giudice, E, Dell’Anna, A, De Luca, M, Felici, E, Filocamo, G, Foschini, Ml, Gallizzi, R, Giordano, S, Lanciotti, S, Lattanzi, B, Lazzerotti, A, Licciardi, F, Manerba, A, Mannarino, S, Marino, A, Marolda, A, Martelli, L, Martini, G, Mazza, A, Minasi, D, Miniaci, A, Minoia, F, Olivieri, A, Pennoni, G, Pignataro, R, Rigante, Donato, Rossi, M, Santagati, C, Moliani, M, Sonego, S, Sperlì, D, Teruzzi, Bl, Tierno, E, Utytatnikova, T, Valentini, Piero, Vergine, G &amp, Italian Society of Pediatric Rheumatology, (ReumaPed), Rigante D (ORCID:0000-0001-7032-7779), Valentini P (ORCID:0000-0001-6095-9510), Taddio, A, Della Paolera, S, Abbagnato, L, Agrusti, A, Badolato, R, Biscaro, F, Caorsi, R, Consolaro, A, Dellepiane, Rm, Fabi, M, Floretta, I, Gattorno, M, Giangreco, M, La Torre, F, Maggio, Mc, Mambelli, L, Mauro, A, Mastrolia, Mv, Meneghel, A, Montin, D, Ricci, F, Simonini, G, Smarrazzo, A, Sottile, R, Stucchi, S, Tardi, M, Verdoni, L, Zuccotti, G, Zunica, F, Ravelli, A, Cattalini, M, Adamoli, P, Alberelli, Mc, Alessio, M, Alizzi, C, Barone, P, Baselli, La, Bennato, V, Boscarol, G, Bossi, G, Campana, A, Campus, S, Carone, M, Civino, A, Conti, G, Dei Rossi, E, Del Giudice, E, Dell’Anna, A, De Luca, M, Felici, E, Filocamo, G, Foschini, Ml, Gallizzi, R, Giordano, S, Lanciotti, S, Lattanzi, B, Lazzerotti, A, Licciardi, F, Manerba, A, Mannarino, S, Marino, A, Marolda, A, Martelli, L, Martini, G, Mazza, A, Minasi, D, Miniaci, A, Minoia, F, Olivieri, A, Pennoni, G, Pignataro, R, Rigante, Donato, Rossi, M, Santagati, C, Moliani, M, Sonego, S, Sperlì, D, Teruzzi, Bl, Tierno, E, Utytatnikova, T, Valentini, Piero, Vergine, G &amp, Italian Society of Pediatric Rheumatology, (ReumaPed), Rigante D (ORCID:0000-0001-7032-7779), and Valentini P (ORCID:0000-0001-6095-9510)

Abstract

Objective: The main aim of this study was to define the best treatment option for multisystem inflammatory syndrome in children (MIS-C) and to analyse the role of anakinra. Methods: This is a multicentre retrospective cohort study. Patients were treated according to the attending physician's decision. The patients were divided into four groups on the basis of the first treatment at time of admittance: (i) IVIG, (ii) IVIG and methylprednisolone (≤2 mg/kg/day), (iii) IVIG with high-dose methylprednisolone (>2 mg/kg/day) and (iv) anakinra with or without IVIG and/or methylprednisolone. Primary outcomes were defined as the presence of at least one of the following features: death, the failure of initial treatment, meaning the need for additional treatment for clinical worsening and cardiac involvement at the end of follow-up. Results: Two hundred thirty-nine patients were recruited. At univariate analysis, persistent heart involvement at discharge was more frequent in those not receiving anakinra as initial treatment (3/21 vs 66/189; P = 0.047). After comparisons between the four treatment regimens, adjusting for the propensity score, we observed that early treatment with anakinra was associated with a lower probability of developing persistent heart disease at the end of follow-up (odds ratio: 0.6; 95% CI: 0.4-1.0). Conclusion: We report that early treatment with anakinra is safe and very effective in patients with severe MIS-C. In addition, our study suggests that early treatment with anakinra is the most favourable option for patients with a higher risk of developing a severe disease outcome.

Published
2024

2. Revisiting the semiclassical gravity scenario for gravitational collapse

Author

Barcelo, C., Liberati, S., Sonego, S., and Visser, M.

Subjects
General Relativity and Quantum Cosmology
Abstract

The existence of extremely dark and compact astronomical bodies is by now a well established observational fact. On the other hand, classical General Relativity predicts the existence of black holes which fit very well with the observations, but do lead to important conceptual problems. In this contribution we ask ourselves the straightforward question: Are the dark and compact objects that we have observational evidence for black holes in the sense of General Relativity? By revising the semiclassical scenario of stellar collapse we find out that as the result of a collapse some alternative objects could be formed which might supplant black holes., Comment: 8 pages, proceedings of the ERE2008, aipproc style

Published
2009
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3. Optical geometry for gravitational collapse and Hawking radiation

Author

Sonego, S., Almergren, J., and Abramowicz, M.

Subjects
General Relativity and Quantum Cosmology
Abstract

The notion of optical geometry, introduced more than twenty years ago as a formal tool in quantum field theory on a static background, has recently found several applications to the study of physical processes around compact objects. In this paper we define optical geometry for spherically symmetric gravitational collapse, with the purpose of extending the current formalism to physically interesting spacetimes which are not conformally static. The treatment is fully general but, as an example, we also discuss the special case of the Oppenheimer-Snyder model. The analysis of the late time behaviour shows a close correspondence between the structure of optical spacetime for gravitational collapse and that of flat spacetime with an accelerating boundary. Thus, optical geometry provides a natural physical interpretation for derivations of the Hawking effect based on the ``moving mirror analogy.'' Finally, we briefly discuss the issue of back-reaction in black hole evaporation and the information paradox from the perspective of optical geometry., Comment: 13 pages, 10 figures, aps, revtex, To be published in PRD

Published
2000
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4. Nonthermal nature of incipient extremal black holes

Author

Liberati, S., Rothman, T., and Sonego, S.

