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1. Phenotyping COVID-19 respiratory failure in spontaneously breathing patients with AI on lung CT-scan.

Author

Rezoagli, Emanuele, Xin, Yi, Signori, Davide, Sun, Wenli, Gerard, Sarah, Delucchi, Kevin, Magliocca, Aurora, Vitale, Giovanni, Giacomini, Matteo, Mussoni, Linda, Montomoli, Jonathan, Subert, Matteo, Ponti, Alessandra, Spadaro, Savino, Poli, Giancarla, Casola, Francesco, Herrmann, Jacob, Foti, Giuseppe, Calfee, Carolyn, Laffey, John, Bellani, Giacomo, and Cereda, Maurizio

Subjects
Artificial intelligence, COVID-19, Computed tomography, Latent class analysis, Respiratory failure, Subphenotypes, Humans, COVID-19, Tomography, X-Ray Computed, Female, Male, Middle Aged, Phenotype, Lung, Aged, Respiratory Insufficiency, Cohort Studies, Adult
Abstract

BACKGROUND: Automated analysis of lung computed tomography (CT) scans may help characterize subphenotypes of acute respiratory illness. We integrated lung CT features measured via deep learning with clinical and laboratory data in spontaneously breathing subjects to enhance the identification of COVID-19 subphenotypes. METHODS: This is a multicenter observational cohort study in spontaneously breathing patients with COVID-19 respiratory failure exposed to early lung CT within 7 days of admission. We explored lung CT images using deep learning approaches to quantitative and qualitative analyses; latent class analysis (LCA) by using clinical, laboratory and lung CT variables; regional differences between subphenotypes following 3D spatial trajectories. RESULTS: Complete datasets were available in 559 patients. LCA identified two subphenotypes (subphenotype 1 and 2). As compared with subphenotype 2 (n = 403), subphenotype 1 patients (n = 156) were older, had higher inflammatory biomarkers, and were more hypoxemic. Lungs in subphenotype 1 had a higher density gravitational gradient with a greater proportion of consolidated lungs as compared with subphenotype 2. In contrast, subphenotype 2 had a higher density submantellar-hilar gradient with a greater proportion of ground glass opacities as compared with subphenotype 1. Subphenotype 1 showed higher prevalence of comorbidities associated with endothelial dysfunction and higher 90-day mortality than subphenotype 2, even after adjustment for clinically meaningful variables. CONCLUSIONS: Integrating lung-CT data in a LCA allowed us to identify two subphenotypes of COVID-19, with different clinical trajectories. These exploratory findings suggest a role of automated imaging characterization guided by machine learning in subphenotyping patients with respiratory failure. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04395482. Registration date: 19/05/2020.

Published
2024

2. Prognostic Impact of Bronchoalveolar Lavage Fluid Galactomannan and Aspergillus Culture Results on Survival in COVID-19 Intensive Care Unit Patients: a Post Hoc Analysis from the European Confederation of Medical Mycology (ECMM) COVID-19-Associated Pulmonary Aspergillosis Study

Author

Giacobbe, Daniele Roberto, Prattes, Juergen, Wauters, Joost, Dettori, Silvia, Signori, Alessio, Salmanton-García, Jon, Maertens, Johan, Bourgeois, Marc, Reynders, Marijke, Rutsaert, Lynn, Van Regenmortel, Niels, Lormans, Piet, Feys, Simon, Klimko, Nikolay, Shadrivova, Olga, Cornely, Oliver A, Rautemaa-Richardson, Riina, Koehler, Philipp, Lagrou, Katrien, Bassetti, Matteo, and Hoenigl, Martin

Subjects
Infectious Diseases, Rare Diseases, Lung, Good Health and Well Being, Aspergillus, Bronchoalveolar Lavage Fluid, COVID-19, Critical Illness, Galactose, Humans, Intensive Care Units, Invasive Pulmonary Aspergillosis, Mannans, Mycology, Prognosis, Pulmonary Aspergillosis, Sensitivity and Specificity, CAPA, GM, biomarker, galactomannan, BALF, ECMM-CAPA Study Group, Biological Sciences, Agricultural and Veterinary Sciences, Medical and Health Sciences, Microbiology
Abstract

Critically ill patients with coronavirus disease 2019 (COVID-19) may develop COVID-19-associated pulmonary aspergillosis (CAPA), which impacts their chances of survival. Whether positive bronchoalveolar lavage fluid (BALF) mycological tests can be used as a survival proxy remains unknown. We conducted a post hoc analysis of a previous multicenter, multinational observational study with the aim of assessing the differential prognostic impact of BALF mycological tests, namely, positive (optical density index of ≥1.0) BALF galactomannan (GM) and positive BALF Aspergillus culture alone or in combination for critically ill patients with COVID-19. Of the 592 critically ill patients with COVID-19 enrolled in the main study, 218 were included in this post hoc analysis, as they had both test results available. CAPA was diagnosed in 56/218 patients (26%). Most cases were probable CAPA (51/56 [91%]) and fewer were proven CAPA (5/56 [9%]). In the final multivariable model adjusted for between-center heterogeneity, an independent association with 90-day mortality was observed for the combination of positive BALF GM and positive BALF Aspergillus culture in comparison with both tests negative (hazard ratio, 2.53; 95% CI confidence interval [CI], 1.28 to 5.02; P = 0.008). The other independent predictors of 90-day mortality were increasing age and active malignant disease. In conclusion, the combination of positive BALF GM and positive BALF Aspergillus culture was associated with increased 90-day mortality in critically ill patients with COVID-19. Additional study is needed to explore the possible prognostic value of other BALF markers.

Published
2022

3. Disease‐Modifying Therapies and Coronavirus Disease 2019 Severity in Multiple Sclerosis

Author

Sormani, Maria P, De Rossi, Nicola, Schiavetti, Irene, Carmisciano, Luca, Cordioli, Cinzia, Moiola, Lucia, Radaelli, Marta, Immovilli, Paolo, Capobianco, Marco, Trojano, Maria, Zaratin, Paola, Tedeschi, Gioacchino, Comi, Giancarlo, Battaglia, Mario A, Patti, Francesco, Salvetti, Marco, Nozzolillo, Agostino, Bellacosa, Alessandra, Protti, Alessandra, Di Sapio, Alessia, Signori, Alessio, Petrone, Alfredo, Bisecco, Alvino, Iovino, Aniello, Dutto, Anna, Repice, Anna Maria, Conte, Antonella, Bertolotto, Antonio, Bosco, Antonio, Gallo, Antonio, Zito, Antonio, Sartori, Arianna, Giometto, Bruno, Tortorella, Carla, Antozzi, Carlo, Pozzilli, Carlo, Mancinelli, Chiara Rosa, Zanetta, Chiara, Cordano, Christian, Scandellari, Cinzia, Guaschino, Clara, Gasperini, Claudio, Solaro, Claudio, Fioretti, Cristina, Bezzini, Daiana, Marastoni, Damiano, Paolicelli, Damiano, Vecchio, Domizia, Landi, Doriana, Bucciantini, Elisabetta, Pedrazzoli, Elisabetta, Signoriello, Elisabetta, Sbragia, Elvira, Susani, Emanuela Laura, Curti, Erica, Milano, Eva, Marinelli, Fabiana, Camilli, Federico, Boneschi, Filippo Martinelli, Govone, Flora, Bovis, Francesca, Calabria, Francesca, Caleri, Francesca, Rinaldi, Francesca, Vitetta, Francesca, Corea, Francesco, Crescenzo, Francesco, Teatini, Francesco, Tabiadon, Giulietta, Granella, Franco, Boffa, Giacomo, Lus, Giacomo, Brichetto, Giampaolo, Maniscalco, Giorgia Teresa, Borriello, Giovanna, De Luca, Giovanna, Konrad, Giovanna, Vaula, Giovanna, Marfia, Girolama Alessandra, Mallucci, Giulia, Liberatore, Giuseppe, Salemi, Giuseppe, Miele, Giuseppina, Sibilia, Grazia, Pesci, Ilaria, Brambilla, Laura, Lopiano, Leonardo, Sinisi, Leonardo, Pasquali, Livia, Saraceno, Lorenzo, Chiveri, Luca, Mancinelli, Luca, and Grimaldi, Luigi ME

Subjects
Pneumonia & Influenza, Neurodegenerative, Clinical Research, Autoimmune Disease, Brain Disorders, Lung, Multiple Sclerosis, Pneumonia, Neurosciences, Neurological, Good Health and Well Being, Adolescent, Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Humanized, COVID-19, Dimethyl Fumarate, Female, Fingolimod Hydrochloride, Hospitalization, Humans, Immunologic Factors, Immunosuppressive Agents, Intensive Care Units, Interferons, Male, Middle Aged, Mortality, Natalizumab, SARS-CoV-2, Severity of Illness Index, Young Adult, Musc-19 Study Group, Clinical Sciences, Neurology & Neurosurgery
Abstract

ObjectiveThis study was undertaken to assess the impact of immunosuppressive and immunomodulatory therapies on the severity of coronavirus disease 2019 (COVID-19) in people with multiple sclerosis (PwMS).MethodsWe retrospectively collected data of PwMS with suspected or confirmed COVID-19. All the patients had complete follow-up to death or recovery. Severe COVID-19 was defined by a 3-level variable: mild disease not requiring hospitalization versus pneumonia or hospitalization versus intensive care unit (ICU) admission or death. We evaluated baseline characteristics and MS therapies associated with severe COVID-19 by multivariate and propensity score (PS)-weighted ordinal logistic models. Sensitivity analyses were run to confirm the results.ResultsOf 844 PwMS with suspected (n = 565) or confirmed (n = 279) COVID-19, 13 (1.54%) died; 11 of them were in a progressive MS phase, and 8 were without any therapy. Thirty-eight (4.5%) were admitted to an ICU; 99 (11.7%) had radiologically documented pneumonia; 96 (11.4%) were hospitalized. After adjusting for region, age, sex, progressive MS course, Expanded Disability Status Scale, disease duration, body mass index, comorbidities, and recent methylprednisolone use, therapy with an anti-CD20 agent (ocrelizumab or rituximab) was significantly associated (odds ratio [OR] = 2.37, 95% confidence interval [CI] = 1.18-4.74, p = 0.015) with increased risk of severe COVID-19. Recent use (

Published
2021

4. Impact of Human Immunodeficiency Virus Type 1 Minority Variants on the Virus Response to a Rilpivirine-Based First-line Regimen

Author

Raymond, Stéphanie, Nicot, Florence, Pallier, Coralie, Bellecave, Pantxika, Maillard, Anne, Trabaud, Mary Anne, Morand-Joubert, Laurence, Rodallec, Audrey, Amiel, Corinne, Mourez, Thomas, Bocket, Laurence, Beby-Defaux, Agnès, Bouvier-Alias, Magali, Lambert-Niclot, Sidonie, Charpentier, Charlotte, Malve, Brice, Mirand, Audrey, Dina, Julia, Le Guillou-Guillemette, Hélène, Marque-Juillet, Stéphanie, Signori-Schmuck, Anne, Barin, Francis, Si-Mohamed, Ali, Fenoel, Véronique Avettand, Roussel, Catherine, Calvez, Vincent, Saune, Karine, Marcelin, Anne Geneviève, Rodriguez, Christophe, Descamps, Diane, Izopet, Jacques, Lagier, E, Roussel, C, Le Guillou-Guillemette, H, Alloui, C, Bettinger, D, Pallier, C, Fleury, H, Reigadas, S, Bellecave, P, Recordon-Pinson, P, Payan, C, Vallet, S, Vabret, A, Dina, J, Henquell, C, Mirand, A, Bouvier-Alias, M, de Rougemont, A, Dos Santos, G, Morand, P, Signori-Schmuck, A, Bocket, L, Rogez, S, Andre, P, Tardy, JC, Trabaud, MA, Tamalet, C, Delamare, C, Montes, B, Schvoerer, E, Ferré, V, André-Garnier, E, Cottalorda, J, Guinard, J, Guiguon, A, Descamps, D, Brun-Vézinet, F, Charpentier, C, Visseaux, B, Peytavin, G, Krivine, A, Si-Mohamed, A, Avettand-Fenoel, V, Marcelin, AG, Calvez, V, Lambert-Niclot, S, Soulié, C, Wirden, M, Morand-Joubert, L, Delaugerre, C, Chaix, ML, Amiel, C, Schneider, V, Giraudeau, G, Defaux, A Beby-, Brodard, V, Maillard, A, Plantier, JC, Chaplain, C, Bourlet, T, Fafi-Kremer, S, Stoll-Keller, F, Schmitt, MP, Barth, H, Yerly, S, Poggi, C, Izopet, J, Raymond, S, and Barin, F

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Clinical Sciences, Immunology, Antimicrobial Resistance, Genetics, HIV/AIDS, Clinical Research, Infectious Diseases, Aetiology, 2.1 Biological and endogenous factors, Infection, Good Health and Well Being, Adult, Drug Resistance, Viral, Female, Genetic Variation, HIV Infections, HIV-1, Humans, Male, Mutation, Rilpivirine, Viral Load, minority resistant variants, rilpivirine, first-line antiretroviral therapy, ultra-deep sequencing, French National Agency for Research on AIDS and Viral Hepatitis (ANRS) AC11 Resistance Study Group, Biological Sciences, Medical and Health Sciences, Microbiology, Clinical sciences
Abstract

BackgroundMinority resistant variants of human immunodeficiency virus type 1 (HIV-1) could influence the virological response to treatment based on nonnucleoside reverse transcriptase inhibitors (NNRTIs). Data on minority rilpivirine-resistant variants are scarce. This study used next-generation sequencing (NGS) to identify patients harboring minority resistant variants to nucleos(t)ide reverse transcriptase inhibitors and NNRTIs and to assess their influence on the virological response (VR).MethodsAll the subjects, 541 HIV-1-infected patients started a first-line regimen containing rilpivirine. VR was defined as a HIV-1 RNA load 20% in 29% of samples. We identified 43 (8.8%) and 36 (7.4%) patients who harbored rilpivirine-resistant variants with a 1% sensitivity threshold according to the French National Agency for Research on AIDS and Viral Hepatitis and Stanford algorithms, respectively. The VR was 96.9% at month 12. Detection of minority rilpivirine resistant variants was not associated with virological failure (VF). Multivariate analysis indicated that VF at month 12 was associated with a CD4 count

Published
2018

5. Impact of the mutational load on the virological response to a first-line rilpivirine-based regimen.

Author

Dimeglio, Chloé, Raymond, Stéphanie, Nicot, Florence, Jeanne, Nicolas, Carcenac, Romain, Lefebvre, Caroline, Izopet, Jacques, Roussel, C, Guillou-Guillemette, H Le, Alloui, C, Bettinger, D, Pallier, C, Fleury, H, Bellecave, P, Recordon-Pinson, P, Payan, C, Vallet, S, Vabret, A, Dina, J, Henquell, C, Mirand, A, Bouvier-Alias, M, de Rougemont, A, Si-Mohammed, A, Santos, G Dos, Morand, P, Signori-Schmuck, A, Bocket, L, Rogez, S, Andre, P, Tardy, JC, Trabaud, MA, Tamalet, C, Delamare, C, Montes, B, Schvoerer, E, Jeulin, H, Ferré, V, Rodallec, A, Guen, L Le, Cottalorda, J, Guinard, J, Guiguon, A, Descamps, D, Charpentier, C, Visseaux, B, Peytavin, G, Krivine, A, Bouviers-Alias, M, Avettand-Fenoel, V, Marcelin, AG, Calvez, V, Soulié, C, Wirden, M, Morand-Joubert, L, Lambert-Niclot, S, Fofana, D, Delaugerre, C, Chaix, ML, Mahjoub, N, Amiel, C, Schneider, V, Giraudeau, G, Beby-Defaux, A, Brodard, V, Maillard, A, Plantier, JC, Mourez, T, Leoz, M, Chaplain, C, Bourlet, T, Fafi-Kremer, S, Stoll-Keller, F, Schmitt, MP, Barth, H, Yerly, S, Poggi, C, Izopet, J, Raymond, S, Barin, F, Chaillon, A, Marque-Juillet, S, Roque-Afonso, AM, Haïm-Boukobza, S, Flandre, P, Grudé, M, Assoumou, L, and Costagliola, D

Subjects
Clinical Research, Genetics, HIV/AIDS, Infectious Diseases, Infection, Antiretroviral Therapy, Highly Active, Drug Resistance, Viral, Female, Genome, Viral, Genotype, HIV Infections, HIV-1, High-Throughput Nucleotide Sequencing, Humans, Male, Mutation, Rilpivirine, Treatment Outcome, Viral Load, French National Agency for Research on AIDS and Viral Hepatitis (ANRS) AC11 Resistance Study Group, Microbiology, Medical Microbiology, Pharmacology and Pharmaceutical Sciences
Abstract

ObjectivesTo determine how the load of rilpivirine-resistant variants (mutational load) influences the virological response (VR) of HIV-1-infected patients to a rilpivirine-based first-line regimen.Patients and methodsFour hundred and eighty-nine patients infected with HIV-1 whose reverse transcriptase gene had been successfully resistance genotyped using next-generation sequencing were given a first-line regimen containing rilpivirine. Variables associated with the VR at 12 months were identified using a logistic model. The results were used to build a multivariate model for each mutational load threshold and the R2 variations were analysed to identify the mutational load threshold that best predicted the VR.ResultsThe mutational load at baseline was the only variable linked to the VR at 12 months (P  1700 copies/mL and to 50% when the mutational load was > 9000 copies/mL. The threshold of 9000 copies/mL was associated with the VR at 12 months with an OR of 36.7 (95% CI 4.7-285.1). The threshold of 1700 copies/mL was associated with the VR at 12 months with an OR of 7.2 (95% CI 1.4-36.8).ConclusionsThere is quantifiable evidence that determining a mutational load threshold can be used to identify those patients on a first-line regimen containing rilpivirine who are at risk of virological failure. The clinical management of HIV-infected patients can be improved by evaluating the frequency of mutant variants at a threshold of

Published
2019

6. Cross-resistance to elvitegravir and dolutegravir in 502 patients failing on raltegravir: a French national study of raltegravir-experienced HIV-1-infected patients

Author

Fourati, Slim, Charpentier, Charlotte, Amiel, Corinne, Morand-Joubert, Laurence, Reigadas, Sandrine, Trabaud, Mary-Anne, Delaugerre, Constance, Nicot, Florence, Rodallec, Audrey, Maillard, Anne, Mirand, Audrey, Jeulin, Hélène, Montès, Brigitte, Barin, Francis, Bettinger, Dominique, Le Guillou-Guillemette, Hélène, Vallet, Sophie, Signori-Schmuck, Anne, Descamps, Diane, Calvez, Vincent, Flandre, Philippe, Marcelin, Anne-Genevieve, Lagier, E, Roussel, C, Le Guillou, H, Alloui, C, Bettinger, D, Pallier, C, Fleury, H, Reigadas, S, Bellecave, P, Recordon-Pinson, P, Payan, C, Vallet, S, Vabret, A, Henquell, C, Mirand, A, Bouvier-Alias, M, de Rougemont, A, Dos Santos, G, Morand, P, Signori-Schmuck, A, Bocket, L, Rogez, S, Andre, P, Tardy, JC, Trabaud, MA, Tamalet, C, Delamare, C, Montes, B, Schvoerer, E, Ferre, V, André-Garnier, E, Cottalorda, J, Guinard, J, Guiguon, A, Descamps, D, Brun-Vézinet, F, Charpentier, C, Visseaux, B, Peytavin, G, Krivine, A, Si-Mohamed, A, Avettand-Fenoel, V, Marcelin, AG, Calvez, V, Lambert-Niclot, S, Soulié, C, Wirden, M, Morand-Joubert, L, Delaugerre, C, Chaix, ML, Amiel, C, Schneider, V, Giraudeau, G, Brodard, V, Maillard, A, Plantier, JC, Chaplain, C, Bourlet, T, Fafi-Kremer, S, Stoll-Keller, F, Schmitt, MP, Barth, H, Yerly, S, Poggi, C, Izopet, J, Raymond, S, Barin, F, Chaillon, A, Marque-Juillet, S, Roque-Afonso, AM, Haïm-Boukobza, S, Flandre, P, Grudé, M, Assoumou, L, Costagliola, D, Allegre, T, Schmit, JL, and Chennebault, JM

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Infectious Diseases, Genetics, Aetiology, 2.1 Biological and endogenous factors, Infection, Adult, Anti-HIV Agents, Drug Resistance, Viral, Female, France, HIV Infections, HIV Integrase, HIV Protease, HIV Reverse Transcriptase, HIV-1, Heterocyclic Compounds, 3-Ring, Humans, Male, Middle Aged, Mutant Proteins, Oxazines, Piperazines, Pyridones, Quinolones, Raltegravir Potassium, Sequence Analysis, DNA, integrase, inhibitors, mutations, patterns, ANRS AC11 Resistance Study Group, Microbiology, Pharmacology and Pharmaceutical Sciences, Clinical sciences, Pharmacology and pharmaceutical sciences
Abstract

ObjectivesThe objectives of this study were to determine the prevalence and patterns of resistance to integrase strand transfer inhibitors (INSTIs) in patients experiencing virological failure on raltegravir-based ART and the impact on susceptibility to INSTIs (raltegravir, elvitegravir and dolutegravir).Patients and methodsData were collected from 502 treatment-experienced patients failing a raltegravir-containing regimen in a multicentre study. Reverse transcriptase, protease and integrase were sequenced at failure for each patient. INSTI resistance-associated mutations investigated were those included in the last ANRS genotypic algorithm (v23).ResultsAmong the 502 patients, at failure, median baseline HIV-1 RNA (viral load) was 2.9 log10 copies/mL. Patients had been previously exposed to a median of five NRTIs, one NNRTI and three PIs. Seventy-one percent harboured HIV-1 subtype B and the most frequent non-B subtype was CRF02_AG (13.3%). The most frequent mutations observed were N155H/S (19.1%), Q148G/H/K/R (15.4%) and Y143C/G/H/R/S (6.7%). At failure, viruses were considered as fully susceptible to all INSTIs in 61.0% of cases, whilst 38.6% were considered as resistant to raltegravir, 34.9% to elvitegravir and 13.9% to dolutegravir. In the case of resistance to raltegravir, viruses were considered as susceptible to elvitegravir in 11% and to dolutegravir in 64% of cases. High HIV-1 viral load at failure (P

Published
2015

7. Antiretroviral-naive and -treated HIV-1 patients can harbour more resistant viruses in CSF than in plasma

Author

Soulie, C, Descamps, D, Grude, M, Schneider, V, Trabaud, M-A, Morand-Joubert, L, Delaugerre, C, Montes, B, Barin, F, Ferre, V, Raymond, S, Jeulin, H, Alloui, C, Yerly, S, Pallier, C, Reigadas, S, Signori-Schmuck, A, Guigon, A, Fafi-Kremer, S, Haim-Boukobza, S, Mirand, A, Maillard, A, Vallet, S, Roussel, C, Assoumou, L, Calvez, V, Flandre, P, Marcelin, A-G, Lagier, E, Le Guillou, H, Bettinger, D, Fleury, H, Bellecave, P, Recordon-Pinson, P, Payan, C, Vabret, A, Henquell, C, Bouvier-Alias, M, de Rougemont, A, Dos Santos, G, Morand, P, Bocket, L, Rogez, S, Andre, P, Tardy, JC, Trabaud, MA, Tamalet, C, Delamare, C, Schvoerer, E, Andre-Garnier, E, Cottalorda, J, Guinard, J, Guiguon, A, Brun-Vezinet, F, Charpentier, C, Visseaux, B, Peytavin, G, Krivine, A, Si-Mohamed, A, Avettand-Fenoel, V, Marcelin, AG, Lambert-Niclot, S, Wirden, M, Chaix, ML, Amiel, C, Giraudeau, G, Brodard, V, Plantier, JC, Chaplain, C, Bourlet, T, Stoll-Keller, F, Schmitt, MP, Barth, H, Poggi, C, Izopet, J, Chaillon, A, Marque-Juillet, S, and Roque-Afonso, AM

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Clinical Sciences, HIV/AIDS, Infectious Diseases, Antimicrobial Resistance, Genetics, Clinical Research, Neurosciences, Infection, Adult, Anti-HIV Agents, Antiretroviral Therapy, Highly Active, Drug Resistance, Viral, Female, Genotype, HIV Infections, HIV-1, Humans, Male, Microbial Sensitivity Tests, Middle Aged, Mutation, Nervous System Diseases, Viral Load, ANRS Resistance AC11 Group, ARV, CSF, HIV, resistance, Microbiology, Pharmacology and Pharmaceutical Sciences, Clinical sciences, Pharmacology and pharmaceutical sciences
Abstract

OBJECTIVES: The neurological disorders in HIV-1-infected patients remain prevalent. The HIV-1 resistance in plasma and CSF was compared in patients with neurological disorders in a multicentre study. METHODS: Blood and CSF samples were collected at time of neurological disorders for 244 patients. The viral loads were >50 copies/mL in both compartments and bulk genotypic tests were realized. RESULTS: On 244 patients, 89 and 155 were antiretroviral (ARV) naive and ARV treated, respectively. In ARV-naive patients, detection of mutations in CSF and not in plasma were reported for the reverse transcriptase (RT) gene in 2/89 patients (2.2%) and for the protease gene in 1/89 patients (1.1%). In ARV-treated patients, 19/152 (12.5%) patients had HIV-1 mutations only in the CSF for the RT gene and 30/151 (19.8%) for the protease gene. Two mutations appeared statistically more prevalent in the CSF than in plasma: M41L (P=0.0455) and T215Y (P=0.0455). CONCLUSIONS: In most cases, resistance mutations were present and similar in both studied compartments. However, in 3.4% of ARV-naive and 8.8% of ARV-treated patients, the virus was more resistant in CSF than in plasma. These results support the need for genotypic resistance testing when lumbar puncture is performed.

Published
2015

8. A real‐world study of alemtuzumab in a cohort of Italian patients

Author

Paola Cavalla, Laura Brambilla, Roberta Grasso, Cinzia Cordioli, Alice Laroni, Alessia Giugno, Valentina Torri Clerici, Maria Pia Sormani, Pietro Annovazzi, Francesco Saccà, Eleonora Cocco, Jessica Frau, Elisabetta Signoriello, Antonio Gallo, Marinella Clerico, Stefania Federica De Mercanti, Antonio Carotenuto, Simona Bonavita, Cinzia Valeria Russo, Giuseppe Fenu, Caterina Lapucci, Giorgia Teresa Maniscalco, Arianna Sartori, Francesca Caleri, Marco Capobianco, Alessio Signori, Rosa Iodice, Sara La Gioia, Giacomo Lus, Mauro Zaffaroni, Damiano Baroncini, Valeria Di Francescantonio, Russo, C. V., Sacca, F., Frau, J., Annovazzi, P., Signoriello, E., Bonavita, S., Grasso, R., Clerico, M., Cordioli, C., Laroni, A., Capobianco, M., Torri Clerici, V., Sartori, A., Cavalla, P., Maniscalco, G. T., La Gioia, S., Caleri, F., Giugno, A., Iodice, R., Carotenuto, A., Cocco, E., Fenu, G., Zaffaroni, M., Baroncini, D., Lus, G., Gallo, A., De Mercanti, S. F., Lapucci, C., Di Francescantonio, V., Brambilla, L., Sormani, M. P., Signori, A., Russo, CINZIA VALERIA, Sacca', Francesco, Frau, Jessica, Annovazzi, Pietro, Signoriello, Elisabetta, Bonavita, Simona, Grasso, Roberta, Clerico, Marinella, Cordioli, Cinzia, Laroni, Alice, Capobianco, Marco, Torri Clerici, Valentina, Sartori, Arianna, Cavalla, Paola, Teresa Maniscalco, Giorgia, La Gioia, Sara, Caleri, Francesca, Giugno, Alessia, Iodice, Rosa, Carotenuto, Antonio, Cocco, Eleonora, Fenu, Giuseppe, Zaffaroni, Mauro, Baroncini, Damiano, Lus, Giacomo, Gallo, Antonio, Federica De Mercanti, Stefania, Lapucci, Caterina, Di Francescantonio, Valeria, Brambilla, Laura, Pia Sormani, Maria, and Signori, Alessio

Subjects
Adult, safety, medicine.medical_specialty, efficacy, Multiple Sclerosis, Relapsing-Remitting, Natalizumab, Internal medicine, alemtuzumab, medicine, Humans, Glatiramer acetate, real-world evidence, Retrospective Studies, Expanded Disability Status Scale, Fingolimod Hydrochloride, business.industry, Multiple sclerosis, Glatiramer Acetate, cohort, medicine.disease, Fingolimod, Neurology, Relative risk, Cohort, Alemtuzumab, Neurology (clinical), business, medicine.drug
Abstract

Background and purpose: Real-world data on alemtuzumab are limited and do not provide evidence of its effectiveness after various disease-modifying therapies (DMTs). Our aim was to provide real-world data on the impact of clinical variables and previous DMTs on clinical response to alemtuzumab. Methods: Sixteen Italian multiple sclerosis centers retrospectively included patients who started alemtuzumab from January 2015 to December 2018, and recorded demographics, previous therapies, washout duration, relapses, Expanded Disability Status Scale (EDSS) score, and magnetic resonance imaging data. Negative binomial regression models were used to assess the effect of factors on annualized relapse (ARR) after alemtuzumab initiation. Results: We studied 322 patients (mean age 36.8years, median EDSS score 3, median follow-up 1.94years). Previous treatments were: fingolimod (106), natalizumab (80), first-line oral agents (56), first-line injectables (interferon/glatiramer acetate; 30), and other drugs (15). Thirty-five patients were treatment-naïve. The pre-alemtuzumab ARR was 0.99 and decreased to 0.13 during alemtuzumab treatment (p&nbsp

Published
2021

9. Compressed sensing (CS) MP2RAGE versus standard MPRAGE: A comparison of derived brain volume measurements

Author

Pilar Maria Ferraro, Lorenzo Gualco, Mauro Costagli, Simona Schiavi, Marta Ponzano, Alessio Signori, Federico Massa, Matteo Pardini, Lucio Castellan, Fabrizio Levrero, Domenico Zacà, Gian Franco Piredda, Tom Hilbert, Tobias Kober, and Luca Roccatagliata

Subjects
Imaging, Three-Dimensional, Biophysics, Humans, Brain, General Physics and Astronomy, Female, Breast Neoplasms, Radiology, Nuclear Medicine and imaging, General Medicine, Gray Matter, Magnetic Resonance Imaging
Abstract

T1 Magnetization Prepared Two Rapid Acquisition Gradient Echo (MP2RAGE) with compress sensing (CS) has been proposed as an improvement of the standard MPRAGE sequence with multiple advantages including reduced acquisition time needed to provide a quantitative 3D anatomical image coupled with T1-map. Here we investigated the agreement between FreeSurfer-derived volume measurements obtained from MPRAGE and CS MP2RAGE acquisitions.MPRAGE and CS MP2RAGE images of 37 subjects (14 patients with neurodegenerative disorders and 23 healthy controls) were acquired on a 3 T MR scanner and grey matter volumes were extracted using standard FreeSurfer parcellation. Lin's concordance correlation coefficient (Lin's CCC), Bland-Altman analysis, Passing-Bablok regression and DICE similarity coefficient were calculated to assess the agreement between the two.We found a good correspondence for most of the regions examined, with 93.5 % of them showing a mean DICE index0.70. Poorer results were found with Lin's CCC especially for subcortical labels across patients. The Bland-Altman analysis showed CS MP2RAGE tended to measure lower cortical volumes compared to MPRAGE but in most cases the difference wasn't statistically relevant. The Passing-Bablock regression indicated overall an absence of systematic constant and proportional bias when CS MP2RAGE was used instead of MPRAGE.We found a good concordance for volumes obtained from MPRAGE and CS MP2RAGE images using FreeSurfer, suggesting a possible role of CS MP2RAGE for structural analysis with significant advantages like shorter acquisition time and the possibility to simultaneously obtain quantitative T1-maps of the brain enriching the diagnostic power of this technique.

