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1. A fungi hotspot deep in the ocean: explaining the presence of Gjaerumia minor in equatorial Pacific bathypelagic waters

Author

Massimo C. Pernice, Irene Forn, Ramiro Logares, and Ramon Massana

Subjects
Medicine, Science
Abstract

Abstract A plant parasite associated with the white haze disease in apples, the Basidiomycota Gjaerumia minor, has been found in most samples of the global bathypelagic ocean. An analysis of environmental 18S rDNA sequences on 12 vertical profiles of the Malaspina 2010 expedition shows that the relative abundance of this cultured species increases with depth while its distribution is remarkably different between the deep waters of the Pacific and Atlantic oceans, being present in higher concentrations in the former. This is evident from sequence analysis and a microscopic survey with a species-specific newly designed TSA-FISH probe. Several hints point to the hypothesis that G. minor is transported to the deep ocean attached to particles, and the absence of G. minor in bathypelagic Atlantic waters could then be explained by the absence of this organism in surface waters of the equatorial Atlantic. The good correlation of G. minor biomass with Apparent Oxygen Utilization, recalcitrant carbon and free-living prokaryotic biomass in South Pacific waters, together with the identification of the observed cells as yeasts and not as resting spores (teliospores), point to the possibility that once arrived at deep layers this species keeps on growing and thriving.

Published
2024
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2. Marine picoplankton metagenomes and MAGs from eleven vertical profiles obtained by the Malaspina Expedition

Author

Pablo Sánchez, Felipe H. Coutinho, Marta Sebastián, Massimo C. Pernice, Raquel Rodríguez-Martínez, Guillem Salazar, Francisco Miguel Cornejo-Castillo, Stéphane Pesant, Xabier López-Alforja, Ester María López-García, Susana Agustí, Takashi Gojobori, Ramiro Logares, Maria Montserrat Sala, Dolors Vaqué, Ramon Massana, Carlos M. Duarte, Silvia G. Acinas, and Josep M. Gasol

Subjects
Science
Abstract

Abstract The Ocean microbiome has a crucial role in Earth’s biogeochemical cycles. During the last decade, global cruises such as Tara Oceans and the Malaspina Expedition have expanded our understanding of the diversity and genetic repertoire of marine microbes. Nevertheless, there are still knowledge gaps regarding their diversity patterns throughout depth gradients ranging from the surface to the deep ocean. Here we present a dataset of 76 microbial metagenomes (MProfile) of the picoplankton size fraction (0.2–3.0 µm) collected in 11 vertical profiles covering contrasting ocean regions sampled during the Malaspina Expedition circumnavigation (7 depths, from surface to 4,000 m deep). The MProfile dataset produced 1.66 Tbp of raw DNA sequences from which we derived: 17.4 million genes clustered at 95% sequence similarity (M-GeneDB-VP), 2,672 metagenome-assembled genomes (MAGs) of Archaea and Bacteria (Malaspina-VP-MAGs), and over 100,000 viral genomic sequences. This dataset will be a valuable resource for exploring the functional and taxonomic connectivity between the photic and bathypelagic tropical and sub-tropical ocean, while increasing our general knowledge of the Ocean microbiome.

Published
2024
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3. Immune-Mediated Inflammatory Diseases Awareness and Management among Physicians Treating Patients with Inflammatory Bowel Disease: An IG-IBD Survey

Author

Marta Vernero, Cristina Bezzio, Davide G. Ribaldone, Flavio A. Caprioli, Massimo C. Fantini, Stefano Festa, Fabio S. Macaluso, Ambrogio Orlando, Daniela Pugliese, Sara Renna, Antonio Rispo, Edoardo V. Savarino, Angela Variola, and Simone Saibeni

Subjects
IMID, IBD, Crohn’s disease, ulcerative colitis, healthcare, survey, Medicine
Abstract

(1) Background: Inflammatory bowel disease (IBD) is frequently associated to other immune-mediated inflammatory diseases (IMIDs). This study aims at assessing physicians’ awareness of the issue and the current status of IMID management. (2) Methods: A web-based survey was distributed to all 567 physicians affiliated to IG-IBD. (3) Results: A total of 249 (43.9%) physicians completed the survey. Over 90% of the responding physicians were gastroenterology specialists, primarily working in public hospitals. About 51.0% of the physicians had access to an integrated outpatient clinic, where gastroenterologists collaborated with rheumatologists and 28.5% with dermatologists. However, for 36.5% of physicians, integrated ambulatory care was not feasible. Designated appointment slots for rheumatologists and dermatologists were accessible to 72.2% and 58.2% of physicians, respectively, while 20.1% had no access to designated slots. About 5.2% of physicians report investigating signs or symptoms of IMIDs only during the initial patient assessment. However, 87.9% inquired about the presence of concomitant IMIDs at the initial assessment and actively investigated any signs or symptoms during subsequent clinical examination. (4) Conclusions: While Italian physicians recognize the importance of IMIDs associated with IBD, organizational challenges impede the attainment of optimal multidisciplinary collaboration. Efforts should be directed toward enhancing practical frameworks to improve the overall management of these complex conditions.

Published
2024
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4. Automated flow cytometry as a tool to obtain a fine-grain picture of marine prokaryote community structure along an entire oceanographic cruise

Author

Massimo C. Pernice and Josep M. Gasol

Subjects
flow cytometry, marine prokaryotes, DNA stain, automatization, online cytometry, Microbiology, QR1-502
Abstract

On a standard oceanographic cruise, flow cytometry data are usually collected sparsely through a bottle-based sampling and with stations separated by kilometers leading to a fragmented view of the ecosystem; to improve the resolution of the datasets produced by this technique here it is proposed the application of an automatic method of sampling and staining. The system used consists of a flow-cytometer (Accuri-C6) connected to an automated continuous sampler (OC-300) that collects samples of marine surface waters every 15 min. We tested this system for five days during a brief Mediterranean cruise with the aim of estimating the abundance, relative size and phenotypic diversity of prokaryotes. Seawater was taken by a faucet linked to an inlet pump (ca. 5 m depth). Once the sample was taken, the Oncyt-300 stained it and sent it to the flow cytometer. A total of 366 samples were collected, effectively achieving a fine-grained scale view of microbial community composition both through space and time. A significative positive relationship was found comparing data obtained with the automatic method and 10 samples collected from the faucet but processed with the standard protocol. Abundance values retrieved varied from 3.56·105 cell mL−1 in the coastal area till 6.87 105 cell mL−1 in open waters, exceptional values were reached in the harbor area where abundances peaked to 1.28 106 cell mL−1. The measured features (abundance and size) were associated with metadata (temperature, salinity, conductivity) also taken in continuous, of which conductivity was the one that better explained the variability of abundance. A full 24 h measurement cycle was performed resulting in slightly higher median bacterial abundances values during daylight hours compared to night. Alpha diversity, calculated using computational cytometry techniques, showed a higher value in the coastal area above 41° of latitude and had a strong inverse relationship with both salinity and conductivity. This is the first time to our knowledge that the OC-300 is directly applied to the marine environment during an oceanographic cruise; due to its high-resolution, this set-up shows great potential both to cover large sampling areas, and to monitor day-night cycles in situ.

Published
2023
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5. Large-scale ocean connectivity and planktonic body size

Author

Ernesto Villarino, James R. Watson, Bror Jönsson, Josep M. Gasol, Guillem Salazar, Silvia G. Acinas, Marta Estrada, Ramón Massana, Ramiro Logares, Caterina R. Giner, Massimo C. Pernice, M. Pilar Olivar, Leire Citores, Jon Corell, Naiara Rodríguez-Ezpeleta, José Luis Acuña, Axayacatl Molina-Ramírez, J. Ignacio González-Gordillo, Andrés Cózar, Elisa Martí, José A. Cuesta, Susana Agustí, Eugenio Fraile-Nuez, Carlos M. Duarte, Xabier Irigoien, and Guillem Chust

Subjects
Science
Abstract

Body size is hypothesised to be a major determinant of β-diversity in passively-dispersing marine organisms. Here, Villarino et al. show that plankton body size determines rates of dispersal along marine currents, with shorter dispersal and higher species spatial turnover in larger organisms.

Published
2018
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6. Tbet Expression in Regulatory T Cells Is Required to Initiate Th1-Mediated Colitis

Author

Martina Di Giovangiulio, Angelamaria Rizzo, Eleonora Franzè, Flavio Caprioli, Federica Facciotti, Sara Onali, Agnese Favale, Carmine Stolfi, Hans-Joerg Fehling, Giovanni Monteleone, and Massimo C. Fantini

Subjects
Treg cells, Tbet, Th1-like Tregs, inflammatory bowel disease, inflammation, Immunologic diseases. Allergy, RC581-607
Abstract

In normal conditions gut homeostasis is maintained by the suppressive activity of regulatory T cells (Tregs), characterized by the expression of the transcription factor FoxP3. In human inflammatory bowel disease, which is believed to be the consequence of the loss of tolerance toward antigens normally contained in the gut lumen, Tregs have been found to be increased and functionally active, thus pointing against their possible role in the pathogenesis of this immune-mediated disease. Though, in inflammatory conditions, Tregs have been shown to upregulate the T helper (Th) type 1-related transcription factor Tbet and to express the pro-inflammatory cytokine IFNγ, thus suggesting that at a certain point of the inflammatory process, Tregs might contribute to inflammation rather than suppress it. Starting from the observation that Tregs isolated from the lamina propria of active but not inactive IBD patients or uninflamed controls express Tbet and IFNγ, we investigated the functional role of Th1-like Tregs in the dextran sulfate model of colitis. As observed in human IBD, Th1-like Tregs were upregulated in the inflamed lamina propria of treated mice and the expression of Tbet and IFNγ in Tregs preceded the accumulation of conventional Th1 cells. By using a Treg-specific Tbet conditional knockout, we demonstrated that Tbet expression in Tregs is required for the development of colitis. Indeed, Tbet knockout mice developed milder colitis and showed an impaired Th1 immune response. In these mice not only the Tbet deficient Tregs but also the Tbet proficient conventional T cells showed reduced IFNγ expression. However, Tbet deficiency did not affect the Tregs suppressive capacity in vitro and in vivo in the adoptive transfer model of colitis. In conclusion here we show that Tbet expression by Tregs sustains the early phase of the Th1-mediated inflammatory response in the gut.