Subjects
General Relativity and Quantum Cosmology
Abstract

We examine particle production from spherical bodies collapsing into extremal Reissner-Nordstr\"om black holes. Kruskal coordinates become ill-defined in the extremal case, but we are able to find a simple generalization of them that is good in this limit. The extension allows us to calculate the late-time worldline of the center of the collapsing star, thus establishing a correspondence with a uniformly accelerated mirror in Minkowski spacetime. The spectrum of created particles associated with such uniform acceleration is nonthermal, indicating that a temperature is not defined. Moreover, the spectrum contains a constant that depends on the history of the collapsing object. At first sight this points to a violation of the no-hair theorems; however, the expectation value of the stress-energy-momentum tensor is zero and its variance vanishes as a power law at late times. Hence, both the no-hair theorems and the cosmic censorship conjecture are preserved. The power-law decay of the variance is in distinction to the exponential fall-off of a nonextremal black hole. Therefore, although the vanishing of the stress tensor's expectation value is consistent with a thermal state at zero temperature, the incipient black hole does not behave as a thermal object at any time and cannot be regarded as the thermodynamic limit of a nonextremal black hole, regardless of the fact that the final product of collapse is quiescent., Comment: 13 pages, 2 epsf figures, RevTeX 3. Minor changes, version published in PRD

Published
2000
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5. On Relativistic Perturbations of Second and Higher Order

Author

Bruni, M., Matarrese, S., Mollerach, S., and Sonego, S.

Subjects
General Relativity and Quantum Cosmology, Astrophysics
Abstract

We present the results of a study of the gauge dependence of spacetime perturbations. In particular, we consider gauge invariance in general, we give a generating formula for gauge transformations to an arbitrary order n, and explicit transformation rules at second order., Comment: 6 pages, latex, with special style included, Proceedings of the 12th Italian Conference on General Relativity and Gravitational Physics

Published
1996

6. Defining Kawasaki disease and pediatric inflammatory multisystem syndrome-temporally associated to SARS-CoV-2 infection during SARS-CoV-2 epidemic in Italy: results from a national, multicenter survey

Author

Cattalini, M, Della Paolera, S, Zunica, F, Bracaglia, C, Giangreco, M, Verdoni, L, Meini, A, Sottile, R, Caorsi, R, Zuccotti, G, Fabi, M, Montin, D, Meneghel, A, Consolaro, A, Dellepiane, Rm, Maggio, Mc, La Torre, F, Marchesi, A, Simonini, G, Villani, A, Cimaz, R, Ravelli, A, Taddio, A, Adamoli, P, Alberelli, Mc, Alizzi, C, Barone, P, Bennato, V, Biscaro, F, Bossi, G, Campana, A, Carone, M, Civino, A, Conti, Giorgio, Dei Rossi, E, Del Giudice, E, Dell'Anna, A, De Luca, M, Felici, E, Filocamo, G, Floretta, I, Foschini, Ml, Lanari, M, Lattanzi, B, Lazzerotti, A, Licciardi, F, Manerba, A, Mannarino, S, Marino, A, Marolda, A, Martelli, L, Martini, G, Mauro, A, Mastrolia, Mv, Mazza, A, Miniaci, A, Minoia, F, Olivieri, A, Pennoni, G, Pignataro, R, Ricci, F, Rigante, Donato, Rossi, M, Santagati, C, Soliani, M, Sonego, S, Sperlì, D, Stucchi, S, Teruzzi, B, Tierno, E, Utytatnikova, T, Valentini, Piero, Vergine, G, Conti G (ORCID:0000-0002-8566-9365), Rigante D (ORCID:0000-0001-7032-7779), Valentini P (ORCID:0000-0001-6095-9510), Cattalini, M, Della Paolera, S, Zunica, F, Bracaglia, C, Giangreco, M, Verdoni, L, Meini, A, Sottile, R, Caorsi, R, Zuccotti, G, Fabi, M, Montin, D, Meneghel, A, Consolaro, A, Dellepiane, Rm, Maggio, Mc, La Torre, F, Marchesi, A, Simonini, G, Villani, A, Cimaz, R, Ravelli, A, Taddio, A, Adamoli, P, Alberelli, Mc, Alizzi, C, Barone, P, Bennato, V, Biscaro, F, Bossi, G, Campana, A, Carone, M, Civino, A, Conti, Giorgio, Dei Rossi, E, Del Giudice, E, Dell'Anna, A, De Luca, M, Felici, E, Filocamo, G, Floretta, I, Foschini, Ml, Lanari, M, Lattanzi, B, Lazzerotti, A, Licciardi, F, Manerba, A, Mannarino, S, Marino, A, Marolda, A, Martelli, L, Martini, G, Mauro, A, Mastrolia, Mv, Mazza, A, Miniaci, A, Minoia, F, Olivieri, A, Pennoni, G, Pignataro, R, Ricci, F, Rigante, Donato, Rossi, M, Santagati, C, Soliani, M, Sonego, S, Sperlì, D, Stucchi, S, Teruzzi, B, Tierno, E, Utytatnikova, T, Valentini, Piero, Vergine, G, Conti G (ORCID:0000-0002-8566-9365), Rigante D (ORCID:0000-0001-7032-7779), and Valentini P (ORCID:0000-0001-6095-9510)