Published
2022

10. Mild behavioral impairment as a potential marker of predementia risk states in motor neuron diseases

Author

Pilar M. Ferraro, Ester Gervino, Emiliano De Maria, Giuseppe Meo, Marta Ponzano, Matteo Pardini, Alessio Signori, Angelo Schenone, Luca Roccatagliata, and Claudia Caponnetto

Subjects
Neurology, Amyotrophic Lateral Sclerosis, Humans, Cognitive Dysfunction, Dementia, Neurology (clinical), Neuropsychological Tests, Motor Neuron Disease
Abstract

Mild behavioral impairment (MBI) has been increasingly regarded as the neurobehavioral axis of predementia risk states, but a specific investigation of its detection as a potential marker of prodromal dementia in motor neuron diseases (MNDs) is still lacking. The aims of our study were therefore to explore MBI in MNDs both at onset and over the disease course, and to evaluate its relationship with baseline and longitudinal cognitive features.Sixty MND patients with cognitive/behavioral, mood, and motor examinations were recruited and followed longitudinally for up to 15 months. Associations between baseline MBI symptoms and clinical features were tested using the Spearman correlation coefficient. Based on longitudinal data, relative deltas of variation for each cognitive measure were generated, and linear regression models were then used to evaluate the role of baseline MBI symptoms in predicting longitudinal rates of cognitive decline.At disease onset, the most impaired MBI domain was affective/emotional dysregulation, followed by impulse dyscontrol, apathy, and social inappropriateness. Greater MBI symptoms correlated with more severe baseline motor, cognitive/behavioral, and mood disturbances (p values from0.001 to 0.05). Longitudinally, the greatest decline was observed in the affective/emotional dysregulation domain, followed by impulse dyscontrol, apathy, and social inappropriateness. Greater MBI symptoms at onset were significant predictors of more severe longitudinal cognitive decline in both amyotrophic lateral sclerosis (ALS)-specific and ALS-nonspecific functions (p values from0.001 to 0.03).MBI represents a valuable clinical marker of incident cognitive decline in MNDs, and its evaluation has good potential for detecting dementia in its preclinical/prodromal phase.

Published
2022

11. Signs and symptoms of COVID-19 in patients with multiple sclerosis

Author

Schiavetti I., Carmisciano L., Ponzano M., Cordioli C., Cocco E., Marfia G. A., Inglese M., Filippi M., Radaelli M., Bergamaschi R., Immovilli P., Capobianco M., De Rossi N., Brichetto G., Scandellari C., Cavalla P., Pesci I., Confalonieri P., Perini P., Trojano M., Lanzillo R., Tedeschi G., Comi G., Battaglia M. A., Patti F., Salvetti M., Sormani M. P., Abbadessa G., Aguglia U., Allegorico L., Rossi Allegri B. M., Alteno A., Amato M. P., Annovazzi P., Antozzi C., Appendino L., Arena S., Baione V., Balgera R., Barcella V., Baroncini D., Barrila C., Bellacosa A., Bellucci G., Bergamaschi V., Bezzini D., Biolzi B., Bisecco A., Bonavita S., Borriello G., Bosa C., Bosco A., Bovis F., Bozzali M., Brambilla L., Brescia Morra V., Buccafusca M., Bucciantini E., Bucello S., Buscarinu M. C., Cabboi M. P., Calabrese M., Calabria F., Caleri F., Camilli F., Caniatti L. M., Cantello R., Capra R., Capuano R., Carta P., Celani M. G., Cellerino M., Cerqua R., Chisari C., Clerici R., Clerico M., Cola G., Conte A., Conti M. Z., Cordano C., Cordera S., Corea F., Correale C., Cottone S., Crescenzo F., Curti E., d'Ambrosio A., D'Amico E., Danni M. C., d'Arma A., Dattola V., de Biase S., De Luca G., De Mercanti S. F., De Mitri P., De Stefano N., Della Cava F. M., Cava M. D., Di Lemme S., di Napoli M., Di Sapio A., Docimo R., Dutto A., Evangelista L., Fanara S., Fantozzi R., Ferraro D., Ferro M. T., Fioretti C., Fratta M., Frau J., Fronza M., Furlan R., Gajofatto A., Gallo A., Gallo P., Gasperini C., Ghazaryan A., Giometto B., Gobbin F., Govone F., Granella F., Grange E., Grasso M. G., Grimaldi L. M. E., Guareschi A., Guaschino C., Guerrieri S., Guidetti D., Juergenson I. B., Iaffaldano P., Ianniello A., Iasevoli L., Imperiale D., Infante M. T., Iodice R., Iovino A., Konrad G., Landi D., Lapucci C., Lavorgna L., L'Episcopo M. R., Leva S., Liberatore G., Lo Re M., Longoni M., Lopiano L., Lorefice L., Lucchini M., Lus G., Maimone D., Malentacchi M., Mallucci G., Malucchi S., Mancinelli C. R., Mancinelli L., Manganotti P., Maniscalco G. T., Mantero V., Marangoni S., Marastoni D., Marinelli F., Marti A., Boneschi Martinelli F., Masserano Z. F., Matta F., Mendozzi L., Meucci G., Miante S., Miele G., Milano E., Mirabella M., Missione R., Moccia M., Moiola L., Montepietra S., MontiBragadin M., Montini F., Motta R., Nardone R., Gabri Nicoletti C., Nobile-Orazio E., Nozzolillo A., Onofrj M., Orlandi R., Palmieri A., Paolicelli D., Pasquali L., Pasto L., Pedrazzoli E., Petracca M., Petrone A., Piantadosi C., Pietroboni A. M., Pinardi F., Portaccio E., Pozzato M., Pozzilli C., Prosperini L., Protti A., Ragonese P., Rasia S., Realmuto S., Repice A., Rigoni E., Rilla M. T., Rinaldi F., Romano C. M., Ronzoni M., Rovaris M., Ruscica F., Sabattini L., Salemi G., Saraceno L., Sartori A., Sbragia E., Scarano G. I., Scarano V., Sessa M., Sgarito C., Sibilia G., Siciliano G., Signori A., Signoriello E., Sinisi L., Sireci F., Sola P., Solaro C., Sotgiu S., Sparaco M., Stromillo M. L., Strumia S., Susani E. L., Tabiadon G., Teatini F., Tomassini V., Tonietti S., Torri V., Tortorella C., Toscano S., Totaro R., Trotta M., Turano G., Ulivelli M., Valentino M., Vaula G., Vecchio D., Vercellino M., Verrengia E. P., Vianello M., Virgilio E., Vitetta F., Vollaro S., Zaffaroni M., Zampolini M., Zarbo I. R., Zito A., Zuliani L., Schiavetti, Irene, Carmisciano, Luca, Ponzano, Marta, Cordioli, Cinzia, Cocco, Eleonora, Marfia, Girolama Alessandra, Inglese, Matilde, Filippi, Massimo, Radaelli, Marta, Bergamaschi, Roberto, Immovilli, Paolo, Capobianco, Marco, De Rossi, Nicola, Brichetto, Giampaolo, Scandellari, Cinzia, Cavalla, Paola, Pesci, Ilaria, Confalonieri, Paolo, Perini, Paola, Trojano, Maria, Lanzillo, Roberta, Tedeschi, Gioacchino, Comi, Giancarlo, Battaglia, Mario Alberto, Patti, Francesco, Salvetti, Marco, Sormani, Maria Pia, Gianmarco, Abbadessa, Umberto, Aguglia, Allegorico, Lia, Beatrice Maria Rossi Allegri, Anastasia, Alteno, Amato, MARIA PIA, Pietro, Annovazzi, Carlo, Antozzi, Lucia, Appendino, Sebastiano, Arena, Viola, Baione, Roberto, Balgera, Valeria, Barcella, Damiano, Baroncini, Caterina, Barrilà, Alessandra, Bellacosa, Gianmarco, Bellucci, Valeria, Bergamaschi, Daiana, Bezzini, Beatrice, Biolzi, Bisecco, Alvino, Simona, Bonavita, Giovanna, Borriello, Chiara, Bosa, Antonio, Bosco, Francesca, Bovi, Marco, Bozzali, Laura, Brambilla, BRESCIA MORRA, Vincenzo, Maria, Buccafusca, Elisabetta, Bucciantini, Sebastiano, Bucello, Maria Chiara Buscarinu, Maria Paola Cabboi, Massimiliano, Calabrese, Francesca, Calabria, Francesca, Caleri, Federico, Camilli, Luisa Maria Caniatti, Roberto, Cantello, Ruggero, Capra, Rocco, Capuano, Patrizia, Carta, Maria Grazia Celani, Maria, Cellerino, Raffaella, Cerqua, Clara, Chisari, Raffaella, Clerici, Marinella, Clerico, Gaia, Cola, Antonella, Conte, Marta Zaffira Conti, Christian, Cordano, Susanna, Cordera, Francesco, Corea, Claudio, Correale, Salvatore, Cottone, Francesco, Crescenzo, Erica, Curti, Alessandro, D’Ambrosio, Emanuele, D’Amico, Maura Chiara Danni, Alessia, D’Arma, Vincenzo, Dattola, Stefano de Biase, Giovanna De Luca, Stefania Federica De Mercanti, Paolo De Mitri, Nicola De Stefano, Fabio Maria Della Cava, Marco Della Cava, Sonia Di Lemme, Mario di Napoli, Alessia Di Sapio, Renato, Docimo, Anna, Dutto, Luana, Evangelista, Salvatore, Fanara, Roberta, Fantozzi, Diana, Ferraro, Maria Teresa Ferrò, Cristina, Fioretti, Mario, Fratta, Jessica, Frau, Marzia, Fronza, Roberto, Furlan, Alberto, Gajofatto, Gallo, Antonio, Paolo, Gallo, Claudio, Gasperini, Anna, Ghazaryan, Bruno, Giometto, Francesca, Gobbin, Flora, Govone, Franco, Granella, Erica, Grange, Grasso, MARIA GRAZIA, Grimaldi, Luigi M. E., Angelica, Guareschi, Clara, Guaschino, Simone, Guerrieri, Donata, Guidetti, Ina Barbara Juergenson, Pietro, Iaffaldano, Ianniello, Antonio, Luigi, Iasevoli, Daniele, Imperiale, Maria Teresa Infante, Iodice, Rosa, Iovino, Aniello, Giovanna, Konrad, Doriana, Landi, Caterina, Lapucci, Luigi, Lavorgna, Maria Rita L’Episcopo, Serena, Leva, Giuseppe, Liberatore, Marianna Lo Re, Marco, Longoni, Leonardo, Lopiano, Lorena, Lorefice, Matteo, Lucchini, Lus, Giacomo, Maimone, Davide, Maria, Malentacchi, Giulia, Mallucci, Simona, Malucchi, Chiara Rosa Mancinelli, Luca, Mancinelli, Paolo, Manganotti, Giorgia Teresa Maniscalco, Vittorio, Mantero, Sabrina, Marangoni, Damiano, Marastoni, Fabiana, Marinelli, Marti, NICOLA ALESSANDRO, Filippo Boneschi Martinelli, Zoli Federco Masserano, Francesca, Matta, Laura, Mendozzi, Giuseppe, Meucci, Silvia, Miante, Giuseppina, Miele, Eva, Milano, Massimiliano, Mirabella, Rosanna, Missione, Moccia, Marcello, Lucia, Moiola, Sara, Montepietra, Margherita, Montibragadin, Federico, Montini, Roberta, Motta, Raffaele, Nardone, Carolina Gabri Nicoletti, Eduardo, Nobile‐orazio, Nozzolillo, Agostino, Marco, Onofrj, Riccardo, Orlandi, Anna, Palmieri, Damiano, Paolicelli, Livia, Pasquali, Luisa, Pastò, Elisabetta, Pedrazzoli, Petracca, Maria, Alfredo, Petrone, Carlo, Piantadosi, Pietroboni, Anna M., Federica, Pinardi, Emilio, Portaccio, Mattia, Pozzato, Pozzilli, Carlo, Luca, Prosperini, Alessandra, Protti, Paolo, Ragonese, Sarah, Rasia, Sabrina, Realmuto, Anna, Repice, Eleonora, Rigoni, Maria Teresa Rilla, DELLA RATTA RINALDI, Francesca, Calogero Marcello Romano, Marco, Ronzoni, Marco, Rovari, Francesca, Ruscica, Loredana, Sabattini, Giuseppe, Salemi, Lorenzo, Saraceno, Alessia, Sartori, Arianna, Sartori, Elvira, Sbragia, Giuditta Ilaria Scarano, Valentina, Scarano, Maria, Sessa, Caterina, Sgarito, Sibilia, Grazia, Gabriele, Siciliano, Alessio, Signori, Signoriello, Elisabetta, Sinisi, Leonardo, Francesca, Sireci, Patrizia, Sola, Claudio, Solaro, Stefano, Sotgiu, Maddalena, Sparaco, Maria Laura Stromillo, Silvia, Strumia, Emanuela Laura Susani, Giulietta, Tabiadon, Francesco, Teatini, Valentina, Tomassini, Simone, Tonietti, Valentina, Torri, Tortorella, Carla, Simona, Toscano, Rocco, Totaro, Maria, Trotta, Gabriella, Turano, Monica, Ulivelli, Manzo, Valentino, Giovanna, Vaula, Domizia, Vecchio, Marco, Vercellino, Elena Pinuccia Verrengia, Marika, Vianello, Eleonora, Virgilio, Francesca, Vitetta, Vollaro, Stefano, Mauro, Zaffaroni, Mauro, Zampolini, Ignazio Roberto Zarbo, Antonio, Zito, and Luigi Zuliani, Schiavetti, I., Carmisciano, L., Ponzano, M., Cordioli, C., Cocco, E., Marfia, G. A., Inglese, M., Filippi, M., Radaelli, M., Bergamaschi, R., Immovilli, P., Capobianco, M., De Rossi, N., Brichetto, G., Scandellari, C., Cavalla, P., Pesci, I., Confalonieri, P., Perini, P., Trojano, M., Lanzillo, R., Tedeschi, G., Comi, G., Battaglia, M. A., Patti, F., Salvetti, M., Sormani, M. P., Abbadessa, G., Aguglia, U., Allegorico, L., Rossi Allegri, B. M., Alteno, A., Amato, M. P., Annovazzi, P., Antozzi, C., Appendino, L., Arena, S., Baione, V., Balgera, R., Barcella, V., Baroncini, D., Barrila, C., Bellacosa, A., Bellucci, G., Bergamaschi, V., Bezzini, D., Biolzi, B., Bisecco, A., Bonavita, S., Borriello, G., Bosa, C., Bosco, A., Bovis, F., Bozzali, M., Brambilla, L., Brescia Morra, V., Buccafusca, M., Bucciantini, E., Bucello, S., Buscarinu, M. C., Cabboi, M. P., Calabrese, M., Calabria, F., Caleri, F., Camilli, F., Caniatti, L. M., Cantello, R., Capra, R., Capuano, R., Carta, P., Celani, M. G., Cellerino, M., Cerqua, R., Chisari, C., Clerici, R., Clerico, M., Cola, G., Conte, A., Conti, M. Z., Cordano, C., Cordera, S., Corea, F., Correale, C., Cottone, S., Crescenzo, F., Curti, E., D'Ambrosio, A., D'Amico, E., Danni, M. C., D'Arma, A., Dattola, V., de Biase, S., De Luca, G., De Mercanti, S. F., De Mitri, P., De Stefano, N., Della Cava, F. M., Cava, M. D., Di Lemme, S., di Napoli, M., Di Sapio, A., Docimo, R., Dutto, A., Evangelista, L., Fanara, S., Fantozzi, R., Ferraro, D., Ferro, M. T., Fioretti, C., Fratta, M., Frau, J., Fronza, M., Furlan, R., Gajofatto, A., Gallo, A., Gallo, P., Gasperini, C., Ghazaryan, A., Giometto, B., Gobbin, F., Govone, F., Granella, F., Grange, E., Grasso, M. G., Grimaldi, L. M. E., Guareschi, A., Guaschino, C., Guerrieri, S., Guidetti, D., Juergenson, I. B., Iaffaldano, P., Ianniello, A., Iasevoli, L., Imperiale, D., Infante, M. T., Iodice, R., Iovino, A., Konrad, G., Landi, D., Lapucci, C., Lavorgna, L., L'Episcopo, M. R., Leva, S., Liberatore, G., Lo Re, M., Longoni, M., Lopiano, L., Lorefice, L., Lucchini, M., Lus, G., Maimone, D., Malentacchi, M., Mallucci, G., Malucchi, S., Mancinelli, C. R., Mancinelli, L., Manganotti, P., Maniscalco, G. T., Mantero, V., Marangoni, S., Marastoni, D., Marinelli, F., Marti, A., Boneschi Martinelli, F., Masserano, Z. F., Matta, F., Mendozzi, L., Meucci, G., Miante, S., Miele, G., Milano, E., Mirabella, M., Missione, R., Moccia, M., Moiola, L., Montepietra, S., Montibragadin, M., Montini, F., Motta, R., Nardone, R., Gabri Nicoletti, C., Nobile-Orazio, E., Nozzolillo, A., Onofrj, M., Orlandi, R., Palmieri, A., Paolicelli, D., Pasquali, L., Pasto, L., Pedrazzoli, E., Petracca, M., Petrone, A., Piantadosi, C., Pietroboni, A. M., Pinardi, F., Portaccio, E., Pozzato, M., Pozzilli, C., Prosperini, L., Protti, A., Ragonese, P., Rasia, S., Realmuto, S., Repice, A., Rigoni, E., Rilla, M. T., Rinaldi, F., Romano, C. M., Ronzoni, M., Rovaris, M., Ruscica, F., Sabattini, L., Salemi, G., Saraceno, L., Sartori, A., Sbragia, E., Scarano, G. I., Scarano, V., Sessa, M., Sgarito, C., Sibilia, G., Siciliano, G., Signori, A., Signoriello, E., Sinisi, L., Sireci, F., Sola, P., Solaro, C., Sotgiu, S., Sparaco, M., Stromillo, M. L., Strumia, S., Susani, E. L., Tabiadon, G., Teatini, F., Tomassini, V., Tonietti, S., Torri, V., Tortorella, C., Toscano, S., Totaro, R., Trotta, M., Turano, G., Ulivelli, M., Valentino, M., Vaula, G., Vecchio, D., Vercellino, M., Verrengia, E. P., Vianello, M., Virgilio, E., Vitetta, F., Vollaro, S., Zaffaroni, M., Zampolini, M., Zarbo, I. R., Zito, A., and Zuliani, L.

Subjects
Multiple Sclerosis, Anosmia, Clinical Sciences, neurological disorders, Neurodegenerative, Settore MED/26, demyelinating disease, COVID-19, demyelinating diseases, disease-modifying treatment, multiple sclerosis, Humans, neurological disorder, Aged, Neurology & Neurosurgery, SARS-CoV-2, Pain Research, Neurosciences, Brain Disorders, Settore MED/26 - NEUROLOGIA, Good Health and Well Being, Neurology, multiple sclerosi, Neurology (clinical), MuSC-19 Study Group, Ageusia, Human
Abstract

Background and purpose: Clinical outcomes of multiple sclerosis (MS) patients affected by coronavirus disease 2019 (COVID-19) have been thoroughly investigated, but a further analysis on main signs and symptoms and their risk factors still needs attention. The objective of this study was to group together and describe based on similarity the most common signs and symptoms of COVID-19 in MS patients and identify all factors associated with their manifestation. Method: Logistic and linear regression models were run to recognize factors associated with each pooled group of symptoms and their total number. Results: From March 2020 to November 2021, data were collected from 1354 MS patients with confirmed infection of COVID-19. Ageusia and anosmia was less frequent in older people (odds ratio [OR] 0.98; p=0.005) and more in smoker patients (OR 1.39; p=0.049). Smoke was also associated with an incremental number of symptoms (OR 1.24; p=0.031), substance abuse (drugs or alcohol), conjunctivitis and rash (OR 5.20; p=0.042) and the presence of at least one comorbidity with shortness of breath, tachycardia or chest pain (OR 1.24; p=0.008). Some disease-modifying therapies were associated with greater frequencies of certain COVID-19 symptoms (association between anti-CD20 therapies and increment in the number of concomitant symptoms: OR 1.29; p=0.05). Differences in frequencies between the three waves were found for flu-like symptoms (G1, p=0.024), joint or muscle pain (G2, p=0.013) and ageusia and anosmia (G5, p < 0.001). All cases should be referred to variants up to Delta. Conclusion: Several factors along with the choice of specific therapeutic approaches might have a different impact on the occurrence of some COVID-19 symptoms.

Published
2022

12. The effect of air pollution on COVID‐19 severity in a sample of patients with multiple sclerosis

Author

Bergamaschi, Roberto, Ponzano, Marta, Schiavetti, Irene, Carmisciano, Luca, Cordioli, Cinzia, Filippi, Massimo, Radaelli, Marta, Immovilli, Paolo, Capobianco, Marco, De Rossi, Nicola, Brichetto, Giampaolo, Cocco, Eleonora, Scandellari, Cinzia, Cavalla, Paola, Pesci, Ilaria, Zito, Antonio, Confalonieri, Paolo, Marfia, Girolama Alessandra, Perini, Paola, Inglese, Matilde, Trojano, Maria, Brescia Morra, Vincenzo, Pisoni, Enrico, Tedeschi, Gioacchino, Comi, Giancarlo, Battaglia, Mario Alberto, Patti, Francesco, Salvetti, Marco, Sormani, Maria Pia, Gianmarco Abbadessa, Umberto Aguglia, Lia Allegorico, Rossi Beatrice Maria Allegri, Anastasia Alteno, Maria Pia Amato, Pietro Annovazzi, Carlo Antozzi, Lucia Appendino, Sebastiano Arena, Viola Baione, Roberto Balgera, Valeria Barcella, Damiano Baroncini, Caterina Barrilà, Mario A Battaglia, Alessandra Bellacosa, Gianmarco Bellucci, Roberto Bergamaschi, Valeria Bergamaschi, Daiana Bezzini, Beatrice Biolzi, Alvino Bisecco, Simona Bonavita, Giovanna Borriello, Chiara Bosa, Antonio Bosco, Francesca Bovis, Marco Bozzali, Laura Brambilla, Morra Vincenzo Brescia, Giampaolo Brichetto, Maria Buccafusca, Elisabetta Bucciantini, Sebastiano Bucello, Maria Chiara Buscarinu, Maria Paola Cabboi, Massimiliano Calabrese, Francesca Calabria, Francesca Caleri, Federico Camilli, Luisa Maria Caniatti, Roberto Cantello, Marco Capobianco, Ruggero Capra, Rocco Capuano, Luca Carmisciano, Patrizia Carta, Paola Cavalla, Maria Grazia Celani, Maria Cellerino, Raffaella Cerqua, Clara Chisari, Raffaella Clerici, Marinella Clerico, Eleonora Cocco, Gaia Cola, Giancarlo Comi, Paolo Confalonieri, Antonella Conte, Marta Zaffira Conti, Christian Cordano, Susanna Cordera, Cinzia Cordioli, Francesco Corea, Claudio Correale, Salvatore Cottone, Francesco Crescenzo, Erica Curti, Alessandro d'Ambrosio, Emanuele D'Amico, Maura Chiara Danni, Alessia d'Arma, Vincenzo Dattola, Stefano de Biase, Giovanna De Luca, Stefania Federica De Mercanti, Paolo De Mitri, Nicola De Rossi, Nicola De Stefano, Cava Marco Della, Mario di Napoli, Alessia Di Sapio, Renato Docimo, Anna Dutto, Luana Evangelista, Salvatore Fanara, Diana Ferraro, Maria Teresa Ferrò, Massimo Filippi, Cristina Fioretti, Mario Fratta, Jessica Frau, Marzia Fronza, Roberto Furlan, Alberto Gajofatto, Antonio Gallo, Paolo Gallo, Claudio Gasperini, Anna Ghazaryan, Bruno Giometto, Francesca Gobbin, Flora Govone, Franco Granella, Erica Grange, Maria Grazia Grasso, Angelica Guareschi, Clara Guaschino, Simone Guerrieri, Donata Guidetti, Pietro Iaffaldano, Antonio Ianniello, Luigi Iasevoli, Paolo Immovilli, Daniele Imperiale, Maria Teresa Infante, Matilde Inglese, Rosa Iodice, Aniello Iovino, Giovanna Konrad, Doriana Landi, Roberta Lanzillo, Caterina Lapucci, Luigi Lavorgna, Maria Rita L'Episcopo, Serena Leva, Giuseppe Liberatore, Re Marianna Lo, Marco Longoni, Leonardo Lopiano, Lorena Lorefice, Matteo Lucchini, Giacomo Lus, Davide Maimone, Maria Malentacchi, Giulia Mallucci, Simona Malucchi, Chiara Rosa Mancinelli, Luca Mancinelli, Paolo Manganotti, Giorgia Teresa Maniscalco, Vittorio Mantero, Sabrina Marangoni, Damiano Marastoni, Girolama Alessandra Marfia, Fabiana Marinelli, Alessandro Marti, Boneschi Filippo Martinelli, Zoli Federco Masserano, Francesca Matta, Laura Mendozzi, Giuseppe Meucci, Silvia Miante, Giuseppina Miele, Eva Milano, Massimiliano Mirabella, Rosanna Missione, Marcello Moccia, Lucia Moiola, Sara Montepietra, Margherita MontiBragadin, Federico Montini, Roberta Motta, Raffaele Nardone, Carolina Gabri Nicoletti, Eduardo Nobile-Orazio, Agostino Nozzolillo, Marco Onofrj, Riccardo Orlandi, Anna Palmieri, Damiano Paolicelli, Livia Pasquali, Luisa Pastò, Francesco Patti, Elisabetta Pedrazzoli, Paola Perini, Ilaria Pesci, Maria Petracca, Alfredo Petrone, Carlo Piantadosi, Anna M Pietroboni, Federica Pinardi, Marta Ponzano, Emilio Portaccio, Mattia Pozzato, Carlo Pozzilli, Luca Prosperini, Alessandra Protti, Marta Radaelli, Paolo Ragonese, Sarah Rasia, Sabrina Realmuto, Anna Repice, Eleonora Rigoni, Maria Teresa Rilla, Francesca Rinaldi, Calogero Marcello Romano, Marco Ronzoni, Marco Rovaris, Francesca Ruscica, Loredana Sabattini, Giuseppe Salemi, Marco Salvetti, Lorenzo Saraceno, Alessia Sartori, Arianna Sartori, Elvira Sbragia, Cinzia Scandellari, Giuditta Ilaria Scarano, Valentina Scarano, Irene Schiavetti, Maria Sessa, Caterina Sgarito, Grazia Sibilia, Gabriele Siciliano, Alessio Signori, Elisabetta Signoriello, Leonardo Sinisi, Francesca Sireci, Patrizia Sola, Claudio Solaro, Maria Pia Sormani, Stefano Sotgiu, Maddalena Sparaco, Maria Laura Stromillo, Silvia Strumia, Emanuela Laura Susani, Giulietta Tabiadon, Francesco Teatini, Gioacchino Tedeschi, Valentina Tomassini, Simone Tonietti, Clerici Valentina Torri, Carla Tortorella, Simona Toscano, Rocco Totaro, Maria Trojano, Maria Trotta, Gabriella Turano, Monica Ulivelli, Manzo Valentino, Giovanna Vaula, Domizia Vecchio, Marco Vercellino, Elena Pinuccia Verrengia, Marika Vianello, Eleonora Virgilio, Francesca Vitetta, Stefano Vollaro, Mauro Zaffaroni, Mauro Zampolini, Ignazio Roberto Zarbo, Antonio Zito, Luigi Zuliani, Bergamaschi, R, Ponzano, M, Schiavetti, I, Carmisciano, L, Cordioli, C, Filippi, M, Radaelli, M, Immovilli, P, Capobianco, M, De Rossi, N, Brichetto, G, Cocco, E, Scandellari, C, Cavalla, P, Pesci, I, Zito, A, Confalonieri, P, Marfia, Ga, Perini, P, Inglese, M, Trojano, M, Brescia Morra, V, Pisoni, E, Tedeschi, G, Comi, G, Battaglia, Ma, Patti, F, Salvetti, M, Sormani, Mp, Abbadessa, Gianmarco, Umberto, Aguglia, Lia, Allegorico, Rossi Beatrice Maria Allegri, Anastasia, Alteno, Maria Pia Amato, Pietro, Annovazzi, Carlo, Antozzi, Lucia, Appendino, Sebastiano, Arena, Viola, Baione, Roberto, Balgera, Valeria, Barcella, Damiano, Baroncini, Caterina, Barrilà, Mario, A Battaglia, Alessandra, Bellacosa, Gianmarco, Bellucci, Roberto, Bergamaschi, Valeria, Bergamaschi, Daiana, Bezzini, Beatrice, Biolzi, Bisecco, Alvino, Bonavita, Simona, Giovanna, Borriello, Chiara, Bosa, Bosco, Antonio, Francesca, Bovi, Marco, Bozzali, Laura, Brambilla, Morra Vincenzo Brescia, Giampaolo, Brichetto, Maria, Buccafusca, Elisabetta, Bucciantini, Sebastiano, Bucello, Maria Chiara Buscarinu, Maria Paola Cabboi, Massimiliano, Calabrese, Francesca, Calabria, Francesca, Caleri, Federico, Camilli, Luisa Maria Caniatti, Roberto, Cantello, Marco, Capobianco, Ruggero, Capra, Capuano, Rocco, Luca, Carmisciano, Patrizia, Carta, Paola, Cavalla, Maria Grazia Celani, Maria, Cellerino, Raffaella, Cerqua, Clara, Chisari, Raffaella, Clerici, Marinella, Clerico, Eleonora, Cocco, Gaia, Cola, Giancarlo, Comi, Paolo, Confalonieri, Antonella, Conte, Marta Zaffira Conti, Christian, Cordano, Susanna, Cordera, Cinzia, Cordioli, Corea, Francesco, Claudio, Correale, Salvatore, Cottone, Francesco, Crescenzo, Erica, Curti, Alessandro, D'Ambrosio, Emanuele, D'Amico, Maura Chiara Danni, Alessia, D'Arma, Vincenzo, Dattola, Stefano de Biase, Giovanna De Luca, Stefania Federica De Mercanti, Paolo De Mitri, Nicola De Rossi, Nicola De Stefano, Cava Marco Della, Mario di Napoli, Alessia Di Sapio, Docimo, Renato, Anna, Dutto, Luana, Evangelista, Salvatore, Fanara, Diana, Ferraro, Maria Teresa Ferrò, Massimo, Filippi, Cristina, Fioretti, Fratta, Mario, Jessica, Frau, Marzia, Fronza, Roberto, Furlan, Alberto, Gajofatto, Gallo, Antonio, Paolo, Gallo, Claudio, Gasperini, Anna, Ghazaryan, Bruno, Giometto, Francesca, Gobbin, Flora, Govone, Franco, Granella, Erica, Grange, Maria Grazia Grasso, Angelica, Guareschi, Clara, Guaschino, Simone, Guerrieri, Donata, Guidetti, Pietro, Iaffaldano, Antonio, Ianniello, Luigi, Iasevoli, Paolo, Immovilli, Daniele, Imperiale, Maria Teresa Infante, Matilde, Inglese, Rosa, Iodice, Aniello, Iovino, Giovanna, Konrad, Doriana, Landi, Roberta, Lanzillo, Caterina, Lapucci, Luigi, Lavorgna, Maria Rita L'Episcopo, Serena, Leva, Giuseppe, Liberatore, Re Marianna Lo, Marco, Longoni, Leonardo, Lopiano, Lorena, Lorefice, Matteo, Lucchini, Lus, Giacomo, Davide, Maimone, Maria, Malentacchi, Giulia, Mallucci, Simona, Malucchi, Chiara Rosa Mancinelli, Luca, Mancinelli, Paolo, Manganotti, Giorgia Teresa Maniscalco, Vittorio, Mantero, Sabrina, Marangoni, Damiano, Marastoni, Girolama Alessandra Marfia, Fabiana, Marinelli, Alessandro, Marti, Boneschi Filippo Martinelli, Zoli Federco Masserano, Francesca, Matta, Laura, Mendozzi, Giuseppe, Meucci, Silvia, Miante, Miele, Giuseppina, Eva, Milano, Massimiliano, Mirabella, Missione, Rosanna, Marcello, Moccia, Lucia, Moiola, Sara, Montepietra, Margherita, Montibragadin, Federico, Montini, Roberta, Motta, Raffaele, Nardone, Carolina Gabri Nicoletti, Eduardo, Nobile-Orazio, Agostino, Nozzolillo, Marco, Onofrj, Riccardo, Orlandi, Palmieri, Anna, Damiano, Paolicelli, Livia, Pasquali, Luisa, Pastò, Francesco, Patti, Elisabetta, Pedrazzoli, Paola, Perini, Ilaria, Pesci, Maria, Petracca, Alfredo, Petrone, Carlo, Piantadosi, Anna, M Pietroboni, Federica, Pinardi, Marta, Ponzano, Emilio, Portaccio, Mattia, Pozzato, Carlo, Pozzilli, Luca, Prosperini, Alessandra, Protti, Marta, Radaelli, Paolo, Ragonese, Sarah, Rasia, Sabrina, Realmuto, Anna, Repice, Eleonora, Rigoni, Maria Teresa Rilla, Francesca, Rinaldi, Calogero Marcello Romano, Marco, Ronzoni, Marco, Rovari, Francesca, Ruscica, Loredana, Sabattini, Giuseppe, Salemi, Marco, Salvetti, Lorenzo, Saraceno, Alessia, Sartori, Arianna, Sartori, Elvira, Sbragia, Cinzia, Scandellari, Giuditta Ilaria Scarano, Valentina, Scarano, Irene, Schiavetti, Maria, Sessa, Caterina, Sgarito, Grazia, Sibilia, Gabriele, Siciliano, Alessio, Signori, Signoriello, Elisabetta, Leonardo, Sinisi, Francesca, Sireci, Patrizia, Sola, Claudio, Solaro, Maria Pia Sormani, Stefano, Sotgiu, Sparaco, Maddalena, Maria Laura Stromillo, Silvia, Strumia, Emanuela Laura Susani, Giulietta, Tabiadon, Francesco, Teatini, Tedeschi, Gioacchino, Valentina, Tomassini, Simone, Tonietti, Clerici Valentina Torri, Carla, Tortorella, Simona, Toscano, Rocco, Totaro, Maria, Trojano, Trotta, Maria Consiglia, Gabriella, Turano, Monica, Ulivelli, Manzo, Valentino, Giovanna, Vaula, Domizia, Vecchio, Marco, Vercellino, Elena Pinuccia Verrengia, Marika, Vianello, Eleonora, Virgilio, Francesca, Vitetta, Stefano, Vollaro, Mauro, Zaffaroni, Mauro, Zampolini, Ignazio Roberto Zarbo, Zito, Guido Antonio, Bergamaschi, R., Ponzano, M., Schiavetti, I., Carmisciano, L., Cordioli, C., Filippi, M., Radaelli, M., Immovilli, P., Capobianco, M., De Rossi, N., Brichetto, G., Cocco, E., Scandellari, C., Cavalla, P., Pesci, I., Zito, A., Confalonieri, P., Marfia, G. A., Perini, P., Inglese, M., Trojano, M., Brescia Morra, V., Pisoni, E., Tedeschi, G., Comi, G., Battaglia, M. A., Patti, F., Salvetti, M., Sormani, M. P., Bergamaschi, Roberto, Ponzano, Marta, Schiavetti, Irene, Carmisciano, Luca, Cordioli, Cinzia, Filippi, Massimo, Radaelli, Marta, Immovilli, Paolo, Capobianco, Marco, De Rossi, Nicola, Brichetto, Giampaolo, Cocco, Eleonora, Scandellari, Cinzia, Cavalla, Paola, Pesci, Ilaria, Zito, Antonio, Confalonieri, Paolo, Marfia, Girolama Alessandra, Perini, Paola, Inglese, Matilde, Trojano, Maria, Brescia Morra, Vincenzo, Pisoni, Enrico, Comi, Giancarlo, Battaglia, Mario Alberto, Patti, Francesco, Salvetti, Marco, Sormani, Maria, Pia, Gianmarco, Abbadessa, Alvino, Bisecco, Simona, Bonavita, Antonio, Bosco, Rocco, Capuano, Francesco, Corea, Renato, Docimo, Mario, Fratta, Antonio, Gallo, Iodice, Rosa, Iovino, Aniello, Lanzillo, Roberta, Giacomo, Lu, Giuseppina, Miele, Rosanna, Missione, Moccia, Marcello, Anna, Palmieri, Elisabetta, Signoriello, Maddalena, Sparaco, Gioacchino, Tedeschi, Maria, Trotta, Antonio, Zito, and Luigi, Zuliani