Published
2019
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7. A Short Comparison of Two Marine Planktonic Diazotrophic Symbioses Highlights an Un-quantified Disparity

Author

Andrea Caputo, Marcus Stenegren, Massimo C. Pernice, and Rachel A. Foster

Subjects
cyanobacteria, diazotrophs, diatoms, symbiosis, DDA, UCYN-A, Science, General. Including nature conservation, geographical distribution, QH1-199.5
Abstract

Some N2-fixing cyanobacteria form symbiosis with diverse protists. In the plankton two groups of diazotrophic symbioses are described: (1) a collective group of diatoms which associate with heterocystous cyanobacteria (Diatom Diazotroph Associations, DDA), and (2) the microalgal prymnesiophyte Braarudosphaera bigelowii and its relatives which associate with the unicellular cyanobacterium Candidatus Atelocyanobacterium thalassa (hereafter as UCYN-A). Both symbiotic systems co-occur, and in both partnerships the symbionts function as a nitrogen (N) source. In this perspective, we provide a brief comparison between the DDAs and the prymnesiophyte-UCYN-A symbioses highlighting similarities and differences in both systems, and present a bias in the attention and current methodology that has led to an under-detection and under-estimation of the DDAs.

Published
2018
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9. Marine picoplankton metagenomes and MAGs from eleven vertical profiles obtained by the Malaspina Expedition

Author

Sánchez, Pablo, Coutinho, Felipe H., Sebastián, Marta, Pernice, Massimo C., Rodríguez-Martínez, Raquel, Salazar, Guillem, Cornejo-Castillo, Francisco Miguel, Pesant, Stéphane, López-Alforja, Xabier, López-García, Ester María, Agustí, Susana, Gojobori, Takashi, Logares, Ramiro, Sala, Maria Montserrat, Vaqué, Dolors, Massana, Ramon, Duarte, Carlos M., Acinas, Silvia G., and Gasol, Josep M.

Published
2024
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10. A Mobile Habitat for Human Lunar Exploration

Author

Sumini, Valentina, Chesi, Claudio, Florenzano, Daniele, Botti, Michela, Calogero, Lorenzo, Caracas, Ana Carolina Corrêa, Caruso, Alessandro, Comparini, Massimo C., Ferrone, Enrico, Hoffman, Jeffrey, Maggiore, Paolo, Mattioli, Marta, Paradiso, Joseph, Perino, Maria Antonietta, Portolani, Marco, Rizzo, Angela, Signorotto, Giulia, di Prisco, Marco, Series Editor, Chen, Sheng-Hong, Series Editor, Vayas, Ioannis, Series Editor, Kumar Shukla, Sanjay, Series Editor, Sharma, Anuj, Series Editor, Kumar, Nagesh, Series Editor, Wang, Chien Ming, Series Editor, Cui, Zhen-Dong, Series Editor, Gabriele, Stefano, editor, Manuello Bertetto, Amedeo, editor, Marmo, Francesco, editor, and Micheletti, Andrea, editor

Published
2024
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11. A Mobile Habitat for Human Lunar Exploration

Author

Sumini, Valentina, primary, Chesi, Claudio, additional, Florenzano, Daniele, additional, Botti, Michela, additional, Calogero, Lorenzo, additional, Caracas, Ana Carolina Corrêa, additional, Caruso, Alessandro, additional, Comparini, Massimo C., additional, Ferrone, Enrico, additional, Hoffman, Jeffrey, additional, Maggiore, Paolo, additional, Mattioli, Marta, additional, Paradiso, Joseph, additional, Perino, Maria Antonietta, additional, Portolani, Marco, additional, Rizzo, Angela, additional, and Signorotto, Giulia, additional

Published
2023
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12. Immune-Mediated Inflammatory Diseases Awareness and Management among Physicians Treating Patients with Inflammatory Bowel Disease: An IG-IBD Survey

Author

Vernero, Marta, primary, Bezzio, Cristina, additional, Ribaldone, Davide G., additional, Caprioli, Flavio A., additional, Fantini, Massimo C., additional, Festa, Stefano, additional, Macaluso, Fabio S., additional, Orlando, Ambrogio, additional, Pugliese, Daniela, additional, Renna, Sara, additional, Rispo, Antonio, additional, Savarino, Edoardo V., additional, Variola, Angela, additional, and Saibeni, Simone, additional

Published
2024
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16. Defining Comprehensive Disease Control for use as a Treatment Target for Ulcerative Colitis in Clinical Practice : International Delphi Consensus Recommendations

Author

Schreiber, Stefan, Danese, Silvio, Dignass, Axel, Domènech, Eugeni, Fantini, Massimo C., Ferrante, Marc, Halfvarson, Jonas, Hart, Ailsa, Magro, Fernando, Lees, Charlie W., Leone, Salvo, Pierik, Marieke J., Peters, Michele, Field, Polly, Fishpool, Helen, Peyrin-Biroulet, Laurent, Schreiber, Stefan, Danese, Silvio, Dignass, Axel, Domènech, Eugeni, Fantini, Massimo C., Ferrante, Marc, Halfvarson, Jonas, Hart, Ailsa, Magro, Fernando, Lees, Charlie W., Leone, Salvo, Pierik, Marieke J., Peters, Michele, Field, Polly, Fishpool, Helen, and Peyrin-Biroulet, Laurent

Abstract

BACKGROUND AND AIMS: Treatment of ulcerative colitis (UC) requires a patient-centric, definition of comprehensive disease control that considers improvements in aspects not typically captured by classical landmark trial endpoints. In an international initiative we reviewed aspects of UC that affect patients and/or indicate mucosal inflammation, to achieve consensus on which aspects to combine in a definition of comprehensive disease control, using a modified Delphi process. METHODS: The Delphi panel comprised 12 gastroenterologists and one patient advocate. Two gastroenterologists were elected as chairs and did not vote. To inform statements, we asked 18 patients and the panel members about their experiences of remission and reviewed published literature. Panel members voted on statements anonymously in three rounds, with a live discussion before round 3. Consensus was met if ≥ 67% of the panel agreed. Statements without consensus in rounds 1 and 2 were revised or discarded after round 3. RESULTS: The panel agreed to measure individual patient benefit using a definition of comprehensive disease control that combines aspects currently measured in trials (rectal bleeding, stool frequency, disease-related quality of life, endoscopy, histological inflammatory activity, inflammatory biomarkers, and corticosteroid use), with additional patient-reported symptoms (bowel urgency, abdominal pain, extraintestinal manifestations, fatigue, and sleep disturbance). The panel agreed on scoring systems and thresholds for many aspects. CONCLUSIONS: Using a robust methodology, we defined comprehensive disease control in UC. Next, we will combine the measurement and scoring of these aspects into a multi-component tool and adopt comprehensive disease control as a treatment target in clinical practice and trials.

Published
2024
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17. Clinical characteristics and outcomes of vaccinated patients hospitalised with SARS-CoV-2 breakthrough infection: Multi-IPV, a multicentre study in Northern Italy