Abstract

Background: There is mounting evidence on the existence of a Pediatric Inflammatory Multisystem Syndrome temporally associated to SARS-CoV-2 infection (PIMS-TS), sharing similarities with Kawasaki Disease (KD). The main outcome of the study were to better characterize the clinical features and the treatment response of PIMS-TS and to explore its relationship with KD determining whether KD and PIMS are two distinct entities. Methods: The Rheumatology Study Group of the Italian Pediatric Society launched a survey to enroll patients diagnosed with KD (Kawasaki Disease Group – KDG) or KD-like (Kawacovid Group - KCG) disease between February 1st 2020, and May 31st 2020. Demographic, clinical, laboratory data, treatment information, and patients’ outcome were collected in an online anonymized database (RedCAP®). Relationship between clinical presentation and SARSCoV-2 infection was also taken into account. Moreover, clinical characteristics of KDG during SARS-CoV-2 epidemic (KDG-CoV2) were compared to Kawasaki Disease patients (KDG-Historical) seen in three different Italian tertiary pediatric hospitals (Institute for Maternal and Child Health, IRCCS “Burlo Garofolo”, Trieste; AOU Meyer, Florence;IRCCS Istituto Giannina Gaslini, Genoa) from January 1st 2000 to December 31st 2019. Chi square test or exact Fisher test and non-parametric Wilcoxon Mann-Whitney test were used to study differences between two groups. Results: One-hundred-forty-nine cases were enrolled, (96 KDG and 53 KCG). KCG children were significantly older and presented more frequently from gastrointestinal and respiratory involvement. Cardiac involvement was more common in KCG, with 60,4% of patients with myocarditis. 37,8% of patients among KCG presented hypotension/ non-cardiogenic shock. Coronary artery abnormalities (CAA) were more common in the KDG. The risk of ICU admission were higher in KCG. Lymphopenia, higher CRP levels, elevated ferritin and troponin-T characterized KCG. KDG received more freque

Published
2021

20. Defining Kawasaki disease and pediatric inflammatory multisystem syndrome-temporally associated to SARS-CoV-2 infection during SARS-CoV-2 epidemic in Italy: results from a national, multicenter survey