Subjects
air pollution, coronavirus, multiple sclerosis, medicine.medical_specialty, Multivariate analysis, Coronavirus disease 2019 (COVID-19), Clinical Sciences, Air pollution, Sample (statistics), Neurodegenerative, Settore MED/26, medicine.disease_cause, Autoimmune Disease, law.invention, Sustainable Cities and Communities, Clinical Research, law, Humans, Medicine, Climate-Related Exposures and Conditions, Neurology & Neurosurgery, MuSC-19 study group, SARS-CoV-2, business.industry, Multiple sclerosis, Neurosciences, COVID-19, Retrospective cohort study, Original Articles, medicine.disease, Intensive care unit, Particulate Matter, Air Pollution, Multiple Sclerosis, Brain Disorders, coronaviru, Settore MED/26 - NEUROLOGIA, Good Health and Well Being, Neurology, multiple sclerosi, Emergency medicine, Original Article, Neurology (clinical), Ordered logit, business, Human
Abstract

Background and purpose Some studies have shown that air pollution, often assessed by thin particulate matter with diameter below 2.5 µg/m3 (PM2.5), may contribute to severe COVID‐19 courses, as well as play a role in the onset and evolution of multiple sclerosis (MS). However, the impact of air pollution on COVID‐19 has never been explored specifically amongst patients with MS (PwMS). This retrospective observational study aims to explore associations between PM2.5 and COVID‐19 severity amongst PwMS. Methods Data were retrieved from an Italian web‐based platform (MuSC‐19) which includes PwMS with COVID‐19. PM2.5 2016–2018 average concentrations were provided by the Copernicus Atmospheric Monitoring Service. Italian patients inserted in the platform from 15 January 2020 to 9 April 2021 with a COVID‐19 positive test were included. Ordered logistic regression models were used to study associations between PM2.5 and COVID‐19 severity. Results In all, 1087 patients, of whom 13% required hospitalization and 2% were admitted to an intensive care unit or died, were included. Based on the multivariate analysis, higher concentrations of PM2.5 increased the risk of worse COVID‐19 course (odds ratio 1.90; p = 0.009). Conclusions Even if several other factors explain the unfavourable course of COVID‐19 in PwMS, the role of air pollutants must be considered and further investigated., Air pollution, often assessed by particulate matter with diameter below 2.5 µg/m3, may contribute to severe COVID‐19 courses. 1087 patients were included, of whom 13% required hospitalization and 2% were admitted to an intensive care unit or died. Even if several other factors explain the unfavourable course of COVID‐19 in patients with multiple sclerosis, the role of air pollutants must be considered and further investigated.

Published
2021

13. Systemic therapy for pre-treated malignant mesothelioma: A systematic review, meta-analysis and network meta-analysis of randomised controlled trials

Author

Giuseppe Luigi Banna, Alessio Signori, Alessandra Curioni-Fontecedro, Alessio Cortellini, Marta Ponzano, Emilio Francesco Giunta, Sara Elena Rebuzzi, Samuel Chan, Vittorio Gebbia, Ronwyn van Eeden, Alfredo Addeo, and Christian Ottensmeier

Subjects
CTLA4, Mesothelioma, Cancer Research, Mesothelioma, Malignant, Antibodies, Monoclonal, Angiogenesis Inhibitors, Pre-treated, Randomised controlled trials, PD1, Meta-analysis, Oncology, Systematic review, Humans, Chemotherapy, Immunotherapy, Network meta-analysis
Abstract

Randomised controlled trials (RCTs) with systemic therapies for patients with pre-treated mesothelioma have reported equivocal efficacy results and generated a degree of clinical uncertainty about the choice of active treatment in this poor prognosis malignancy.To compare the effectiveness and safety and weigh the benefit of different systemic treatments in patients with pre-treated mesothelioma by systematic review, meta-analysis and network meta-analysis of RCTs. Full-text articles and abstracts were searched on PubMed, EMBASE, Cochrane Library and oncology conferences proceedings from 2005 through November 2021 for phase 2 and 3 RCTs. The protocol was submitted to the PROSPERO registry. Reporting followed the PRISMA guideline. Outcomes of interest were overall survival (OS) and progression-free (PFS), grade ≥3 treatment-related (Tr) adverse events (AEs), Tr-deaths and Tr-AEs leading to treatment discontinuation.Nine trials at low risk of bias by Cochrane Collaboration's methodology were included, encompassing 2789 patients. Five studies showed PFS benefit in the experimental treatment. In two studies, OS was prolonged by immunotherapy (versus placebo) or by adding an antiangiogenic agent to chemotherapy. Reported Tr-AE were lower with single-agent anti-PD1 compared with chemotherapy or placebo. The meta-analysis revealed a beneficial global effect on OS and PFS from experimental treatments (HR 0.86, 95% CI 0.77-0.96, p = 0.0083 and HR 0.79, 95% CI 0.72-0.86, p 0.001), that for the PFS significantly favoured the comparison with non-active treatments (HR 0.73, 95% CI 0.66-0.81, p 0.001). Younger patients (i.e. 65-70 years) appeared to benefit the most in OS (HR 0.71, 95% CI 0.55-0.92, p = 0.04). The risk of serious Tr-AEs and Tr-deaths was not significantly increased by experimental treatments (RR 1.38, 95% CI 0.81-2.35, p = 0.24 and RR 2.07, 95% CI 0.69-6.24, p = 0.19, respectively) that instead increased TrAEs leading to treatment discontinuation (RR 2.9, 95% CI 1.44-6.08, p = 0.003). The network meta-analysis did not identify any superior treatment in PFS.For patients with pre-treated MPM, single-agent anti-PD1 or chemotherapy ± the antiangiogenic agent can be considered active and safe systemic therapeutic options, particularly for younger patients.

Published
2022

14. Prevalence of disability improvement in relapsing–remitting multiple sclerosis patients treated with cladribine tablets

Author

Alessio Signori, Marta Ponzano, Nektaria Alexandri, Gavin Giovannoni, and Maria Pia Sormani

Subjects
Multiple Sclerosis, Relapsing-Remitting, Neurology, Prevalence, Cladribine, Humans, Neurology (clinical), Immunosuppressive Agents, Tablets
Abstract

The aim was to show the application of the prevalence estimator of Expanded Disability Status Scale (EDSS) improvement over time in patients treated with cladribine tablets in the phase III CLARITY/CLARITY extension trials.Relapsing-remitting multiple sclerosis patients who entered the CLARITY extension study were evaluated. Patients originally randomized in CLARITY to cladribine tablets 3.5 mg/kg and placebo in CLARITY extension (early cladribine [EC]) were compared to patients originally randomized to placebo and then assigned to cladribine tablets 3.5 mg/kg (delayed cladribine [DC]). The EC group was compared to the DC group on the prevalence of EDSS improvement over time and on the cumulative incidence of EDSS improvement. Prevalence of improvement was assessed by a new approach based on the difference of Kaplan-Meier estimators, whilst the incidence of improvement was assessed by standard Kaplan-Meier curves.A total of 98 patients in the EC group and 244 patients in the DC group were compared. Patients in the EC group showed a significantly higher (p = 0.011) prevalence of improvement at year 2 (EC 21.3%, 95% confidence interval [CI] 13.6-29.3; DC 8.9%, 95% CI 5.5-12.8) and at year 5 (EC 15.7%, 95% CI 8.2-23.7; DC 8.3%, 95% CI 4.5-12.4). The cumulative incidence of improvement was also significantly different (hazard ratio 1.82, 95% CI 1.13-2.94, p = 0.013).Assessment of the prevalence of EDSS improvement is an alternative outcome to assess if a treatment induces and maintains an improvement over the long term. This estimator was found to be more powerful than the cumulative incidence of improvement to detect a treatment effect of cladribine versus placebo over 5 years.

Published
2022

15. Spin of information and inconsistency between abstract and full text in RCTs investigating upper limb rehabilitation after stroke: An overview study

Author

Diego Tosatto, Daniele Bonacina, Alessio Signori, Leonardo Pellicciari, Francesca Cecchi, Cesare Maria Cornaggia, Daniele Piscitelli, Tosatto, D, Bonacina, D, Signori, A, Pellicciari, L, Cecchi, F, Cornaggia, C, and Piscitelli, D

Subjects
Upper Extremity, neurological rehabilitation, Developmental Neuroscience, Neurology, Abstracting and Indexing, randomized controlled trial, spin bia, Humans, Data accuracy, Neurology (clinical), stroke, Checklist
Abstract

Background: Researchers may be tempted to favorably distort the interpretation of their findings when reporting the abstract (i.e., spin). Spin bias overemphasizes the beneficial effects of the intervention compared with the results shown in the full text. Objective: To assess the occurrence of spin bias and incompleteness in reporting abstracts in post-stroke upper limb (UL) rehabilitation randomized clinical trials (RCTs). Methods: A sample of 120 post-stroke UL rehabilitation RCTs (indexed in PEDro database), published in English between 2012 and 2020, was included. The completeness of reporting and spin were assessed using the Consolidated Standards of Reporting Trials for Abstracts (CONSORT-A) and the spin checklist. The relationship between CONSORT-A and spin checklist scores with RCT and journal characteristics was assessed. Results: CONSORT-A and spin checklist scored 5.3±2.4 (max 15-points, higher scores indicating better reporting) and 5.5±2.0 (max 7-points, higher scores indicating presence of spin), respectively; Significant differences were detected between abstract and full-text scores in the CONSORT-A checklist (p

Published
2022

16. Upper transversal hepatectomy with double hepatic vein resection and reconstruction to treat colorectal cancer liver metastases at the hepatocaval confluence: a strategy to achieve R0 liver-sparing resection

Author

Lucio Urbani, Nicolò Roffi, Stefano Signori, Riccardo Balestri, Piero Colombatto, Gabriella Licitra, Chiara Leoni, Daniele Meiattini, Roberto Moretto, Chiara Cremolini, Gianluca Masi, Piero Boraschi, Francesca Quilici, Piero Buccianti, and Marco Puccini

Subjects
Liver Neoplasms, Hepatectomy, Humans, Surgery, Hepatic Veins, Colorectal Neoplasms
Abstract

Repeated hepatectomies in the therapeutic route of patients with colorectal liver metastases (CRLM) may improve their long term survival. Hepatic vein (HV) resection and reconstruction allows parenchyma-sparing hepatectomy (PSH) and R0 resections for CRLM in contact with one HV. We aimed at verifying the feasibility of PSH with double HV resection and direct reconstruction for CRLM in contact with two HVs at the hepatocaval confluence.Out of 106 consecutive PSH performed for CRLM deep-located in segments I-IVa-VII-VIII, four (3.7%) PSH were performed with resection of CRLM en bloc with two adjacent HVs which were both reconstructed with double direct HV anastomosis: 3 cases between right-HV and middle-HV and 1 case between middle-HV and left-HV. Two patients had previously undergone liver resection. Three patients had one single lesion and one had 5 CRLMs.Median size of CRLMs in contact with HVs was 25 mm (range 22-30 mm). At histological examination, all resections were R0 except one R1-vascular (detachment from glissonean pedicle): in all cases at least one HV and in 1 case both HVs were infiltrated by the tumor cells. After median follow-up of 18 (range 3.5-41.2) months, all HVs were patent. All patients were alive and in good general conditions, and 3 patients were disease free (one of them following a liver re-resection). One patient experienced a grade IIIa complication. Median hospital-stay was 11 (range 9-13) days.In patients with CRLMs involving two adjacent HVs at the hepatocaval confluence, liver resection with double HV resection and direct reconstruction is feasible and may be considered to guarantee oncological radicality (R0) and spare health parenchyma.

Published
2022

17. Gene’s expression underpinning the divergent predictive value of [18F]F-fluorodeoxyglucose and prostate-specific membrane antigen positron emission tomography in primary prostate cancer: a bioinformatic and experimental study

Author

Matteo Bauckneht, Cecilia Marini, Vanessa Cossu, Cristina Campi, Mattia Riondato, Silvia Bruno, Anna Maria Orengo, Francesca Vitale, Sonia Carta, Silvia Chiola, Sabrina Chiesa, Alberto Miceli, Francesca D’Amico, Giuseppe Fornarini, Carlo Terrone, Michele Piana, Silvia Morbelli, Alessio Signori, Paola Barboro, and Gianmario Sambuceti

Subjects
Male, Glucose, Fluorodeoxyglucose F18, Positron-Emission Tomography, Positron Emission Tomography Computed Tomography, Prostate, Humans, Prostatic Neoplasms, General Medicine, General Biochemistry, Genetics and Molecular Biology
Abstract

Background Positron Emission Tomography (PET) imaging with Prostate-Specific Membrane Antigen (PSMA) and Fluorodeoxyglucose (FDG) represent promising biomarkers for risk-stratification of Prostate Cancer (PCa). We verified whether the expression of genes encoding for PSMA and enzymes regulating FDG cellular uptake are independent and additive prognosticators in PCa. Methods mRNA expression of genes involved in glucose metabolism and PSMA regulation obtained from primary PCa specimens were retrieved from open-source databases and analyzed using an integrative bioinformatics approach. Machine Learning (ML) techniques were used to create predictive Progression-Free Survival (PFS) models. Cellular models of primary PCa with different aggressiveness were used to compare [18F]F-PSMA-1007 and [18F]F-FDG uptake kinetics in vitro. Confocal microscopy, immunofluorescence staining, and quantification analyses were performed to assess the intracellular and cellular membrane PSMA expression. Results ML analyses identified a predictive functional network involving four glucose metabolism-related genes: ALDOB, CTH, PARP2, and SLC2A4. By contrast, FOLH1 expression (encoding for PSMA) did not provide any additive predictive value to the model. At a cellular level, the increase in proliferation rate and migratory potential by primary PCa cells was associated with enhanced FDG uptake and decreased PSMA retention (paralleled by the preferential intracellular localization). Conclusions The overexpression of a functional network involving four glucose metabolism-related genes identifies a higher risk of disease progression since the earliest phases of PCa, in agreement with the acknowledged prognostic value of FDG PET imaging. By contrast, the prognostic value of PSMA PET imaging is independent of the expression of its encoding gene FOLH1. Instead, it is influenced by the protein docking to the cell membrane, regulating its accessibility to tracer binding.

Published
2023

18. Impact of Natural Killer (NK) Cells on Immune Reconstitution, and Their Potential as a Biomarker of Disease Activity, in Alemtuzumab-Treated Patients with Relapsing Remitting Multiple Sclerosis: An Observational Study

Author

Serena Palmeri, Marta Ponzano, Federico Ivaldi, Alessio Signori, Caterina Lapucci, Valentina Casella, Maria Teresa Ferrò, Tiziana Vigo, Matilde Inglese, Giovanni Luigi Mancardi, Antonio Uccelli, and Alice Laroni

Subjects
Adult, Male, Killer Cells, Natural, Psychiatry and Mental health, Antineoplastic Agents, Immunological, Multiple Sclerosis, Relapsing-Remitting, Italy, Humans, Female, Pharmacology (medical), Longitudinal Studies, Neurology (clinical), Alemtuzumab, Biomarkers
Abstract

Defining immune mechanisms leading to multiple sclerosis (MS) is difficult, due to the great inter-individual difference in immune system responses. The anti-CD52 antibody alemtuzumab transiently abolishes differences in immune parameters among individuals, allowing analysis of subsequent immune cell repopulation patterns, and their possible role in MS.To evaluate the correlation between innate and adaptive immune cell subsets and disease activity in MS in the context of treatment with alemtuzumab.A two-center observational cohort of patients treated with alemtuzumab underwent immune profiling of T, B, and natural killer (NK) cells, biomarker, clinical and radiological follow-up.After treatment, the percentage of NK and B cells increased; NK, T- and B-cell populations underwent a profound rearrangement. Within the effector T-cell compartment, treatment led to a transient decrease, followed by an increase, of T-helper 1 cells, and to a transient decrease of T-helper 17 cells. Within the T-regulatory compartment, naïve T-regulatory cells increased. Within the B-cell compartment, memory B cells and mature B cells decreased, whereas transitional B cells increased. Within the NK cell compartment, CD56The results of this study provide novel evidence that NK cells influence reconstitution of adaptive immune cells upon alemtuzumab and that patients with a successful response to alemtuzumab have an early immune reconstitution dominated by NK cells.

Published
2021

19. The role of human milk and sucrose on cariogenicity of microcosm biofilms

Author

Cácia SIGNORI, Andréia Drawanz HARTWIG, Ivam Freire da SILVA-JÚNIOR, Marcos Britto CORREA, Marina Sousa AZEVEDO, and Maximiliano Sérgio CENCI

Subjects
Dental Caries, Milk, Humans, Sucrose, Biofilms, Dentistry, RK1-715
Abstract

Abstract This study investigated the effect of human milk, alone and associated with sucrose, in the cariogenicity of biofilms in a microcosm biofilm model and compared with the cariogenicity of sucrose and bovine milk. Microcosm biofilms were grown in enamel discs in 24-well plates. Six growth conditions were studied: DMM (chemically defined artificial saliva - negative control), DMM with 1% of sucrose (DMM+s) (positive control), human milk with DMM, human milk with DMM+s, bovine milk with DMM, and bovine milk with DMM+s. After 5 days, the outcome variables surface hardness change (%SHC), microbiological composition of biofilms, and pH of supernatant were analyzed. All groups had significantly lower hardness loss compared to the DMM group with 1% of sucrose. Human and bovine milk associated with sucrose showed higher hardness loss. The supernatant pH values after 6 hours of different treatments were similar for the groups sucrose and human milk associated with sucrose (p>0.05). After 18 hours at rest in pure DMM, an increase in the pH of the supernatant was observed. Higher values of total microorganisms count were found for sucrose and bovine milk groups compared to the group supplemented only by DMM. Bovine milk group showed greater amount of total aciduric microorganisms in comparison to human milk group. Within the limits of this study, it can be infered that both human and cow milks have some cariogenic potential, although differing from sucrose in terms of mineral loss.

Published
2018
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20. The prognostic value of the previous nephrectomy in pretreated metastatic renal cell carcinoma receiving immunotherapy: a sub-analysis of the Meet-URO 15 study

Author

Sara Elena Rebuzzi, Alessio Signori, Giuseppe Luigi Banna, Annalice Gandini, Giuseppe Fornarini, Alessandra Damassi, Marco Maruzzo, Ugo De Giorgi, Umberto Basso, Silvia Chiellino, Luca Galli, Paolo Andrea Zucali, Emanuela Fantinel, Emanuele Naglieri, Giuseppe Procopio, Michele Milella, Francesco Boccardo, Lucia Fratino, Stefania Pipitone, Riccardo Ricotta, Stefano Panni, Veronica Mollica, Mariella Sorarù, Matteo Santoni, Alessio Cortellini, Veronica Prati, Hector Josè Soto Parra, Daniele Santini, Francesco Atzori, Marilena Di Napoli, Orazio Caffo, Marco Messina, Franco Morelli, Giuseppe Prati, Franco Nolè, Francesca Vignani, Alessia Cavo, Giandomenico Roviello, Pasquale Rescigno, and Sebastiano Buti

Subjects
Nivolumab, Cytokines, Humans, Immunotherapy, General Medicine, Prognosis, Carcinoma, Renal Cell, Nephrectomy, Kidney Neoplasms, General Biochemistry, Genetics and Molecular Biology, Retrospective Studies
Abstract

Background Nephrectomy is considered the backbone of managing patients with localized and selected metastatic renal cell carcinoma (mRCC). The prognostic role of nephrectomy has been widely investigated with cytokines and targeted therapy, but it is still unclear in the immunotherapy era. Methods We investigated the Meet-URO-15 study dataset of 571 pretreated mRCC patients receiving nivolumab as second or further lines about the prognostic role of the previous nephrectomy (received in either the localized or metastatic setting) in the overall population and according to the Meet-URO score groups. Results Patients who underwent nephrectomy showed a significantly reduced risk of death (HR 0.44, 95% CI 0.32–0.60, p p = 0.17). It was statistically significant when merging group 1 with 2 and 3 and group 4 with 5 (p = 0.038) and associated with a longer OS for the first three prognostic groups (p p = 0.54). Conclusions Our study suggests an overall positive impact of the previous nephrectomy on the outcome of pretreated mRCC patients receiving immunotherapy. The clinical relevance of cytoreductive nephrectomy, optimal timing and patient selection deserves further investigation, especially for patients with Meet-URO scores of 1 to 3, who are the once deriving benefit in our analyses. However, that benefit is not evident for IMDC poor-risk patients (including the Meet-URO score groups 4 and 5) and a subgroup of IMDC intermediate-risk patients defined as group 4 by the Meet-URO score.

Published
2022

21. Delirium and Clusters of Older Patients Affected by Multimorbidity in Acute Hospitals

Author

Monacelli, F, Signori, A, Marengoni, A, Di Santo, S, Rossi, E, Valsecchi, Mg, Morandi, A, Bellelli, G, Tarasconi, A, Sella, M, Auriemma, S, Paternò, G, Faggian, G, Lucarelli, C, De Grazia, N, Alberto, C, Porcella, L, Nardiello, I, Chimenti, E, Zeni, M, Giani, A, Famularo, S, Romairone, E, Minaglia, C, Ceccotti, C, Guerra, G, Mantovani, G, Candiani, T, Ballestrero, A, Santolini, F, Rosso, M, Bono, V, Sibilla, S, Dal Santo, P, Ceci, M, Barone, P, Schirinzi, T, Formenti, A, Nastasi, G, Isaia, G, Gonella, D, Battuello, A, Casson, S, Calvani, D, Boni, F, Ciaccio, A, Rosa, R, Sanna, G, Manfredini, S, Cortese, L, Rizzo, M, Prestano, R, Greco, A, Lauriola, M, Gelosa, G, Piras, V, Arena, M, Cosenza, D, Bellomo, A, Lamontagna, M, Gabbani, L, Lambertucci, L, Perego, S, Parati, G, Basile, G, Gallina, V, Pilone, G, Giudice, C, Pietrogrande, L, Mosca, M, Corazzin, I, Rossi, P, Nunziata, V, D'Amico, F, Grippa, A, Giardini, S, Barucci, R, Cossu, A, Fiorin, L, Distefano, M, Lunardelli, M, Brunori, M, Ruffini, I, Abraham, E, Varutti, A, Fabbro, E, Catalano, A, Martino, G, Leotta, D, Marchet, A, Dell'Aquila, G, Scrimieri, A, Davoli, M, Casella, M, Cartei, A, Polidori, G, Brischetto, D, Motta, S, Saponara, R, Perrone, P, Russo, G, Del, D, Car, C, Pirina, T, Franzoni, S, Cotroneo, A, Ghiggia, F, Volpi, G, Menichetti, C, Bo, M, Panico, A, Calogero, P, Corvalli, G, Mauri, M, Lupia, E, Manfredini, R, Fabbian, F, March, A, Pedrotti, M, Veronesi, M, Strocchi, E, Borghi, C, Bianchetti, A, Crucitti, A, Difrancesco, V, Fontana, G, Bonanni, L, Barbone, F, Serrati, C, Ballardini, G, Simoncelli, M, Ceschia, G, Scarpa, C, Brugiolo, R, Fusco, S, Ciarambino, T, Biagini, C, Tonon, E, Porta, M, Venuti, D, Delsette, M, Poeta, M, Barbagallo, G, Trovato, G, Delitala, A, Arosio, P, Reggiani, F, Zuliani, G, Ortolani, B, Mussio, E, Girardi, A, Coin, A, Ruotolo, G, Castagna, A, Masina, M, Cimino, R, Pinciaroli, A, Tripodi, G, Cannistrà, U, Cassadonte, F, Vatrano, M, Scaglione, L, Fogliacco, P, Muzzuilini, C, Romano, F, Padovani, A, Rozzini, L, Cagnin, A, Fragiacomo, F, Desideri, G, Liberatore, E, Bruni, A, Orsitto, G, Franco, M, Bonfrate, L, Bonetto, M, Pizio, N, Magnani, G, Cecchetti, G, Longo, A, Bubba, V, Marinan, L, Cotelli, M, Turla, M, Sessa, M, Abruzzi, L, Castoldi, G, Lovetere, D, Musacchio, C, Novello, M, Cavarape, A, Bini, A, Leonardi, A, Seneci, F, Grimaldi, W, Fimognari, F, Bambara, V, Saitta, A, Corica, F, Braga, M, Ettorre, E, Camellini, C, Annoni, G, Crescenzo, A, Noro, G, Turco, R, Ponzetto, M, Giuseppe, L, Mazzei, B, Maiuri, G, Costaggiu, D, Damato, R, Formilan, M, Patrizia, G, Santuari, L, Gallucci, M, Paragona, M, Bini, P, Modica, D, Abati, C, Clerici, M, Barbera, I, Nigroimperiale, F, Manni, A, Votino, C, Castiglioni, C, Degl'Innocenti, M, Moscatelli, G, Guerini, S, Casini, C, Dini, D, D'Imporzano, E, Denotariis, S, Bonometti, F, Paolillo, C, Riccardi, A, Tiozzo, A, Samy Salama Fahmy, A, Dibari, M, Vanni, S, Scarpa, A, Zara, D, Ranieri, P, Alessandro, M, Pezzoni, D, Platto, C, D'Ambrosio, V, Ivaldi, C, Milia, P, Desalvo, F, Solaro, C, Strazzacappa, M, Cazzadori, M, Confente, S, Grasso, M, Troisi, E, Guerini, V, Bernardini, B, Corsini, C, Boffelli, S, Filippi, A, Delpin, K, Faraci, B, Bertoletti, E, Vannucci, M, Tesi, F, Crippa, P, Malighetti, A, Caltagirone, C, Disant, S, Bettini, D, Maltese, F, Abruzzese, G, Cosimo, D, Azzini, M, Colombo, M, Procino, G, Fascendini, S, Barocco, F, Del, P, Mazzone, A, Riva, E, Dell'Acqua, D, Cottino, M, Vezzadini, G, Avanzi, S, Brambilla, C, Orini, S, Sgrilli, F, Mello, A, Lombardi, L, Muti, E, Dijk, B, Fenu, S, Pes, C, Gareri, P, Passamonte, M, Rigo, R, Locusta, L, Caser, L, Rosso, G, Cesarini, S, Cozzi, R, Santini, C, Carbone, P, Cazzaniga, I, Lovati, R, Cantoni, A, Ranzani, P, Barra, D, Pompilio, G, Dimori, S, Cernesi, S, Riccò, C, Piazzolla, F, Capittini, E, Rota, C, Gottardi, F, Merla, L, Barelli, A, Millul, A, Morrone, G, Bigolari, M, Macchi, M, Zambon, F, Pizzorni, C, Dicasaleto, G, Menculini, G, Marcacci, M, Catanese, G, Sprini, D, Dicasalet, T, Bocci, M, Borga, S, Caironi, P, Cingolani, E, Avalli, L, Greco, G, Citerio, G, Gandini, L, Cornara, G, Lerda, R, Brazzi, L, Simeone, F, Caciorgna, M, Alampi, D, Francesconi, S, Beck, E, Antonini, B, Vettoretto, K, Meggiolaro, M, Garofalo, E, Notaro, S, Varutti, R, Bassi, F, Mistraletti, G, Marino, A, Rona, R, Rondelli, E, Riva, I, Cortegiani, A, Vitale, F, Pistidda, L, D'Andrea, R, Querci, L, Gnesin, P, Todeschini, M, Lugano, M, Castelli, G, Ortolani, M, Cotoia, A, Maggiore, S, Ditizio, L, Graziani, R, Testa, I, Ferretti, E, Castioni, C, Lombardi, F, Caserta, R, Pasqua, M, Simoncini, S, Baccarini, F, Rispoli, M, Grossi, F, Cancelliere, L, Carnelli, M, Puccini, F, Biancofiore, G, Siniscalchi, A, Laici, C, Mossello, E, Torrini, M, Pasetti, G, Palmese, S, Oggioni, R, Mangani, V, Pini, S, Martelli, M, Rigo, E, Zuccalà, F, Cherri, A, Spina, R, Calamai, I, Petrucci, N, Caicedo, A, Ferri, F, Gritti, P, Brienza, N, Fonnesu, R, Dessena, M, Fullin, G, Saggioro, D., Monacelli, F, Signori, A, Marengoni, A, Di Santo, S, Rossi, E, Valsecchi, M, Morandi, A, and Bellelli, G

Subjects
medicine.medical_specialty, multimorbidity, Delirium, multimorbidity, Socio-culturale, Older patients, mental disorders, Medicine, Dementia, Multimorbidity, Humans, Medical history, LS4_4, General Nursing, Aged, Aged, 80 and over, Routine screening, business.industry, Health Policy, Delirium, General Medicine, Targeted interventions, medicine.disease, Hospitals, Cross-Sectional Studies, Charlson comorbidity index, Emergency medicine, Geriatrics and Gerontology, medicine.symptom, business
Abstract

Objectives Delirium is commonly seen in older adults with multimorbidity, during a hospitalization, resulting from the interplay between predisposing factors such as advanced age, frailty, and dementia, and a series of precipitating factors. The association between delirium and specific multimorbidity is largely unexplored so far although of potential key relevance for targeted interventions. The aim of the study was to check for a potential association of multimorbidity with delirium in a large cohort of older patients hospitalized for an acute medical or surgical condition. Design This is a cross-sectional study nested in the 2017 Delirium Day project. Setting and Participants The study includes 1829 hospitalized patients (age: 81.8, SD: 5.5). Of them, 419 (22.9%) had delirium. Methods Sociodemographic and medical history were collected. The 4AT was used to assess the presence of delirium. The Charlson Comorbidity index was used to assess multimorbidity. Results The results identified neurosensorial multimorbidity as the most prevalent, including patients with dementia, cerebrovascular diseases, and sensory impairments. In light of the highest co-occurrence of 3 neurosensorial chronic conditions, we could hypothesize that a baseline altered brain functional and neural connectivity might determine the vulnerability signature for incipient overall system disruption in presence of acute insults. Conclusions and Implications Eventually, our findings moved a step forward in supporting the key importance of routine screening for sensory impairments and cognitive status of older patients for the highest risk of in-hospital delirium. In fact, preventive interventions could be particularly relevant and effective in preventing delirium in such vulnerable populations and might help refining this early diagnosis.