Author

Lombardi, A, Villa, S, Colaneri, M, Scaglione, G, Bai, F, Varisco, B, Bono, V, Vena, A, Dentone, C, Russo, C, Tettamanti, M, Renisi, G, Viero, G, Azzarà, C, Mantero, M, Peyvandi, F, Bassetti, M, Marchetti, G, Muscatello, A, Nobili, A, Gori, A, Bandera, A, Bosari, S, Scudeller, L, Fusetti, G, Rusconi, L, Dell’Orto, S, Prati, D, Valenti, L, Giovannelli, S, Manunta, M, Lamorte, G, Ferarri, F, Gori., A, Mangioni, D, Alagna, L, Bozzi, G, Lombardi., A, Ungaro, R, Ancona, G, Mussa, M, Mariani, B, Bolis, M, Iannotti, N, Ludovisi, S, Comelli, A, Biscarini, S, Castelli, V, Palomba, E, Fava, M, Peri, C, Saltini, P, Itri, T, Ferroni, V, Pastore, V, Massafra, R, Liparoti, A, Muheberimana, T, Giommi, A, Bianco, R, Chitani, G, Bobbio, C, De Matteis, I, Bonomi, A, Gualtierotti, R, Ferrari, B, Rossio, R, Boasi, N, Pagliaro, E, Massimo, C, De Caro, M, Giachi, A, Montano, N, Vigone, B, Bellocchi, C, Carandina, A, Fiorelli, E, Melli, V, Tobaldini, E, Blasi, F, Aliberti, S, Spotti, M, Terranova, L, Misuraca, S, D’Adda, A, Della Fiore, S, Di Pasquale, M, Mantero., M, Contarini, M, Ori, M, Morlacchi, L, Rossetti, V, Gramegna, A, Pappalettera, M, Cavallini, M, Buscemi, A, Vicenzi, M, Rota, I, Costantino, G, Solbiati, M, Furlan, L, Mancarella, M, Colombo, G, Fanin, A, Passarella, M, Monzani, V, Canetta, C, Rovellini, A, Barbetta, L, Billi, F, Folli, C, Accordino, S, Maira, D, Hu, C, Motta, I, Scaramellini, N, Fracanzani, A, Lombardi, R, Cespiati, A, Cesari, M, Lucchi, T, Proietti, M, Calcaterra, L, Mandelli, C, Coppola, C, Cerizza, A, Pesenti, A, Grasselli, G, Galazzi, A, Nobili., A, Monti, I, Galbussera, A, Crisafulli, E, Girelli, D, Maroccia, A, Gabbiani, D, Busti, F, Vianello, A, Biondan, M, Sartori, F, Faverio, P, Pesci, A, Zucchetti, S, Bonfanti, P, Rossi, M, Beretta, I, Spolti, A, Harari, S, Elia, D, Cassandro, R, Caminati, A, Cipollone, F, Guagnano, M, D’Ardes, D, Rossi, I, Vezzani, F, Spanevello, A, Cherubino, F, Visca, D, Contoli, M, Papi, A, Morandi, L, Battistini, N, Moreo, G, Iannuzzi, P, Fumagalla, D, Leone, S, Lombardi, Andrea, Villa, Simone, Colaneri, Marta, Scaglione, Giovanni, Bai, Francesca, Varisco, Benedetta, Bono, Valeria, Vena, Antonio, Dentone, Chiara, Russo, Chiara, Tettamanti, Mauro, Renisi, Giulia, Viero, Giulia, Azzarà, Cecilia, Mantero, Marco, Peyvandi, Flora, Bassetti, Matteo, Marchetti, Giulia, Muscatello, Antonio, Nobili, Alessandro, Gori, Andrea, Bandera, Alessandra, Bosari, Silvano, Scudeller, Luigia, Fusetti, Giuliana, Rusconi, Laura, Dell’Orto, Silvia, Prati, Daniele, Valenti, Luca, Giovannelli, Silvia, Manunta, Maria, Lamorte, Giuseppe, Ferarri, Francesca, Gori. , Andrea, Mangioni, Davide, Alagna, Laura, Bozzi, Giorgio, Lombardi. , Andrea, Ungaro, Riccardo, Ancona, Giuseppe, Mussa, Marco, Mariani, Bianca Veronica, Bolis, Matteo, Iannotti, Nathalie, Ludovisi, Serena, Comelli, Agnese, Biscarini, Simona, Castelli, Valeria, Palomba, Emanuele, Fava, Marco, Peri, Carlo Alberto, Saltini, Paola, Itri, Teresa, Ferroni, Valentina, Pastore, Valeria, Massafra, Roberta, Liparoti, Arianna, Muheberimana, Toussaint, Giommi, Alessandro, Bianco, Rosaria, Chitani, Grazia Eliana, Bobbio, Chiara, De Matteis, Irene, Bonomi, Angelo Bianchi, Gualtierotti, Roberta, Ferrari, Barbara, Rossio, Raffaella, Boasi, Nadia, Pagliaro, Erica, Massimo, Costanza, De Caro, Michele, Giachi, Andrea, Montano, Nicola, Vigone, Barbara, Bellocchi, Chiara, Carandina, Angelica, Fiorelli, Elisa, Melli, Valerie, Tobaldini, Eleonora, Blasi, Francesco, Aliberti, Stefano, Spotti, Maura, Terranova, Leonardo, Misuraca, Sofia, D’Adda, Alice, Della Fiore, Silvia, Di Pasquale, Marta, Mantero. , Marco, Contarini, Martina, Ori, Margherita, Morlacchi, Letizia, Rossetti, Valeria, Gramegna, Andrea, Pappalettera, Maria, Cavallini, Mirta, Buscemi, Agata, Vicenzi, Marco, Rota, Irena, Costantino, Giorgio, Solbiati, Monica, Furlan, Ludovico, Mancarella, Marta, Colombo, Giulia, Colombo, Giorgio, Fanin, Alice, Passarella, Mariele, Monzani, Valter, Canetta, Ciro, Rovellini, Angelo, Barbetta, Laura, Billi, Filippo, Folli, Christian, Accordino, Silvia, Maira, Diletta, Hu, Cinzia Maria, Motta, Irene, Scaramellini, Natalia, Fracanzani, Anna Ludovica, Lombardi, Rosa, Cespiati, Annalisa, Cesari, Matteo, Lucchi, Tiziano, Proietti, Marco, Calcaterra, Laura, Mandelli, Clara, Coppola, Carlotta, Cerizza, Arturo, Pesenti, Antonio Maria, Grasselli, Giacomo, Galazzi, Alessandro, Nobili. , Alessandro, Monti, Igor, Galbussera, Alessia Antonella, Crisafulli, Ernesto, Girelli, Domenico, Maroccia, Alessio, Gabbiani, Daniele, Busti, Fabiana, Vianello, Alice, Biondan, Marta, Sartori, Filippo, Faverio, Paola, Pesci, Alberto, Zucchetti, Stefano, Bonfanti, Paolo, Rossi, Marianna, Beretta, Ilaria, Spolti, Anna, Harari, Sergio, Elia, Davide, Cassandro, Roberto, Caminati, Antonella, Cipollone, Francesco, Guagnano, Maria Teresa, D’Ardes, Damiano, Rossi, Ilaria, Vezzani, Francesca, Spanevello, Antonio, Cherubino, Francesca, Visca, Dina, Contoli, Marco, Papi, Alberto, Morandi, Luca, Battistini, Nicholas, Moreo, Guido Luigi, Iannuzzi, Pasqualina, Fumagalla, Daniele, Leone, Sara, Lombardi, A, Villa, S, Colaneri, M, Scaglione, G, Bai, F, Varisco, B, Bono, V, Vena, A, Dentone, C, Russo, C, Tettamanti, M, Renisi, G, Viero, G, Azzarà, C, Mantero, M, Peyvandi, F, Bassetti, M, Marchetti, G, Muscatello, A, Nobili, A, Gori, A, Bandera, A, Bosari, S, Scudeller, L, Fusetti, G, Rusconi, L, Dell’Orto, S, Prati, D, Valenti, L, Giovannelli, S, Manunta, M, Lamorte, G, Ferarri, F, Gori., A, Mangioni, D, Alagna, L, Bozzi, G, Lombardi., A, Ungaro, R, Ancona, G, Mussa, M, Mariani, B, Bolis, M, Iannotti, N, Ludovisi, S, Comelli, A, Biscarini, S, Castelli, V, Palomba, E, Fava, M, Peri, C, Saltini, P, Itri, T, Ferroni, V, Pastore, V, Massafra, R, Liparoti, A, Muheberimana, T, Giommi, A, Bianco, R, Chitani, G, Bobbio, C, De Matteis, I, Bonomi, A, Gualtierotti, R, Ferrari, B, Rossio, R, Boasi, N, Pagliaro, E, Massimo, C, De Caro, M, Giachi, A, Montano, N, Vigone, B, Bellocchi, C, Carandina, A, Fiorelli, E, Melli, V, Tobaldini, E, Blasi, F, Aliberti, S, Spotti, M, Terranova, L, Misuraca, S, D’Adda, A, Della Fiore, S, Di Pasquale, M, Mantero., M, Contarini, M, Ori, M, Morlacchi, L, Rossetti, V, Gramegna, A, Pappalettera, M, Cavallini, M, Buscemi, A, Vicenzi, M, Rota, I, Costantino, G, Solbiati, M, Furlan, L, Mancarella, M, Colombo, G, Fanin, A, Passarella, M, Monzani, V, Canetta, C, Rovellini, A, Barbetta, L, Billi, F, Folli, C, Accordino, S, Maira, D, Hu, C, Motta, I, Scaramellini, N, Fracanzani, A, Lombardi, R, Cespiati, A, Cesari, M, Lucchi, T, Proietti, M, Calcaterra, L, Mandelli, C, Coppola, C, Cerizza, A, Pesenti, A, Grasselli, G, Galazzi, A, Nobili., A, Monti, I, Galbussera, A, Crisafulli, E, Girelli, D, Maroccia, A, Gabbiani, D, Busti, F, Vianello, A, Biondan, M, Sartori, F, Faverio, P, Pesci, A, Zucchetti, S, Bonfanti, P, Rossi, M, Beretta, I, Spolti, A, Harari, S, Elia, D, Cassandro, R, Caminati, A, Cipollone, F, Guagnano, M, D’Ardes, D, Rossi, I, Vezzani, F, Spanevello, A, Cherubino, F, Visca, D, Contoli, M, Papi, A, Morandi, L, Battistini, N, Moreo, G, Iannuzzi, P, Fumagalla, D, Leone, S, Lombardi, Andrea, Villa, Simone, Colaneri, Marta, Scaglione, Giovanni, Bai, Francesca, Varisco, Benedetta, Bono, Valeria, Vena, Antonio, Dentone, Chiara, Russo, Chiara, Tettamanti, Mauro, Renisi, Giulia, Viero, Giulia, Azzarà, Cecilia, Mantero, Marco, Peyvandi, Flora, Bassetti, Matteo, Marchetti, Giulia, Muscatello, Antonio, Nobili, Alessandro, Gori, Andrea, Bandera, Alessandra, Bosari, Silvano, Scudeller, Luigia, Fusetti, Giuliana, Rusconi, Laura, Dell’Orto, Silvia, Prati, Daniele, Valenti, Luca, Giovannelli, Silvia, Manunta, Maria, Lamorte, Giuseppe, Ferarri, Francesca, Gori. , Andrea, Mangioni, Davide, Alagna, Laura, Bozzi, Giorgio, Lombardi. , Andrea, Ungaro, Riccardo, Ancona, Giuseppe, Mussa, Marco, Mariani, Bianca Veronica, Bolis, Matteo, Iannotti, Nathalie, Ludovisi, Serena, Comelli, Agnese, Biscarini, Simona, Castelli, Valeria, Palomba, Emanuele, Fava, Marco, Peri, Carlo Alberto, Saltini, Paola, Itri, Teresa, Ferroni, Valentina, Pastore, Valeria, Massafra, Roberta, Liparoti, Arianna, Muheberimana, Toussaint, Giommi, Alessandro, Bianco, Rosaria, Chitani, Grazia Eliana, Bobbio, Chiara, De Matteis, Irene, Bonomi, Angelo Bianchi, Gualtierotti, Roberta, Ferrari, Barbara, Rossio, Raffaella, Boasi, Nadia, Pagliaro, Erica, Massimo, Costanza, De Caro, Michele, Giachi, Andrea, Montano, Nicola, Vigone, Barbara, Bellocchi, Chiara, Carandina, Angelica, Fiorelli, Elisa, Melli, Valerie, Tobaldini, Eleonora, Blasi, Francesco, Aliberti, Stefano, Spotti, Maura, Terranova, Leonardo, Misuraca, Sofia, D’Adda, Alice, Della Fiore, Silvia, Di Pasquale, Marta, Mantero. , Marco, Contarini, Martina, Ori, Margherita, Morlacchi, Letizia, Rossetti, Valeria, Gramegna, Andrea, Pappalettera, Maria, Cavallini, Mirta, Buscemi, Agata, Vicenzi, Marco, Rota, Irena, Costantino, Giorgio, Solbiati, Monica, Furlan, Ludovico, Mancarella, Marta, Colombo, Giulia, Colombo, Giorgio, Fanin, Alice, Passarella, Mariele, Monzani, Valter, Canetta, Ciro, Rovellini, Angelo, Barbetta, Laura, Billi, Filippo, Folli, Christian, Accordino, Silvia, Maira, Diletta, Hu, Cinzia Maria, Motta, Irene, Scaramellini, Natalia, Fracanzani, Anna Ludovica, Lombardi, Rosa, Cespiati, Annalisa, Cesari, Matteo, Lucchi, Tiziano, Proietti, Marco, Calcaterra, Laura, Mandelli, Clara, Coppola, Carlotta, Cerizza, Arturo, Pesenti, Antonio Maria, Grasselli, Giacomo, Galazzi, Alessandro, Nobili. , Alessandro, Monti, Igor, Galbussera, Alessia Antonella, Crisafulli, Ernesto, Girelli, Domenico, Maroccia, Alessio, Gabbiani, Daniele, Busti, Fabiana, Vianello, Alice, Biondan, Marta, Sartori, Filippo, Faverio, Paola, Pesci, Alberto, Zucchetti, Stefano, Bonfanti, Paolo, Rossi, Marianna, Beretta, Ilaria, Spolti, Anna, Harari, Sergio, Elia, Davide, Cassandro, Roberto, Caminati, Antonella, Cipollone, Francesco, Guagnano, Maria Teresa, D’Ardes, Damiano, Rossi, Ilaria, Vezzani, Francesca, Spanevello, Antonio, Cherubino, Francesca, Visca, Dina, Contoli, Marco, Papi, Alberto, Morandi, Luca, Battistini, Nicholas, Moreo, Guido Luigi, Iannuzzi, Pasqualina, Fumagalla, Daniele, and Leone, Sara