Author

Cattalini M, Della Paolera S, Zunica F, Bracaglia C, Giangreco M, Verdoni L, Meini A, Sottile R, Caorsi R, Zuccotti G, Fabi M, Montin D, Meneghel A, Consolaro A, Dellepiane RM, Maggio MC, La Torre F, Marchesi A, Simonini G, Villani A, Cimaz R, Ravelli A, Taddio A Maria Concetta Alberelli: UOC Pediatria, Marche-Nord, Clotilde Alizzi: Department of Health Promotion Sciences Maternal and Infantile Care, Internal Medicine and Medical Specialities 'G. D’Alessandro', University of Palermo, Palermo Italy, Patrizia Barone: Unità Operativa Complessa di Broncopneumologia Pediatrica AOU 'Policlinico - Vittorio Emanuele Via Santa Sofia 78 Catania, Lucia Augusta Baselli: Pediatric Intermediate Care Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan Italy, Veronica Bennato: U. O. Pediatria, Ospedale A, Manzoni Lecco, Francesca Biscaro: UOC Pediatria, Ospedale Ca’ Foncello, Treviso, Grazia Bossi: UOC Pediatria, Fondazione IRCCS Policlinico San Matteo, Pavia Italy, Andrea Campana: Bambino Gesù Children’s Hospital, Rome Italy, Maurizio Carone: UO Malattie Infettive, Ospedale Pediatrico ‘Giovanni XXIII’, Bari Italy, Adele Civino: U. O. C. Pediatria P. O. Vito Fazzi, Lecce, Giovanni Conti: Nefrologia e Reumatologia Pediatrica con Dialisi, Azienda Ospedaliero-Universitario 'G. Martino', Eleonora Dei Rossi: University of Trieste, Trieste Italy, Emanuela Del Giudice: Department of Maternal Infantile and Urological Sciences, Sapeinza University of Rome, Polo Pontini, Alice Dell’Anna: U. O. C. Pediatria P. O. Vito Fazzi Lecce, Maia De Luca: Bambino Gesù Children’s Hospital, Piazza S. Onofrio n. 4, 00165 Rome, Italy, Enrico Felici: Pediatric and Pediatric Emergency Unit, The Children Hospital, AO SS Antonio e Biago e C. Arrigo, Alessandria Italy, Giovanni Filocamo: Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, Milano, Ilenia Floretta: Pediatria, Ospedale Santa Chiara, Trento Italy, Maria Loreta Foschini: SC Pediatria, PO SAN MICHELE AOBrotzu, Cagliari Italy, Marcello Lanari: Department of Pediatrics, University of Bologna, IRCCS S. Orsola-Malpighi Hospital, Bologna Italy, Bianca Lattanzi: SOD Pediatria, Ospedali Riuniti, Ancona Italy, Alessandra Lazzerotti: Clinica Pediatrica, Università Milano Bicocca, Fondazione MBBM - onlus c/o Ospedale San Gerardo, Monza Italy, Francesco Licciardi: Department of Pediatrics and Public Health, University of Turin, Turin Italy, Alessandra Manerba: Child Cardiology, ASST Spedali Civili di Brescia and University of Brescia, Brescia Italy, Savina Mannarino: Division of Cardiology, Children’s Hospital V Buzzi, ASST FBF Sacco, Achille Marino: Department of Pediatrics, Desio Hospital, ASST Monza, Desio Italy, Agostina Marolda: Pediatrics and Neonatology Dipartment, ASST Ovest Milanese, 'G. Fornaroli' Hospital, Magenta Milan, Laura Martelli: Paediatric Department, Hospital Papa Giovanni XXIII, Bergamo Italy, Giorgia Martini, Department of Woman’s and Child’s Health, University of Padova, Padua Italy, Angela Mauro: Department of Paediatrics, Emergency Department, Santobono-Pausilipon Children’s Hospital, Naples, Italy. Maria Vincenza Mastrolia: Pediatric Rheumatology Unit, AOU Meyer, University of Florence, Florence, Italy. Angelo Mazza: Paediatric Department, Angela Miniaci: Clinica Pediatrica, Reumatologia, Azienda Ospedaliero-Universitaria di Bologna, Francesca Minoia: Fondazione IRCCS Cà Granda, Alma Olivieri: Dipartimento della donna, del bambino e di chirurgia generale e specialistica, Università della Campania, 'L Vanvitelli, Napoli, Guido Pennoni: Dipartimento Materno-Infantile, Gubbio-Gualdo Tadino, Italy, Rossana Pignataro: UOC Pediatria e Neonatologia, ASST Lodi, Lodi, Francesca Ricci, Clinica Pediatrica, ASST Spedali Civili di Brescia e Università degli Studi di Brescia, Donato Rigante: Department of Pediatrics, Univarsità Cattolica Sacro Cuore, Matilde Rossi: UOC di Pediatrai e Neonatologia, Ospedale di Macerata, Macerata, Claudia Santagati: Dipartimento di Pediatria, Ospedale di Rovigo, Rovigo, Martina Soliani: Pediatria ASST Cremona, Italy, Silvia Sonego: University of Trieste, Domenico Sperlì: UOC di Pediatria, S. O. 'Annunziata' - A. O. di Cosenza, Sara Stucchi: Maternal and Child Health, Division of Paediatrics, ASST Grande Ospedale Metropolitano Niguarda, Milano Italy, Barbara Teruzzi: Maternal and Child Health, Elpidio Tierno: UOC di Pediatria, Dipartimento della Salute della Donna e del Bambin, AORN 'Sant’Anna e San Sebastiano'- Caserta, Tatiana Utytatnikova: Dipartimento Materno-Infantile, Pediatria, ASST Bergamo-EST, Seriate Bergamo, Piero Valentini, Department of Pediatrics, Gianluca Vergine, UOC Pediatria Rimini, Ospedale Infermi, ASL Romagna, Rimini Italy., Cattalini, Marco, Della Paolera, Sara, Zunica, Fiammetta, Bracaglia, Claudia, Giangreco, Manuela, Verdoni, Lucio, Meini, Antonella, Sottile, Rita, Caorsi, Roberta, Zuccotti, Gianvincenzo, Fabi, Marianna, Montin, Davide, Meneghel, Alessandra, Consolaro, Alessandro, Dellepiane, Rosa Maria, Maggio, Maria Cristina, La Torre, Francesco, Marchesi, Alessandra, Simonini, Gabriele, Villani, Alberto, Cimaz, Rolando, Ravelli, Angelo, Taddio, Andrea, Cattalini, M, Della Paolera, S, Zunica, F, Bracaglia, C, Giangreco, M, Verdoni, L, Meini, A, Sottile, R, Caorsi, R, Zuccotti, G, Fabi, M, Montin, D, Meneghel, A, Consolaro, A, Dellepiane, Rm, Maggio, Mc, La Torre, F, Marchesi, A, Simonini, G, Villani, A, Cimaz, R, Ravelli, A, Taddio, A Maria Concetta Alberelli: UOC Pediatria, Marche-Nord, Clotilde Alizzi: Department of Health Promotion Sciences Maternal and Infantile, Care, Internal Medicine and Medical Specialities 'G., D’Alessandro', University of, Palermo, Palermo, Italy, Patrizia Barone: Unità Operativa Complessa di Broncopneumologia Pediatrica AOU 'Policlinico, - Vittorio Emanuele Via Santa Sofia 78 Catania, Lucia Augusta Baselli: Pediatric Intermediate Care, Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore, Policlinico, Milan, Italy, Veronica Bennato: U. O., Pediatria, Ospedale, A, Manzoni, Lecco, Francesca Biscaro: UOC, Pediatria, Ospedale Ca’, Foncello, Treviso, Grazia Bossi: UOC, Pediatria, Fondazione IRCCS Policlinico San, Matteo, Pavia, Italy, Andrea Campana: Bambino Gesù Children’s, Hospital, Rome, Italy, Maurizio Carone: UO Malattie, Infettive, Ospedale Pediatrico ‘Giovanni, Xxiii’, Bari, Italy, Adele Civino: U. O. C. Pediatria P. O. Vito Fazzi, Lecce, Giovanni Conti: Nefrologia e Reumatologia Pediatrica con Dialisi, Azienda Ospedaliero-Universitario 'G. Martino', Eleonora Dei Rossi: University of, Trieste, Trieste, Italy, Emanuela Del Giudice: Department of Maternal Infantile and Urological, Science, Sapeinza University of, Rome, Polo, Pontini, Alice Dell’Anna: U. O. C. Pediatria P. O., Vito Fazzi Lecce, Maia De Luca: Bambino Gesù Children’s, Hospital, Piazza, S. Onofrio n. 4., 00165, Rome, Italy, Enrico Felici: Pediatric and Pediatric Emergency, Unit, The Children, Hospital, AO SS Antonio e Biago e C., Arrigo, Alessandria, Italy, Giovanni Filocamo: Fondazione IRCCS Cà, Granda, Ospedale Maggiore, Policlinico, Milano, Ilenia Floretta:, Pediatria, Ospedale Santa, Chiara, Trento, Italy, Maria Loreta Foschini: SC, Pediatria, PO SAN MICHELE, Aobrotzu, Cagliari, Italy, Marcello Lanari: Department of, Pediatric, University of, Bologna, IRCCS S., Orsola-Malpighi Hospital, Bologna, Italy, Bianca Lattanzi: SOD, Pediatria, Ospedali, Riuniti, Ancona, Italy, Alessandra Lazzerotti: Clinica, Pediatrica, Università Milano, Bicocca, Fondazione MBBM, - onlus c/o Ospedale San Gerardo, Monza, Italy, Francesco Licciardi: Department of Pediatrics and Public, Health, University of, Turin, Turin, Italy, Alessandra Manerba: Child, Cardiology, ASST Spedali Civili di Brescia and University of, Brescia, Brescia, Italy, Savina Mannarino: Division of, Cardiology, Children’s Hospital, V Buzzi, ASST FBF, Sacco, Achille Marino: Department of, Pediatric, Desio, Hospital, Asst, Monza, Desio, Italy, Agostina Marolda: Pediatrics and Neonatology, Dipartment, ASST Ovest, Milanese, 'G., Fornaroli' Hospital, Magenta, Milan, Laura Martelli: Paediatric, Department, Hospital Papa Giovanni, Xxiii, Bergamo, Italy, Giorgia, Martini, Department of Woman’s and Child’s, Health, University of, Padova, Padua, Italy, Angela Mauro: Department of, Paediatric, Emergency, Department, Santobono-Pausilipon Children’s, Hospital, Naples, Italy., Maria Vincenza Mastrolia: Pediatric Rheumatology Unit, Aou, Meyer, University of, Florence, Florence, Italy., Angelo Mazza: Paediatric Department, Angela Miniaci: Clinica, Pediatrica, Reumatologia, Azienda Ospedaliero-Universitaria di, Bologna, Francesca Minoia: Fondazione IRCCS Cà, Granda, Alma Olivieri: Dipartimento della, Donna, del bambino e di chirurgia generale, e specialistica, Università della, Campania, 'L, Vanvitelli, Napoli, Claudio, Guido Pennoni: Dipartimento, Materno-Infantile, Gubbio-Gualdo Tadino, Italy, Rossana Pignataro: UOC Pediatria, e Neonatologia, Asst, Lodi, Lodi, Francesca, Ricci, Clinica, Pediatrica, ASST Spedali Civili di Brescia, e Università degli Studi di Brescia, Donato Rigante: Department of, Pediatric, Univarsità Cattolica Sacro, Cuore, Matilde Rossi: UOC di Pediatrai, e Neonatologia, Ospedale di, Macerata, Macerata, Claudia Santagati: Dipartimento di, Pediatria, Ospedale di, Rovigo, Rovigo, Martina Soliani: Pediatria ASST Cremona, Italy, Silvia Sonego: University of, Trieste, Domenico Sperlì: UOC di Pediatria, S. O. 'Annunziata' - A. O. di Cosenza, Sara Stucchi: Maternal and Child, Health, Division of, Paediatric, ASST Grande Ospedale Metropolitano, Niguarda, Milano, Italy, Barbara Teruzzi: Maternal and Child, Health, Elpidio Tierno: UOC di, Pediatria, Dipartimento della Salute della Donna, e del Bambin, AORN 'Sant’Anna, e San Sebastiano'- Caserta, Tatiana Utytatnikova: Dipartimento, Materno-Infantile, Pediatria, Asst, Bergamo-EST, Seriate, Bergamo, Piero, Valentini, Department of, Pediatric, Gianluca, Vergine, UOC Pediatria, Rimini, Ospedale, Infermi, Asl, Romagna, Rimini, Italy., Cattalini M., Della Paolera S., Zunica F., Bracaglia C., Giangreco M., Verdoni L., Meini A., Sottile R., Caorsi R., Zuccotti G., Fabi M., Montin D., Meneghel A., Consolaro A., Dellepiane R.M., Maggio M.C., La Torre F., Marchesi A., Simonini G., Villani A., Cimaz R., Ravelli A., Taddio A., Adamoli P., Alberelli M.C., Alizzi C., Barone P., Bennato V., Biscaro F., Bossi G., Campana A., Carone M., Civino A., Conti G., Rossi E.D., Del Giudice E., Dell'Anna A., De Luca M., Felici E., Filocamo G., Floretta I., Foschini M.L., Lanari M., Lattanzi B., Lazzerotti A., Licciardi F., Manerba A., Mannarino S., Marino A., Marolda A., Martelli L., Martini G., Mauro A., Mastrolia M.V., Mazza A., Miniaci A., Minoia F., Olivieri A., Pennoni G., Pignataro R., Ricci F., Rigante D., Rossi M., Santagati C., Soliani M., Sonego S., Sperli D., Stucchi S., Teruzzi B., Tierno E., Utytatnikova T., Valentini P., and Vergine G.