Published
2022

22. What happens after fingolimod discontinuation? A multicentre real-life experience

Author

Eleonora Cocco, Maria Cellerino, Carolina Gabri Nicoletti, Girolama Alessandra Marfia, Marta Ponzano, Marzia Fronza, Giacomo Boffa, Maria Elena Ricchiuto, Elisabetta Mancuso, Jessica Frau, Doriana Landi, Giuseppe Fenu, Matilde Inglese, and Alessio Signori

Subjects
Adult, medicine.medical_specialty, Multiple Sclerosis, Neurology, Discontinuation, Relapsing-Remitting, Settore MED/26, Logistic regression, 03 medical and health sciences, Multiple Sclerosis, Relapsing-Remitting, 0302 clinical medicine, Internal medicine, Humans, Medicine, 030212 general & internal medicine, Risk factor, Expanded Disability Status Scale, Fingolimod Hydrochloride, business.industry, Multiple sclerosis, Fingolimod, Reactivation, medicine.disease, Magnetic Resonance Imaging, Lymphocyte count, Cohort, Female, Neurology (clinical), business, Immunosuppressive Agents, 030217 neurology & neurosurgery, medicine.drug
Abstract

To analyse the course of multiple sclerosis (MS) after fingolimod withdrawal in a multicentre cohort. Patients who discontinued fingolimod were included. Relapses, Expanded Disability Status Scale (EDSS), and new/gadolinium-enhancing lesions on magnetic resonance imaging (MRI) were assessed during the last year on fingolimod, and in the year after discontinuation. Wilcoxon test was used to analyse the difference in EDSS and relapses between the two periods, and to compare lymphocyte counts at discontinuation and 3 months later. Demographic and clinical variables were evaluated using univariable and multivariable logistic regression analyses. Patients were 230 (females 66.1%; mean age 38 years; median EDSS 3). Fingolimod was discontinued due to inefficacy in 57%, and 87.4% started another treatment. Relapse was observed in 33% of the patients in the year after discontinuation. Severe reactivation was observed in 15%. During the first 6 months after discontinuation, new/enhancing lesions were seen in 62/116 patients. Higher age at the fingolimod discontinuation was found to be associated with a lower probability of inflammatory activity (p = 0.001) and severe reactivation (p = 0.007) during the year after discontinuation. Lower lymphocyte count was a risk factor for clinical, radiological, and severe activity (p = 0.02, p = 0.002, p = 0.01, respectively). The main reason for the discontinuation of fingolimod was inefficacy. One-third of the patients had a relapse during the year after discontinuation, 15% experienced a severe reactivation, and approximately 50% of patients with available MRI scan had new/enhancing lesions. The risk factors for disease activity after discontinuation were low lymphocyte count and younger age.

Published
2021

23. Lifestyle and Mediterranean diet adherence in a cohort of Southern Italian patients with Multiple Sclerosis

Author

G. Tedeschi, Alessio Signori, Francesca Trojsi, Simona Bonavita, Luigi Lavorgna, V. Brescia Morra, Antonio Gallo, Simone Cepparulo, Luca Carmisciano, Camilla Russo, Maddalena Sparaco, Elisabetta Signoriello, G. T. Maniscalco, Sabrina Esposito, Giacomo Lus, Francesco Saccà, R Lanzillo, Esposito, S, Sparaco, M, Maniscalco, G T, Signoriello, E, Lanzillo, R, Russo, C, Carmisciano, L, Cepparulo, S, Lavorgna, L, Gallo, A, Trojsi, F, Brescia Morra, V, Lus, G, Tedeschi, G, Saccà, F, Signori, A, Bonavita, S, Esposito, S., Sparaco, M., Maniscalco, G. T., Signoriello, E., Lanzillo, R., Russo, C., Carmisciano, L., Cepparulo, S., Lavorgna, L., Gallo, A., Trojsi, F., Brescia Morra, V., Lus, G., Tedeschi, G., Sacca, F., Signori, A., and Bonavita, S.

Subjects
medicine.medical_specialty, Multiple Sclerosis, Mediterranean diet, Physical examination, Systemic inflammation, Diet, Mediterranean, 03 medical and health sciences, 0302 clinical medicine, Retrospective Studie, Internal medicine, medicine, Outpatient clinic, Humans, Multiple sclerosi, 030212 general & internal medicine, Life Style, Retrospective Studies, Cross-Sectional Studie, Expanded Disability Status Scale, medicine.diagnostic_test, business.industry, Multiple sclerosis, General Medicine, medicine.disease, Cardiovascular risk, Lifestyle, Cross-Sectional Studies, Neurology, Italy, Cohort, Neurology (clinical), medicine.symptom, business, Body mass index, 030217 neurology & neurosurgery, Human
Abstract

Background/objectives Several studies supported the beneficial effects of the Mediterranean diet (MeDi) on chronic diseases. In Multiple Sclerosis (MS), the MeDi might interfere with systemic inflammatory state, gut microbiota, and comorbidities. The Med Diet Score (MDS) estimates the adherence to the MeDi and the cardiovascular (CV) risk. Aims of our study were i) to photograph lifestyle and diet habits of a southern Italy cohort of people with MS (pwMS), and ii) to investigate the impact of the MeDi on MS clinical outcomes. Subjects/methods We conducted a multi-center, cross-sectional study, enrolling 435 consecutive consenting pwMS, attending the outpatient clinics for routine follow-up visits. Participants underwent a clinical examination and a 29-item self-administered questionnaire on life and dietary habits. Disease phenotype, Expanded Disability Status Scale (EDSS), MS Severity Score (MSSS), waist circumference (WC), Body Mass Index (BMI), therapies, and comorbidities, were updated. MDS was assessed and correlated with current and retrospective clinical data. Results 75.8% of respondents were interested in nutrition, 72.8% were non-smokers, 52.9% performed physical activity, and 45.6% used food supplements. MDS was higher in pwMS with normal WC (p = 0.031), and inversely correlated with MSSS (p = 0.013) and EDSS (p = 0.012) at survey time. MDS did not correlate with the total number of relapses (before and after diagnosis) (p = 0.372). Metabolic comorbidities were associated with an increased 10-year CV risk (r = 0.85, p = 0.002). Conclusion Our findings suggest a putative beneficial effect of the MeDi on WC, MS course and disability. Given the role of chronic systemic inflammation in maintenance of autoimmunity and secondary neurodegeneration, both involved in long-term disability, we may suppose a beneficial effect of the MeDi on MS long-term disability outcomes, probably mediated by a modulation of the gut microbiota and the low-grade chronic systemic inflammation.

Published
2021

24. Disease-Modifying Therapies and Coronavirus Disease 2019 Severity in Multiple Sclerosis

Author

Sormani, Maria P., Nicola De Rossi, Irene, Schiavetti, Luca, Carmisciano, Cinzia, Cordioli, Lucia, Moiola, Marta, Radaelli, Paolo, Immovilli, Marco, Capobianco, Maria, Trojano, Paola, Zaratin, Gioacchino, Tedeschi, Giancarlo, Comi, Battaglia, Mario A., Francesco, Patti, Marco, Salvetti, Agostino, Nozzolillo, Alessandra, Bellacosa, Alessandra, Protti, Alessia Di Sapio, Alessio, Signori, Alfredo, Petrone, Alvino, Bisecco, Aniello, Iovino, Anna, Dutto, Anna Maria Repice, Antonella, Conte, Antonio, Bertolotto, Antonio, Bosco, Antonio, Gallo, Antonio, Zito, Arianna, Sartori, Bruno, Giometto, Carla, Tortorella, Carlo, Antozzi, Carlo, Pozzilli, Chiara Rosa Mancinelli, Chiara, Zanetta, Christian, Cordano, Cinzia, Scandellari, Clara, Guaschino, Claudio, Gasperini, Claudio, Solaro, Cristina, Fioretti, Daiana, Bezzini, Damiano, Marastoni, Damiano, Paolicelli, Domizia, Vecchio, Doriana, Landi, Elisabetta, Bucciantini, Elisabetta, Pedrazzoli, Elisabetta, Signoriello, Elvira, Sbragia, Emanuela Laura Susani, Erica, Curti, Eva, Milano, Fabiana, Marinelli, Federico, Camilli, Filippo Martinelli Boneschi, Flora, Govone, Francesca, Bovis, Francesca, Calabria, Francesca, Caleri, Francesca, Rinaldi, Francesca, Vitetta, Francesco, Corea, Francesco, Crescenzo, Francesco, Teatini, Giulietta, Tabiadon, Franco, Granella, Giacomo, Boffa, Giacomo, Lus, Giampaolo, Brichetto, Giorgia Teresa Maniscalco, Giovanna, Borriello, Giovanna De Luca, Giovanna, Konrad, Giovanna, Vaula, Girolama Alessandra Marfia, Giulia, Mallucci, Giuseppe, Liberatore, Giuseppe, Salemi, Giuseppina, Miele, Grazia, Sibilia, Ilaria, Pesci, Laura, Brambilla, Leonardo, Lopiano, Leonardo, Sinisi, Pasquali, Livia, Lorenzo, Saraceno, Luca, Chiveri, Luca, Mancinelli, Grimaldi, Luigi M. E., Luisa Maria Caniatti, Marco Della Cava, Marco, Onofrj, Marco, Rovaris, Marco, Vercellino, Margherita Monti Bragadin, Maria, Buccafusca, Maria Chiara Buscarinu, Maria Grazia Celani, Maria Grazia Grasso, Maria Laura Stromillo, Maria, Petracca, Maria Pia Amato, Maria Pia Sormani, Maria Rita L'Episcopo, Maria, Sessa, Maria Teresa Ferrò, Maria Vittoria Ercolani, Mariangela, Bianco, Marianna Lo Re, Marika, Vianello, Marinella, Clerico, Mario Alberto Battaglia, Mario di Napoli, Marta, Ponzano, Marta Zaffira Conti, Massimiliano, Calabrese, Massimiliano, Mirabella, Massimo, Filippi, Matilde, Inglese, Matteo, Lucchini, Matteo, Pozzato, Maura Chiara Danni, Mauro, Zaffaroni, Mauro, Zampolini, Michela, Ponzio, Milena De Riz, Nicola De Stefano, Paola, Cavalla, Paola De Mitri, Paola, Grossi, Paolo, Confalonieri, Paolo, Gallo, Paolo, Ragonese, Patrizia, Sola, Pietro, Annovazzi, Pietro, Iaffaldano, Raffaele, Nardone, Raffaella, Cerqua, Raffaella, Clerici, Roberta, Lanzillo, Roberta, Motta, Roberto, Balgera, Roberto, Bergamaschi, Rocco, Totaro, Rosa, Iodice, Ruggero, Capra, Sabrina, Marangoni, Sabrina, Realmuto, Salvatore, Cottone, Sara, Montepietra, Sarah, Rasia, Sebastiano, Arena, Sebastiano, Bucello, Silvia, Banfi, Simona, Bonavita, Simona, Malucchi, Simone, Tonietti, Stefano, Vollaro, Susanna, Cordera, Umberto, Aguglia, Valentina Torri Clerici, Valeria, Barcella, Valeria, Bergamaschi, Vincenzo Brescia Morra, Vincenzo, Dattola, and Vittorio Mantero, Sormani, M. P., De Rossi, N., Schiavetti, I., Carmisciano, L., Cordioli, C., Moiola, L., Radaelli, M., Immovilli, P., Capobianco, M., Trojano, M., Zaratin, P., Tedeschi, G., Comi, G., Battaglia, M. A., Patti, F., Salvetti, M., P Sormani, Maria, De Rossi, Nicola, Schiavetti, Irene, Carmisciano, Luca, Cordioli, Cinzia, Moiola, Lucia, Radaelli, Marta, Immovilli, Paolo, Capobianco, Marco, Trojano, Maria, Zaratin, Paola, Tedeschi, Gioacchino, Comi, Giancarlo, A Battaglia, Mario, Patti, Francesco, Salvetti, Marco, Nozzolillo, Agostino, Bellacosa, Alessandra, Protti, Alessandra, Di Sapio, Alessia, Signori, Alessio, Petrone, Alfredo, Bisecco, Alvino, Iovino, Aniello, Dutto, Anna, Maria Repice, Anna, Conte, Antonella, Bertolotto, Antonio, Bosco, Antonio, Gallo, Antonio, Zito, Antonio, Sartori, Arianna, Giometto, Bruno, Tortorella, Carla, Antozzi, Carlo, Pozzilli, Carlo, Rosa Mancinelli, Chiara, Zanetta, Chiara, Cordano, Christian, Scandellari, Cinzia, Guaschino, Clara, Gasperini, Claudio, Solaro, Claudio, Fioretti, Cristina, Bezzini, Daiana, Marastoni, Damiano, Paolicelli, Damiano, Vecchio, Domizia, Landi, Doriana, Bucciantini, Elisabetta, Pedrazzoli, Elisabetta, Signoriello, Elisabetta, Sbragia, Elvira, Laura Susani, Emanuela, Curti, Erica, Milano, Eva, Marinelli, Fabiana, Camilli, Federico, Martinelli Boneschi, Filippo, Govone, Flora, Bovis, Francesca, Calabria, Francesca, Caleri, Francesca, Rinaldi, Francesca, Vitetta, Francesca, Corea, Francesco, Crescenzo, Francesco, Teatini, Francesco, Tabiadon, Giulietta, Granella, Franco, Boffa, Giacomo, Lus, Giacomo, Brichetto, Giampaolo, Teresa Maniscalco, Giorgia, Borriello, Giovanna, De Luca, Giovanna, Konrad, Giovanna, Vaula, Giovanna, Alessandra Marfia, Girolama, Mallucci, Giulia, Liberatore, Giuseppe, Salemi, Giuseppe, Miele, Giuseppina, Sibilia, Grazia, Pesci, Ilaria, Brambilla, Laura, Lopiano, Leonardo, Sinisi, Leonardo, Pasquali, Livia, Saraceno, Lorenzo, Chiveri, Luca, Mancinelli, Luca, E Grimaldi, Luigi M, Maria Caniatti, Luisa, Della Cava, Marco, Onofrj, Marco, Rovaris, Marco, Vercellino, Marco, Monti Bragadin, Margherita, Buccafusca, Maria, Chiara Buscarinu, Maria, Grazia Celani, Maria, Grazia Grasso, Maria, Laura Stromillo, Maria, Petracca, Maria, Pia Amato, Maria, Pia Sormani, Maria, Rita L'Episcopo, Maria, Sessa, Maria, Teresa Ferrò, Maria, Vittoria Ercolani, Maria, Bianco, Mariangela, Lo Re, Marianna, Vianello, Marika, Clerico, Marinella, Alberto Battaglia, Mario, di Napoli, Mario, Ponzano, Marta, Zaffira Conti, Marta, Calabrese, Massimiliano, Mirabella, Massimiliano, Filippi, Massimo, Inglese, Matilde, Lucchini, Matteo, Pozzato, Matteo, Chiara Danni, Maura, Zaffaroni, Mauro, Zampolini, Mauro, Ponzio, Michela, De Riz, Milena, De Stefano, Nicola, Cavalla, Paola, De Mitri, Paola, Grossi, Paola, Confalonieri, Paolo, Gallo, Paolo, Ragonese, Paolo, Sola, Patrizia, Annovazzi, Pietro, Iaffaldano, Pietro, Nardone, Raffaele, Cerqua, Raffaella, Clerici, Raffaella, Lanzillo, Roberta, Motta, Roberta, Balgera, Roberto, Bergamaschi, Roberto, Totaro, Rocco, Iodice, Rosa, Capra, Ruggero, Marangoni, Sabrina, Realmuto, Sabrina, Cottone, Salvatore, Montepietra, Sara, Rasia, Sarah, Arena, Sebastiano, Bucello, Sebastiano, Banfi, Silvia, Bonavita, Simona, Malucchi, Simona, Tonietti, Simone, Vollaro, Stefano, Cordera, Susanna, Aguglia, Umberto, Torri Clerici, Valentina, Barcella, Valeria, Bergamaschi, Valeria, Brescia Morra, Vincenzo, Dattola, Vincenzo, Mantero, Vittorio, Mp, Sormani, N, De Rossi, I, Schiavetti, L, Carmisciano, C, Cordioli, L, Moiola, M, Radaelli, P, Immovilli, M, Capobianco, M, Trojano, P, Zaratin, G, Tedeschi, G, Comi, Ma, Battaglia, F, Patti, M, Salvetti, Study Group Agostino Nozzolillo, Musc-19, Grimaldi, Luigi M. E., Vittorio Mantero, And, Nozzolillo, A., Bellacosa, A., Protti, A., Di Sapio, A., Signori, A., Petrone, A., Bisecco, A., Iovino, A., Dutto, A., Repice, A. M., Conte, A., Bertolotto, A., Bosco, A., Gallo, A., Zito, A., Sartori, A., Giometto, B., Tortorella, C., Antozzi, C., Pozzilli, C., Mancinelli, C. R., Zanetta, C., Cordano, C., Scandellari, C., Guaschino, C., Gasperini, C., Solaro, C., Fioretti, C., Bezzini, D., Marastoni, D., Paolicelli, D., Vecchio, D., Landi, D., Bucciantini, E., Pedrazzoli, E., Signoriello, E., Sbragia, E., Susani, E. L., Curti, E., Milano, E., Marinelli, F., Camilli, F., Boneschi, F. M., Govone, F., Bovis, F., Calabria, F., Caleri, F., Rinaldi, F., Vitetta, F., Corea, F., Crescenzo, F., Teatini, F., Tabiadon, G., Granella, F., Boffa, G., Lus, G., Brichetto, G., Maniscalco, G. T., Borriello, G., De Luca, G., Konrad, G., Vaula, G., Marfia, G. A., Mallucci, G., Liberatore, G., Salemi, G., Miele, G., Sibilia, G., Pesci, I., Brambilla, L., Lopiano, L., Sinisi, L., Pasquali, L., Saraceno, L., Chiveri, L., Mancinelli, L., Grimaldi, L. M. E., Caniatti, L. M., Cava, M. D., Onofrj, M., Rovaris, M., Vercellino, M., Bragadin, M. M., Buccafusca, M., Buscarinu, M. C., Celani, M. G., Grasso, M. G., Stromillo, M. L., Petracca, M., Amato, M. P., L'Episcopo, M. R., Sessa, M., Ferro, M. T., Ercolani, M. V., Bianco, M., Re, M. L., Vianello, M., Clerico, M., di Napoli, M., Ponzano, M., Conti, M. Z., Calabrese, M., Mirabella, M., Filippi, M., Inglese, M., Lucchini, M., Pozzato, M., Danni, M. C., Zaffaroni, M., Zampolini, M., Ponzio, M., De Riz, M., De Stefano, N., Cavalla, P., De Mitri, P., Grossi, P., Confalonieri, P., Gallo, P., Ragonese, P., Sola, P., Annovazzi, P., Iaffaldano, P., Nardone, R., Cerqua, R., Clerici, R., Lanzillo, R., Motta, R., Balgera, R., Bergamaschi, R., Totaro, R., Iodice, R., Capra, R., Marangoni, S., Realmuto, S., Cottone, S., Montepietra, S., Rasia, S., Arena, S., Bucello, S., Banfi, S., Bonavita, S., Malucchi, S., Tonietti, S., Vollaro, S., Cordera, S., Aguglia, U., Clerici, V. T., Barcella, V., Bergamaschi, V., Morra, V. B., Dattola, V., Mantero, V., Sormani M.P., De Rossi N., Schiavetti I., Carmisciano L., Cordioli C., Moiola L., Radaelli M., Immovilli P., Capobianco M., Trojano M., Zaratin P., Tedeschi G., Comi G., Battaglia M.A., Patti F., Salvetti M., Nozzolillo A., Bellacosa A., Protti A., Di Sapio A., Signori A., Petrone A., Bisecco A., Iovino A., Dutto A., Repice A.M., Conte A., Bertolotto A., Bosco A., Gallo A., Zito A., Sartori A., Giometto B., Tortorella C., Antozzi C., Pozzilli C., Mancinelli C.R., Zanetta C., Cordano C., Scandellari C., Guaschino C., Gasperini C., Solaro C., Fioretti C., Bezzini D., Marastoni D., Paolicelli D., Vecchio D., Landi D., Bucciantini E., Pedrazzoli E., Signoriello E., Sbragia E., Susani E.L., Curti E., Milano E., Marinelli F., Camilli F., Boneschi F.M., Govone F., Bovis F., Calabria F., Caleri F., Rinaldi F., Vitetta F., Corea F., Crescenzo F., Teatini F., Tabiadon G., Granella F., Boffa G., Lus G., Brichetto G., Maniscalco G.T., Borriello G., De Luca G., Konrad G., Vaula G., Marfia G.A., Mallucci G., Liberatore G., Salemi G., Miele G., Sibilia G., Pesci I., Brambilla L., Lopiano L., Sinisi L., Pasquali L., Saraceno L., Chiveri L., Mancinelli L., Grimaldi L.M.E., Caniatti L.M., Cava M.D., Onofrj M., Rovaris M., Vercellino M., Bragadin M.M., Buccafusca M., Buscarinu M.C., Celani M.G., Grasso M.G., Stromillo M.L., Petracca M., Amato M.P., L'Episcopo M.R., Sessa M., Ferro M.T., Ercolani M.V., Bianco M., Re M.L., Vianello M., Clerico M., di Napoli M., Ponzano M., Conti M.Z., Calabrese M., Mirabella M., Filippi M., Inglese M., Lucchini M., Pozzato M., Danni M.C., Zaffaroni M., Zampolini M., Ponzio M., De Riz M., De Stefano N., Cavalla P., De Mitri P., Grossi P., Confalonieri P., Gallo P., Ragonese P., Sola P., Annovazzi P., Iaffaldano P., Nardone R., Cerqua R., Clerici R., Lanzillo R., Motta R., Balgera R., Bergamaschi R., Totaro R., Iodice R., Capra R., Marangoni S., Realmuto S., Cottone S., Montepietra S., Rasia S., Arena S., Bucello S., Banfi S., Bonavita S., Malucchi S., Tonietti S., Vollaro S., Cordera S., Aguglia U., Clerici V.T., Barcella V., Bergamaschi V., Morra V.B., Dattola V., and Mantero V.

Subjects
Male, 0301 basic medicine, Dimethyl Fumarate, Neurodegenerative, multiple sclerosis, coronavirus, pneumonia, Severity of Illness Index, law.invention, Immunosuppressive Agent, Immunologic Factor, 0302 clinical medicine, Natalizumab, law, Monoclonal, Multiple Sclerosi, 80 and over, Lung, Humanized, Research Articles, Aged, 80 and over, Middle Aged, Intensive care unit, Hospitalization, Settore MED/26 - NEUROLOGIA, Intensive Care Units, Neurology, Methylprednisolone, Neurological, Pneumonia & Influenza, Interferon, Female, Immunosuppressive Agents, Research Article, Human, medicine.drug, Adult, medicine.medical_specialty, Musc-19 Study Group, Multiple Sclerosis, Adolescent, Clinical Sciences, Intensive Care Unit, Clinical Neurology, Settore MED/26, Antibodies, Monoclonal, Humanized, Autoimmune Disease, Antibodies, Young Adult, 03 medical and health sciences, Clinical Research, Internal medicine, Severity of illness, medicine, Humans, Immunologic Factors, Mortality, Aged, COVID-19, Fingolimod Hydrochloride, Interferons, SARS-CoV-2, Neurology & Neurosurgery, Expanded Disability Status Scale, business.industry, Multiple sclerosis, Neurosciences, Pneumonia, Odds ratio, medicine.disease, Brain Disorders, Good Health and Well Being, 030104 developmental biology, Ocrelizumab, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract

Objective: This study was undertaken to assess the impact of immunosuppressive and immunomodulatory therapies on the severity of coronavirus disease 2019 (COVID-19) in people with multiple sclerosis (PwMS). Methods: We retrospectively collected data of PwMS with suspected or confirmed COVID-19. All the patients had complete follow-up to death or recovery. Severe COVID-19 was defined by a 3-level variable: mild disease not requiring hospitalization versus pneumonia or hospitalization versus intensive care unit (ICU) admission or death. We evaluated baseline characteristics and MS therapies associated with severe COVID-19 by multivariate and propensity score (PS)-weighted ordinal logistic models. Sensitivity analyses were run to confirm the results. Results: Of 844 PwMS with suspected (n = 565) or confirmed (n = 279) COVID-19, 13 (1.54%) died; 11 of them were in a progressive MS phase, and 8 were without any therapy. Thirty-eight (4.5%) were admitted to an ICU; 99 (11.7%) had radiologically documented pneumonia; 96 (11.4%) were hospitalized. After adjusting for region, age, sex, progressive MS course, Expanded Disability Status Scale, disease duration, body mass index, comorbidities, and recent methylprednisolone use, therapy with an anti-CD20 agent (ocrelizumab or rituximab) was significantly associated (odds ratio [OR] = 2.37, 95% confidence interval [CI] = 1.18–4.74, p = 0.015) with increased risk of severe COVID-19. Recent use (

Published
2021

25. Switch from sequestering to anti-CD20 depleting treatment: disease activity outcomes during wash-out and in the first 6 months of ocrelizumab therapy

Author

Maria Pia Sormani, Antonio Carotenuto, Jessica Frau, Doriana Landi, Girolama Alessandra Marfia, Alessio Signori, Erica Curti, Francesco Saccà, Giorgia Teresa Maniscalco, Simone Cepparulo, Elisabetta Signoriello, Francesca Caleri, Mauro Zaffaroni, Damiano Baroncini, Carolina Gabri Nicoletti, Simona Bonavita, Giacomo Lus, Roberta Lanzillo, Viviana Nociti, Arianna Sartori, Signoriello, E., Lus, G., Bonavita, S., Lanzillo, R., Sacca, F., Landi, D., Frau, J., Baroncini, D., Zaffaroni, M., Maniscalco, G. T., Curti, E., Sartori, A., Cepparulo, S., Marfia, G. A., Nicoletti, C. G., Carotenuto, A., Nociti, V., Caleri, F., Sormani, M. P., Signori, A., Signoriello, Elisabetta, Lus, Giacomo, Bonavita, Simona, Lanzillo, Roberta, Sacc??, Francesco, Landi, Doriana, Frau, Jessica, Baroncini, Damiano, Zaffaroni, Mauro, Teresa Maniscalco, Giorgia, Curti, Erica, Sartori, Arianna, Cepparulo, Simone, Alessandra Marfia, Girolama, Gabri Nicoletti, Carolina, Carotenuto, Antonio, Nociti, Viviana, Caleri, Francesca, Pia Sormani, Maria, and Signori, Alessio

Subjects
Oncology, medicine.medical_specialty, Antibodies, Monoclonal, Humanized, Settore MED/26, Disease activity, Multiple sclerosis, 03 medical and health sciences, 0302 clinical medicine, Natalizumab, Multiple Sclerosis, Relapsing-Remitting, natalizumab, ocrelizumab, Internal medicine, medicine, Humans, Multiple sclerosi, 030212 general & internal medicine, Anti cd20, fingolimod, switch, Retrospective Studies, business.industry, Fingolimod Hydrochloride, medicine.disease, Fingolimod, Disease control, Neurology, Ocrelizumab, Neurology (clinical), business, 030217 neurology & neurosurgery, Immunosuppressive Agents, medicine.drug
Abstract

Objectives: Switching between treatments is an opportunity for patients with multiple sclerosis (MS) to ameliorate disease control or safety. The aim of this study was to investigate the impact of switching from fingolimod (FTY) or natalizumab (NTZ) to ocrelizumab (OCR) on disease activity. Methods: We retrospectively enrolled 165 patients treated with OCR from 11 MS centres. We assessed the association of demographic and clinical characteristics on relapse rate (RR) and activity on magnetic resonance imaging (MRI) during wash-out and after 6 months of treatment with OCR through univariable and multivariable negative binomial regression models. Results: We registered a total of 35 relapses during the wash-out period. Previous treatment with FTY, relapses in the previous year, and relapsing-remitting course were associated with higher RR. In the first 6 months of OCR, 12 patients had clinical or MRI disease activity. Higher Expanded Disability Status Scale (EDSS) and higher lymphocyte count at OCR start were associated with a reduced probability of relapse. Discussion and Conclusion: This study confirms that withdrawal from sequestering agents as FTY increases the risk of relapses in the wash-out period. Nevertheless, starting OCR before achieving complete immune reconstitution could limit its effectiveness in the first 6 months probably because trapped lymphocytes escape the CD20-mediated depletion.