Abstract

Background: Despite the well-known efficacy of anti-COVID-19 vaccines in preventing morbidity and mortality, several vaccinated individuals are diagnosed with SARS-CoV-2 breakthrough infection, which might require hospitalisation. This multicentre, observational, and retrospective study aimed to investigate the clinical characteristics and outcomes of vaccinated vs. non-vaccinated patients, both hospitalised with SARS-CoV-2 infection in 3 major hospitals in Northern Italy. Methods: Data collection was retrospective, and paper and electronic medical records of adult patients with a diagnosed SARS-CoV-2 infection were pseudo-anonymised and analysed. Vaccinated and non-vaccinated individuals were manually paired, using a predetermined matching criterion (similar age, gender, and date of hospitalisation). Demographic, clinical, treatment, and outcome data were compared between groups differing by vaccination status using Pearson's Chi-square and Mann-Whitney tests. Moreover, multiple logistic regression analyses were performed to assess the impact of vaccination status on ICU admission or intra-hospital mortality. Results: Data from 360 patients were collected. Vaccinated patients presented with a higher prevalence of relevant comorbidities, like kidney replacement therapy or haematological malignancy, despite a milder clinical presentation at the first evaluation. Non-vaccinated patients required intensive care more often than their vaccinated counterparts (8.8% vs. 1.7%, p = 0.002). Contrariwise, no difference in intra-hospital mortality was observed between the two groups (19% vs. 20%, p = 0.853). These results were confirmed by multivariable logistic regressions, which showed that vaccination was significantly associated with decreased risk of ICU admission (aOR=0.172, 95%CI: 0.039–0.542, p = 0.007), but not of intra-hospital mortality (aOR=0.996, 95%CI: 0.582–1.703, p = 0.987). Conclusions: This study provides real-world data on vaccinated patients hospitalised wit

Published
2024

23. Evaluation of the Geographical Accessibility of Genome-Matched Clinical Trials on a National Experience.

Author

Crimini, Edoardo, Tini, Giulia, Tarantino, Paolo, Ascione, Liliana, Repetto, Matteo, Beria, Paolo, Ranghiero, Alberto, Marra, Antonio, Belli, Carmen, Criscitiello, Carmen, Esposito, Angela, Rocco, Elena Guerini, Barberis, Massimo C P, Mazzarella, Luca, and Curigliano, Giuseppe

Subjects
HEALTH services accessibility, CLINICAL trials, POPULATION geography, RETROSPECTIVE studies, INDIVIDUALIZED medicine, NATIONAL health services, CANCER patients, GENOMES, GENOMICS, GENES, TUMORS, CANCER patient medical care
Abstract

Background Molecular-driven oncology allows oncologists to identify treatments that match a cancer's genomic profile. Clinical trials are promoted as an effective modality to deliver a molecularly matched treatment. We explore the role of geographical accessibility in Italy, and its impact on patient access to clinical trials. Material and Methods We retrospectively reviewed molecular data from a single-institutional case series of patients receiving next-generation sequencing testing between March 2019 and July 2020. Actionable alterations were defined as the ones with at least one matched treatment on Clinicaltrials.gov at the time of genomic report signature. We then calculated the hypothetical distance to travel to reach the nearest assigned clinical trial. Results We identified 159 patients eligible for analysis. One hundred and one could be potentially assigned to a clinical trial in Italy, and the median distance that patients needed to travel to reach the closest location with a suitable clinical trial was 76 km (interquartile range = 127.46 km). Geographical distribution of clinical trials in Italy found to be heterogeneous, with Milan and Naples being the areas with a higher concentration. We then found that the probability of having a clinical trial close to a patient's hometown increased over time, according to registered studies between 2015 and 2020. Conclusions The median distance to be travelled to the nearest trial was generally acceptable for patients, and trials availability is increasing. Nevertheless, many areas are still lacking trials, so efforts are required to increase and homogenize the possibilities to be enrolled in clinical trials for Italian patients with cancer. [ABSTRACT FROM AUTHOR]

Published
2024
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24. Evaluation of the Geographical Accessibility of Genome-Matched Clinical Trials on a National Experience

Author

Crimini, Edoardo, primary, Tini, Giulia, additional, Tarantino, Paolo, additional, Ascione, Liliana, additional, Repetto, Matteo, additional, Beria, Paolo, additional, Ranghiero, Alberto, additional, Marra, Antonio, additional, Belli, Carmen, additional, Criscitiello, Carmen, additional, Esposito, Angela, additional, Guerini Rocco, Elena, additional, Barberis, Massimo C P, additional, Mazzarella, Luca, additional, and Curigliano, Giuseppe, additional

Published
2023
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25. Defining Comprehensive Disease Control for use as a Treatment Target for Ulcerative Colitis in Clinical Practice: International Delphi Consensus Recommendations

Author

Schreiber, Stefan, primary, Danese, Silvio, additional, Dignass, Axel, additional, Domènech, Eugeni, additional, Fantini, Massimo C, additional, Ferrante, Marc, additional, Halfvarson, Jonas, additional, Hart, Ailsa, additional, Magro, Fernando, additional, Lees, Charlie W, additional, Leone, Salvo, additional, Pierik, Marieke J, additional, Peters, Michele, additional, Field, Polly, additional, Fishpool, Helen, additional, and Peyrin-Biroulet, Laurent, additional

Published
2023
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29. External validation of risk scores to predict in-hospital mortality in patients hospitalized due to coronavirus disease 2019