Subjects
Coronary artery abnormalities, Hypotension, Kawasaki disease, Multisystem inflammatory syndrome associated with coronavirus disease, Myocarditis, Pediatric inflammatory multisystem syndrome-temporally associated to SARS-CoV-2 infection, SARS-CoV-2, Age Distribution, Antirheumatic Agents, Aspirin, C-Reactive Protein, COVID-19, Child, Child, Preschool, Coronary Artery Disease, Cough, Diarrhea, Dyspnea, Female, Glucocorticoids, Heart Failure, Humans, Hyperferritinemia, Immunoglobulins, Intravenous, Immunologic Factors, Infant, Intensive Care Units, Pediatric, Interleukin 1 Receptor Antagonist Protein, Italy, Lymphopenia, Male, Mucocutaneous Lymph Node Syndrome, Platelet Aggregation Inhibitors, Shock, Systemic Inflammatory Response Syndrome, Tachypnea, Troponin T, Vomiting, lcsh:Diseases of the musculoskeletal system, coronary artery abnormalities, hypotension, kawasaki disease, multisystem inflammatory syndrome associated with coronavirus disease, myocarditis, pediatric inflammatory multisystem syndrome-temporally associated to SARS-CoV-2 infection, age distribution, antirheumatic agents, aspirin, C-reactive protein, child, preschool, coronary artery disease, cough, diarrhea, yspnea, female, glucocorticoids, heart failure, humans, hyperferritinemia, immunoglobulins, intravenous, immunologic factors, infant, intensive care units, pediatric, interleukin 1 receptor antagonist protein, italy, lymphopenia, male, mucocutaneous lymph node syndrome, platelet aggregation inhibitors, shock, systemic inflammatory response syndrome, tachypnea, troponin T, vomiting, Myocarditi, 030204 cardiovascular system & hematology, SARS-CoV-2, Kawasaki disease, Pediatric inflammatory multisystem syndrome-temporally associated to SARS-CoV-2 infection, Myocarditis, Hypotension, Multisystem inflammatory syndrome associated with coronavirus disease, Coronary artery abnormalities, Coronary artery disease, Settore MED/38 - Pediatria Generale E Specialistica, 0302 clinical medicine, Glucocorticoid, Immunologic Factor, Immunology and Allergy, Coronary artery abnormalitie, Fisher's exact test, Pediatric, biology, lcsh:RJ1-570, Antirheumatic Agent, Settore MED/38, Intensive Care Units, Cohort, symbols, Platelet aggregation inhibitor, Intravenous, Human, Research Article, medicine.medical_specialty, Immunoglobulins, 03 medical and health sciences, symbols.namesake, Rheumatology, Internal medicine, medicine, Preschool, 030203 arthritis & rheumatology, business.industry, Platelet Aggregation Inhibitor, lcsh:Pediatrics, medicine.disease, Systemic inflammatory response syndrome, Immunoglobulins, Intravenou, Pediatrics, Perinatology and Child Health, biology.protein, lcsh:RC925-935, business
Abstract