Published
2021

26. Combined aerobic and strength training for fitness outcomes in heart failure: meta-analysis and meta-regression

Author

Felipe Barreto Schuch, Luis Ulisses Signori, Natiele Camponogara Righi, Tainara Tolves, Antônio Marcos Vargas da Silva, Angélica Trevisan De Nardi, and Geovana de Almeida Righi

Subjects
030506 rehabilitation, medicine.medical_specialty, Strength training, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, medicine, Humans, Aerobic exercise, Muscle Strength, Exercise, Aerobic capacity, Heart Failure, Exercise Tolerance, business.industry, Rehabilitation, Resistance Training, Random effects model, medicine.disease, Strictly standardized mean difference, Heart failure, Meta-analysis, Cardiology, 0305 other medical science, business, 030217 neurology & neurosurgery
Abstract

Purpose To compare the effects of combined training (CT) versus aerobic training (AT) or versus control on VO2 peak and quadriceps muscle strength in patients with heart failure (HF). Materials and methods Major electronic databases were searched, from inception to November 2020, for randomized clinical trials comparing the effects of CT against AT or control on VO2 peak and/or quadriceps muscle strength in patients with HF. Random effects meta-analyses were conducted, calculating the standardized mean difference (SMD). Results Twenty-eight articles were included. An increase on VO2 peak (SMD = 0.77, 95%CI 0.39-1.14, I2=80.1%) and quadriceps muscle strength (SMD = 0.67, 95%CI 0.18-1.16, I2=0%) was found in CT compared to control. CT increased quadriceps muscle strength, versus AT (SMD = 0.44, 95%CI 0.15-0.74, I2=0%). There were no differences between CT and AT on VO2 peak (SMD=-0.01, 95%CI -0.36 to 0.34, I2=65%). Time of session and training duration moderate the effects of CT over control on VO2 peak. Conclusions CT promotes increases on quadriceps muscle strength and aerobic capacity over control and provides additional gains on quadriceps muscle strength, having the same effects on VO2 peak compared to AT. A longer time of session is associated with greater benefits to aerobic capacity.Implications for rehabilitationCombining aerobic and strength training increases the functional capacity and quadriceps muscle strength in heart failure patients.Using longer sessions of training has a greater impact on aerobic capacity.

Published
2021

27. Quantitative Comparison of Human and Software Reliability in the Categorization of Sit-to-Stand Motion Pattern

Author

Mirko Job, Marco Testa, Simone Battista, Alessio Signori, and Ronny Stanzani

Subjects
Standards, 030506 rehabilitation, medicine.medical_specialty, Movement, Sensors activity recognition, Biomedical Engineering, Software reliability, Sitting, Motion (physics), 03 medical and health sciences, 0302 clinical medicine, Physical medicine and rehabilitation, Software, kinematics, sensor systems, Aged, Biomechanical Phenomena, Humans, Reproducibility of Results, Torso, Internal Medicine, medicine, Ground reaction force, Software analysis pattern, Force, Visualization, Hip, business.industry, Event (computing), General Neuroscience, Particle measurements, Rehabilitation, Software quality, Categorization, 0305 other medical science, business, Psychology, Protocols, 030217 neurology & neurosurgery
Abstract

The Sit-to-Stand (STS) test is used in clinical practice as an indicator of lower-limb functionality decline, especially for older adults. Due to its high variability, there is no standard approach for categorising the STS movement and recognising its motion pattern. This paper presents a comparative analysis between visual assessments and an automated-software for the categorisation of STS, relying on registrations from a force plate. 5 participants (30 ± 6 years) took part in 2 different sessions of visual inspections on 200 STS movements under self-paced and controlled speed conditions. Assessors were asked to identify three specific STS events from the Ground Reaction Force, simultaneously with the software analysis: the start of the trunk movement (Initiation), the beginning of the stable upright stance (Standing) and the sitting movement (Sitting). The absolute agreement between the repeated raters' assessments as well as between the raters' and software's assessment in the first trial, were considered as indexes of human and software performance, respectively. No statistical differences between methods were found for the identification of the Initiation and the Sitting events at self-paced speed and for only the Sitting event at controlled speed. The estimated significant values of maximum discrepancy between visual and automated assessments were 0.200 [0.039; 0.361] s in unconstrained conditions and 0.340 [0.014; 0.666] s for standardised movements. The software assessments displayed an overall good agreement against visual evaluations of the Ground Reaction Force, relying, at the same time, on objective measures.

Published
2021

28. Efficacy outcomes and prognostic factors from real-world patients with advanced non-small-cell lung cancer treated with first-line chemoimmunotherapy: The Spinnaker retrospective study

Author

Banna, Giuseppe L, Cantale, Ornella, Muthuramalingam, Sethupathi, Cave, Judith, Comins, Charles, Cortellini, Alessio, Addeo, Alfredo, Signori, Alessio, McKenzie, Hayley, Escriu, Carles, Barone, Gloria, Chan, Samuel, Hicks, Alexander, Bainbridge, Hannah, Pinato, David J, Ottensmeier, Christian, and Gomes, Fabio

Subjects
Pharmacology, Lung Neoplasms, Neutrophils, Carcinoma, Non-Small-Cell Lung, Immunology, Carcinoma, Squamous Cell, Immunology and Allergy, Humans, Lymphocytes, Prognosis, Retrospective Studies
Abstract

Background: efficacy outcomes and prognostic factors of real-world patients with advanced non-small cell lung cancer (aNSCLC) treated with first-line chemoimmunotherapy are still limited.Patients and methods: in the retrospective Spinnaker study, data was collected from patients in six United Kingdom and one Swiss oncology centres with first-line pembrolizumab plus platinum-based chemotherapy. Efficacy outcomes and potential prognostic factors were estimated aiming at developing a prognostic model.Results: three-hundred-eight patients were included, 32% ≥ 70 years, with ≥ 3 metastatic sites in 33%, brain or liver metastases in 10% and 12%, respectively. With a median follow-up of 18.0 months (mo.) (range, 15.9-20.1), median overall survival (OS) and progression-free survival (PFS) were 12.7 mo. (range, 10.2-15.2), and 8.0 mo. (range, 7.1-8.8), respectively. The neutrophils-to-lymphocytes ratio (NLR) and systemic immune-inflammatory index (SII) (i.e., NLR × platelet count) were both significantly higher in ECOG PS 1 (p = 0.0147 and p = 0.0018, respectively), underweight or normal body mass index (p = 0.0456 and p = 0.0062, respectively), ≥3 metastatic sites (p = 0.0069 and p = 0.112), pretreatment steroids (p = 0.0019 and p = 0.0017). By MVA, the number of metastatic sites ≥ 3 (p < 0.001 and p = 0.002), squamous histology (p = 0.033 and p = 0.013) and SII ≥ 1444 (p = 0.031 and p = 0.009, respectively) were associated with both worse OS and PFS and led to a highly discriminating three-class risk prognostic model.Conclusions: real-world PFS with chemoimmunotherapy in aNSCLC patients is similar to that reported in clinical trials. A high number of metastatic sites, squamous histology and high SII are adverse prognostic factors that might contribute to a clinically useful prognostic model.

Published
2022

29. Prognostic Impact of Bronchoalveolar Lavage Fluid Galactomannan and Aspergillus Culture Results on Survival in COVID-19 Intensive Care Unit Patients: a

Author

Daniele Roberto, Giacobbe, Juergen, Prattes, Joost, Wauters, Silvia, Dettori, Alessio, Signori, Jon, Salmanton-García, Johan, Maertens, Marc, Bourgeois, Marijke, Reynders, Lynn, Rutsaert, Niels, Van Regenmortel, Piet, Lormans, Simon, Feys, Nikolay, Klimko, Olga, Shadrivova, Oliver A, Cornely, Riina, Rautemaa-Richardson, Philipp, Koehler, Katrien, Lagrou, Matteo, Bassetti, and Martin, Hoenigl

Subjects
Invasive Pulmonary Aspergillosis, Mannans, Intensive Care Units, Aspergillus, Critical Illness, COVID-19, Galactose, Humans, Mycology, Pulmonary Aspergillosis, Prognosis, Bronchoalveolar Lavage Fluid, Sensitivity and Specificity
Abstract

Critically ill patients with coronavirus disease 2019 (COVID-19) may develop COVID-19-associated pulmonary aspergillosis (CAPA), which impacts their chances of survival. Whether positive bronchoalveolar lavage fluid (BALF) mycological tests can be used as a survival proxy remains unknown. We conducted a

Published
2022

30. Human Immunodeficiency Virus Continuum of Care in 11 European Union Countries at the End of 2016 Overall and by Key Population: Have We Made Progress?

Author

Vourli, G., Noori, T., Pharris, A., Porter, K., Axelsson, M., Begovac, J., Cazein, F., Costagliola, D., Cowan, S., Croxford, S., Monforte, A. D., Delpech, V., Diaz, A., Girardi, E., Gunsenheimer-Bartmeyer, B., Hernando, V., Leierer, G., Lot, F., Nunez, O., Obel, N., Op de Coul, E., Paraskeva, D., Patrinos, S., Reiss, P., Schmid, D., Sonnerborg, A., Suligoi, B., Supervie, V., van Sighem, A., Zangerle, R., Touloumi, G., Egle, A., Kanatschnig, M., Ollinger, A., Rieger, A., Schmied, B., Wallner, E., Dewasurendra, D., Gisinger, M., Kitchen, M., Plattner, A., Rieser, E., Sarcletti, M., Greil, R., Schachner, M., Skocic, M., Muller, M., Aichwalder, R., Chromy, D., Grabmeier-Pfstershammer, K., Skoll, M., Touzeau, V., Cichon, P., Wolf-Nussmuller, S., Laferl, H., Zoufaly, A., Genger-Hackl, C., Kapper, A., Schneeberger, T., Trattner, E., Schober, G., Atzl, M., Hartmann, B., Puchhammer-Stockl, E., Berg, J., Appoyer, H., Rappold, M., Strickner, S., Schindelwig, K., Ledergerber, B., Fatkenheuer, G., Gerstof, J., Kronborg, G., Pedersen, C., Larsen, C. S., Pedersen, G., Mohey, R., Nielsen, L., Weise, L., Kvinesdal, B., Jensen, J., Abgrall, S., Bernard, L., Billaud, E., Boue, F., Boyer, L., Cabie, A., Caby, F., Canestri, A., Cotte, L., de Truchis, P., Duval, X., Duvivier, C., Enel, P., Fischer, H., Gasnault, J., Gaud, C., Grabar, S., Khuong-Josses, M. A., Launay, O., Marchand, L., Mary-Krause, M., Matheron, S., Melica-Gregoire, G., Melliez, H., Meynard, J. L., Nacher, M., Pavie, J., Piroth, L., Poizot-Martin, I., Pradier, C., Reynes, J., Rouveix, E., Simon, A., Slama, L., Tattevin, P., Tissot-Dupont, H., Biga, J., Kurth, T., Jacquemet, N., Guiguet, M., Leclercq, S., Lievre, L., Marshall, E., Roul, H., Selinger-Leneman, H., Potard, V., Benveniste, O., Breton, G., Lupin, C., Bourzam, E., Girard, P. M., Fonquernie, L., Valin, N., Lefebvre, B., Sebire, M., Pialoux, G., Lebrette, M. G., Tibaut, P., Adda, A., Hamidi, M., Cadranel, J., Lavole, A., Parrot, A., Bouchaud, O., Vignier, N., Mechai, F., Makhlouf, S., Honore, P., Bergmann, J. F., Delcey, V., Lopes, A., Sellier, P., Parrinello, M., Oksenhendler, E., Gerard, L., Molina, J. M., Rozenbaum, W., Denis, B., De Castro, N., Lascoux, C., Yazdanpanah, Y., Lariven, S., Joly, V., Rioux, C., Poupard, M., Taverne, B., Sutton, L., Masse, V., Genet, P., Wifaq, B., Gerbe, J., Grefe, S., Dupont, C., Freire Maresca, A., Reimann, E., Bloch, M., Meier, F., Mortier, E., Zeng, F., Montoya, B., Perronne, C., Mathez, D., Marigot-Outtandy, D., Berthe, H., Greder Belan, A., Terby, A., Godin Collet, C., Marque Juillet, S., Ruquet, M., Roussin-Bretagne, S., Colardelle, P., Granier, F., Laurichesse, J. J., Perronne, V., Akpan, T., Marcou, M., Daneluzzi, V., Veyssier-Belot, C., Masson, H., Welker, Y., Brazille, P., Kahn, J. E., Zucman, D., Majerholc, C., Fourn, E., Bornarel, D., Chambrin, V., Kansau, I., Raho-Moussa, M., Lelievre, J. 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M., Makhlouf, D., Brunel, F., Chiarello, P., Hoen, B., Lamaury, I., Fabre, I., Samar, K., Duvallon, E., Clavel, C., Stegmann, S., Walter, V., Adriouch, L., Huber, F., Vanticlke, V., Couppie, P., Abel, S., Pierre-Francois, S., Ricaud, C., Rodet, R., Wartel, G., Sautron, C., Poubeau, P., Borgherini, G., Camuset, G., Arasteh, K., Kowohl Vivantes, S., Schurmann, D., Warncke Charite, M., Rockstroh, J., Wasmuth, J., Hass, S., Jensen, B. O., Feind, C., Esser, S., Schenk-Westkamp, P., Haberl, A., Stephan, C., Plettenberg, A., Kuhlendahl, F., Adam, A., Weitner, L., Schewe, K., Goey, H., Fenske, S., Buhk, T., Stellbrink, H. J., Hofmann, C., Hansen, S., Degen, O., Heuer, M., Stoll, M., Gerschmann, S., Horst, H., Trautmann, S., Gillor, D., Bogner, J., Sonntag, B., Salzberger, B., Fritzsche, C., Adamis, G., Antoniadou, A., Chini, M., Chrysos, G., Gikas, A., Gogos, H. A., Katsarou, O., Lazanas, M., Metallidis, S., Panagopoulos, P., Paparizos, V., Papastamopoulos, V., Paraskevis, D., Psychogiou, M., Sambatakou, H., Sipsas, N. V., Pantazis, N., Papadopoulos, A., Nitsotolis, T., Xylomenos, G., Marangos, M. N., Kouramba, A., Kontos, A., Lioni, A., Tsachouridou, O., Kourkounti, S., Ganitis, A., Barbounakis, E., d'Arminio Monforte, A., Antinori, A., Andreoni, M., Castagna, A., Castelli, F., Cauda, R., Di Perri, G., Galli, M., Iardino, R., Ippolito, G., Lazzarin, A., Marchetti, G. C., Rezza, G., von Schloesser, F., Viale, P., Ceccherini-Silberstein, F., Cozzi-Lepri, A., Lo Caputo, S., Mussini, C., Puoti, M., Perno, C. F., Bai, F., Balotta, C., Bandera, A., Bonora, S., Borderi, M., Calcagno, A., Capetti, A., Capobianchi, M. 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E., Gorgolas, M., Svedhem-Johansson, V., Flamholc, L., Gisslen, M., Hejdeman, B., Norgren, H., Wendahl, S., European Centre for Disease Prevention and Control (ECDC), Esser, Stefan (Beitragende*r), Schenk-Westkamp, Pia (Herausgeber*in), Vourli G., Noori T., Pharris A., Porter K., Axelsson M., Begovac J., Cazein F., Costagliola D., Cowan S., Croxford S., Monforte A.D., Delpech V., Diaz A., Girardi E., Gunsenheimer-Bartmeyer B., Hernando V., Leierer G., Lot F., Nunez O., Obel N., Op de Coul E., Paraskeva D., Patrinos S., Reiss P., Schmid D., Sonnerborg A., Suligoi B., Supervie V., van Sighem A., Zangerle R., Touloumi G., Egle A., Kanatschnig M., Ollinger A., Rieger A., Schmied B., Wallner E., Dewasurendra D., Gisinger M., Kitchen M., Plattner A., Rieser E., Sarcletti M., Greil R., Schachner M., Skocic M., Muller M., Aichwalder R., Chromy D., Grabmeier-Pfstershammer K., Skoll M., Touzeau V., Cichon P., Wolf-Nussmuller S., Laferl H., Zoufaly A., Genger-Hackl C., Kapper A., Schneeberger T., Trattner E., Schober G., Atzl M., Hartmann B., Puchhammer-Stockl E., Berg J., Appoyer H., Rappold M., Strickner S., Schindelwig K., Ledergerber B., Fatkenheuer G., Gerstof J., Kronborg G., Pedersen C., Larsen C.S., Pedersen G., Mohey R., Nielsen L., Weise L., Kvinesdal B., Jensen J., Abgrall S., Bernard L., Billaud E., Boue F., Boyer L., Cabie A., Caby F., Canestri A., Cotte L., de Truchis P., Duval X., Duvivier C., Enel P., Fischer H., Gasnault J., Gaud C., Grabar S., Khuong-Josses M.A., Launay O., Marchand L., Mary-Krause M., Matheron S., Melica-Gregoire G., Melliez H., Meynard J.L., Nacher M., Pavie J., Piroth L., Poizot-Martin I., Pradier C., Reynes J., Rouveix E., Simon A., Slama L., Tattevin P., Tissot-Dupont H., Biga J., Kurth T., Jacquemet N., Guiguet M., Leclercq S., Lievre L., Marshall E., Roul H., Selinger-Leneman H., Potard V., Benveniste O., Breton G., Lupin C., Bourzam E., Girard P.M., Fonquernie L., Valin N., Lefebvre B., Sebire M., Pialoux G., Lebrette M.G., Tibaut P., Adda A., Hamidi M., Cadranel J., Lavole A., Parrot A., Bouchaud O., Vignier N., Mechai F., Makhlouf S., Honore P., Bergmann J.F., Delcey V., Lopes A., Sellier P., Parrinello M., Oksenhendler E., Gerard L., Molina J.M., Rozenbaum W., Denis B., De Castro N., Lascoux C., Yazdanpanah Y., Lariven S., Joly V., Rioux C., Poupard M., Taverne B., Sutton L., Masse V., Genet P., Wifaq B., Gerbe J., Grefe S., Dupont C., Freire Maresca A., Reimann E., Bloch M., Meier F., Mortier E., Zeng F., Montoya B., Perronne C., Mathez D., Marigot-Outtandy D., Berthe H., Greder Belan A., Terby A., Godin Collet C., Marque Juillet S., Ruquet M., Roussin-Bretagne S., Colardelle P., Granier F., Laurichesse J.J., Perronne V., Akpan T., Marcou M., Daneluzzi V., Veyssier-Belot C., Masson H., Welker Y., Brazille P., Kahn J.E., Zucman D., Majerholc C., Fourn E., Bornarel D., Chambrin V., Kansau I., Raho-Moussa M., Lelievre J.D., Saidani M., Chesnel C., Dumont C., Vittecoq D., Derradji O., Bolliot C., Goujard C., Teicher E., Mole M., Bourdic K., Salmon D., Le Jeunne C., Guet P., Pietri M.P., Pannier Metzger E., Marcou V., Loulergue P., Dupin N., Morini J.P., Deleuze J., Gerhardt P., Chanal J., Weiss L., Lucas M.L., Jung C., Ptak M., Viard J.P., Ghosn J., Gazalet P., Cros A., Maignan A., Lortholary O., Rouzaud C., Touam F., Benhadj K., Consigny P.H., Bossi P., Gergely A., Cessot G., Durand F., Beck-Wirth G., Michel C., Benomar M., Rey D., Partisani M., Cheneau C., Batard M.L., Fischer P., Leclercq P., Blanc M., Morand P., Epaulard O., Signori-Schmuck A., Laurichesse H., Jacomet C., Vidal M., Coban D., Casanova S., Fresard A., Guglielminotti C., Botelho-Nevers E., Brunon-Gagneux A., Ronat V., Verdon R., Dargere S., Haustraete E., Feret P., Goubin P., Chavanet P., Fillion A., Croisier D., Gohier S., Arvieux C., Souala F., Chapplain J.M., Ratajczak M., Rohan J., Faller J.P., Ruyer O., Gendrin V., Toko L., Chirouze C., Hustache-Mathieu L., Faucher J.F., Proust A., Magy-Bertrand N., Gil H., Meaux-Ruault N., Sotto A., Rouanet I., Mauboussin J.M., Doncesco R., Jacques G., May T., Rabaud C., Andre M., Delestan M., Bouillon M.P., Bani-Sadr F., Rouger C., Berger J.L., Nguyen Y., Marchou B., Delobel P., Martin Blondel G., Cuzin L., Biezunski N., Alric L., Bonnet D., Guivarch M., Palacin A., Payssan V., Ajana F., Meybeck A., Viget N., Pugliese P., Roger P.M., Rosenthal E., Durant J., Cua E., Naqvi A., Perbost I., Risso K., Quinsat D., Raphael St., Del Giudice P., Dides P.Y., Sambuc R., Antolini-Bouvenot M.S., Druart P., Meddeb L., Ravaux I., Menard A., Tomei C., Dhiver C., Moreau J., Mokhtari S., Soavi M.J., Tomas V., Bregigeon S., Faucher O., Obry-Roguet V., Ritleng A.S., Petit N., Bartoli C., Ruiz J.M., Blanc D., Allegre T., Sordage M., Riou J.M., Faudon C., Slama B., Zerazhi H., Boulat O., Chebrek S., Beyrne M., Granet Brunello P., Pellissier L., Bonnabel D., Cohen Valensi R., Mouchet B., Mboungou G., Lafeuillade A., Hope-Rapp E., Hittinger G., Philip G., Lambry V., Raf F., Allavena C., Hall N., Reliquet V., Chidiac C., Ferry T., Perpoint T., Miailhes P., Boibieux A., Livrozet J.M., Makhlouf D., Brunel F., Chiarello P., Hoen B., Lamaury I., Fabre I., Samar K., Duvallon E., Clavel C., Stegmann S., Walter V., Adriouch L., Huber F., Vanticlke V., Couppie P., Abel S., Pierre-Francois S., Ricaud C., Rodet R., Wartel G., Sautron C., Poubeau P., Borgherini G., Camuset G., Arasteh K., Kowohl Vivantes S., Schurmann D., Warncke Charite M., Rockstroh J., Wasmuth J., Hass S., Jensen B.O., Feind C., Esser S., Schenk-Westkamp P., Haberl A., Stephan C., Plettenberg A., Kuhlendahl F., Adam A., Weitner L., Schewe K., Goey H., Fenske S., Buhk T., Stellbrink H.J., Hofmann C., Hansen S., Degen O., Heuer M., Stoll M., Gerschmann S., Horst H., Trautmann S., Gillor D., Bogner J., Sonntag B., Salzberger B., Fritzsche C., Adamis G., Antoniadou A., Chini M., Chrysos G., Gikas A., Gogos H.A., Katsarou O., Lazanas M., Metallidis S., Panagopoulos P., Paparizos V., Papastamopoulos V., Paraskevis D., Psychogiou M., Sambatakou H., Sipsas N.V., Pantazis N., Papadopoulos A., Nitsotolis T., Xylomenos G., Marangos M.N., Kouramba A., Kontos A., Lioni A., Tsachouridou O., Kourkounti S., Ganitis A., Barbounakis E., d'Arminio Monforte A., Antinori A., Andreoni M., Castagna A., Castelli F., Cauda R., Di Perri G., Galli M., Iardino R., Ippolito G., Lazzarin A., Marchetti G.C., Rezza G., von Schloesser F., Viale P., Ceccherini-Silberstein F., Cozzi-Lepri A., Lo Caputo S., Mussini C., Puoti M., Perno C.F., Bai F., Balotta C., Bandera A., Bonora S., Borderi M., Calcagno A., Capetti A., Capobianchi M.R., Cicalini S., Cingolani A., Cinque P., Di Biagio A., Gianotti N., Gori A., Guaraldi G., Lapadula G., Lichtner M., Madeddu G., Maggiolo F., Marchetti G., Monno L., Nozza S., Pinnetti C., Quiros Roldan E., Rossotti R., Rusconi S., Santoro M.M., Saracino A., Sarmati L., Fanti I., Galli L., Lorenzini P., Rodano A., Macchia M., Tavelli A., Carletti F., Carrara S., Di Caro A., Graziano S., Petroni F., Prota G., Trufa S., Giacometti A., Costantini A., Barocci V., Angarano G., Milano E., Suardi C., Donati V., Verucchi G., Castelnuovo F., Minardi C., Menzaghi B., Abeli C., Cacopardo B., Celesia B., Vecchiet J., Falasca K., Pan A., Lorenzotti S., Sighinolf L., Segala D., Blanc P., Vichi F., Cassola G., Viscoli C., Alessandrini A., Bobbio N., Mazzarello G., Fondaco L., Bonfanti P., Molteni C., Chiodera A., Milini P., Nunnari G., Pellicano G., Rizzardini G., Cannizzo E.S., Moioli M.C., Piolini R., Bernacchia D., Salpietro S., Tincati C., Puzzolante C., Migliorino C., Sangiovanni V., Borgia G., Esposito V., Di Flumeri G., Gentile I., Rizzo V., Cattelan A.M., Marinello S., Cascio A., Trizzino M., Francisci D., Schiaroli E., Parruti G., Sozio F., Magnani G., Ursitti M.A., Cristaudo A., Vullo V., Acinapura R., Moschese D., Capozzi M., Mondi A., Rivano Capparuccia M., Iaiani G., Latini A., Gagliardini R., Plazzi M.M., De Girolamo G., Vergori A., Cecchetto M., Viviani F., De Vito A., Rossetti 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L.J.M., Nobel H., Damen M., van Kasteren M.E.E., Berrevoets M.A.H., Brouwer A.E., Adams A., de Kruijf-Van de Wiel B.A.F.M., Keelan-Pfaf S., van der Ven B., Buiting A.G.M., Murck J.L., Versteeg D., de Vries-Sluijs T.E.M.S., Bax H.I., van Gorp E.C.M., Nouwen J.L., Rijnders B.J.A., Schurink C.A.M., Verbon A., de Jong-Peltenburg N.C., Bassant N., van Beek J.E.A., Vriesde M., van Zonneveld L.M., van den Berg-Cameron H.J., de Groot J., Boucher C.A.B., Koopmans M.P.G., van Kampen J.J.A., Fraaij P.L.A., van Rossum A.M.C., Vermont C.L., van der Knaap L.C., Visser E., Branger J., Douma R.A., Duijf-Van de Ven C.J.H.M., Schippers E.F., van Nieuwkoop C., van IJperen J.M., Geilings J., van der Hut G., van Burgel N.D., Leyten E.M.S., Gelinck L.B.S., Mollema F., Davids-Veldhuis S., Wildenbeest G.S., Heikens E., Groeneveld P.H.P., Bouwhuis J.W., Lammers A.J.J., Kraan S., van Hulzen A.G.W., Kruiper M.S.M., van der Bliek G.L., Bor P.C.J., Bloembergen P., Wolfagen M.J.H.M., Ruijs G.J.H.M., Kroon F.P., de 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Pedreira J.D., Galera C., Albendin H., Iborra A., Campillo M.A., Vidal A., Amador C., Pasquau F., Ena J., Benito C., Fenoll V., Mohamed-Balghata M.O., Gomez M.A., Alberto de Zarraga M., Rivas M.E., Gorgolas M., Svedhem-Johansson V., Flamholc L., Gisslen M., Hejdeman B., Norgren H., Wendahl S., Global Health, Infectious diseases, AII - Infectious diseases, APH - Aging & Later Life, ANS - Neuroinfection & -inflammation, Internal medicine, Medical Microbiology and Infection Prevention, AMS - Rehabilitation & Development, VU University medical center, Amsterdam Gastroenterology Endocrinology Metabolism, Pediatric surgery, Neurology, Amsterdam Neuroscience - Neurodegeneration, Pulmonary medicine, Psychiatry, APH - Mental Health, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Ethics, Law & Medical humanities, APH - Quality of Care, ACS - Pulmonary hypertension & thrombosis, Amsterdam Neuroscience - Neuroinfection & -inflammation, Amsterdam Reproduction & Development (AR&D), APH - Societal Participation & Health, Pediatrics, HAL-SU, Gestionnaire, National and Kapodistrian University of Athens (NKUA), University College of London [London] (UCL), Public Health Agency of Sweden, University of Zagreb, Santé publique France - French National Public Health Agency [Saint-Maurice, France], Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Statens Serum Institut [Copenhagen], Public Health England [London], Università degli Studi di Milano = University of Milan (UNIMI), Instituto de Salud Carlos III [Madrid] (ISC), Istituto Nazionale di Malattie Infettive 'Lazzaro Spallanzani' (INMI), Robert Koch Institute [Berlin] (RKI), Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), University of Copenhagen = Københavns Universitet (UCPH), National Institute for Public Health and the Environment [Bilthoven] (RIVM), Hellenic Center for Disease Control and Prevention, Amsterdam UMC - Amsterdam University Medical Center, Austrian Agency for Health and Food Safety (AGES), Department of Infectious Diseases, Institution of Medicine, Karolinska University Hospital and Karolinska Institutet, Istituto Superiore di Sanita [Rome], Stichting HIV Monitoring [Amsterdam], Universiteit van Amsterdam (UvA), University of Athens Medical School [Athens], Vourli, G, Noori, T, Pharris, A, Porter, K, Axelsson, M, Begovac, J, Cazein, F, Costagliola, D, Cowan, S, Croxford, S, Monforte, A, Delpech, V, Diaz, A, Girardi, E, Gunsenheimer-Bartmeyer, B, Hernando, V, Leierer, G, Lot, F, Nunez, O, Obel, N, Op de Coul, E, Paraskeva, D, Patrinos, S, Reiss, P, Schmid, D, Sonnerborg, A, Suligoi, B, Supervie, V, van Sighem, A, Zangerle, R, Touloumi, G, Egle, A, Kanatschnig, M, Ollinger, A, Rieger, A, Schmied, B, Wallner, E, Dewasurendra, D, Gisinger, M, Kitchen, M, Plattner, A, Rieser, E, Sarcletti, M, Greil, R, Schachner, M, Skocic, M, Muller, M, Aichwalder, R, Chromy, D, Grabmeier-Pfstershammer, K, Skoll, M, Touzeau, V, Cichon, P, Wolf-Nussmuller, S, Laferl, H, Zoufaly, A, Genger-Hackl, C, Kapper, A, Schneeberger, T, Trattner, E, Schober, G, Atzl, M, Hartmann, B, Puchhammer-Stockl, E, Berg, J, Appoyer, H, Rappold, M, Strickner, S, Schindelwig, K, Ledergerber, B, Fatkenheuer, G, Gerstof, J, Kronborg, G, Pedersen, C, Larsen, C, Pedersen, G, Mohey, R, Nielsen, L, Weise, L, Kvinesdal, B, Jensen, J, Abgrall, S, Bernard, L, Billaud, E, Boue, F, Boyer, L, Cabie, A, Caby, F, Canestri, A, Cotte, L, de Truchis, P, Duval, X, Duvivier, C, Enel, P, Fischer, H, Gasnault, J, Gaud, C, Grabar, S, Khuong-Josses, M, Launay, O, Marchand, L, Mary-Krause, M, Matheron, S, Melica-Gregoire, G, Melliez, H, Meynard, J, Nacher, M, Pavie, J, Piroth, L, Poizot-Martin, I, Pradier, C, Reynes, J, Rouveix, E, Simon, A, Slama, L, Tattevin, P, Tissot-Dupont, H, Biga, J, Kurth, T, Jacquemet, N, Guiguet, M, Leclercq, S, Lievre, L, Marshall, E, Roul, H, Selinger-Leneman, H, Potard, V, Benveniste, O, Breton, G, Lupin, C, Bourzam, E, Girard, P, Fonquernie, L, Valin, N, Lefebvre, B, Sebire, M, Pialoux, G, Lebrette, M, Tibaut, P, Adda, A, Hamidi, M, Cadranel, J, Lavole, A, Parrot, A, Bouchaud, O, Vignier, N, Mechai, F, Makhlouf, S, Honore, P, Bergmann, J, Delcey, V, Lopes, A, Sellier, P, Parrinello, M, Oksenhendler, E, Gerard, L, Molina, J, Rozenbaum, W, Denis, B, De Castro, N, Lascoux, C, Yazdanpanah, Y, Lariven, S, Joly, V, Rioux, C, Poupard, M, Taverne, B, Sutton, L, Masse, V, Genet, P, Wifaq, B, Gerbe, J, Grefe, S, Dupont, C, Freire Maresca, A, Reimann, E, Bloch, M, Meier, F, Mortier, E, Zeng, F, Montoya, B, Perronne, C, Mathez, D, Marigot-Outtandy, D, Berthe, H, Greder Belan, A, Terby, A, Godin Collet, C, Marque Juillet, S, Ruquet, M, Roussin-Bretagne, S, Colardelle, P, Granier, F, Laurichesse, J, Perronne, V, Akpan, T, Marcou, M, Daneluzzi, V, Veyssier-Belot, C, Masson, H, Welker, Y, Brazille, P, Kahn, J, Zucman, D, Majerholc, C, Fourn, E, Bornarel, D, Chambrin, V, Kansau, I, Raho-Moussa, M, Lelievre, J, Saidani, M, Chesnel, C, Dumont, C, Vittecoq, D, Derradji, O, Bolliot, C, Goujard, C, Teicher, E, Mole, M, Bourdic, K, Salmon, D, Le Jeunne, C, Guet, P, Pietri, M, Pannier Metzger, E, Marcou, V, Loulergue, P, Dupin, N, Morini, J, Deleuze, J, Gerhardt, P, Chanal, J, Weiss, L, Lucas, M, Jung, C, Ptak, M, Viard, J, Ghosn, J, Gazalet, P, Cros, A, Maignan, A, Lortholary, O, Rouzaud, C, Touam, F, Benhadj, K, Consigny, P, Bossi, P, Gergely, A, Cessot, G, Durand, F, Beck-Wirth, G, Michel, C, Benomar, M, Rey, D, Partisani, M, Cheneau, C, Batard, M, Fischer, P, Leclercq, P, Blanc, M, Morand, P, Epaulard, O, Signori-Schmuck, A, Laurichesse, H, Jacomet, C, Vidal, M, Coban, D, Casanova, S, Fresard, A, Guglielminotti, C, Botelho-Nevers, E, Brunon-Gagneux, A, Ronat, V, Verdon, R, Dargere, S, Haustraete, E, Feret, P, Goubin, P, Chavanet, P, Fillion, A, Croisier, D, Gohier, S, 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B, Scharnhorst, V, van Eeden, A, Brokking, W, Elsenburg, L, Nobel, H, Damen, M, van Kasteren, M, Berrevoets, M, Brouwer, A, Adams, A, de Kruijf-Van de Wiel, B, Keelan-Pfaf, S, van der Ven, B, Buiting, A, Murck, J, Versteeg, D, de Vries-Sluijs, T, Bax, H, van Gorp, E, Nouwen, J, Rijnders, B, Schurink, C, Verbon, A, de Jong-Peltenburg, N, Bassant, N, van Beek, J, Vriesde, M, van Zonneveld, L, van den Berg-Cameron, H, de Groot, J, Boucher, C, Koopmans, M, van Kampen, J, Fraaij, P, van Rossum, A, Vermont, C, van der Knaap, L, Visser, E, Branger, J, Douma, R, Duijf-Van de Ven, C, Schippers, E, van Nieuwkoop, C, van IJperen, J, Geilings, J, van der Hut, G, van Burgel, N, Leyten, E, Gelinck, L, Mollema, F, Davids-Veldhuis, S, Wildenbeest, G, Heikens, E, Groeneveld, P, Bouwhuis, J, Lammers, A, Kraan, S, van Hulzen, A, Kruiper, M, van der Bliek, G, Bor, P, Bloembergen, P, Wolfagen, M, Ruijs, G, Kroon, F, de Boer, M, Scheper, H, Jolink, H, Dorama, W, van Holten, N, Claas, E, Wessels, E, den Hollander, J, El Moussaoui, R, Pogany, K, Kastelijns, M, Smit, J, Smit, E, Struik-Kalkman, D, Tearno, C, van Niekerk, T, Pontesilli, O, Lowe, S, Oude Lashof, A, Posthouwer, D, Ackens, R, Burgers, K, Schippers, J, Weijenberg-Maes, B, van Loo, I, Havenith, T, Weijer, S, van Vonderen, M, Kampschreur, L, Faber, S, Steeman-Bouma, R, Weel, J, Kootstra, G, Delsing, C, van der Burg-Van de Plas, M, Heins, H, Kortmann, W, van Twillert, G, Renckens, R, Ruiter-Pronk, D, van Truijen-Oud, F, Cohen Stuart, J, Jansen, E, Hoogewerf, M, Rozemeijer, W, van der Reijden, W, Sinnige, J, Brinkman, K, van den Berk, G, Blok, W, Frissen, P, Lettinga, K, Schouten, W, Veenstra, J, Vrouenraets, S, Brouwer, C, Geerders, G, Hoeksema, K, Kleene, M, Knapen, M, van der Meche, I, Mulder-Seeleman, E, Toonen, A, Wijnands, S, Kwa, D, van Crevel, R, van Aerde, K, Doferhof, A, Henriet, S, ter Hofstede, H, Hoogerwerf, J, Keuter, M, Richel, O, Albers, M, Grintjes-Huisman, K, de Haan, M, Marneef, M, Strik-Albers, R, Rahamat-Langendoen, J, Stelma, F, Burger, D, Gisolf, E, Hassing, R, Claassen, M, ter Beest, G, van Bentum, P, Langebeek, N, Tiemessen, R, Swanink, C, van Lelyveld, S, Soetekouw, R, van der Prijt, L, van der Swaluw, J, Bermon, N, Jansen, R, Herpers, B, Veenendaal, D, Verhagen, D, Lauw, F, van Broekhuizen, M, van Wijk, M, Bierman, W, Bakker, M, Kleinnijenhuis, J, Kloeze, E, Middel, A, Scholvinck, E, Stienstra, Y, Verhage, A, Wouthuyzen-Bakker, K, Boonstra, A, de Groot-De Jonge, H, van der Meulen, P, de Weerd, D, Niesters, H, van Leer-Buter, C, Knoester, M, Hoepelman, A, Arends, J, Barth, R, Bruns, A, Ellerbroek, P, Mudrikova, T, Oosterheert, J, de Regt, M, Schadd, E, van Zoelen, M, Aarsman, K, Grifoen-Van Santen, B, de Kroon, I, van Rooijen, C, van Berkel, M, Schuurman, R, Verduyn-Lunel, F, Wensing, A, Bont, L, Geelen, S, Loefen, Y, Wolfs, T, Nauta, N, Zaheri, S, Boyd, A, Bezemer, D, Smit, C, Hillebregt, M, de Jong, A, Woudstra, T, Bergsma, D, Meijering, R, van de Sande, L, Rutkens, T, van der Vliet, S, de Groot, L, van den Akker, M, Bakker, Y, El Berkaoui, A, Bezemer, M, Bretin, N, Djoechro, E, Geerlinks, J, Kruijne, E, Lodewijk, C, Lucas, E, van der Meer, R, Munjishvili, L, Paling, F, Peeck, B, Ree, C, Regtop, R, Ruijs, Y, Schoorl, M, Schnorr, P, Tuijn, E, Veenenberg, L, Witte, E, Tuk, B, Moreno, S, del Amo, J, Dalmau, D, Navarro, M, Gonzalez, M, Blanco, J, Garcia, F, Rubio, R, Iribarren, J, Gutierrez, F, Vidal, F, Berenguer, J, Gonzalez, J, Sobrino, P, Alejos, B, Alvarez, D, Jarrin, I, Moreno, C, Munoz-Fernandez, M, Garcia-Merino, I, Rico, C, de la Fuente, J, Torre, A, Portilla, J, Merino, E, Reus, S, Boix, V, Giner, L, Gadea, C, Portilla, I, Pampliega, M, Diez, M, Rodriguez, J, Sanchez-Paya, J, Podzamczer, D, Imaz, E, Van Den Eyncle, E, Di Yacovo, S, Sumoy, M, Gomez, J, Hernandez, J, Aleman, M, Alonso, M, Hernandez, M, Diaz-Flores, F, Garcia, D, Pelazas, R, Asensi, V, Valle, E, Carton, J, Perez, V, Molina, M, Garcia, J, Carrera, E, Pulido, F, Bisbal, O, Matarranz, M, Lagarde, M, Rubio-Martin, R, Hernando, A, Bermejo, L, Dominguez, L, Arrizabalaga, J, Aramburu, M, Camino, X, Rodriguez-Arrondo, F, von Wichmann, M, Tome, L, Goenaga, M, Bustinduy, M, Galparsoro, H, Ibarguren, M, Aguado, M, Umerez, M, Masia, M, Lopez, C, Padilla, S, Navarro, A, Montolio, F, Robledano, C, Colome, J, Adsuar, A, Pascual, R, Carlos, F, Martinez, M, Fernandez, M, Garcia, E, Muga, R, Tor, J, Sanvisens, A, Bernaldo de Quiros Lopez, J, Miralles, P, Gutierrez, I, Ramirez, M, Padilla, B, Gijon, P, Carrero, A, Aldamiz-Echevarria, T, Tejerina, F, Parras, F, Balsalobre, P, Diez, C, Peraire, J, Vilades, C, Veloso, S, Vargas, M, Lopez-Dupla, M, Olona, M, Aguilar, A, Sirvent, J, Alba, V, Calavia, O, Montero, M, Lacruz, J, Blanes, M, Calabuig, E, Cuellar, S, Lopez, J, Salavert, M, de la Serna, I, Arribas, J, Montes, M, Pena, J, Arribas, B, Castro, J, Zamora, J, Perez, I, Estebanez, M, Garcia, S, Diaz, M, Alcariz, N, Mingorance, J, Montero, D, Gonzalez, A, Isabel de Jose, M, de los Santos, I, Sanz, J, Salas, A, Sarria, C, Berrocal, A, Garcia-Fraile, L, Oteo, J, Ibarra, V, Metola, L, Sanz, M, Perez-Martinez, L, Pascual, A, Ramos, C, Arazo, P, Gil, D, Jaen, A, Cairo, M, Irigoyen, D, Jordano, Q, Xercavins, M, Martinez-Lacasa, J, Velli, P, Font, R, Sanmarti, M, Ibanez, L, Rivero, M, Casado, M, Diaz, J, Uriz, J, Reparaz, J, Irigoyen, C, Arraiza, M, Segura, F, Amengual, M, Navarro, G, Sala, M, Cervantes, M, Pineda, V, Segura, V, Anton, E, Nogueras, M, Casado, J, Dronda, F, Moreno, A, Elias, M, Lopez, D, Gutierrez, C, Madrid, N, Lamas, A, Marti, P, de Diaz, A, Serrrano, S, Donat, L, Cano, A, Bernal, E, Munoz, A, Pena, A, Munoz, L, Parra, J, Alvarez, M, Chueca, N, Guillot, V, Vinuesa, D, Fernandez, J, Del Romero, J, Rodriguez, C, Puerta, T, Carrio, J, Vera, M, Ballesteros, J, Domingo, P, Sambeat, M, Lamarca, K, Mateo, G, Gutierrez, M, Fernandez, I, Antela, A, Losada, E, Riera, M, Penaranda, M, Leyes, M, Ribas, M, Campins, A, Vidal, C, Gil, L, Fanjul, F, 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Subjects
Male, 0301 basic medicine, Psychological intervention, Human immunodeficiency virus (HIV), Medizin, Continuum of care, Europe, HIV infection, Key population, Sex, Anti-Retroviral Agents, Continuity of Patient Care, European Union, HIV, Humans, HIV Infections, medicine.disease_cause, key population, 0302 clinical medicine, HIV Infection, 030212 general & internal medicine, Men having sex with men, media_common, education.field_of_study, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Transmission (medicine), Infectious Diseases, AcademicSubjects/MED00290, HIV infection, continuum of care, sex, key population, Europe, Microbiology (medical), Population, Socio-culturale, 03 medical and health sciences, Acquired immunodeficiency syndrome (AIDS), SDG 3 - Good Health and Well-being, medicine, media_common.cataloged_instance, European union, education, Pandemics, continuum of care, sex, business.industry, SARS-CoV-2, COVID-19, medicine.disease, 030112 virology, Major Articles and Commentaries, Anti-Retroviral Agent, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Demography
Abstract