Author

Hassan, S, Ramspek, C, Ferrari, B, van Diepen, M, Rossio, R, Knevel, R, la Mura, V, Artoni, A, Martinelli, I, Bandera, A, Nobili, A, Gori, A, Blasi, F, Canetta, C, Montano, N, Rosendaal, F, Peyvandi, F, Bosari, S, Scudeller, L, Fusetti, G, Rusconi, L, Dell'Orto, S, Prati, D, Valenti, L, Giovannelli, S, Manunta, M, Lamorte, G, Ferarri, F, Muscatello, A, Mangioni, D, Alagna, L, Bozzi, G, Lombardi, A, Ungaro, R, Ancona, G, Zuglian, G, Bolis, M, Iannotti, N, Ludovisi, S, Comelli, A, Renisi, G, Biscarini, S, Castelli, V, Palomba, E, Fava, M, Fortina, V, Peri, C, Saltini, P, Viero, G, Itri, T, Ferroni, V, Pastore, V, Massafra, R, Liparoti, A, Muheberimana, T, Giommi, A, Bianco, R, De Azevedo, R, Chitani, G, Gualtierotti, R, Boasi, N, Pagliaro, E, Massimo, C, De Caro, M, Giachi, A, Vigone, B, Bellocchi, C, Carandina, A, Fiorelli, E, Melli, V, Tobaldini, E, Aliberti, S, Spotti, M, Terranova, L, Misuraca, S, D'Adda, A, Fiore, S, Di Pasquale, M, Mantero, M, Contarini, M, Ori, M, Morlacchi, L, Rossetti, V, Gramegna, A, Pappalettera, M, Cavallini, M, Buscemi, A, Vicenzi, M, Rota, I, Costantino, G, Solbiati, M, Furlan, L, Mancarella, M, Colombo, G, Fanin, A, Passarella, M, Monzani, V, Rovellini, A, Barbetta, L, Billi, F, Folli, C, Accordino, S, Maira, D, Hu, C, Motta, I, Scar-Amellini, N, Fracanzani, A, Lombardi, R, Cespiati, A, Cesari, M, Lucchi, T, Proietti, M, Calcaterra, L, Mandelli, C, Coppola, C, Cerizza, A, Maria Pesenti, A, Grasselli, G, Galazzi, A, Tet-Tamanti, M, Monti, I, Galbussera, A, Crisafulli, E, Girelli, D, Maroccia, A, Gabbiani, D, Busti, F, Vianello, A, Biondan, M, Sartori, F, Faverio, P, Pesci, A, Zucchetti, S, Bonfanti, P, Rossi, M, Beretta, I, Spolti, A, Harari, S, Elia, D, Cassandro, R, Caminati, A, Cipollone, F, Guagnano, M, D'Ardes, D, Rossi, I, Vezzani, F, Spanevello, A, Cherubino, F, Visca, D, Contoli, M, Papi, A, Morandi, L, Battistini, N, Luigi Moreo, G, Iannuzzi, P, Fumagalli, D, Leone, S, Oud, J, Baysan, M, Wigb, J, van Heurn, L, ter Haar, S, Toppenberg, A, Heerdink, L, van IJlzinga Veenstra, A, Eikenboom, A, Wubbolts, J, Uzorka, J, Lijferink, W, Meier, R, de Jonge, I, Arbous, S, de Boer, M, van der Bom, J, Dekkers, O, Hassan S., Ramspek C. L., Ferrari B., van Diepen M., Rossio R., Knevel R., la Mura V., Artoni A., Martinelli I., Bandera A., Nobili A., Gori A., Blasi F., Canetta C., Montano N., Rosendaal F. R., Peyvandi F., Bosari S., Scudeller L., Fusetti G., Rusconi L., Dell'Orto S., Prati D., Valenti L., Giovannelli S., Manunta M., Lamorte G., Ferarri F., Muscatello A., Mangioni D., Alagna L., Bozzi G., Lombardi A., Ungaro R., Ancona G., Zuglian G., Bolis M., Iannotti N., Ludovisi S., Comelli A., Renisi G., Biscarini S., Castelli V., Palomba E., Fava M., Fortina V., Peri C. A., Saltini P., Viero G., Itri T., Ferroni V., Pastore V., Massafra R., Liparoti A., Muheberimana T., Giommi A., Bianco R., De Azevedo R. M., Chitani G. E., Gualtierotti R., Boasi N., Pagliaro E., Massimo C., De Caro M., Giachi A., Vigone B., Bellocchi C., Carandina A., Fiorelli E., Melli V., Tobaldini E., Aliberti S., Spotti M., Terranova L., Misuraca S., D'Adda A., Fiore S. D., Di Pasquale M., Mantero M., Contarini M., Ori M., Morlacchi L., Rossetti V., Gramegna A., Pappalettera M., Cavallini M., Buscemi A., Vicenzi M., Rota I., Costantino G., Solbiati M., Furlan L., Mancarella M., Colombo G., Fanin A., Passarella M., Monzani V., Rovellini A., Barbetta L., Billi F., Folli C., Accordino S., Maira D., Hu C. M., Motta I., Scar-Amellini N., Fracanzani A. L., Lombardi R., Cespiati A., Cesari M., Lucchi T., Proietti M., Calcaterra L., Mandelli C., Coppola C., Cerizza A., Maria Pesenti A., Grasselli G., Galazzi A., Tet-Tamanti M., Monti I., Galbussera A. A., Crisafulli E., Girelli D., Maroccia A., Gabbiani D., Busti F., Vianello A., Biondan M., Sartori F., Faverio P., Pesci A., Zucchetti S., Bonfanti P., Rossi M., Beretta I., Spolti A., Harari S., Elia D., Cassandro R., Caminati A., Cipollone F., Guagnano M. T., D'Ardes D., Rossi I., Vezzani F., Spanevello A., Cherubino F., Visca D., Contoli M., Papi A., Morandi L., Battistini N., Luigi Moreo G., Iannuzzi P., Fumagalli D., Leone S., Oud J. A., Baysan M., Wigb J., van Heurn L. J., ter Haar S. B., Toppenberg A. G. L., Heerdink L., van IJlzinga Veenstra A. A., Eikenboom A. M., Wubbolts J., Uzorka J., Lijferink W., Meier R., de Jonge I. -B., Arbous S. M., de Boer M. G. J., van der Bom J. G., Dekkers O. M., Hassan, S, Ramspek, C, Ferrari, B, van Diepen, M, Rossio, R, Knevel, R, la Mura, V, Artoni, A, Martinelli, I, Bandera, A, Nobili, A, Gori, A, Blasi, F, Canetta, C, Montano, N, Rosendaal, F, Peyvandi, F, Bosari, S, Scudeller, L, Fusetti, G, Rusconi, L, Dell'Orto, S, Prati, D, Valenti, L, Giovannelli, S, Manunta, M, Lamorte, G, Ferarri, F, Muscatello, A, Mangioni, D, Alagna, L, Bozzi, G, Lombardi, A, Ungaro, R, Ancona, G, Zuglian, G, Bolis, M, Iannotti, N, Ludovisi, S, Comelli, A, Renisi, G, Biscarini, S, Castelli, V, Palomba, E, Fava, M, Fortina, V, Peri, C, Saltini, P, Viero, G, Itri, T, Ferroni, V, Pastore, V, Massafra, R, Liparoti, A, Muheberimana, T, Giommi, A, Bianco, R, De Azevedo, R, Chitani, G, Gualtierotti, R, Boasi, N, Pagliaro, E, Massimo, C, De Caro, M, Giachi, A, Vigone, B, Bellocchi, C, Carandina, A, Fiorelli, E, Melli, V, Tobaldini, E, Aliberti, S, Spotti, M, Terranova, L, Misuraca, S, D'Adda, A, Fiore, S, Di Pasquale, M, Mantero, M, Contarini, M, Ori, M, Morlacchi, L, Rossetti, V, Gramegna, A, Pappalettera, M, Cavallini, M, Buscemi, A, Vicenzi, M, Rota, I, Costantino, G, Solbiati, M, Furlan, L, Mancarella, M, Colombo, G, Fanin, A, Passarella, M, Monzani, V, Rovellini, A, Barbetta, L, Billi, F, Folli, C, Accordino, S, Maira, D, Hu, C, Motta, I, Scar-Amellini, N, Fracanzani, A, Lombardi, R, Cespiati, A, Cesari, M, Lucchi, T, Proietti, M, Calcaterra, L, Mandelli, C, Coppola, C, Cerizza, A, Maria Pesenti, A, Grasselli, G, Galazzi, A, Tet-Tamanti, M, Monti, I, Galbussera, A, Crisafulli, E, Girelli, D, Maroccia, A, Gabbiani, D, Busti, F, Vianello, A, Biondan, M, Sartori, F, Faverio, P, Pesci, A, Zucchetti, S, Bonfanti, P, Rossi, M, Beretta, I, Spolti, A, Harari, S, Elia, D, Cassandro, R, Caminati, A, Cipollone, F, Guagnano, M, D'Ardes, D, Rossi, I, Vezzani, F, Spanevello, A, Cherubino, F, Visca, D, Contoli, M, Papi, A, Morandi, L, Battistini, N, Luigi Moreo, G, Iannuzzi, P, Fumagalli, D, Leone, S, Oud, J, Baysan, M, Wigb, J, van Heurn, L, ter Haar, S, Toppenberg, A, Heerdink, L, van IJlzinga Veenstra, A, Eikenboom, A, Wubbolts, J, Uzorka, J, Lijferink, W, Meier, R, de Jonge, I, Arbous, S, de Boer, M, van der Bom, J, Dekkers, O, Hassan S., Ramspek C. L., Ferrari B., van Diepen M., Rossio R., Knevel R., la Mura V., Artoni A., Martinelli I., Bandera A., Nobili A., Gori A., Blasi F., Canetta C., Montano N., Rosendaal F. R., Peyvandi F., Bosari S., Scudeller L., Fusetti G., Rusconi L., Dell'Orto S., Prati D., Valenti L., Giovannelli S., Manunta M., Lamorte G., Ferarri F., Muscatello A., Mangioni D., Alagna L., Bozzi G., Lombardi A., Ungaro R., Ancona G., Zuglian G., Bolis M., Iannotti N., Ludovisi S., Comelli A., Renisi G., Biscarini S., Castelli V., Palomba E., Fava M., Fortina V., Peri C. A., Saltini P., Viero G., Itri T., Ferroni V., Pastore V., Massafra R., Liparoti A., Muheberimana T., Giommi A., Bianco R., De Azevedo R. M., Chitani G. E., Gualtierotti R., Boasi N., Pagliaro E., Massimo C., De Caro M., Giachi A., Vigone B., Bellocchi C., Carandina A., Fiorelli E., Melli V., Tobaldini E., Aliberti S., Spotti M., Terranova L., Misuraca S., D'Adda A., Fiore S. D., Di Pasquale M., Mantero M., Contarini M., Ori M., Morlacchi L., Rossetti V., Gramegna A., Pappalettera M., Cavallini M., Buscemi A., Vicenzi M., Rota I., Costantino G., Solbiati M., Furlan L., Mancarella M., Colombo G., Fanin A., Passarella M., Monzani V., Rovellini A., Barbetta L., Billi F., Folli C., Accordino S., Maira D., Hu C. M., Motta I., Scar-Amellini N., Fracanzani A. L., Lombardi R., Cespiati A., Cesari M., Lucchi T., Proietti M., Calcaterra L., Mandelli C., Coppola C., Cerizza A., Maria Pesenti A., Grasselli G., Galazzi A., Tet-Tamanti M., Monti I., Galbussera A. A., Crisafulli E., Girelli D., Maroccia A., Gabbiani D., Busti F., Vianello A., Biondan M., Sartori F., Faverio P., Pesci A., Zucchetti S., Bonfanti P., Rossi M., Beretta I., Spolti A., Harari S., Elia D., Cassandro R., Caminati A., Cipollone F., Guagnano M. T., D'Ardes D., Rossi I., Vezzani F., Spanevello A., Cherubino F., Visca D., Contoli M., Papi A., Morandi L., Battistini N., Luigi Moreo G., Iannuzzi P., Fumagalli D., Leone S., Oud J. A., Baysan M., Wigb J., van Heurn L. J., ter Haar S. B., Toppenberg A. G. L., Heerdink L., van IJlzinga Veenstra A. A., Eikenboom A. M., Wubbolts J., Uzorka J., Lijferink W., Meier R., de Jonge I. -B., Arbous S. M., de Boer M. G. J., van der Bom J. G., and Dekkers O. M.

Abstract

Background: The coronavirus disease 2019 (COVID-19) presents an urgent threat to global health. Prediction models that accurately estimate mortality risk in hospitalized patients could assist medical staff in treatment and allocating limited resources. Aims: To externally validate two promising previously published risk scores that predict in-hospital mortality among hospitalized COVID-19 patients. Methods: Two prospective cohorts were available; a cohort of 1028 patients admitted to one of nine hospitals in Lombardy, Italy (the Lombardy cohort) and a cohort of 432 patients admitted to a hospital in Leiden, the Netherlands (the Leiden cohort). The endpoint was in-hospital mortality. All patients were adult and tested COVID-19 PCR-positive. Model discrimination and calibration were assessed. Results: The C-statistic of the 4C mortality score was good in the Lombardy cohort (0.85, 95CI: 0.82−0.89) and in the Leiden cohort (0.87, 95CI: 0.80−0.94). Model calibration was acceptable in the Lombardy cohort but poor in the Leiden cohort due to the model systematically overpredicting the mortality risk for all patients. The C-statistic of the CURB-65 score was good in the Lombardy cohort (0.80, 95CI: 0.75−0.85) and in the Leiden cohort (0.82, 95CI: 0.76−0.88). The mortality rate in the CURB-65 development cohort was much lower than the mortality rate in the Lombardy cohort. A similar but less pronounced trend was found for patients in the Leiden cohort. Conclusion: Although performances did not differ greatly, the 4C mortality score showed the best performance. However, because of quickly changing circumstances, model recalibration may be necessary before using the 4C mortality score.

Published
2022

30. The role of the acceptance and commitment therapy in the treatment of social anxiety: An updated scoping review

Author

Caletti, E, Massimo, C, Magliocca, S, Moltrasio, C, Brambilla, P, Delvecchio, G, Caletti E., Massimo C., Magliocca S., Moltrasio C., Brambilla P., Delvecchio G., Caletti, E, Massimo, C, Magliocca, S, Moltrasio, C, Brambilla, P, Delvecchio, G, Caletti E., Massimo C., Magliocca S., Moltrasio C., Brambilla P., and Delvecchio G.

Abstract

Background: Social Anxiety Disorder (SAD) or Social Phobia is characterized by fear and anxiety of social circumstances that negatively impact an individual's occupational and relational life. There are several treatment options for this disorder ranging from pharmacological therapy to psychotherapies. In particular, the Acceptance and Commitment Therapy (ACT), a form of cognitive-behavioral therapy that practices acceptance and awareness strategies with behavior change strategies in order to increase an individual's mental flexibility, has been found to be effective. In this review, we aimed to provide an overview of recent studies that examined ACT's efficacy in SAD, also taking into consideration the comparison with traditional Cognitive-behavioral Therapy (CBT) interventions. Methods: A bibliographic search on PubMed, EMBASE and Scopus was conducted from inception to the 3rd of February 2022 of all studies investigating the effect of ACT in SAD individuals without any comorbidity. Among the articles retrieved, 11 met the inclusion criteria. Results: From the reviewed studies, ACT may be considered a promising treatment of social phobia by improving attentional bias, awareness, emotion regulation, and safety/avoidance behaviors; however, the results have not yet demonstrated a valid alternative to the CBT. Limitations: Only four studies considered a follow-up evaluation, which is paramount to exploring the effectiveness of ACT and several studies have a very small sample size. Concerning the review itself we only considered original English articles and we did not measure the risk of publication bias and the risk of bias between studies. Conclusions: The results of this study suggest that ACT can be a promising treatment for improving selective psychological problems often observed in SAD. However, larger longitudinal studies further exploring the effectiveness of the behavioral and cognitive “third-wave” psychotherapies, based mainly on acceptance of SAD, are ne

Published
2022

31. Clinical factors associated with death in 3044 COVID-19 patients managed in internal medicine wards in Italy: comment