Background There is mounting evidence on the existence of a Pediatric Inflammatory Multisystem Syndrome-temporally associated to SARS-CoV-2 infection (PIMS-TS), sharing similarities with Kawasaki Disease (KD). The main outcome of the study were to better characterize the clinical features and the treatment response of PIMS-TS and to explore its relationship with KD determining whether KD and PIMS are two distinct entities. Methods The Rheumatology Study Group of the Italian Pediatric Society launched a survey to enroll patients diagnosed with KD (Kawasaki Disease Group – KDG) or KD-like (Kawacovid Group - KCG) disease between February 1st 2020, and May 31st 2020. Demographic, clinical, laboratory data, treatment information, and patients’ outcome were collected in an online anonymized database (RedCAP®). Relationship between clinical presentation and SARS-CoV-2 infection was also taken into account. Moreover, clinical characteristics of KDG during SARS-CoV-2 epidemic (KDG-CoV2) were compared to Kawasaki Disease patients (KDG-Historical) seen in three different Italian tertiary pediatric hospitals (Institute for Maternal and Child Health, IRCCS “Burlo Garofolo”, Trieste; AOU Meyer, Florence; IRCCS Istituto Giannina Gaslini, Genoa) from January 1st 2000 to December 31st 2019. Chi square test or exact Fisher test and non-parametric Wilcoxon Mann-Whitney test were used to study differences between two groups. Results One-hundred-forty-nine cases were enrolled, (96 KDG and 53 KCG). KCG children were significantly older and presented more frequently from gastrointestinal and respiratory involvement. Cardiac involvement was more common in KCG, with 60,4% of patients with myocarditis. 37,8% of patients among KCG presented hypotension/non-cardiogenic shock. Coronary artery abnormalities (CAA) were more common in the KDG. The risk of ICU admission were higher in KCG. Lymphopenia, higher CRP levels, elevated ferritin and troponin-T characterized KCG. KDG received more frequently immunoglobulins (IVIG) and acetylsalicylic acid (ASA) (81,3% vs 66%; p = 0.04 and 71,9% vs 43,4%; p = 0.001 respectively) as KCG more often received glucocorticoids (56,6% vs 14,6%; p Conclusion Our study suggests that SARS-CoV-2 infection might determine two distinct inflammatory diseases in children: KD and PIMS-TS. Older age at onset and clinical peculiarities like the occurrence of myocarditis characterize this multi-inflammatory syndrome. Our patients had an optimal response to treatments and a good outcome, with few complications and no deaths.

Published
2020

22. Spatial Memory and Microglia Activation in a Mouse Model of Chronic Neuroinflammation and the Anti-inflammatory Effects of Apigenin.

Author

Chesworth R, Gamage R, Ullah F, Sonego S, Millington C, Fernandez A, Liang H, Karl T, Münch G, Niedermayer G, and Gyengesi E

Abstract

Chronic neuroinflammation characterized by microglia reactivity is one of the main underlying processes in the initiation and progression of neurodegenerative diseases such as Alzheimer's disease. This project characterized spatial memory during healthy aging and prolonged neuroinflammation in the chronic neuroinflammatory model, glial fibrillary acidic protein-interleukin 6 (GFAP-IL6). We investigated whether chronic treatment with the natural flavonoid, apigenin, could reduce microglia activation in the hippocampus and improve spatial memory. GFAP-IL6 transgenic and wild-type-like mice were fed with apigenin-enriched or control chow from 4 months of age and tested for spatial memory function at 6 and 22 months using the Barnes maze. Brain tissue was collected at 22 months to assess microgliosis and morphology using immunohistochemistry, stereology, and 3D single cell reconstruction. GFAP-IL6 mice showed age-dependent loss of spatial memory recall compared with wild-type-like mice. Chronic apigenin treatment decreased the number of Iba-1 + microglia in the hippocampus of GFAP-IL6 mice and changed microglial morphology. Apigenin did not reverse spatial memory recall impairment in GFAP-IL6 mice at 22 months of age. GFAP-IL6 mice may represent a suitable model for age-related neurodegenerative disease. Chronic apigenin supplementation significantly reduced microglia activation, but this did not correspond with spatial memory improvement in the Barnes Maze., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chesworth, Gamage, Ullah, Sonego, Millington, Fernandez, Liang, Karl, Münch, Niedermayer and Gyengesi.)