Background High uptake of antiretroviral treatment (ART) is essential to reduce human immunodeficiency virus (HIV) transmission and related mortality; however, gaps in care exist. We aimed to construct the continuum of HIV care (CoC) in 2016 in 11 European Union (EU) countries, overall and by key population and sex. To estimate progress toward the Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 target, we compared 2016 to 2013 estimates for the same countries, representing 73% of the population in the region. Methods A CoC with the following 4 stages was constructed: number of people living with HIV (PLHIV); proportion of PLHIV diagnosed; proportion of those diagnosed who ever initiated ART; and proportion of those ever treated who achieved viral suppression at their last visit. Results We estimated that 87% of PLHIV were diagnosed; 92% of those diagnosed had ever initiated ART; and 91% of those ever on ART, or 73% of all PLHIV, were virally suppressed. Corresponding figures for men having sex with men were: 86%, 93%, 93%, 74%; for people who inject drugs: 94%, 88%, 85%, 70%; and for heterosexuals: 86%, 92%, 91%, 72%. The proportion suppressed of all PLHIV ranged from 59% to 86% across countries. Conclusions The EU is close to the 90-90-90 target and achieved the UNAIDS target of 73% of all PLHIV virally suppressed, significant progress since 2013 when 60% of all PLHIV were virally suppressed. Strengthening of testing programs and treatment support, along with prevention interventions, are needed to achieve HIV epidemic control., Standardized definitions were used to estimate a 4-stage continuum of human immunodeficiency virus (HIV) care in 11 European Union (EU) countries in 2016. The EU is close to the 90-90-90 target, with the main challenge being the percentage of undiagnosed infections.

Published
2020

31. Cladribine vs other drugs in MS: Merging randomized trial with real-life data

Author

Domenico Ippolito, Sara La Gioia, Sabrina Esposito, Valentina Torri Clerici, Giorgia Teresa Maniscalco, Cinzia Cordioli, Lorena Pareja-Gutierrez, Elisabetta Signoriello, Cinzia Valeria Russo, Roberta Grasso, Doriana Landi, B. Frigeni, Andrea Visconti, Caterina Barrilà, Valeria Barcella, Raffaella Cerqua, Alice Laroni, Simona Bonavita, Stefania Barone, P. Perini, Sarah Rasia, Arianna Sartori, Maria Laura Stromillo, Roberta Lanzillo, Damiano Baroncini, Jessica Frau, Francesco Saccà, Luigi Lavorgna, Alessio Signori, Ignazio Roberto Zarbo, Giorgia Mataluni, Eleonora Cocco, Maria Pia Sormani, E Binello, Pietro Annovazzi, M Clerico, Simona Pontecorvo, Giuseppe Fenu, Alessia Di Sapio, Anna Maria Repice, Signori, A., Sacca, F., Lanzillo, R., Maniscalco, G. T., Signoriello, E., Repice, A. M., Annovazzi, P., Baroncini, D., Clerico, M., Binello, E., Cerqua, R., Mataluni, G., Perini, P., Bonavita, S., Lavorgna, L., Zarbo, I. R., Laroni, A., Pareja-Gutierrez, L., La Gioia, S., Frigeni, B., Barcella, V., Frau, J., Cocco, E., Fenu, G., Clerici, V. T., Sartori, A., Rasia, S., Cordioli, C., Stromillo, M. L., Di Sapio, A., Pontecorvo, S., Grasso, R., Barone, S., Barrila, C., Russo, C. V., Esposito, S., Ippolito, D., Landi, D., Visconti, A., Sormani, M. P., Signori, Alessio, Saccà, Francesco, Lanzillo, Roberta, Maniscalco, Giorgia Teresa, Signoriello, Elisabetta, Repice, Anna Maria, Annovazzi, Pietro, Baroncini, Damiano, Clerico, Marinella, Binello, Eleonora, Cerqua, Raffaella, Mataluni, Giorgia, Perini, Paola, Bonavita, Simona, Lavorgna, Luigi, Zarbo, Ignazio Roberto, Laroni, Alice, Pareja-Gutierrez, Lorena, La Gioia, Sara, Frigeni, Barbara, Barcella, Valeria, Frau, Jessica, Cocco, Eleonora, Fenu, Giuseppe, Clerici, Valentina Torri, Sartori, Arianna, Rasia, Sarah, Cordioli, Cinzia, Stromillo, Maria Laura, Di Sapio, Alessia, Pontecorvo, Simona, Grasso, Roberta, Barone, Stefania, Barrilà, Caterina, Russo, Cinzia Valeria, Esposito, Sabrina, Ippolito, Domenico, Landi, Doriana, Visconti, Andrea, and Sormani, Maria Pia

Subjects
Adult, Male, medicine.medical_specialty, Databases, Factual, Datasets as Topic, Settore MED/26, Placebo, Severity of Illness Index, law.invention, Multiple Sclerosis, Relapsing-Remitting, Natalizumab, Randomized controlled trial, law, Internal medicine, Outcome Assessment, Health Care, Severity of illness, medicine, Humans, Immunologic Factors, Multicenter Studies as Topic, Glatiramer acetate, Cladribine, Randomized Controlled Trials as Topic, Retrospective Studies, business.industry, Middle Aged, Fingolimod, Observational Studies as Topic, Neurology, Propensity score matching, Disease Progression, Female, Neurology (clinical), business, medicine.drug
Abstract

ObjectiveCladribine tablets were tested against placebo in randomized controlled trials (RCTs). In this study, the effectiveness of cladribine vs other approved drugs in patients with relapsing-remitting MS (RRMS) was compared by matching RCT to observational data.MethodsData from the pivotal trial assessing cladribine tablets vs placebo (CLARITY) were propensity score matched to data from the Italian multicenter database i-MuST. This database included 3,150 patients diagnosed between 2010 and 2018 at 24 Italian MS centers who started a disease-modifying drug. The annualized relapse rate (ARR) over 2 years from treatment start and the 24-week confirmed disability progression were compared between patients treated with cladribine and other approved drugs (interferon, glatiramer acetate, fingolimod, natalizumab, and dimethyl fumarate), with comparisons with placebo as a reference. Treatment effects were estimated by the inverse probability weighting negative binomial regression model for ARR and Cox model for disability progression. The treatment effect has also been evaluated according to baseline disease activity.ResultsAll weighted baseline characteristics were well balanced between groups. All drugs tested had an effect vs placebo close to that detected in the RCT. Patients treated with cladribine had a significantly lower ARR compared with interferon (relapse ratio [RR] = 0.48; p < 0.001), glatiramer acetate (RR = 0.49; p < 0.001), and dimethyl fumarate (RR = 0.6; p = 0.001); a similar ARR to that with fingolimod (RR = 0.74; p = 0.24); and a significantly higher ARR than natalizumab (RR = 2.13; p = 0.014), confirming results obtained by indirect treatment comparisons from RCTs (network meta-analyses). The relative effect of cladribine tablets 10 mg (cumulative dose 3.5 mg/kg over 2 years) was higher in patients with high disease activity vs all treatments except fingolimod and natalizumab. Effects on disability progression were largely nonsignificant, probably due to lack of power for such analysis.ConclusionIn patients with RRMS, cladribine tablets showed lower ARR compared with matched patients who started interferon, glatiramer acetate, or dimethyl fumarate; was similar to fingolimod; and was higher than natalizumab. The beneficial effect of cladribine tablets was generally amplified in the subgroup of patients with high disease activity.Classification of evidenceThis study provides Class III evidence that for patients with RRMS, cladribine-treated patients had lower ARR compared with interferon, glatiramer acetate, or dimethyl fumarate; similar ARR compared with fingolimod; and higher ARR compared with natalizumab.

Published
2020

32. Treatment of multiple sclerosis with rituximab: A multicentric Italian–Swiss experience

Author

Antonio Gallo, Gianmarco Abbadessa, Chiara Zecca, Giancarlo Coghe, Giuseppe Salemi, Antonio Uccelli, Marco Capobianco, Stefania Barone, Rosaria Sacco, Lorena Lorefice, Claudia Mechi, Giorgia Mataluni, Elio Prestipino, Jessica Frau, Claudio Gobbi, Alessandro Barilaro, Giorgia Teresa Maniscalco, Erica Curti, E. Magnani, Bahia Hakiki, Maria Malentacchi, Simona Bonavita, Alessia Di Sapio, Francesca Bovis, Maria Cellerino, Franco Granella, Roberta Lanzillo, Anna Maria Repice, Marcello De Angelis, Isabella Maraffi, Laura Brambilla, Giuseppe Fenu, Elisabetta Signoriello, Alessio Signori, Paola Cavalla, Maria Pia Sormani, Agostino Nozzolillo, Giacomo Boffa, Simona Malucchi, Maria Pia Amato, Giovanni Novi, Sabrina Realmuto, Francesca Sperli, Ilaria Maietta, Vincenzo Brescia Morra, Zecca, C., Bovis, F., Novi, G., Capobianco, M., Lanzillo, R., Frau, J., Repice, A. M., Hakiki, B., Realmuto, S., Bonavita, S., Curti, E., Brambilla, L., Mataluni, G., Cavalla, P., Di Sapio, A., Signoriello, E., Barone, S., Maniscalco, G. T., Maietta, I., Maraffi, I., Boffa, G., Malucchi, S., Nozzolillo, A., Coghe, G., Mechi, C., Salemi, G., Gallo, A., Sacco, R., Cellerino, M., Malentacchi, M., De Angelis, M., Lorefice, L., Magnani, E., Prestipino, E., Sperli, F., Brescia Morra, V., Fenu, G., Barilaro, A., Abbadessa, G., Signori, A., Granella, F., Amato, M. P., Uccelli, A., Gobbi, C., Sormani, M. P., Zecca, Chiara, Bovis, Francesca, Novi, Giovanni, Capobianco, Marco, Lanzillo, Roberta, Frau, Jessica, Repice, Anna Maria, Hakiki, Bahia, Realmuto, Sabrina, Bonavita, Simona, Curti, Erica, Brambilla, Laura, Mataluni, Giorgia, Cavalla, Paola, Di Sapio, Alessia, Signoriello, Elisabetta, Barone, Stefania, Maniscalco, Giorgia T, Maietta, Ilaria, Maraffi, Isabella, Boffa, Giacomo, Malucchi, Simona, Nozzolillo, Agostino, Coghe, Giancarlo, Mechi, Claudia, Salemi, Giuseppe, Gallo, Antonio, Sacco, Rosaria, Cellerino, Maria, Malentacchi, Maria, De Angelis, Marcello, Lorefice, Lorena, Magnani, Eliana, Prestipino, Elio, Sperli, Francesca, Brescia Morra, Vincenzo, Fenu, Giuseppe, Barilaro, Alessandro, Abbadessa, Gianmarco, Signori, Alessio, Granella, Franco, Amato, Maria Pia, Uccelli, Antonio, Gobbi, Claudio, and Sormani, Maria Pia

Subjects
Multiple Sclerosis, medicine.drug_class, Lymphocyte depletion, relapsing–remitting, Monoclonal antibody, Primary progressive, 03 medical and health sciences, 0302 clinical medicine, Multiple Sclerosis, Relapsing-Remitting, real life, medicine, Humans, Immunologic Factors, 030212 general & internal medicine, Secondary progressive, Retrospective Studies, primary progressive, business.industry, Multiple sclerosis, Rituximab, multiple sclerosis, secondary progressive, Treatment options, medicine.disease, Neurology, Relapsing remitting, Italy, multiple sclerosi, Immunology, Settore MED/26 - Neurologia, Neurology (clinical), business, 030217 neurology & neurosurgery, Switzerland, medicine.drug
Abstract

Background: Rituximab, an anti-CD20 monoclonal antibody leading to B lymphocyte depletion, is increasingly used as an off-label treatment option for multiple sclerosis (MS). Objective: To investigate the effectiveness and safety of rituximab in relapsing–remitting (RR) and progressive MS. Methods: This is a multicenter, retrospective study on consecutive MS patients treated off-label with rituximab in 22 Italian and 1 Swiss MS centers. Relapse rate, time to first relapse, Expanded Disability Status Scale (EDSS) progression, incidence of adverse events, and radiological outcomes from 2009 to 2019 were analyzed. Results: A total of 355/451 enrolled subjects had at least one follow-up visit and were included in the outcome analysis. Annualized relapse rate significantly decreases after rituximab initiation versus the pre-rituximab start year in RRMS (from 0.86 to 0.09, p Conclusion: Consistently with other observational studies, our data show effectiveness of rituximab in reducing disease activity in patients with MS.

Published
2020

33. Use of colistin in adult patients: a cross-sectional study

Author

Giacobbe, Daniele Roberto, Saffioti, Carolina, Losito, Angela Raffaella, Rinaldi, Matteo, Aurilio, Caterina, Bolla, Cesare, Boni, Silvia, Borgia, Guglielmo, Carannante, Novella, Cassola, Giovanni, Ceccarelli, Giancarlo, Corcione, Silvia, Gasperina, Daniela Dalla, De Rosa, Francesco Giuseppe, Dentone, Chiara, Di Bella, Stefano, Di Lauria, Nicoletta, Feasi, Marcello, Fiore, Marco, Fossati, Sara, Franceschini, Erica, Gori, Andrea, Granata, Guido, Grignolo, Sara, Grossi, Paolo Antonio, Guadagnino, Giuliana, Lagi, Filippo, Maraolo, Alberto Enrico, Marinò, Valeria, Mazzitelli, Maria, Mularoni, Alessandra, Oliva, Alessandra, Pace, Maria Caterina, Parisini, Andrea, Patti, Francesca, Petrosillo, Nicola, Pota, Vincenzo, Raffaelli, Francesca, Rossi, Marianna, Santoro, Antonella, Tascini, Carlo, Torti, Carlo, Trecarichi, Enrico Maria, Venditti, Mario, Viale, Pierluigi, Signori, Alessio, Del Bono, Valerio, Giannella, Maddalena, Mikulska, Malgorzata, Tumbarello, Mario, Viscoli, Claudio, Passavanti, Maria Beatrice, Rogati, C, Sansone, Pasquale, Sarteschi, G, Roberto Giacobbe, Daniele, Saffioti1, Carolina, Raffaella Losito, Angela, Rinaldi, Matteo, Aurilio, Caterina, Bolla, Cesare, Boni, Silvia, Borgia, Guglielmo, Carannante, Novella, Cassola, Giovanni, Ceccarelli, Giancarlo, Corcione, Silvia, Dalla Gasperina, Daniela, Giuseppe De Rosa, Francesco, Dentone, Chiara, DI BELLA, Stefano, Di Lauria, Nicoletta, Feasi, Marcello, Fiore, Marco, Fossati, Sara, Franceschini, Erica, Gori, Andrea, Granata, Guido, Grignolo, Sara, Antonio Grossi, Paolo, Guadagnino, Giuliana, Lagi, Filippo, Enrico Maraolo, Alberto, Marinò, Valeria, Mazzitelli, Maria, Mularoni, Alessandra, Oliva, Alessandra, Caterina Pace, Maria, Parisini, Andrea, Patti, Francesca, Petrosillo, Nicola, Pota, Vincenzo, Raffaelli, Francesca, Rossi, Marianna, Santoro, Antonella, Tascini, Carlo, Torti, Carlo, Maria Trecarichi, Enrico, Venditti, Mario, Viale, Pierluigi, Signori, Alessio, Bassetti, Matteo, Del Bono, Valerio, Giannella, Maddalena, Mikulska, Malgorzata, Tumbarello, Mario, Viscoli, Claudio, Giacobbe, Daniele Roberto, Saffioti, Carolina, Losito, Angela Raffaella, Gasperina, Daniela Dalla, De Rosa, Francesco Giuseppe, Di Bella, Stefano, Grossi, Paolo Antonio, Maraolo, Alberto Enrico, Pace, Maria Caterina, Trecarichi, Enrico Maria, Passavanti, Maria Beatrice, Rogati, C, Sansone, Pasquale, Sarteschi, G, Giacobbe D.R., Saffioti C., Losito A.R., Rinaldi M., Aurilio C., Bolla C., Boni S., Borgia G., Carannante N., Cassola G., Ceccarelli G., Corcione S., Dalla Gasperina D., De Rosa F.G., Dentone C., Di Bella S., Di Lauria N., Feasi M., Fiore M., Fossati S., Franceschini E., Gori A., Granata G., Grignolo S., Grossi P.A., Guadagnino G., Lagi F., Maraolo A.E., Marino V., Mazzitelli M., Mularoni A., Oliva A., Pace M.C., Parisini A., Patti F., Petrosillo N., Pota V., Raffaelli F., Rossi M., Santoro A., Tascini C., Torti C., Trecarichi E.M., Venditti M., Viale P., Signori A., Bassetti M., Del Bono V., Giannella M., Mikulska M., Tumbarello M., and Viscoli C.