Author

Bandera, A, Nobili, A, Tettamanti, M, Harari, S, Bosari, S, Mannucci, P, Scudeller, L, Fusetti, G, Rusconi, L, Dell'Orto, S, Prati, D, Valenti, L, Giovannelli, S, Manunta, M, Lamorte, G, Ferrari, F, Gori, A, Muscatello, A, Mangioni, D, Alagna, L, Bozzi, G, Lombardi, A, Ungaro, R, Ancona, G, Zuglian, G, Bolis, M, Iannotti, N, Ludovisi, S, Comelli, A, Renisi, G, Biscarini, S, Castelli, V, Palomba, E, Fava, M, Fortina, V, Peri, C, Saltini, P, Viero, G, Itri, T, Ferroni, V, Pastore, V, Massafra, R, Liparoti, A, Muheberimana, T, Giommi, A, Bianco, R, De Azevedo, R, Chitani, G, Peyvandi, F, Gualtierotti, R, Ferrari, B, Rossio, R, Boasi, N, Pagliaro, E, Massimo, C, De Caro, M, Montano, N, Vigone, B, Bellocchi, C, Carandina, A, Fiorelli, E, Melli, V, Tobaldini, E, Blasi, F, Aliberti, S, Spotti, M, Terranova, L, Misuraca, S, D'Adda, A, Della Fiore, S, Di Pasquale, M, Contarini, M, Ori, M, Morlacchi, L, Rossetti, V, Gramegna, A, Pappalettera, M, Cavallini, M, Buscemi, A, Vicenzi, M, Rota, I, Costantino, G, Solbiati, M, Furlan, L, Mancarella, M, Colombo, G, Fanin, A, Passarella, M, Monzani, V, Canetta, C, Rovellini, A, Barbetta, L, Billi, F, Folli, C, Accordino, S, Maira, D, Hu, C, Motta, I, Scaramellini, N, Fracanzani, A, Lombardi, R, Cespiati, A, Cesari, M, Lucchi, T, Proietti, M, Calcaterra, L, Mandelli, C, Coppola, C, Cerizza, A, Pesenti, A, Grasselli, G, Galazzi, A, Monti, I, Galbussera, A, Crisafulli, E, Girelli, D, Maroccia, A, Gabbiani, D, Busti, F, Vianello, A, Biondan, M, Sartori, F, Faverio, P, Pesci, A, Zucchetti, S, Bonfanti, P, Rossi, M, Beretta, I, Spolti, A, Elia, D, Cassandro, R, Caminati, A, Cipollone, F, Guagnano, M, D'Ardes, D, Rossi, I, Vezzani, F, Spanevello, A, Cherubino, F, Visca, D, Contoli, M, Papi, A, Morandi, L, Battistini, N, Moreo, G, Iannuzzi, P, Fumagalli, D, Leone, S, Bandera A., Nobili A., Tettamanti M., Harari S., Bosari S., Mannucci P. M., Scudeller L., Fusetti G., Rusconi L., Dell'Orto S., Prati D., Valenti L., Giovannelli S., Manunta M., Lamorte G., Ferrari F., Gori A., Muscatello A., Mangioni D., Alagna L., Bozzi G., Lombardi A., Ungaro R., Ancona G., Zuglian G., Bolis M., Iannotti N., Ludovisi S., Comelli A., Renisi G., Biscarini S., Castelli V., Palomba E., Fava M., Fortina V., Peri C. A., Saltini P., Viero G., Itri T., Ferroni V., Pastore V., Massafra R., Liparoti A., Muheberimana T., Giommi A., Bianco R., De Azevedo R. M., Chitani G. E., Peyvandi F., Gualtierotti R., Ferrari B., Rossio R., Boasi N., Pagliaro E., Massimo C., De Caro M., Montano N., Vigone B., Bellocchi C., Carandina A., Fiorelli E., Melli V., Tobaldini E., Blasi F., Aliberti S., Spotti M., Terranova L., Misuraca S., D'Adda A., Della Fiore S., Di Pasquale M., Contarini M. M. M., Ori M., Morlacchi L., Rossetti V., Gramegna A., Pappalettera M., Cavallini M., Buscemi A., Vicenzi M., Rota I., Costantino G., Solbiati M., Furlan L., Mancarella M., Colombo G., Fanin A., Passarella M., Monzani V., Canetta C., Rovellini A., Barbetta L., Billi F., Folli C., Accordino S., Maira D., Hu C. M., Motta I., Scaramellini N., Fracanzani A. L., Lombardi R., Cespiati A., Cesari M., Lucchi T., Proietti M., Calcaterra L., Mandelli C., Coppola C., Cerizza A., Pesenti A. M., Grasselli G., Galazzi A., Monti I., Galbussera A. A., Crisafulli E., Girelli D., Maroccia A., Gabbiani D., Busti F., Vianello A., Biondan M., Sartori F., Faverio P., Pesci A., Zucchetti S., Bonfanti P., Rossi M., Beretta I., Spolti A., Elia D., Cassandro R., Caminati A., Cipollone F., Guagnano M. T., D'Ardes D., Rossi I., Vezzani F., Spanevello A., Cherubino F., Visca D., Contoli M., Papi A., Morandi L., Battistini N., Moreo G. L., Iannuzzi P., Fumagalli D., Leone S., Bandera, A, Nobili, A, Tettamanti, M, Harari, S, Bosari, S, Mannucci, P, Scudeller, L, Fusetti, G, Rusconi, L, Dell'Orto, S, Prati, D, Valenti, L, Giovannelli, S, Manunta, M, Lamorte, G, Ferrari, F, Gori, A, Muscatello, A, Mangioni, D, Alagna, L, Bozzi, G, Lombardi, A, Ungaro, R, Ancona, G, Zuglian, G, Bolis, M, Iannotti, N, Ludovisi, S, Comelli, A, Renisi, G, Biscarini, S, Castelli, V, Palomba, E, Fava, M, Fortina, V, Peri, C, Saltini, P, Viero, G, Itri, T, Ferroni, V, Pastore, V, Massafra, R, Liparoti, A, Muheberimana, T, Giommi, A, Bianco, R, De Azevedo, R, Chitani, G, Peyvandi, F, Gualtierotti, R, Ferrari, B, Rossio, R, Boasi, N, Pagliaro, E, Massimo, C, De Caro, M, Montano, N, Vigone, B, Bellocchi, C, Carandina, A, Fiorelli, E, Melli, V, Tobaldini, E, Blasi, F, Aliberti, S, Spotti, M, Terranova, L, Misuraca, S, D'Adda, A, Della Fiore, S, Di Pasquale, M, Contarini, M, Ori, M, Morlacchi, L, Rossetti, V, Gramegna, A, Pappalettera, M, Cavallini, M, Buscemi, A, Vicenzi, M, Rota, I, Costantino, G, Solbiati, M, Furlan, L, Mancarella, M, Colombo, G, Fanin, A, Passarella, M, Monzani, V, Canetta, C, Rovellini, A, Barbetta, L, Billi, F, Folli, C, Accordino, S, Maira, D, Hu, C, Motta, I, Scaramellini, N, Fracanzani, A, Lombardi, R, Cespiati, A, Cesari, M, Lucchi, T, Proietti, M, Calcaterra, L, Mandelli, C, Coppola, C, Cerizza, A, Pesenti, A, Grasselli, G, Galazzi, A, Monti, I, Galbussera, A, Crisafulli, E, Girelli, D, Maroccia, A, Gabbiani, D, Busti, F, Vianello, A, Biondan, M, Sartori, F, Faverio, P, Pesci, A, Zucchetti, S, Bonfanti, P, Rossi, M, Beretta, I, Spolti, A, Elia, D, Cassandro, R, Caminati, A, Cipollone, F, Guagnano, M, D'Ardes, D, Rossi, I, Vezzani, F, Spanevello, A, Cherubino, F, Visca, D, Contoli, M, Papi, A, Morandi, L, Battistini, N, Moreo, G, Iannuzzi, P, Fumagalli, D, Leone, S, Bandera A., Nobili A., Tettamanti M., Harari S., Bosari S., Mannucci P. M., Scudeller L., Fusetti G., Rusconi L., Dell'Orto S., Prati D., Valenti L., Giovannelli S., Manunta M., Lamorte G., Ferrari F., Gori A., Muscatello A., Mangioni D., Alagna L., Bozzi G., Lombardi A., Ungaro R., Ancona G., Zuglian G., Bolis M., Iannotti N., Ludovisi S., Comelli A., Renisi G., Biscarini S., Castelli V., Palomba E., Fava M., Fortina V., Peri C. A., Saltini P., Viero G., Itri T., Ferroni V., Pastore V., Massafra R., Liparoti A., Muheberimana T., Giommi A., Bianco R., De Azevedo R. M., Chitani G. E., Peyvandi F., Gualtierotti R., Ferrari B., Rossio R., Boasi N., Pagliaro E., Massimo C., De Caro M., Montano N., Vigone B., Bellocchi C., Carandina A., Fiorelli E., Melli V., Tobaldini E., Blasi F., Aliberti S., Spotti M., Terranova L., Misuraca S., D'Adda A., Della Fiore S., Di Pasquale M., Contarini M. M. M., Ori M., Morlacchi L., Rossetti V., Gramegna A., Pappalettera M., Cavallini M., Buscemi A., Vicenzi M., Rota I., Costantino G., Solbiati M., Furlan L., Mancarella M., Colombo G., Fanin A., Passarella M., Monzani V., Canetta C., Rovellini A., Barbetta L., Billi F., Folli C., Accordino S., Maira D., Hu C. M., Motta I., Scaramellini N., Fracanzani A. L., Lombardi R., Cespiati A., Cesari M., Lucchi T., Proietti M., Calcaterra L., Mandelli C., Coppola C., Cerizza A., Pesenti A. M., Grasselli G., Galazzi A., Monti I., Galbussera A. A., Crisafulli E., Girelli D., Maroccia A., Gabbiani D., Busti F., Vianello A., Biondan M., Sartori F., Faverio P., Pesci A., Zucchetti S., Bonfanti P., Rossi M., Beretta I., Spolti A., Elia D., Cassandro R., Caminati A., Cipollone F., Guagnano M. T., D'Ardes D., Rossi I., Vezzani F., Spanevello A., Cherubino F., Visca D., Contoli M., Papi A., Morandi L., Battistini N., Moreo G. L., Iannuzzi P., Fumagalli D., and Leone S.