Published
2021
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23. Investigation Into the Effects of Tenilsetam on Markers of Neuroinflammation in GFAP-IL6 Mice.

Author

Gyengesi E, Liang H, Millington C, Sonego S, Sirijovski D, Gunawardena D, Dhananjayan K, Venigalla M, Niedermayer G, and Münch G

Subjects
Alzheimer Disease drug therapy, Animals, Anti-Inflammatory Agents, Non-Steroidal chemistry, Biomarkers metabolism, Cerebellum drug effects, Cerebellum pathology, Chronic Disease, Hippocampus drug effects, Hippocampus pathology, Humans, Inflammation drug therapy, Inflammation metabolism, Inflammation pathology, Interleukin-6 metabolism, Mice, Inbred C57BL, Mice, Transgenic, Microglia drug effects, Microglia pathology, Piperazines chemistry, Pyruvaldehyde metabolism, Thiophenes chemistry, Tissue Distribution, Tumor Necrosis Factor-alpha metabolism, Anti-Inflammatory Agents, Non-Steroidal pharmacology, Piperazines pharmacology, Thiophenes pharmacology
Abstract

Purpose: To test the short- and long-term effects of Tenilsetam on chronic neuroinflammation in the GFAP-IL6 mouse., Methods: From 3 months of age, GFAP-IL6 mice were divided into 2 groups and fed with Tenilsetam enriched food pellets or control food pellets, respectively, for either 5 or 15 months. Total numbers of Iba-1 + microglia, TSPO + cells were determined using an unbiased stereological method. Levels of methylglyoxal and TNF-α in the cerebellar homogenate were tested using HPLC and ELISA, respectively., Results: Tenilsetam decreased the total number of Iba-1 + microglia in both the cerebellum and the hippocampus of GFAP-IL6 mice at 8 months and in the cerebellum at 18 months. In the cerebellum, it decreased the density of microglia in GFAP-IL6 mice to a similar level after 5 and 15 months' feeding. Tenilsetam prevented the volume loss of the cerebellum at 8 months. It also significantly decreased TNF-α in the cerebellum of GFAP-IL6 mice to a similar level of WT mice after 15 months of feeding., Conclusion: Tenilsetam has anti-inflammatory effects evidenced by the decreased number of microglia in both the cerebellum and hippocampus, and decreased TNF-α levels in the GFAP-IL6 Tenilsetam fed animals.

Published
2018
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24. Novel promising therapeutics against chronic neuroinflammation and neurodegeneration in Alzheimer's disease.

Author

Venigalla M, Sonego S, Gyengesi E, Sharman MJ, and Münch G

Subjects
Alzheimer Disease metabolism, Animals, Antioxidants isolation & purification, Biological Products isolation & purification, Chronic Disease, Curcumin isolation & purification, Curcumin therapeutic use, Fish Oils isolation & purification, Fish Oils therapeutic use, Humans, Inflammation metabolism, Inflammation pathology, Inflammation prevention & control, Neurodegenerative Diseases metabolism, Neurodegenerative Diseases pathology, Neurodegenerative Diseases prevention & control, Neurofibrillary Tangles drug effects, Neurofibrillary Tangles metabolism, Neurofibrillary Tangles pathology, Neuroprotective Agents isolation & purification, Randomized Controlled Trials as Topic methods, Resveratrol, Stilbenes isolation & purification, Stilbenes therapeutic use, Alzheimer Disease drug therapy, Alzheimer Disease pathology, Antioxidants therapeutic use, Biological Products therapeutic use, Neuroprotective Agents therapeutic use
Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder, characterized by deposition of amyloid plaques and neurofibrillary tangles, as well as microglial and astroglial activation, and, finally, leading to neuronal dysfunction and death. Current treatments for AD primarily focus on enhancement of cholinergic transmission. However, these treatments are only symptomatic, and no disease-modifying drug is available for the treatment of AD patients. This review will provide an overview of the antioxidant, anti-inflammatory, anti-amyloidogenic, neuroprotective, and cognition-enhancing effects of a variety of nutraceuticals including curcumin, apigenin, docosahexaenoic acid, epigallocatechin gallate, α-lipoic acid and resveratrol and their potential for AD prevention and treatment. We suggest that therapeutic use of these compounds might lead to a safe strategy to delay the onset of AD or slow down its progression. The continuing investigation of the potential of these substances is necessary as they are promising compounds to yield a possible remedy for this pervasive disease., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Published
2016
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25. Use of non-pharmaceutical interventions to reduce the transmission of influenza in adults: A systematic review.

Author

Smith SM, Sonego S, Wallen GR, Waterer G, Cheng AC, and Thompson P

Subjects
Adult, Humans, Communicable Disease Control, Influenza, Human prevention & control, Influenza, Human transmission
Abstract

During seasonal influenza epidemics and pandemics, virus transmission causes significant public health concern. Reduction of viral transmission by non-pharmaceutical interventions (NPI) has a significant appeal and is often recommended. However, the efficacy of such interventions is unclear. A systematic literature review was undertaken to identify and evaluate the published literature on NPI efficacy to prevent human transmission of influenza virus in adults. Reviewers assessed the quality of eligible studies utilizing the Critical Appraisal Skills Programme for bias and the Scottish Intercollegiate Guidelines Network for methodological quality. Studies were assessed for risk of bias domains of random sequence generation, allocation concealment, attribution bias, selective reporting and blinding. Relevant citations of 2247 were reduced to 100 for full-text evaluation. Only seven met all selection criteria and pooled analysis was not feasible. Of the seven studies, two were randomized controlled trials (RCT) and five were cluster RCT. The main NPI studied were disinfection and hygiene; barriers; and combined NPI. However, these seven RCT had significant design flaws. Only two studies used laboratory confirmed influenza and poor statistical power was a major problem. Positive significant interventions included professional oral hygiene intervention in the elderly and hand washing. Despite the potential for NPI in preventing influenza transmission, there is very limited data available. Hand washing and dental hygiene may be useful, but other interventions have not been fully assessed. Properly designed studies evaluating large populations including 'at risk' patients and in a variety of communities are needed., (© 2015 Asian Pacific Society of Respirology.)