Subjects
0301 basic medicine, Male, Endemic Diseases, Drug Resistance, Carbapenem-resistant enterobacteriaceae, Pseudomona, 0302 clinical medicine, Interquartile range, Levofloxacin, Drug Resistance, Multiple, Bacterial, Klebsiella, polycyclic compounds, Acinetobacter, Antimicrobial resistance, Colistimethate, Colistin, Pseudomonas, Administration, Intravenous, Aged, Anti-Bacterial Agents, Cross-Sectional Studies, Drug Prescriptions, Drug Therapy, Combination, Female, Gram-Negative Bacterial Infections, Humans, Italy, Middle Aged, Respiratory Tract Infections, Sepsis, Immunology and Allergy, 030212 general & internal medicine, colistin, colistimethate, Bacterial, QR1-502, Administration, Combination, lipids (amino acids, peptides, and proteins), antimicrobial resistance, Intravenous, Multiple, medicine.drug, Microbiology (medical), medicine.medical_specialty, Cefepime, 030106 microbiology, Immunology, Microbiology, Loading dose, 03 medical and health sciences, Drug Therapy, Internal medicine, Lower respiratory tract infection, medicine, business.industry, biochemical phenomena, metabolism, and nutrition, medicine.disease, business
Abstract

Objectives The aim of this study was to assess colistin use in a country endemic for multidrug-resistant Gram-negative bacteria (MDR-GNB). Methods Colistin prescription patterns were evaluated in 22 Italian centres. Factors associated with use of colistin in combination with other anti-MDR-GNB agents were also assessed. Results A total of 221 adults receiving colistin were included in the study. Their median age was 64 years (interquartile range 52–73 years) and 134 (61%) were male. Colistin was mostly administered intravenously (203/221; 92%) and mainly for targeted therapy (168/221; 76%). The most frequent indications for colistin therapy were bloodstream infection and lower respiratory tract infection. Intravenous colistin was administered in combination with at least another anti-MDR-GNB agent in 80% of cases (163/203). A loading dose of 9 MU of colistimethate was administered in 79% of patients receiving i.v. colistin and adequate maintenance doses in 85%. In multivariable analysis, empirical therapy [odds ratio (OR) = 3.25, 95% confidence interval (CI) 1.24–8.53;P = 0.017] and targeted therapy for carbapenem-resistant Enterobacterales infection (OR = 4.76, 95% CI 1.69–13.43; P = 0.003) were associated with use of colistin in combination with other agents, whilst chronic renal failure (OR = 0.39, 95% CI 0.17–0.88; P = 0.024) was associated with use of colistin monotherapy. Conclusion Colistin remains an important option for severe MDR-GNB infections when other treatments are not available. Despite inherent difficulties in optimising its use owing to peculiar pharmacokinetic/pharmacodynamic characteristics, colistin was mostly used appropriately in a country endemic for MDR-GNB.

Published
2020

34. Extending the Interval of Natalizumab Dosing: Is Efficacy Preserved?

Author

Marco Iudicello, Cinzia Cordioli, Marinella Clerico, Giorgia Teresa Maniscalco, Luigi Lavorgna, Martina Petruzzo, Giorgia Mataluni, Giacomo Lus, Massimiliano Mirabella, Rita Frangiamore, Damiano Baroncini, Erica Curti, Alice Laroni, Paola Cavalla, Eleonora Cocco, Ruggero Capra, Alessio Signori, Roberta Lanzillo, Gianfranco Costantini, Maria Pia Sormani, Stefania Federica De Mercanti, Viviana Nociti, Simona Bonavita, Ilaria Gandoglia, Arianna Sartori, Doriana Landi, Lorena Lorefice, Elisabetta Signoriello, Clerico, Marinella, De Mercanti, Stefania Federica, Signori, Alessio, Iudicello, Marco, Cordioli, Cinzia, Signoriello, Elisabetta, Lus, Giacomo, Bonavita, Simona, Lavorgna, Luigi, Maniscalco, Giorgia Teresa, Curti, Erica, Lorefice, Lorena, Cocco, Eleonora, Nociti, Viviana, Mirabella, Massimiliano, Baroncini, Damiano, Mataluni, Giorgia, Landi, Doriana, Petruzzo, Martina, Lanzillo, Roberta, Gandoglia, Ilaria, Laroni, Alice, Frangiamore, Rita, Sartori, Arianna, Cavalla, Paola, Costantini, Gianfranco, Sormani, Maria Pia, Capra, Ruggero, Clerico, M., De Mercanti, S. F., Signori, A., Iudicello, M., Cordioli, C., Signoriello, E., Lus, G., Bonavita, S., Lavorgna, L., Maniscalco, G. T., Curti, E., Lorefice, L., Cocco, E., Nociti, V., Mirabella, M., Baroncini, D., Mataluni, G., Landi, D., Petruzzo, M., Lanzillo, R., Gandoglia, I., Laroni, A., Frangiamore, R., Sartori, A., Cavalla, P., Costantini, G., Sormani, M. P., and Capra, R.

Subjects
0301 basic medicine, Standard interval, Adult, Male, medicine.medical_specialty, efficacy, progressive multifocal leukoencephalopathy, law.invention, Cohort Studies, Multiple sclerosis, 03 medical and health sciences, 0302 clinical medicine, Natalizumab, natalizumab, Randomized controlled trial, law, Recurrence, Internal medicine, medicine, Humans, Immunologic Factors, Pharmacology (medical), Multiple sclerosi, extended dose, Dosing, Retrospective Studies, Pharmacology, business.industry, Progressive multifocal leukoencephalopathy, Leukoencephalopathy, Progressive Multifocal, Retrospective cohort study, medicine.disease, Settore MED/26 - NEUROLOGIA, 030104 developmental biology, Treatment Outcome, Italy, Observational study, Female, Original Article, Neurology (clinical), business, 030217 neurology & neurosurgery, medicine.drug, Cohort study
Abstract

Extending the natalizumab interval after the 24th administration could reduce the risk of progressive multifocal leukoencephalopathy (PML). The objective is to evaluate the noninferiority of the efficacy of an extended interval dosing (EID) compared with the standard interval dosing (SID) of natalizumab. It is an observational, multicenter (14 Italian centers), retrospective cohort study, starting from the 24th natalizumab infusion to the loss of follow-up or 2 years after baseline. Patients were grouped in 2 categories according to the mean number of weeks between doses

Published
2020

35. A snapshot on patient-reported outcome measures of people with multiple sclerosis on first-line therapies in a real world setting

Author

Luigi Lavorgna, Teresa Costabile, Luca Carmisciano, R Lanzillo, N. Frattaruolo, Giacomo Lus, Alvino Bisecco, Alessio Signori, Simona Bonavita, A. Strianese, G. T. Maniscalco, V. Brescia Morra, Maddalena Sparaco, Elisabetta Signoriello, Simone Cepparulo, Francesco Saccà, Camilla Russo, Lanzillo, R, Sparaco, M, Lavorgna, L, Carmisciano, L, Signoriello, E, Signori, A, Costabile, T, Maniscalco, G T, Saccà, F, Cepparulo, S, Russo, C V, Bisecco, A, Frattaruolo, N, Strianese, A, Lus, G, Brescia Morra, V, Bonavita, S, Lanzillo, R., Sparaco, M., Lavorgna, L., Carmisciano, L., Signoriello, E., Signori, A., Costabile, T., Maniscalco, G. T., Sacca, F., Cepparulo, S., Russo, C. V., Bisecco, A., Frattaruolo, N., Strianese, A., Lus, G., Brescia Morra, V., and Bonavita, S.

Subjects
medicine.medical_specialty, Neurology, Multiple Sclerosis, Disease-modifying therapies, First-line therapies, Multiple sclerosis, Patient-reported outcomes, Dermatology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Multiple Sclerosis, Relapsing-Remitting, Teriflunomide, medicine, Humans, Multiple sclerosi, Disease-modifying therapie, 030212 general & internal medicine, Effects of sleep deprivation on cognitive performance, Patient Reported Outcome Measures, Glatiramer acetate, First-line therapie, Aged, business.industry, Cognition, General Medicine, Glatiramer Acetate, medicine.disease, humanities, Psychiatry and Mental health, chemistry, Physical therapy, Quality of Life, Patient-reported outcome, Neurology (clinical), Analysis of variance, business, 030217 neurology & neurosurgery, medicine.drug
Abstract

Background: Patient-reported outcomes (PROs) may help patients and clinicians in selecting disease-modifying therapies (DMTs) for multiple sclerosis (MS). Objective: To evaluate PRO differences among first-line DMTs for relapsing-remitting (RR) people with MS (pwMS). Methods: Multicenter study. RR pwMS on first-line DMTs completed Fatigue Severity Scale (FSS), PROs Indices for MS (PRIMUS), 36-item Short-Form Health Survey (SF-36), treatment satisfaction questionnaire for medication (TSQM), Beck Depression Inventory-II (BDI-II), and Symbol Digit Modalities Test (SDMT). Differences among PROs across DMTs were tested by ANOVA. Multivariable linear regressions were used to investigate associations between PROs and the treatment group. Results: Two-hundred eighty pwMS were enrolled: 56% were on interferons (INF), 22% on dimethylfumarate (DMF), 13% on glatiramer acetate, and 9% on teriflunomide (Teri). Compared with INF, pwMS on Teri were the oldest, with higher disability, worst depression at BDI, worst cognitive performances at SDMT (p = 0.001), fatigue at FSS (p = 0.001), and activity limitation and quality of life respectively at PRIMUS (p = 0.005) and SF-36 Mental Composite Score (p < 0.001); pwMS on DMF reported highest side effects and, together with pwMS on Teri, better treatment satisfaction at TSQM. Conclusions: Compared with INF-treated patients, pwMS on DMF and Teri reported the best treatment satisfaction, although DMF-treated pwMS reported higher side effects and those on Teri the worst QoL and fatigue; however, the older age, higher disability and depression, and worse cognitive performance of pwMS on Teri suggest to be careful in evaluating these results.

Published
2019

36. Study protocol for a diagnostic randomized clinical trial to evaluate the effect of the use of two clinical criteria in the assessment of caries lesions around restorations in adults: the Caries Cognition and Identification in Adults (CaCIA) trial

Author

Cácia Signori, Bruna Lorena Pereira Moro, Juliana Lays Stolfo Uehara, Vitor Henrique Digmayer Romero, Elenara Ferreira de Oliveira, Mariana Minatel Braga, Fausto Medeiros Mendes, Maximiliano Sérgio Cenci, and CaCIA Collaborative Group

Subjects
Adult, Caries detection, Dental Caries Susceptibility, Dentistry, Restorations, law.invention, Study Protocol, Visual inspection, 03 medical and health sciences, Cognition, 0302 clinical medicine, Randomized controlled trial, Quality of life, law, Statistical significance, Diagnosis, Humans, Medicine, 030212 general & internal medicine, Dental Restoration, Permanent, General Dentistry, Randomized Controlled Trials as Topic, Permanent teeth, Protocol (science), Proportional hazards model, business.industry, Secondary caries, 030206 dentistry, Dentition, Permanent, Clinical trial, lcsh:RK1-715, lcsh:Dentistry, Quality of Life, Dental treatment, Oral and maxillofacial surgery, Dental caries, Randomized clinical trial, business, Caries around restorations
Abstract

Background The assessment of restored teeth in dentistry remains a challenge, mainly related to the detection of caries around restorations. There is a diversity of clinical criteria available to assess the caries lesions, resulting in differences in the dentists’ diagnosis and treatment decisions. In addition, there is a lack of evidence regarding the best criteria to detect caries lesions around the restorations. Thus, the present protocol aims to evaluate the effect of using 2 visual criteria to assess restored teeth on the outcomes related to oral health in adults. Methods The design protocol of the Caries Cognition and Identification in Adults trial correspond to a triple-blind randomized, controlled clinical trial with parallel-groups. Two groups will be compared: patients who will receive the diagnosis and treatment decision according to FDI (World Dental Federation) criteria—FDI group; and patients who will receive diagnosis and treatment decision according to the “Caries Associated with Restorations or Sealants” criteria defined by the International Caries Classification and Management System (ICCMS group). The participants will be followed up after 6, 12, 18, 24, and 60 months, and the restoration failure will be the primary outcome. The analysis will be conducted through Cox regression with shared frailty. The impact of oral health on quality of life and the cost-effectiveness of the methods used will be the secondary outcomes. Two-tailed analyzes will be used, considering a level of significance of 5%. Discussion This is the first clinical trial to assess the effect of using two visual methods to detect caries lesions around restorations on the outcomes related to oral health in adults. The findings of this study will define what is the best diagnostic strategy for the assessment of caries around restorations in permanent teeth. Trial registration NCT03108586 (registered 11 April 2017).

Published
2020

37. Calcified brain metastases may be more frequent than normally considered

Author

Alessio Signori, Giulia Silvestri, Lucio Castellan, Giacomo Rebella, Luca Roccatagliata, Francesco Lupidi, Jean Louis Ravetti, Nicola Romano, Liliana Belgioia, Laura Saitta, and Gabriele Gaggero

Subjects
medicine.medical_specialty, medicine.medical_treatment, Breast Neoplasms, Metastases, Calcification, 030218 nuclear medicine & medical imaging, Brain neoplasms, Incidence, Tomography X-ray computed, 03 medical and health sciences, 0302 clinical medicine, Hounsfield scale, medicine, Humans, Radiology, Nuclear Medicine and imaging, Retrospective Studies, Lung, business.industry, Calcinosis, Histology, General Medicine, medicine.disease, Primary tumor, Radiation therapy, medicine.anatomical_structure, Adenocarcinoma, Radiology, Neuro, Differential diagnosis, Tomography, X-Ray Computed, business, 030217 neurology & neurosurgery
Abstract

Objectives To verify the incidence of calcified brain metastases (CBM), illustrating the different presentation patterns and histology of primary tumor. Methods A series of 1002 consecutive brain computed tomography (CT) scans of patients with known primary tumors was retrospectively assessed. CBM were defined by the presence of calcification within intra-axial-enhancing lesions; identification of CBM was based on visual examination and ROI analysis (> 85 Hounsfield units). Also, calcifications in the primary tumor of all patients with brain metastases were evaluated. In CBM patients, we investigated the type of calcifications (punctate, nodular, cluster, ring, coarse), the histology of primary tumor, and if a previous RT was performed. Results Among 190 (18.9%) patients with brain metastatic disease, 34 presented with CBM (17.9%). Sixteen patients were previously treated with RT, while 18 presented calcifications ab initio (9.5% of all brain metastases). The majority of patients with CBM had a primitive lung adenocarcinoma (56%), followed by breast ductal invasive carcinoma (20%) and small cell lung carcinoma (11.8%). CBM were single in 44.1% of patients and multiple in 55.9%. With regard to the type of calcifications, the majority of CBM were punctate, without specific correlations between calcification type and histology of primary tumor. No patients with ab initio CBM had calcifications in primary tumor. Conclusion In conclusion, our data show that CBM are more common than usually thought, showing an incidence of 9.5% ab initio in patients with brain metastases. This study underlines that neuroradiologists should not overlook intraparenchymal brain calcifications, especially in oncologic patients. Key Points • Among the differential diagnosis of brain intraparenchymal calcifications, metastases are considered uncommon and found predominantly in patients treated with radiotherapy (RT). • Our data show that CBM are more common than usually thought, showing an incidence of 9.5% ab initio in patients with brain metastases. • A proportion of intraparenchymal brain calcifications, especially in oncologic patients, might represent evolving lesions and neuroradiologists should not overlook them to avoid a delay in diagnosis and treatment.

Published
2020

38. Prevalence of disability improvement as a potential outcome for multiple sclerosis trials

Author

Matilde Inglese, Maria Pia Sormani, Maria Pia Amato, Alessio Signori, Giacomo Boffa, Gianluigi Mancardi, Alice Mariottini, A. Repice, Luca Massacesi, Riccardo Saccardi, and Francesca Bovis

Subjects
medicine.medical_specialty, Multiple Sclerosis, Transplantation, Autologous, Outcome (game theory), 03 medical and health sciences, Multiple Sclerosis, Relapsing-Remitting, 0302 clinical medicine, Prevalence, medicine, Humans, 030212 general & internal medicine, Intensive care medicine, clinical trials, long-term, Expanded Disability Status Scale, business.industry, Multiple sclerosis, medicine.disease, Disability improvement, outcome, prevalence, Clinical trial, Neurology, Disease Progression, Neurology (clinical), Neoplasm Recurrence, Local, business, 030217 neurology & neurosurgery
Abstract

Background: The concept of improvement of disability recently emerged as a new target in multiple sclerosis (MS) studies since the approval of new potent drugs and for testing drugs for neuroprotection and repair. Objective: To propose a simple estimator for assessing and comparing the prevalence of improvement over time between groups. Methods: The prevalence of a transient condition takes into account the incidence and the duration of such condition. We propose here the application of a modified Kaplan–Meier estimator to evaluate and compare between groups the prevalence of improvement over time in a cohort of 121 patients treated with autologous hematopoietic stem cell transplantation. Results: The prevalence of improvement after 5 years from transplant was 50.3% (95%CI: [38.0–63.0]) in relapsing–remitting patients and 6.5% (95%CI: [0–17.8]) in secondary-progressive patients ( p Conclusion: This study shows the relevance of a new estimator of prevalence of improvement in MS. This estimator gives simple information on whether a drug can induce a durable improvement in disability and can be considered a potential outcome for trials assessing drugs for neuroprotection or repair.

Published
2020

39. Degree of microstructural changes within T1-SE versus T1-GE hypointense lesions in multiple sclerosis: relevance for the definition of 'black holes'

Author

Laura Saitta, Matteo Pardini, Matilde Inglese, Alessio Signori, Giacomo Boffa, Simona Schiavi, Lucio Castellan, Caterina Lapucci, Nicola Romano, Luca Roccatagliata, and Antonio Uccelli

Subjects
Adult, Male, medicine.medical_specialty, T1-weighted images, Lesion Number, Hypointense lesions, Magnetic resonance imaging, Microstructural damage, Multiple sclerosis, 030218 nuclear medicine & medical imaging, Lesion, White matter, 03 medical and health sciences, Imaging, Three-Dimensional, 0302 clinical medicine, Fractional anisotropy, Humans, Medicine, Radiology, Nuclear Medicine and imaging, Retrospective Studies, Expanded Disability Status Scale, Clinically isolated syndrome, medicine.diagnostic_test, business.industry, Brain, General Medicine, medicine.disease, Diffusion Magnetic Resonance Imaging, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Female, Radiology, medicine.symptom, business
Abstract

To retrospectively evaluate the different performances of T1-SE and T1-GE sequences in detecting hypointense lesions in multiple sclerosis (MS), to quantify the degree of microstructural damage within lesions and to correlate them with patient clinical status. Sixty clinically isolated syndrome (CIS) and MS patients underwent brain magnetic resonance imaging (MRI) on 1.5-T and 3-T scanners. We identified T2 fluid-attenuated inversion recovery hyperintense lesions with no hypointense signal on T1-SE/T1-GE (a), hypointense lesions only on T1-GE (b), and hypointense lesions on both T1-SE and T1-GE sequences (c). We compared mean lesion number (LN) and volume (LV) identified on T1-SE and T1-GE sequences, correlating them with Expanded Disability Status Scale (EDSS); fractional anisotropy (FA) and mean diffusivity (MD) values inside each lesion type were extracted and normal-appearing white matter (NAWM). Thirty-five patients were female. Mean age was 39.2 (± 7.8); median EDSS was 3 (± 2). There were 23 CIS, 21 relapsing–remitting (RR), and 16 progressive MS. T1-GE and T1-SE LN and LV were significantly different (p

Published
2020

40. Cardiac autonomic modulation assessed by heart rate variability in children with asthma

Author

Linjie Zhang, Abelardo O. S. Júnior, Luis Ulisses Signori, Ozeia Simões Franco, and Sílvio O M Prietsch

Subjects
Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Adolescent, Autonomic Nervous System, Tertiary care, Teaching hospital, 03 medical and health sciences, 0302 clinical medicine, Heart Rate, Interquartile range, 030225 pediatrics, Internal medicine, Asthma control, medicine, Humans, Heart rate variability, Child, Asthma, business.industry, medicine.disease, Uncontrolled asthma, 030228 respiratory system, Pediatrics, Perinatology and Child Health, Cardiology, Female, Autonomic modulation, business
Abstract

Objective To assess cardiac autonomic modulation, measured by short-term frequency domain analysis of heart rate variability (HRV), in children with asthma. Methods We conducted an observational study at a tertiary care teaching hospital. The sample consisted of 119 children aged 7 to 15 years with asthma and 56 age-matched healthy controls. Frequency domain HRV measures included low-frequency (LF; 0.04-0.15 Hz), high-frequency (HF; 0.15-0.4 Hz), and LF/HF ratio. The LF and HF components were expressed in both absolute values of power (ms2 ) and in normalized units (nu). Results Compared with healthy controls, asthmatic children had significantly higher value of HF (nu) (mean ± standard deviation: 45.9 ± 14.6 vs 40.7 ± 13.6; P = .02), and lower values of LF (nu) (54.1 ± 14.6 vs 59.3 ± 13.6; P = .02) and LF/HF ratio (median, interquartile range: 1.12, 0.82-1.88 vs 1.59, 1.02-2.08; P = .03). We did not find significant differences between children with persistent and intermittent asthma, and between children with well-controlled and partially-controlled or uncontrolled asthma, in terms of HRV measures. Conclusions Children with stable chronic asthma may have a cardiac autonomic imbalance with a possible enhanced parasympathetic modulation, as assessed by short-term frequency domain analysis of HRV. Neither asthma severity nor asthma control was significantly associated with HRV measures, but the study did not have enough power to draw a firm conclusion on this point.

Published
2020

41. Serial biologic therapies in psoriasis patients: A 12-year, single-center, retrospective observational study

Author

Alessio Signori, Yiran Wei, Aurora Parodi, Martina Burlando, and Emanuele Cozzani

Subjects
Adult, Male, medicine.medical_specialty, biologic drugs, drug survival, psoriasis, switch, Kaplan-Meier Estimate, Dermatology, Risk Assessment, Severity of Illness Index, Drug Administration Schedule, Etanercept, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Psoriasis Area and Severity Index, Internal medicine, Ustekinumab, Humans, Psoriasis, Medicine, Survival analysis, Aged, Proportional Hazards Models, Academic Medical Centers, Biological Products, Drug Substitution, business.industry, Proportional hazards model, Hazard ratio, Adalimumab, Retrospective cohort study, Odds ratio, Middle Aged, Prognosis, Long-Term Care, Discontinuation, Biological Therapy, Italy, 030220 oncology & carcinogenesis, Female, business, medicine.drug
Abstract

Background Biologic therapy for psoriasis is effective but not always long-lasting and sometimes needs to be switched. Objective We aimed to evaluate the drug survival (ie, the time from initiation to discontinuation) of each biologic and the factors affecting survival to identify better switching strategies and improve drug survival. Methods In total, 195 psoriasis patients treated in our unit during 2006-2018 were retrospectively observed. Descriptive statistical analyses and logistic regression models were performed. Kaplan–Meier survival curves and multivariate Cox models adjusted for confounding variables were used to estimate and compare drug survival. Results Overall, 90.6% of patients achieved an ≥75% reduction in their baseline Psoriasis Area and Severity Index score. In 2018, the most frequently used biologic was ustekinumab (47/169, 27.8%). Patients with higher baseline Psoriasis Area and Severity Index scores were more likely to be switched (P = .0399, odds ratio 1.08). In naive patients, ustekinumab showed longer drug survival (>7.0 years), but in biologic-experienced patients, we found no significant differences in drug survival. Previous biologic therapies increased the need for switching (P = .014, hazard ratio 1.20). Switching between biologic classes yielded longer drug survival than switching within biologic classes (P = .003, hazard ratio 0.48). Limitations As a single-center, retrospective real-life study, the data were not perfectly homogeneous. Conclusion Switching between biologic classes might increase drug survival but retrospective studies designed ad hoc are needed to confirm this better switching strategy.

Published
2020

42. Cost-effective and disposable label-free voltammetric immunosensor for sensitive detection of interleukin-6

Author

Rocco Cancelliere, Alessio Di Tinno, Andrea Maria Di Lellis, Giorgio Contini, Laura Micheli, and Emanuela Signori

Subjects
Immunoassay, Interleukin-6, Cost-Benefit Analysis, Biomedical Engineering, Biophysics, Reproducibility of Results, General Medicine, Biosensing Techniques, Electrochemical Techniques, Biochar, Label-free immunosensor, Settore CHIM/01, Limit of Detection, Electrochemistry, Point-of-care device, Humans, Electrochemical immunosensor, Green-nanocarbon, Electrodes, Biotechnology
Abstract

IL-6 detection is highly desirable since can monitor many diseases in humans and assess the response to treatments. Herein, two novel label-free voltammetric immunosensors for rapid and accurate interleukin-6 (IL-6) detection in human serum are presented. The immunosensors are fabricated by immobilising two different IL-6 antibodies, identified as mAb-IL-6 clone-5 and clone-7, on in-house produced screen-printed electrodes modified with inexpensive recycling biochar (Bio-SPEs). To ensure high structural fidelity and performance, an in-depth electrochemical characterization of the layer-by-layer assembly of the immunosensor was conducted by cyclic voltammetry (CV) and sensing was performed using square wave voltammetry (SWV). The two immunosensors showed good analytical performances in human serum, exhibiting a wide linear range (LR) between 26-125 and 30-138 pg/mL, a good limit of detection (LOD) of 4.8 and 5.4 pg/mL and selectivity for IL-6 over other common cytokines, including IL-1β and TNF-α. Performance comparison of IL-6 immunosensors with those of a commercial spectrophotometric ELISA kit (LOD of 20 pg/mL, RSD% of 15%) denotes a better sensitivity and reproducibility of the proposed label-free devices, associated with a reduced detection time (30 min instead of more than 3 h for ELISA test). Furthermore, the proposed immunosensors were successfully applied in blood samples (with only a dilution of 1:100 v/v in PBS and without additional treatments) with good sensitivity (LOD of 14.3 pg/mL) and reproducibility (RSD% 11%), thus paving the way for their application as viable diagnostic and therapeutic point-of-care tools alternative to the IL-6 detection techniques routinely used (ELISA and Western Blot).

Published
2022

43. Is the effect of drugs in progressive MS only due to an effect on inflammation? A subgroup meta-analysis of randomised trials

Author

Alessio Signori, MARIA PIA SORMANI, and Mirko Capanna

Subjects
Inflammation, treatment, randomised controlled trials, Multiple Sclerosis, Chronic Progressive, Progressive, disability progression, inflammatory activity, meta-analysis, Double-Blind Method, Neurology, Humans, Neurology (clinical), Proportional Hazards Models, Randomized Controlled Trials as Topic
Abstract

Background: It is unclear whether drugs approved for the treatment of progressive multiple sclerosis (PMS) are effective in disability progression only because of their effect on the inflammatory component of the disease. Objective: This meta-analysis aimed to evaluate whether the benefits of PMS treatments are mediated by its effect on the active component of the disease. Methods: We conducted a systematic search to identify randomised, double-blind, placebo-controlled trials evaluating the efficacy of disease-modifying therapies on disability progression for primary or secondary PMS. The primary endpoint of the analysis was disability progression based on the expanded disability status scale. A subgroup meta-analysis evaluated the effects of treatment according to disease activity at baseline. Results: Twelve trials (a total of 8659 PMS cases) were selected. Analysis of the included trials demonstrated that treatment benefit appears to be mainly confined to the group with active disease (hazard ratio (HR) = 0.67; 95% confidence interval (CI): 0.58–0.79) as compared to the group with inactive disease (HR = 0.90; 95% CI: 0.79–1.02, interaction test: p = 0.005). Conclusions: This study showed that the benefit of treating patients with PMS was mostly confined to those with the more active disease. Drugs targeting specific pathological processes leading to disability progression remain necessary.

Published
2022

44. Comparison of two clinical approaches based on visual criteria for secondary caries assessments and treatment decisions in permanent posterior teeth

Author

Cacia, Signori, Juliana Lays Stolfo, Uehara, Vitor Henrique Digmayer, Romero, Bruna Lorena Pereira, Moro, Mariana Minatel, Braga, Fausto Medeiros, Mendes, and Wagner M S, Leal

Subjects
Adult, Reconstructive and regenerative medicine Radboud Institute for Health Sciences [Radboudumc 10], Dental Materials, Cross-Sectional Studies, Dental Caries Susceptibility, Humans, Dental Caries, Dental Restoration, Permanent, General Dentistry
Abstract

Background This cross-sectional study aimed to compare two clinical approaches based on visual criteria for secondary caries assessments and treatment decisions in permanent posterior teeth. Methods The two clinical visual criteria tested for the assessments of restored teeth were: FDI criteria—based on the caries presence, marginal adaptation and staining criteria, adapted from the FDI (International Dental Federation) criteria and CARS criteria—"Caries Associated with Restorations or Sealants" (CARS) criteria described by the International Caries Classification and Management System. Adults were randomized according to the criteria. One calibrated examiner assessed the restorations and assigned the treatment according to the criteria. The primary outcome was replacement indication. Results A total of 185 patients were included, totalling 718 restorations. The strongest correlation founded between the methods was for the presence of caries lesions (Rho = 0.829). A moderate correlation (Rho = 0.420) was founded between the treatment decisions proposed by the CARS and by the FDI criteria. The multilevel regression analysis showed that the FDI criteria indicated five times more replacements when compared to the CARS ( Conclusions The visual criteria used on the restoration's assessment directly influences the treatment decision to intervene or not on the restoration. The use of a minimally invasive based approach for assessing secondary caries may prevent overtreatment.

Published
2022

45. The day 100 score predicts moderate to severe cGVHD, transplant mortality, and survival after hematopoietic cell transplantation

Author

Elisabetta Metafuni, Irene Maria Cavattoni, Teresa Lamparelli, Anna Maria Raiola, Anna Ghiso, Federica Galaverna, Francesca Gualandi, Carmen Di Grazia, Alida Dominietto, Riccardo Varaldo, Alessio Signori, Patrizia Chiusolo, Federica Sora’, Sabrina Giammarco, Luca Laurenti, Simona Sica, Emanuele Angelucci, and Andrea Bacigalupo

Subjects
Settore MED/15 - MALATTIE DEL SANGUE, Transplantation Conditioning, Incidence, Hematopoietic Stem Cell Transplantation, Graft vs Host Disease, Humans, Transplantation, Homologous, Hematology, hematopoietic cell transplantation
Abstract

The aim of this study was to develop a predictive score for moderate-severe chronic graft-versus-host disease (cGVHD) on day +100 after allogeneic stem cell transplantation (HSCT). We studied 1292 patients allografted between 1990 and 2016, alive on day +100 after transplant, without cGVHD, and with full biochemistry laboratory values available. Patients were randomly assigned to a training and a validation cohort (ratio 1:1). In the training cohort, a multivariate analysis identified 4 independent predictors of moderate-severe cGVHD: gamma-glutamyl transferase ≥75 UI/l, creatinine ≥1 mg/dl, cholinesterase ≤4576 UI/l, and albumin ≤4 g/dl. A score of 1 was assigned to each variable, producing a low (0 to 1), intermediate (2 to 3), and high (4) score. The cumulative incidence of moderate-severe cGVHD was 12%, 20%, and 52% (P < .0001) in the training cohort, and 13%, 24%, and 33% (P = .002) in the validation cohort, respectively. The 5-year cumulative incidence of transplant-related mortality (TRM) was 5%, 14%, 27% (P < .0001) and 5%, 16%, 31% (P < .0001), respectively. The 5-year survival was 64%, 57%, 54% (P = .009) and 70%, 59%, 42% (P = .0008) in the 2 cohorts, respectively. In conclusion, Day100 score predicts cGVHD, TRM, and survival and, if validated in a separate group of patients, could be considered for trials of preemptive therapy.