Published
2022

32. Clinical risk scores for the early prediction of severe outocomes in patients hospitalized for COVID-19: comment

Author

Rossio, R, Tettamanti, M, Nobili, A, Harari, S, Mannucci, P, Bandera, A, Peyvandi, F, Bosari, S, Scudeller, L, Fusetti, G, Rusconi, L, Dell'Orto, S, Prati, D, Valenti, L, Giovannelli, S, Manunta, M, Lamorte, G, Ferrari, F, Gori, A, Muscatello, A, Mangioni, D, Alagna, L, Bozzi, G, Lombardi, A, Ungaro, R, Ancona, G, Zuglian, G, Bolis, M, Iannotti, N, Ludovisi, S, Comelli, A, Renisi, G, Biscarini, S, Castelli, V, Palomba, E, Fava, M, Fortina, V, Peri, C, Saltini, P, Viero, G, Itri, T, Ferroni, V, Pastore, V, Massafra, R, Liparoti, A, Muheberimana, T, Giommi, A, Bianco, R, De Azevedo, R, Chitani, G, Gualtierotti, R, Ferrari, B, Boasi, N, Pagliaro, E, Massimo, C, De Caro, M, Giachi, A, Montano, N, Vigone, B, Bellocchi, C, Carandina, A, Fiorelli, E, Melli, V, Tobaldini, E, Blasi, F, Aliberti, S, Spotti, M, Terranova, L, Misuraca, S, D'Adda, A, Fiore, S, Di Pasquale, M, Mantero, M, Contarini, M, Ori, M, Morlacchi, L, Rossetti, V, Gramegna, A, Pappalettera, M, Cavallini, M, Buscemi, A, Vicenzi, M, Rota, I, Costantino, G, Solbiati, M, Furlan, L, Mancarella, M, Colombo, G, Fanin, A, Passarella, M, Monzani, V, Canetta, C, Rovellini, A, Barbetta, L, Billi, F, Folli, C, Accordino, S, Maira, D, Hu, C, Motta, I, Scaramellini, N, Fracanzani, A, Lombardi, R, Cespiati, A, Cesari, M, Lucchi, T, Proietti, M, Calcaterra, L, Mandelli, C, Coppola, C, Cerizza, A, Pesenti, A, Grasselli, G, Galazzi, A, Monti, I, Galbussera, A, Crisafulli, E, Girelli, D, Maroccia, A, Gabbiani, D, Busti, F, Vianello, A, Biondan, M, Sartori, F, Faverio, P, Pesci, A, Zucchetti, S, Bonfanti, P, Rossi, M, Beretta, I, Spolti, A, Elia, D, Cassandro, R, Caminati, A, Cipollone, F, Guagnano, M, D'Ardes, D, Rossi, I, Vezzani, F, Spanevello, A, Cherubino, F, Visca, D, Contoli, M, Papi, A, Morandi, L, Battistini, N, Moreo, G, Iannuzzi, P, Fumagalli, D, Leone, S, Rossio R., Tettamanti M., Nobili A., Harari S., Mannucci P. M., Bandera A., Peyvandi F., Bosari S., Scudeller L., Fusetti G., Rusconi L., Dell'Orto S., Prati D., Valenti L., Giovannelli S., Manunta M., Lamorte G., Ferrari F., Gori A., Muscatello A., Mangioni D., Alagna L., Bozzi G., Lombardi A., Ungaro R., Ancona G., Zuglian G., Bolis M., Iannotti N., Ludovisi S., Comelli A., Renisi G., Biscarini S., Castelli V., Palomba E., Fava M., Fortina V., Peri C. A., Saltini P., Viero G., Itri T., Ferroni V., Pastore V., Massafra R., Liparoti A., Muheberimana T., Giommi A., Bianco R., De Azevedo R. M., Chitani G. E., Gualtierotti R., Ferrari B., Boasi N., Pagliaro E., Massimo C., De Caro M., Giachi A., Montano N., Vigone B., Bellocchi C., Carandina A., Fiorelli E., Melli V., Tobaldini E., Blasi F., Aliberti S., Spotti M., Terranova L., Misuraca S., D'Adda A., Fiore S. D., Di Pasquale M., Mantero M., Contarini M., Ori M., Morlacchi L., Rossetti V., Gramegna A., Pappalettera M., Cavallini M., Buscemi A., Vicenzi M., Rota I., Costantino G., Solbiati M., Furlan L., Mancarella M., Colombo G., Fanin A., Passarella M., Monzani V., Canetta C., Rovellini A., Barbetta L., Billi F., Folli C., Accordino S., Maira D., Hu C. M., Motta I., Scaramellini N., Fracanzani A. L., Lombardi R., Cespiati A., Cesari M., Lucchi T., Proietti M., Calcaterra L., Mandelli C., Coppola C., Cerizza A., Pesenti A. M., Grasselli G., Galazzi A., Monti I., Galbussera A. A., Crisafulli E., Girelli D., Maroccia A., Gabbiani D., Busti F., Vianello A., Biondan M., Sartori F., Faverio P., Pesci A., Zucchetti S., Bonfanti P., Rossi M., Beretta I., Spolti A., Elia D., Cassandro R., Caminati A., Cipollone F., Guagnano M. T., D'Ardes D., Rossi I., Vezzani F., Spanevello A., Cherubino F., Visca D., Contoli M., Papi A., Morandi L., Battistini N., Moreo G. L., Iannuzzi P., Fumagalli D., Leone S., Rossio, R, Tettamanti, M, Nobili, A, Harari, S, Mannucci, P, Bandera, A, Peyvandi, F, Bosari, S, Scudeller, L, Fusetti, G, Rusconi, L, Dell'Orto, S, Prati, D, Valenti, L, Giovannelli, S, Manunta, M, Lamorte, G, Ferrari, F, Gori, A, Muscatello, A, Mangioni, D, Alagna, L, Bozzi, G, Lombardi, A, Ungaro, R, Ancona, G, Zuglian, G, Bolis, M, Iannotti, N, Ludovisi, S, Comelli, A, Renisi, G, Biscarini, S, Castelli, V, Palomba, E, Fava, M, Fortina, V, Peri, C, Saltini, P, Viero, G, Itri, T, Ferroni, V, Pastore, V, Massafra, R, Liparoti, A, Muheberimana, T, Giommi, A, Bianco, R, De Azevedo, R, Chitani, G, Gualtierotti, R, Ferrari, B, Boasi, N, Pagliaro, E, Massimo, C, De Caro, M, Giachi, A, Montano, N, Vigone, B, Bellocchi, C, Carandina, A, Fiorelli, E, Melli, V, Tobaldini, E, Blasi, F, Aliberti, S, Spotti, M, Terranova, L, Misuraca, S, D'Adda, A, Fiore, S, Di Pasquale, M, Mantero, M, Contarini, M, Ori, M, Morlacchi, L, Rossetti, V, Gramegna, A, Pappalettera, M, Cavallini, M, Buscemi, A, Vicenzi, M, Rota, I, Costantino, G, Solbiati, M, Furlan, L, Mancarella, M, Colombo, G, Fanin, A, Passarella, M, Monzani, V, Canetta, C, Rovellini, A, Barbetta, L, Billi, F, Folli, C, Accordino, S, Maira, D, Hu, C, Motta, I, Scaramellini, N, Fracanzani, A, Lombardi, R, Cespiati, A, Cesari, M, Lucchi, T, Proietti, M, Calcaterra, L, Mandelli, C, Coppola, C, Cerizza, A, Pesenti, A, Grasselli, G, Galazzi, A, Monti, I, Galbussera, A, Crisafulli, E, Girelli, D, Maroccia, A, Gabbiani, D, Busti, F, Vianello, A, Biondan, M, Sartori, F, Faverio, P, Pesci, A, Zucchetti, S, Bonfanti, P, Rossi, M, Beretta, I, Spolti, A, Elia, D, Cassandro, R, Caminati, A, Cipollone, F, Guagnano, M, D'Ardes, D, Rossi, I, Vezzani, F, Spanevello, A, Cherubino, F, Visca, D, Contoli, M, Papi, A, Morandi, L, Battistini, N, Moreo, G, Iannuzzi, P, Fumagalli, D, Leone, S, Rossio R., Tettamanti M., Nobili A., Harari S., Mannucci P. M., Bandera A., Peyvandi F., Bosari S., Scudeller L., Fusetti G., Rusconi L., Dell'Orto S., Prati D., Valenti L., Giovannelli S., Manunta M., Lamorte G., Ferrari F., Gori A., Muscatello A., Mangioni D., Alagna L., Bozzi G., Lombardi A., Ungaro R., Ancona G., Zuglian G., Bolis M., Iannotti N., Ludovisi S., Comelli A., Renisi G., Biscarini S., Castelli V., Palomba E., Fava M., Fortina V., Peri C. A., Saltini P., Viero G., Itri T., Ferroni V., Pastore V., Massafra R., Liparoti A., Muheberimana T., Giommi A., Bianco R., De Azevedo R. M., Chitani G. E., Gualtierotti R., Ferrari B., Boasi N., Pagliaro E., Massimo C., De Caro M., Giachi A., Montano N., Vigone B., Bellocchi C., Carandina A., Fiorelli E., Melli V., Tobaldini E., Blasi F., Aliberti S., Spotti M., Terranova L., Misuraca S., D'Adda A., Fiore S. D., Di Pasquale M., Mantero M., Contarini M., Ori M., Morlacchi L., Rossetti V., Gramegna A., Pappalettera M., Cavallini M., Buscemi A., Vicenzi M., Rota I., Costantino G., Solbiati M., Furlan L., Mancarella M., Colombo G., Fanin A., Passarella M., Monzani V., Canetta C., Rovellini A., Barbetta L., Billi F., Folli C., Accordino S., Maira D., Hu C. M., Motta I., Scaramellini N., Fracanzani A. L., Lombardi R., Cespiati A., Cesari M., Lucchi T., Proietti M., Calcaterra L., Mandelli C., Coppola C., Cerizza A., Pesenti A. M., Grasselli G., Galazzi A., Monti I., Galbussera A. A., Crisafulli E., Girelli D., Maroccia A., Gabbiani D., Busti F., Vianello A., Biondan M., Sartori F., Faverio P., Pesci A., Zucchetti S., Bonfanti P., Rossi M., Beretta I., Spolti A., Elia D., Cassandro R., Caminati A., Cipollone F., Guagnano M. T., D'Ardes D., Rossi I., Vezzani F., Spanevello A., Cherubino F., Visca D., Contoli M., Papi A., Morandi L., Battistini N., Moreo G. L., Iannuzzi P., Fumagalli D., and Leone S.