Published
2015
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26. A review of the effectiveness of psychological interventions used for anxiety and depression in chronic obstructive pulmonary disease.

Author

Smith SM, Sonego S, Ketcheson L, and Larson JL

Abstract

Background: Anxiety and depression are recognised co-morbidities associated with COPD and have been related to poor health outcomes. Therapies to relieve anxiety and depression are currently not detailed in clinical guidelines., Methods: A systematic review of psychological interventions for anxiety and depression in adults with COPD was conducted. Meta-analysis utilising the random effects model was undertaken for 4 studies that employed the same psychological intervention type, Cognitive Behavioural Therapy (CBT)., Results: Seven studies met the inclusion criteria. Four studies used CBT. Included studies utilised psychotherapy, uncertainty management and minimal psychological therapy. 70% of participants were male. Many studies had poor methodological quality. The meta-analysis showed a small decrease in symptoms for both anxiety (SMD -0.49, 95% CI -1.04, 0.06, P=0.08, n=193) and depression (SMD -0.37, 95% CI -0.86, 0.11, P=0.13, n=193). No change occurred when sensitivity analyses were conducted., Conclusion: Anxiety and depression in COPD patients are known to impact on health outcomes. Effective psychological interventions such as CBT may assist people with COPD in reducing psychological burden. There remains a need for well-designed studies to provide substantive evidence for the use of psychological interventions in this patient population.

Published
2014
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27. Chronic neuroinflammation in Alzheimer's disease: new perspectives on animal models and promising candidate drugs.

Author

Millington C, Sonego S, Karunaweera N, Rangel A, Aldrich-Wright JR, Campbell IL, Gyengesi E, and Münch G

Subjects
Alzheimer Disease genetics, Alzheimer Disease pathology, Animals, Astrocytes metabolism, Disease Models, Animal, Glial Fibrillary Acidic Protein, Humans, Inflammation genetics, Inflammation pathology, Interleukin-6 genetics, Mice, Mice, Transgenic, Nerve Tissue Proteins genetics, Alzheimer Disease drug therapy, Amyloid beta-Peptides metabolism, Astrocytes pathology, Inflammation drug therapy
Abstract

Chronic neuroinflammation is now considered one of the major factors in the pathogenesis of Alzheimer's disease (AD). However, the most widely used transgenic AD models (overexpressing mutated forms of amyloid precursor protein, presenilin, and/or tau) do not demonstrate the degree of inflammation, neurodegeneration (particularly of the cholinergic system), and cognitive decline that is comparable with the human disease. Hence a more suitable animal model is needed to more closely mimic the resulting cognitive decline and memory loss in humans in order to investigate the effects of neuroinflammation on neurodegeneration. One of these models is the glial fibrillary acidic protein-interleukin 6 (GFAP-IL6) mouse, in which chronic neuroinflammation triggered constitutive expression of the cytokine interleukin-6 (IL-6) in astrocytes. These transgenic mice show substantial and progressive neurodegeneration as well as a decline in motor skills and cognitive function, starting from 6 months of age. This animal model could serve as an excellent tool for drug discovery and validation in vivo. In this review, we have also selected three potential anti-inflammatory drugs, curcumin, apigenin, and tenilsetam, as candidate drugs, which could be tested in this model.

Published
2014
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29. Hawking-like radiation does not require a trapped region.

Author

Barceló C, Liberati S, Sonego S, and Visser M

Abstract

We discuss the issue of quasiparticle production by "analogue black holes" with particular attention paid to the possibility of reproducing Hawking radiation in a laboratory. By constructing simple geometric acoustic models, we obtain a somewhat unexpected result: We show that, in order to obtain a stationary and Planckian emission of quasiparticles, it is not necessary to create a trapped region in the acoustic spacetime (corresponding to a supersonic regime in the fluid flow). It is sufficient to set up a dynamically changing flow asymptotically approaching a sonic regime with sufficient rapidity in laboratory time. This result is generic to curved-space quantum field theory, the "analogue spacetimes" we consider providing a guide to physical intuition, and a possible route to laboratory experiments.

Published
2006
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32. Critical evaluation of various forms of therapy for idiopathic calcium stone disease.

Author

Marangella M, Tricerri A, Sonego S, Ronzani M, Fruttero B, Daniele PG, Bruno M, and Linari F

Subjects
Allopurinol therapeutic use, Clinical Trials as Topic, Combined Modality Therapy, Female, Humans, Hydrochlorothiazide therapeutic use, Kidney Calculi diet therapy, Kidney Calculi drug therapy, Male, Kidney Calculi therapy
Abstract

The results are presented of the dietary management, alone or in association with thiazides and/or allopurinol, evaluated in 143 idiopathic calcium stone formers after a mean follow-up of 18 months. Diet alone proved to be effective in the prevention of stone relapses. The addition of thiazide and/or allopurinol provided mild improvements of urine environment but seemed to give no further clinical benefits irrespective of underlying metabolic abnormalities.

Published
1983

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