Published
2022

46. Breakthrough SARS-CoV-2 infections after COVID-19 mRNA vaccination in MS patients on disease modifying therapies during the Delta and the Omicron waves in Italy

Author

Maria Pia Sormani, Irene Schiavetti, Matilde Inglese, Luca Carmisciano, Alice Laroni, Caterina Lapucci, Valeria Visconti, Carlo Serrati, Ilaria Gandoglia, Tiziana Tassinari, Germana Perego, Giampaolo Brichetto, Paola Gazzola, Antonio Mannironi, Maria Laura Stromillo, Cinzia Cordioli, Doriana Landi, Marinella Clerico, Elisabetta Signoriello, Eleonora Cocco, Jessica Frau, Maria Teresa Ferrò, Alessia Di Sapio, Livia Pasquali, Monica Ulivelli, Fabiana Marinelli, Matteo Pizzorno, Graziella Callari, Rosa Iodice, Giuseppe Liberatore, Francesca Caleri, Anna Maria Repice, Susanna Cordera, Mario Alberto Battaglia, Marco Salvetti, Diego Franciotta, Antonio Uccelli, Alessandro Maglione, Alessio Signori, Aniello Iovino, Carolina Gabri Nicoletti, Chiara Rosa Mancinelli, Daiana Bezzini, Daniele Carmagnini, Davide Brogi, Eduardo Nobile Orazio, Enri Nako, Ester Assandrir, Federica Baldi, Filippo Ansaldi, Francesca Bovis, Gabriele Siciliano, Gaia Cola, Giacomo Lus, Giancarlo Icardi, Gianmarco Bellucci, Giorgio Da Rin, Girolama Alessandra Marfia, Giulia Vazzoler, Giuseppe Trivelli, Ilaria Maietta, Laura Sticchi, Lorena Lorefice, Lucia Ruggiero, Marcello Manzino, Margherita Monti Bragadin, Maria Chiara Buscarinu, Maria Gagliardi, Maria Teresa Rilla, Marta Ponzano, Marzia Fronza, Massimo Del Sette, Matteo Scialabba, Michele Bedognetti, Nicola De Rossi, Nicola De Stefano, Rachele Bigi, Raffaele Dubbioso, Roberta Reniè, Sabrina Fabbri, Sarah Rasia, Simona Rolla, Stefan Platzgummer, Valentina Carlini, Sormani, Maria Pia, Schiavetti, Irene, Inglese, Matilde, Carmisciano, Luca, Laroni, Alice, Lapucci, Caterina, Visconti, Valeria, Serrati, Carlo, Gandoglia, Ilaria, Tassinari, Tiziana, Perego, Germana, Brichetto, Giampaolo, Gazzola, Paola, Mannironi, Antonio, Stromillo, Maria Laura, Cordioli, Cinzia, Landi, Doriana, Clerico, Marinella, Signoriello, Elisabetta, Cocco, Eleonora, Frau, Jessica, Ferrò, Maria Teresa, Di Sapio, Alessia, Pasquali, Livia, Ulivelli, Monica, Marinelli, Fabiana, Pizzorno, Matteo, Callari, Graziella, Iodice, Rosa, Liberatore, Giuseppe, Caleri, Francesca, Repice, Anna Maria, Cordera, Susanna, Battaglia, Mario Alberto, Salvetti, Marco, Franciotta, Diego, and Uccelli, Antonio

Subjects
Vaccines, Synthetic, Vaccines, COVID-19 Vaccines, Multiple Sclerosis, SARS-CoV-2, Messenger, Vaccination, Synthetic, Breakthrough infections, COVID-19, Disease Modifying Treatments, Cohort Studies, Humans, Prospective Studies, RNA, Messenger, mRNA Vaccines, Viral Vaccines, General Medicine, Settore MED/26, General Biochemistry, Genetics and Molecular Biology, Breakthrough infection, RNA, Disease Modifying Treatment
Abstract

Background: In this study we aimed to monitor the risk of breakthrough SARS-CoV-2 infection in patients with MS (pwMS) under different DMTs and to identify correlates of reduced protection. Methods: This is a prospective Italian multicenter cohort study, long-term clinical follow-up of the CovaXiMS (Covid-19 vaccine in Multiple Sclerosis) study. 1855 pwMS scheduled for SARS-CoV-2 mRNA vaccination were enrolled and followed up to a mean time of 10 months. The cumulative incidence of breakthrough Covid-19 cases in pwMS was calculated before and after December 2021, to separate the Delta from the Omicron waves and to account for the advent of the third vaccine dose. Findings: 1705 pwMS received 2 m-RNA vaccine doses, 21/28 days apart. Of them, 1508 (88.5%) had blood assessment 4 weeks after the second vaccine dose and 1154/1266 (92%) received the third dose after a mean interval of 210 days (range 90-342 days) after the second dose. During follow-up, 131 breakthrough Covid-19 infections (33 during the Delta and 98 during the Omicron wave) were observed. The probability to be infected during the Delta wave was associated with SARS-CoV-2 antibody levels measured after 4 weeks from the second vaccine dose (HR=0.57, p&nbsp

Published
2022

47. The role of disconnection in explaining disability in multiple sclerosis

Author

Caterina Lapucci, Simona Schiavi, Alessio Signori, Elvira Sbragia, Giulia Bommarito, Maria Cellerino, Antonio Uccelli, Matilde Inglese, Luca Roccatagliata, and Matteo Pardini

Subjects
Multiple Sclerosis, Recurrence, Brain, Humans, Radiology, Nuclear Medicine and imaging, Female, Magnetic Resonance Imaging, White Matter
Abstract

Background In multiple sclerosis, the correlation between white matter lesion volumes (LV) and expanded disability status scale (EDSS) is at best moderate, leading to the “clinico-radiological paradox”, influenced by many factors, including the lack of information on the spatial localisation of each lesion on synthetic metrics such as LV. We used a probabilistic approach to provide the volume of WM tracts that may be disconnected by lesions and to evaluate its correlation with EDSS. Methods Forty-five patients (aged 37.4 ± 6.8 years, mean ± standard deviation; 30 females; 29 relapsing-remitting, 16 progressive) underwent 3-T magnetic resonance imaging. Both LV and the volume of the tracts crossing the lesioned regions (disconnectome volume, DV) were calculated using BCBtoolkit and correlated with EDSS. Results T1-weighted LV and DV significantly correlated with EDSS (p ≤ 0.006 r ≥ 0.413) as it was for T2-weighted LV and T2-weighted DV (p ≤ 0.004 r ≥ 0.430), but only T1-weighetd and T2-weighted DVs were EDSS significant predictors (p ≤ 0.001). The correlations of T1-weighted and T2-weighted LV with EDSS were significantly mediated by DV, while no effect of LV on the EDSS-DV correlation was observed. Conclusion The volume of disconnected WM bundles mediates the LV-EDSS correlation, representing the lonely EDSS predictor.

Published
2021

48. Orthodontic treatment for posterior crossbites

Author

Philip Riley, Paola Agostino, Alessandro Ugolini, Alessio Signori, Jayne E Harrison, and Armando Silvestrini-Biavati

Subjects
Adult, Palatal Expansion Technique, Adolescent, MEDLINE, Dentistry, Cochrane Library, Overbite, Orthodontics, Corrective, posterior cross-bite, fixes vs removable palatal expansion appliances, Orthodontic Appliances, Bias, medicine, Dentition, Permanent, Humans, Pharmacology (medical), Child, Dental Care, Randomized Controlled Trials as Topic, Orthodontics, Dentition, Permanent, Europe, Malocclusion, Crossbite, business.industry, Temporomandibular Joint Dysfunction Syndrome, medicine.disease, Clinical trial, Child, Preschool, Relative risk, Meta-analysis, business, Orthodontic Retainers
Abstract

BACKGROUND: A posterior crossbite occurs when the top back teeth bite inside the bottom back teeth. The prevalence of posterior crossbite is around 4% and 17% of children and adolescents in Europe and America, respectively. Several treatments have been recommended to correct this problem, which is related to such dental issues as tooth attrition, abnormal development of the jaws, joint problems, and imbalanced facial appearance. Treatments involve expanding the upper jaw with an orthodontic appliance, which can be fixed (e.g. quad‐helix) or removable (e.g. expansion plate). This is the third update of a Cochrane review first published in 2001. OBJECTIVES: To assess the effects of different orthodontic treatments for posterior crossbites. SEARCH METHODS: Cochrane Oral Health's Information Specialist searched four bibliographic databases up to 8 April 2021 and used additional search methods to identify published, unpublished and ongoing studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) of orthodontic treatment for posterior crossbites in children and adults. DATA COLLECTION AND ANALYSIS: Two review authors, independently and in duplicate, screened the results of the electronic searches, extracted data, and assessed the risk of bias of the included studies. A third review author participated to resolve disagreements. We used risk ratios (RR) and 95% confidence intervals (CIs) to summarise dichotomous data (event), unless there were zero values in trial arms, in which case we used odds ratios (ORs). We used mean differences (MD) with 95% CIs to summarise continuous data. We performed meta‐analyses using fixed‐effect models. We used the GRADE approach to assess the certainty of the evidence for the main outcomes. MAIN RESULTS: We included 31 studies that randomised approximately 1410 participants. Eight studies were at low risk of bias, 15 were at high risk of bias, and eight were unclear. Intervention versus observation For children (age 7 to 11 years), quad‐helix was beneficial for posterior crossbite correction compared to observation (OR 50.59, 95% CI 26.77 to 95.60; 3 studies, 149 participants; high‐certainty evidence) and resulted in higher final inter‐molar distances (MD 4.71 mm, 95% CI 4.31 to 5.10; 3 studies, 146 participants; moderate‐certainty evidence). For children, expansion plates were also beneficial for posterior crossbite correction compared to observation (OR 25.26, 95% CI 13.08 to 48.77; 3 studies, 148 participants; high‐certainty evidence) and resulted in higher final inter‐molar distances (MD 3.30 mm, 95% CI 2.88 to 3.73; 3 studies, 145 participants, 3 studies; moderate‐certainty evidence). In addition, expansion plates resulted in higher inter‐canine distances (MD 2.59 mm, 95% CI 2.18 to 3.01; 3 studies, 145 participants; moderate‐certainty evidence). The use of Hyrax is probably effective for correcting posterior crossbite compared to observation (OR 48.02, 95% CI 21.58 to 106.87; 93 participants, 3 studies; moderate‐certainty evidence). Two of the studies focused on adolescents (age 12 to 16 years) and found that Hyrax increased the inter‐molar distance compared with observation (MD 5.80, 95% CI 5.15 to 6.45; 2 studies, 72 participants; moderate‐certainty evidence). Intervention A versus intervention B When comparing quad‐helix with expansion plates in children, quad‐helix was more effective for posterior crossbite correction (RR 1.29, 95% CI 1.13 to 1.46; 3 studies, 151 participants; moderate‐certainty evidence), final inter‐molar distance (MD 1.48 mm, 95% CI 0.91 mm to 2.04 mm; 3 studies, 151 participants; high‐certainty evidence), inter‐canine distance (0.59 mm higher (95% CI 0.09 mm to 1.08 mm; 3 studies, 151 participants; low‐certainty evidence) and length of treatment (MD −3.15 months, 95% CI −4.04 to −2.25; 3 studies, 148 participants; moderate‐certainty evidence). There was no evidence of a difference between Hyrax and Haas for posterior crossbite correction (RR 1.05, 95% CI 0.94 to 1.18; 3 studies, 83 participants; moderate‐certainty evidence) or inter‐molar distance (MD −0.15 mm, 95% CI −0.86 mm to 0.56 mm; 2 studies of adolescents, 46 participants; moderate‐certainty evidence). There was no evidence of a difference between Hyrax and tooth‐bone‐borne expansion for crossbite correction (RR 1.02, 95% CI 0.92 to 1.12; I² = 0%; 3 studies, 120 participants; low‐certainty evidence) or inter‐molar distance (MD −0.66 mm, 95% CI −1.36 mm to 0.04 mm; I² = 0%; 2 studies, 65 participants; low‐certainty evidence). There was no evidence of a difference between Hyrax with bone‐borne expansion for posterior crossbite correction (RR 1.00, 95% CI 0.94 to 1.07; I² = 0%; 2 studies of adolescents, 81 participants; low‐certainty evidence) or inter‐molar distance (MD −0.14 mm, 95% CI −0.85 mm to 0.57 mm; I² = 0%; 2 studies, 81 participants; low‐certainty evidence). AUTHORS' CONCLUSIONS: For children in the early mixed dentition stage (age 7 to 11 years old), quad‐helix and expansion plates are more beneficial than no treatment for correcting posterior crossbites. Expansion plates also increase the inter‐canine distance. Quad‐helix is more effective than expansion plates for correcting posterior crossbite and increasing inter‐molar distance. Treatment duration is shorter with quad‐helix than expansion plates. For adolescents in permanent dentition (age 12 to 16 years old), Hyrax and Haas are similar for posterior crossbite correction and increasing the inter‐molar distance. The remaining evidence was insufficient to draw any robust conclusions for the efficacy of posterior crossbite correction.

Published
2021

49. Modified pediatric Lung Ultrasound Score compared with computed tomography for assessment of lung aeration in children

Author

Oliviero Fochi, Giacomo Bellani, Mirco Nacoti, Stefano Gatti, Thomas H Rozen, Davide Signori, Alfio Bronco, Ezio Bonanomi, Francesco Sala, Fochi, O, Bronco, A, Nacoti, M, Signori, D, Gatti, S, Sala, F, Rozen, T, Bonanomi, E, and Bellani, G

Subjects
ARDS, Computed tomography, 03 medical and health sciences, 0302 clinical medicine, 030202 anesthesiology, medicine, Humans, Intensive care unit, Child, Lung, Ultrasonography, Aged, 80 and over, Pediatric, medicine.diagnostic_test, business.industry, Ultrasound, 030208 emergency & critical care medicine, Gold standard (test), respiratory system, medicine.disease, respiratory tract diseases, Lung ultrasound, Lung density, Anesthesiology and Pain Medicine, medicine.anatomical_structure, Interobserver Variation, Lung disease, Diagnostic imaging, Tomography, X-Ray Computed, business, Nuclear medicine
Abstract

BACKGROUND: Lung ultrasound can be used to assess lung density and aeration at the bedside. A few authors have investigated scores based on the ultrasonographic interstitial syndrome for this purpose, but none have compared them with the gold standard computed tomography in children.METHODS: Children < 10 kilograms undergoing a chest computed tomography for clinical purposes at a tertiary hospital Pediatric Intensive Care Unit were enrolled in the study. An ultrasound scan was performed shortly after computed tomography. Each hemithorax was divided in 6 zones, and each zone was scored: 1 = no B lines; 2 = < 3 B lines; 3 > 3 well separated B lines; 4 = crowded, coalescent B lines; 5 = white lung; 6 = consolidation. The pediatric Lung Ultrasound Score was obtained by adding all zones. Interobserver variation for two separate operators was calculated.RESULTS: Ten children, median age 95 days (range 23 - 721), were enrolled. Mean pediatric Lung Ultrasound Score had a significant correlation with lung density (rho = 0.68) and percentage of hypoaerated lung (rho = 0.51). Median density and percentage of hypoaerated lung increased along the ultrasound patterns values (p < 0.05) although not all patterns were significantly different from adjacent ones in the pairwise comparison. Interobserver variability in scoring of ultrasonographic patterns was moderate.CONCLUSIONS: The pediatric Lung Ultrasound Score correlates with lung density and percentage of hypoaerated lung measured with computed tomography.

Published
2021

50. SARS-CoV-2 serology after COVID-19 in multiple sclerosis: An international cohort study

Author

Maria Pia Sormani, Irene Schiavetti, Doriana Landi, Luca Carmisciano, Nicola De Rossi, Cinzia Cordioli, Lucia Moiola, Marta Radaelli, Paolo Immovilli, Marco Capobianco, Vincenzo Brescia Morra, Maria Trojano, Gioacchino Tedeschi, Giancarlo Comi, Mario Alberto Battaglia, Francesco Patti, Yara Dadalti Fragoso, Sedat Sen, Aksel Siva, Roberto Furlan, Marco Salvetti, Gianmarco Abbadessa, Umberto Aguglia, Lia Allegorico, Rossi Beatrice Maria Allegri, Maria Pia Amato, Pietro Annovazzi, Carlo Antozzi, Lucia Appendino, Sebastiano Arena, Viola Baione, Roberto Balgera, Valeria Barcella, Damiano Baroncini, Caterina Barrilà, Mario A. Battaglia, Alessandra Bellacosa, Gianmarco Bellucci, Roberto Bergamaschi, Valeria Bergamaschi, Daiana Bezzini, Beatrice Biolzi, Alvino Bisecco, Simona Bonavita, Giovanna Borriello, Chiara Bosa, Antonio Bosco, Francesca Bovis, Marco Bozzali, Laura Brambilla, Morra Vincenzo Brescia, Giampaolo Brichetto, Maria Buccafusca, Elisabetta Bucciantini, Sebastiano Bucello, Maria Chiara Buscarinu, Maria Paola Cabboi, Massimiliano Calabrese, Francesca Calabria, Francesca Caleri, Federico Camilli, Luisa Maria Caniatti, Roberto Cantello, Ruggero Capra, Rocco Capuano, Patrizia Carta, Paola Cavalla, Maria Grazia Celani, Maria Cellerino, Raffaella Cerqua, Clara Chisari, Raffaella Clerici, Marinella Clerico, Eleonora Cocco, Gaia Cola, Paolo Confalonieri, Antonella Conte, Marta Zaffira Conti, Christian Cordano, Susanna Cordera, Francesco Corea, Claudio Correale, Salvatore Cottone, Francesco Crescenzo, Erica Curti, Alessandro d’Ambrosio, Emanuele D’Amico, Maura Chiara Danni, Alessia d’Arma, Vincenzo Dattola, Stefano de Biase, Giovanna De Luca, Stefania Federica De Mercanti, Paolo De Mitri, Nicola De Stefano, Marco Della Cava, Mario di Napoli, Alessia Di Sapio, Renato Docimo, Anna Dutto, Luana Evangelista, Salvatore Fanara, Diana Ferraro, Maria Teresa Ferrò, Massimo Filippi, Cristina Fioretti, Mario Fratta, Jessica Frau, Marzia Fronza, Alberto Gajofatto, Antonio Gallo, Paolo Gallo, Claudio Gasperini, Anna Ghazaryan, Bruno Giometto, Francesca Gobbin, Flora Govone, Franco Granella, Erica Grange, Maria Grazia Grasso, Angelica Guareschi, Clara Guaschino, Simone Guerrieri, Donata Guidetti, Pietro Iaffaldano, Antonio Ianniello, Luigi Iasevoli, Daniele Imperiale, Maria Teresa Infante, Matilde Inglese, Rosa Iodice, Aniello Iovino, Giovanna Konrad, Roberta Lanzillo, Caterina Lapucci, Luigi Lavorgna, Rita L’Episcopo Maria, Serena Leva, Giuseppe Liberatore, Marianna Lo Re, Marco Longoni, Leonardo Lopiano, Lorena Lorefice, Matteo Lucchini, Giacomo Lus, Davide Maimone, Maria Malentacchi, Giulia Mallucci, Simona Malucchi, Chiara Rosa Mancinelli, Luca Mancinelli, Paolo Manganotti, Teresa Giorgia Maniscalco, Vittorio Mantero, Sabrina Marangoni, Damiano Marastoni, Alessandra Girolama Marfia, Fabiana Marinelli, Alessandro Marti, Filippo Martinelli Boneschi, Federco Masserano Zoli, Francesca Matta, Laura Mendozzi, Giuseppe Meucci, Silvia Miante, Giuseppina Miele, Eva Milano, Massimiliano Mirabella, Rosanna Missione, Marcello Moccia, Sara Montepietra, Margherita Monti Bragadin, Federico Montini, Roberta Motta, Raffaele Nardone, Carolina Gabri Nicoletti, Eduardo Nobile-Orazio, Agostino Nozzolillo, Marco Onofrj, Riccardo Orlandi, Anna Palmieri, Damiano Paolicelli, Livia Pasquali, Luisa Pastò, Elisabetta Pedrazzoli, Paola Perini, Ilaria Pesci, Maria Petracca, Alfredo Petrone, Carlo Piantadosi, Anna M. Pietroboni, Federica Pinardi, Marta Ponzano, Emilio Portaccio, Mattia Pozzato, Carlo Pozzilli, Luca Prosperini, Alessandra Protti, Paolo Ragonese, Sarah Rasia, Sabrina Realmuto, Anna Repice, Eleonora Rigoni, Maria Teresa Rilla, Francesca Rinaldi, Calogero Marcello Romano, Marco Ronzoni, Marco Rovaris, Francesca Ruscica, Loredana Sabattini, Giuseppe Salemi, Lorenzo Saraceno, Alessia Sartori, Arianna Sartori, Elvira Sbragia, Cinzia Scandellari, Ilaria Scarano Giuditta, Valentina Scarano, Valentina Schillaci, Maria Sessa, Caterina Sgarito, Grazia Sibilia, Gabriele Siciliano, Alessio Signori, Elisabetta Signoriello, Leonardo Sinisi, Francesca Sireci, Patrizia Sola, Claudio Solaro, Stefano Sotgiu, Maddalena Sparaco, Maria Laura Stromillo, Silvia Strumia, Laura Emanuela Susani, Giulietta Tabiadon, Francesco Teatini, Valentina Tomassini, Simone Tonietti, Clerici Valentina Torri, Carla Tortorella, Simona Toscano, Rocco Totaro, Maria Trotta, Gabriella Turano, Monica Ulivelli, Manzo Valentino, Giovanna Vaula, Domizia Vecchio, Marco Vercellino, Elena Pinuccia Verrengia, Marika Vianello, Eleonora Virgilio, Francesca Vitetta, Stefano Vollaro, Mauro Zaffaroni, Mauro Zampolini, Ignazio Roberto Zarbo, Antonio Zito, Luigi Zuliani, Sormani, M. P., Schiavetti, I., Landi, D., Carmisciano, L., De Rossi, N., Cordioli, C., Moiola, L., Radaelli, M., Immovilli, P., Capobianco, M., Brescia Morra, V., Trojano, M., Tedeschi, G., Comi, G., Battaglia, M. A., Patti, F., Fragoso, Y. D., Sen, S., Siva, A., Furlan, R., Salvetti, M., Bisecco, Alvino, Pia Sormani, Maria, Schiavetti, Irene, Landi, Doriana, Carmisciano, Luca, De Rossi, Nicola, Cordioli, Cinzia, Moiola, Lucia, Radaelli, Marta, Immovilli, Paolo, Capobianco, Marco, Brescia Morra, Vincenzo, Trojano, Maria, Tedeschi, Gioacchino, Comi, Giancarlo, Alberto Battaglia, Mario, Patti, Francesco, Dadalti Fragoso, Yara, Sen, Sedat, Siva, Aksel, Furlan, Roberto, Salvetti, Marco, Study Group Gianmarco Abbadessa, MuSC-19, Aguglia, Umberto, Allegorico, Lia, Beatrice Maria Allegri, Rossi, Pia Amato, Maria, Annovazzi, Pietro, Antozzi, Carlo, Appendino, Lucia, Arena, Sebastiano, Baione, Viola, Balgera, Roberto, Barcella, Valeria, Baroncini, Damiano, Barrilà, Caterina, A Battaglia, Mario, Bellacosa, Alessandra, Bellucci, Gianmarco, Bergamaschi, Roberto, Bergamaschi, Valeria, Bezzini, Daiana, Biolzi, Beatrice, Bonavita, Simona, Borriello, Giovanna, Bosa, Chiara, Bosco, Antonio, Bovis, Francesca, Bozzali, Marco, Brambilla, Laura, Vincenzo Brescia, Morra, Brichetto, Giampaolo, Buccafusca, Maria, Bucciantini, Elisabetta, Bucello, Sebastiano, Chiara Buscarinu, Maria, Paola Cabboi, Maria, Calabrese, Massimiliano, Calabria, Francesca, Caleri, Francesca, Camilli, Federico, Maria Caniatti, Luisa, Cantello, Roberto, Capra, Ruggero, Capuano, Rocco, Carta, Patrizia, Cavalla, Paola, Grazia Celani, Maria, Cellerino, Maria, Cerqua, Raffaella, Chisari, Clara, Clerici, Raffaella, Clerico, Marinella, Cocco, Eleonora, Cola, Gaia, Confalonieri, Paolo, Conte, Antonella, Zaffira Conti, Marta, Cordano, Christian, Cordera, Susanna, Corea, Francesco, Correale, Claudio, Cottone, Salvatore, Crescenzo, Francesco, Curti, Erica, D'Ambrosio, Alessandro, D'Amico, Emanuele, Chiara Danni, Maura, D'Arma, Alessia, Dattola, Vincenzo, de Biase, Stefano, De Luca, Giovanna, Federica De Mercanti, Stefania, De Mitri, Paolo, De Stefano, Nicola, Della Cava, Marco, di Napoli, Mario, Di Sapio, Alessia, Docimo, Renato, Dutto, Anna, Evangelista, Luana, Fanara, Salvatore, Ferraro, Diana, Teresa Ferrò, Maria, Filippi, Massimo, Fioretti, Cristina, Fratta, Mario, Frau, Jessica, Fronza, Marzia, Gajofatto, Alberto, Gallo, Antonio, Gallo, Paolo, Gasperini, Claudio, Ghazaryan, Anna, Giometto, Bruno, Gobbin, Francesca, Govone, Flora, Granella, Franco, Grange, Erica, Grazia Grasso, Maria, Guareschi, Angelica, Guaschino, Clara, Guerrieri, Simone, Guidetti, Donata, Iaffaldano, Pietro, Ianniello, Antonio, Iasevoli, Luigi, Imperiale, Daniele, Teresa Infante, Maria, Inglese, Matilde, Iodice, Rosa, Iovino, Aniello, Konrad, Giovanna, Lanzillo, Roberta, Lapucci, Caterina, Lavorgna, Luigi, L'Episcopo Maria, Rita, Leva, Serena, Liberatore, Giuseppe, Lo Re, Marianna, Longoni, Marco, Lopiano, Leonardo, Lorefice, Lorena, Lucchini, Matteo, Lus, Giacomo, Maimone, Davide, Malentacchi, Maria, Mallucci, Giulia, Malucchi, Simona, Rosa Mancinelli, Chiara, Mancinelli, Luca, Manganotti, Paolo, Giorgia Maniscalco, Teresa, Mantero, Vittorio, Marangoni, Sabrina, Marastoni, Damiano, Girolama Marfia, Alessandra, Marinelli, Fabiana, Marti, Alessandro, Martinelli Boneschi, Filippo, Masserano Zoli, Federco, Matta, Francesca, Mendozzi, Laura, Meucci, Giuseppe, Miante, Silvia, Miele, Giuseppina, Milano, Eva, Mirabella, Massimiliano, Missione, Rosanna, Moccia, Marcello, Montepietra, Sara, Monti Bragadin, Margherita, Montini, Federico, Motta, Roberta, Nardone, Raffaele, Gabri Nicoletti, Carolina, Nobile-Orazio, Eduardo, Nozzolillo, Agostino, Onofrj, Marco, Orlandi, Riccardo, Palmieri, Anna, Paolicelli, Damiano, Pasquali, Livia, Pastò, Luisa, Pedrazzoli, Elisabetta, Perini, Paola, Pesci, Ilaria, Petracca, Maria, Petrone, Alfredo, Piantadosi, Carlo, M Pietroboni, Anna, Pinardi, Federica, Ponzano, Marta, Portaccio, Emilio, Pozzato, Mattia, Pozzilli, Carlo, Prosperini, Luca, Protti, Alessandra, Ragonese, Paolo, Rasia, Sarah, Realmuto, Sabrina, Repice, Anna, Rigoni, Eleonora, Teresa Rilla, Maria, Rinaldi, Francesca, Marcello Romano, Calogero, Ronzoni, Marco, Rovaris, Marco, Ruscica, Francesca, Sabattini, Loredana, Salemi, Giuseppe, Saraceno, Lorenzo, Sartori, Alessia, Sartori, Arianna, Sbragia, Elvira, Scandellari, Cinzia, Scarano Giuditta, Ilaria, Scarano, Valentina, Schillaci, Valentina, Sessa, Maria, Sgarito, Caterina, Sibilia, Grazia, Siciliano, Gabriele, Signori, Alessio, Signoriello, Elisabetta, Sinisi, Leonardo, Sireci, Francesca, Sola, Patrizia, Solaro, Claudio, Sotgiu, Stefano, Sparaco, Maddalena, Laura Stromillo, Maria, Strumia, Silvia, Emanuela Susani, Laura, Tabiadon, Giulietta, Teatini, Francesco, Tomassini, Valentina, Tonietti, Simone, Valentina Torri, Clerici, Tortorella, Carla, Toscano, Simona, Totaro, Rocco, Trotta, Maria, Turano, Gabriella, Ulivelli, Monica, Valentino, Manzo, Vaula, Giovanna, Vecchio, Domizia, Vercellino, Marco, Pinuccia Verrengia, Elena, Vianello, Marika, Virgilio, Eleonora, Vitetta, Francesca, Vollaro, Stefano, Zaffaroni, Mauro, Zampolini, Mauro, Roberto Zarbo, Ignazio, Zito, Antonio, Zuliani, Luigi, Abbadessa, Gianmarco, Trotta, Maria Consiglia, and Zito, Guido Antonio

Subjects
0301 basic medicine, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), immunosuppressive therapie, coronavirus, Settore MED/26, medicine.disease_cause, Antibodies, Viral, immunosuppressive therapies, Antibodies, Serology, Cohort Studies, Multiple sclerosis, 03 medical and health sciences, 0302 clinical medicine, Seroepidemiologic Studies, Pandemic, Medicine, Humans, Multiple sclerosi, Viral, Coronavirus, business.industry, immunomodulatory therapie, immunomodulatory therapies, COVID-19, medicine.disease, Virology, coronaviru, Settore MED/26 - NEUROLOGIA, Sars-COV-2, 030104 developmental biology, Neurology, Neurology (clinical), business, SARS-CoV-2, Multiple Sclerosis, 030217 neurology & neurosurgery, Cohort study
Abstract

Background: The MuSC-19 project is an Italian cohort study open to international partners that collects data on multiple sclerosis (MS) patients with COVID-19. During the second wave of the pandemic, serological tests became routinely available. Objective: To evaluate the seroprevalence of anti-SARS-CoV-2 antibodies according to the use of disease-modifying therapy (DMT) in a subset of patients included in the MuSC-19 data set who had undergone a serological test. Methods: We evaluated the association between positive serological test results and time elapsed since infection onset, age, sex, Expanded Disability Status Scale score, comorbidities and DMT exposure using a multivariable logistic model. Results: Data were collected from 423 patients (345 from Italy, 61 from Turkey and 17 from Brazil) with a serological test performed during follow-up. Overall, 325 out of 423 tested patients (76.8%) had a positive serological test. At multivariate analysis, therapy with anti-CD20 was significantly associated with a reduced probability of developing antibodies after COVID-19 (odds ratio (OR) = 0.20, p = 0.002). Conclusion: Patients with MS maintain the capacity to develop humoral immune response against SARS-COV-2, although to a lesser extent when treated with anti-CD20 drugs. Overall, our results are reassuring with respect to the possibility to achieve sufficient immunization with vaccination.

Published
2021

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