Published
2022

33. Suppl. Figure from RORγt-Expressing Tregs Drive the Growth of Colitis-Associated Colorectal Cancer by Controlling IL6 in Dendritic Cells

Author

Rizzo, Angelamaria, primary, Di Giovangiulio, Martina, primary, Stolfi, Carmine, primary, Franzè, Eleonora, primary, Fehling, Hans-Joerg, primary, Carsetti, Rita, primary, Giorda, Ezio, primary, Colantoni, Alfredo, primary, Ortenzi, Angela, primary, Rugge, Massimo, primary, Mescoli, Claudia, primary, Monteleone, Giovanni, primary, and Fantini, Massimo C., primary

Published
2023
Full Text
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34. Data from RORγt-Expressing Tregs Drive the Growth of Colitis-Associated Colorectal Cancer by Controlling IL6 in Dendritic Cells

Author

Rizzo, Angelamaria, primary, Di Giovangiulio, Martina, primary, Stolfi, Carmine, primary, Franzè, Eleonora, primary, Fehling, Hans-Joerg, primary, Carsetti, Rita, primary, Giorda, Ezio, primary, Colantoni, Alfredo, primary, Ortenzi, Angela, primary, Rugge, Massimo, primary, Mescoli, Claudia, primary, Monteleone, Giovanni, primary, and Fantini, Massimo C., primary

Published
2023
Full Text
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35. Data from Smad7 Expression in T cells Prevents Colitis-Associated Cancer

Author

Rizzo, Angelamaria, primary, Waldner, Maximilian J., primary, Stolfi, Carmine, primary, Sarra, Massimiliano, primary, Fina, Daniele, primary, Becker, Christoph, primary, Neurath, Markus F., primary, Macdonald, Thomas T., primary, Pallone, Francesco, primary, Monteleone, Giovanni, primary, and Fantini, Massimo C., primary

Published
2023
Full Text
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38. Data from RORγt-Expressing Tregs Drive the Growth of Colitis-Associated Colorectal Cancer by Controlling IL6 in Dendritic Cells

Author

Massimo C. Fantini, Giovanni Monteleone, Claudia Mescoli, Massimo Rugge, Angela Ortenzi, Alfredo Colantoni, Ezio Giorda, Rita Carsetti, Hans-Joerg Fehling, Eleonora Franzè, Carmine Stolfi, Martina Di Giovangiulio, and Angelamaria Rizzo

Abstract

Chronic inflammation drives colitis-associated colorectal cancer (CAC) in inflammatory bowel disease (IBD). FoxP3+ regulatory T cells (Treg) coexpressing the Th17-related transcription factor RORγt accumulate in the lamina propria of IBD patients, where they are thought to represent an intermediate stage of development toward a Th17 proinflammatory phenotype. However, the role of these cells in CAC is unknown. RORγt+FoxP3+ cells were investigated in human samples of CAC, and their phenotypic stability and function were investigated in an azoxymethane/dextran sulfate sodium model of CAC using Treg fate-mapping reporter and Treg-specific RORγt conditional knockout mice. Tumor development and the intratumoral inflammatory milieu were characterized in these mice. The functional role of CTLA-4 expressed by Tregs and FoxO3 in dendritic cells (DC) was studied in vitro and in vivo by siRNA-silencing experiments. RORγt expression identified a phenotypically stable population of tumor-infiltrating Tregs in humans and mice. Conditional RORγt knockout mice showed reduced tumor incidence, and dysplastic cells exhibited low Ki67 expression and STAT3 activation. Tumor-infiltrating DCs produced less IL6, a cytokine that triggers STAT3-dependent proliferative signals in neoplastic cells. RORγt-deficient Tregs isolated from tumors overexpressed CTLA-4 and induced DCs to have elevated expression of the transcription factor FoxO3, thus reducing IL6 expression. Finally, in vivo silencing of FoxO3 obtained by siRNA microinjection in the tumors of RORγt-deficient mice restored IL6 expression and tumor growth. These data demonstrate that RORγt expressed by tumor-infiltrating Tregs sustains tumor growth by leaving IL6 expression in DCs unchecked. Cancer Immunol Res; 6(9); 1082–92. ©2018 AACR.

Published
2023

41. Data from Smad7 Expression in T cells Prevents Colitis-Associated Cancer

Author

Massimo C. Fantini, Giovanni Monteleone, Francesco Pallone, Thomas T. Macdonald, Markus F. Neurath, Christoph Becker, Daniele Fina, Massimiliano Sarra, Carmine Stolfi, Maximilian J. Waldner, and Angelamaria Rizzo

Abstract

Patients with inflammatory bowel disease (IBD) have an increased risk of developing colorectal cancer due to chronic inflammation. In IBD, chronic inflammation relies upon a TGFβ signaling blockade, but its precise mechanistic relationship to colitis-associated colorectal cancer (CAC) remains unclear. In this study, we investigated the role of the TGFβ signaling inhibitor Smad7 in CAC pathogenesis. In human colonic specimens, Smad7 was downregulated in CD4+ T cells located in the lamina propria of patients with complicated IBD compared with uncomplicated IBD. Therefore, we assessed CAC susceptibility in a transgenic mouse model where Smad7 was overexpressed specifically in T cells. In this model, Smad7 overexpression increased colitis severity, but the mice nevertheless developed fewer tumors than nontransgenic mice. Protection was associated with increased expression of IFNγ and increased accumulation of cytotoxic CD8+ and natural killer T cells in the tumors and peritumoral areas. Moreover, genetic deficiency in IFNγ abolished the Smad7-dependent protection against CAC. Taken together, our findings defined a novel and unexpected role for Smad7 in promoting a heightened inflammatory response that protects against CAC. Cancer Res; 71(24); 7423–32. ©2011 AACR.

Published
2023

42. Cryo-electron microscopy of extracellular vesicles associated with the marine toxic dinoflagellate Alexandrium minutum

Author

Massimo C. Pernice, Daniel Closa, Esther Garcés, Ministerio de Ciencia, Innovación y Universidades (España), and Agencia Estatal de Investigación (España)

Subjects
Alexandrium minutum, Cryo TEM, Plant Science, Aquatic Science, Extracellular vesicles, Conserve and sustainably use the oceans, seas and marine resources for sustainable development, Dinoflagellates
Abstract

7 pages, 5 figures, supplementary materials https://doi.org/10.1016/j.hal.2023.102389.-- Data availability: Data will be made available on request, Extracellular Vesicles (EVs) are likely an important strategy of transport and communication in marine microbial community. Their isolation and characterization from axenic culture of microbial eukaryotes represents a technological challenge not fully solved. Here, for the first time, we isolated EVs from a near-axenic culture of the toxic dinoflagellate Alexandrium minutum. Pictures of the isolated vesicles were done with Cryo TEM (Cryogenic Transmission Electron Microscopy). Based on their morphotype the EVs were clustered in five major groups (rounded, rounded electron-dense, lumen electron-dense, double and irregular) and each EV was measured resulting in an average size of 0.36 µm of diameter. Taking in account that in prokaryotes it has been demonstrated that EVs play an important role in the mechanism of toxicity, this descriptive work aims to be the first step to study the possible role of EVs in the toxicity of dinoflagellates, We thank the Spanish MICINN Project SMART (PID2020-112978GB-I00), and the institutional support of the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019- 000928-S)

Published
2023

44. IL10 Secretion Endows Intestinal Human iNKT Cells with Regulatory Functions Towards Pathogenic T Lymphocytes

Author

Claudia Burrello, Francesco Strati, Georgia Lattanzi, Angelica Diaz-Basabe, Erika Mileti, Maria Rita Giuffrè, Gianluca Lopez, Fulvia Milena Cribiù, Elena Trombetta, Marinos Kallikourdis, Marco Cremonesi, Francesco Conforti, Fiorenzo Botti, Laura Porretti, Maria Rescigno, Maurizio Vecchi, Massimo C Fantini, Flavio Caprioli, Federica Facciotti, Burrello, C, Strati, F, Lattanzi, G, Diaz-Basabe, A, Mileti, E, Giuffrè, M, Lopez, G, Cribiù, F, Trombetta, E, Kallikourdis, M, Cremonesi, M, Conforti, F, Botti, F, Porretti, L, Rescigno, M, Vecchi, M, Fantini, M, Caprioli, F, and Facciotti, F

Subjects
Crohn’s disease, CD4-Positive T-Lymphocytes, Gastroenterology, General Medicine, SCFA, Colitis, Interleukin-10, Crohn Disease, iNKT cell, microbiota, Humans, Natural Killer T-Cells, Intestinal Mucosa, IL10
Abstract

Background and Aims Invariant natural killer T [iNKT] cells perform pleiotropic functions in different tissues by secreting a vast array of pro-inflammatory and cytotoxic molecules. However, the presence and function of human intestinal iNKT cells capable of secreting immunomodulatory molecules such as IL-10 has never been reported so far. Here we describe for the first time the presence of IL10-producing iNKT cells [NKT10 cells] in the intestinal lamina propria of healthy individuals and of Crohn’s disease [CD] patients. Methods Frequency and phenotype of NKT10 cells were analysed ex vivo from intestinal specimens of Crohn’s disease [n = 17] and controls [n = 7]. Stable CD-derived intestinal NKT10 cell lines were used to perform in vitro suppression assays and co-cultures with patient-derived mucosa-associated microbiota. Experimental colitis models were performed by adoptive cell transfer of splenic naïve CD4+ T cells in the presence or absence of IL10-sufficient or -deficient iNKT cells. In vivo induction of NKT10 cells was performed by administration of short chain fatty acids [SCFA] by oral gavage. Results Patient-derived intestinal NKT10 cells demonstrated suppressive capabilities towards pathogenic CD4+ T cells. The presence of increased proportions of mucosal NKT10 cells associated with better clinical outcomes in CD patients. Moreover, an intestinal microbial community enriched in SCFA-producing bacteria sustained the production of IL10 by iNKT cells. Finally, IL10-deficient iNKT cells failed to control the pathogenic activity of adoptively transferred CD4+ T cells in an experimental colitis model. Conclusions These results describe an unprecedentd IL10-mediated immunoregulatory role of intestinal iNKT cells in controlling the pathogenic functions of mucosal T helper subsets and in maintaining the intestinal immune homeostasis.

Published
2022

50. Quercetin and its derivates as antiviral potentials: A comprehensive review

Author

Massimo C. Fantini, Antonella Fais, Amalia Di Petrillo, and Germano Orrù

Subjects
coronavirus, Picornaviridae, Reviews, Filoviridae, Review, Pharmacology, Virus Replication, Antiviral Agents, quercetin, chemistry.chemical_compound, Flaviviridae, influenza virus H1N1, Humans, Coronaviridae, heterocyclic compounds, Flavonoids, biology, HIV, biology.organism_classification, Antimicrobial, antiviral, Hepadnaviridae, chemistry, Viral replication, Virus Diseases, HCV, Quercetin
Abstract

Quercetin, widely distributed in fruits and vegetables, is a flavonoid known for its antioxidant, antiviral, antimicrobial, and antiinflammatory properties. Several studies highlight the potential use of quercetin as an antiviral, due to its ability to inhibit the initial stages of virus infection, to be able to interact with proteases important for viral replication, and to reduce inflammation caused by infection. Quercetin could also be useful in combination with other drugs to potentially enhance the effects or synergistically interact with them, in order to reduce their side effects and related toxicity. Since there is no comprehensive compilation about antiviral activities of quercetin and derivates, the aim of this review is providing a summary of their antiviral activities on a set of human viral infections along with mechanisms of action. Thus, the following family of viruses are examined: Flaviviridae, Herpesviridae, Orthomyxoviridae, Coronaviridae, Hepadnaviridae, Retroviridae, Picornaviridae, Pneumoviridae, and Filoviridae.

Published
2021

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