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457 results on '"Ferrarini M."'

1. Cost-utility of surgical sutureless bioprostheses vs TAVI in aortic valve replacement for patients at intermediate and high surgical risk

Author

Povero M, Miceli A, Pradelli L, Ferrarini M, Pinciroli M, and Glauber M

Subjects
sutureless valve, aortic valve replacement, TAVI, DES model, cost-utility, Medicine (General), R5-920, Therapeutics. Pharmacology, RM1-950
Abstract

Massimiliano Povero,1 Antonio Miceli,2,3 Lorenzo Pradelli,1 Matteo Ferrarini,2 Matteo Pinciroli,4 Mattia Glauber2 1AdRes Health Economics and Outcomes Research, Turin, Italy; 2Minimally Invasive Cardiothoracic Department, Istituto Clinico Sant’Ambrogio, Gruppo Ospedaliero San Donato, Milan, Italy; 3Bristol Heart Institute, University of Bristol, Bristol, UK; 4LivaNova, Milan, Italy Background: Meta-analyses of studies comparing transcatheter aortic valve implants (TAVIs) and sutureless aortic valve replacement (SU-AVR) show differing effectiveness and safety profiles. The approaches also differ in their surgical cost (including operating room and device).Objective: The objective of this study was to assess the incremental cost-utility of SU-AVR vs TAVIs for the treatment of intermediate- to high-risk patients in the US, Germany, France, Italy, UK, and Australia.Methods: A patient-level simulation compares in-hospital pathways of patients undergoing SU-AVR or TAVIs; later, patient history is modeled at the cohort level. Hospital outcomes for TAVIs reproduce data from recent series; in SU-AVR patients, outcomes are obtained by applying relative efficacy estimates in a recent meta-analysis on 1,462 patients. After discharge, survival depends on the development of paravalvular leak and the need for dialysis. A comprehensive third-party payer perspective encompassing both in-hospital and long-term costs was adopted.Results: Due to lower in-hospital (4.1% vs 7.0%) and overall mortality, patients treated with SU-AVR are expected to live an average of 1.25 years more compared with those undergoing TAVIs, with a mean gain of 1.14 quality-adjusted life-years. Both in-hospital and long-term costs were lower for SU-AVR than for TAVIs with total savings ranging from $4,158 (France) to $20,930 (US).Conclusion: SU-AVR results dominant when compared to TAVIs in intermediate- to high-risk patients. Both in-hospital and long-term costs are lower for SU-AVR than for TAVI patients, with concomitant significant gains in life expectancy, both raw and adjusted for the quality of life. Keywords: sutureless valve, aortic valve replacement, TAVI, DES model, cost-utility

Published
2018

2. The time to first treatment is an independent predictor of overall survival in chronic lymphocytic leukemia

Author

Morabito, Francesco, Tripepi, G., Mauro, F. R., Laurenti, Luca, Reda, G., Moia, R., Condoluci, A., Vincelli, I., Chiarenza, A., Vigna, E., Martino, E. A., Bruzzese, Maria Antonella, Mezzatesta, S., Laureana, R., Cutrona, G., Di Raimondo, F., Fronza, G., Zucchetto, A., Bomben, R., Rossi, Federica Maria, Olivieri, J., Zaja, F., Rossi, Dario, Gaidano, G., Del Principe, M. I., Ilariucci, F., Del Poeta, G., Ferrarini, M., Neri, A., Gattei, V., Gentile, M., Morabito F., Laurenti L. (ORCID:0000-0002-8327-1396), Bruzzese A., Rossi F. M., Rossi D., Morabito, Francesco, Tripepi, G., Mauro, F. R., Laurenti, Luca, Reda, G., Moia, R., Condoluci, A., Vincelli, I., Chiarenza, A., Vigna, E., Martino, E. A., Bruzzese, Maria Antonella, Mezzatesta, S., Laureana, R., Cutrona, G., Di Raimondo, F., Fronza, G., Zucchetto, A., Bomben, R., Rossi, Federica Maria, Olivieri, J., Zaja, F., Rossi, Dario, Gaidano, G., Del Principe, M. I., Ilariucci, F., Del Poeta, G., Ferrarini, M., Neri, A., Gattei, V., Gentile, M., Morabito F., Laurenti L. (ORCID:0000-0002-8327-1396), Bruzzese A., Rossi F. M., and Rossi D.

Abstract

NA

Published
2023

3. Myelomonocytic cells in giant cell arteritis activate trained immunity programs sustaining inflammation and cytokine production

Author

Cantoni, E, Merelli, I, Stefanoni, D, Tomelleri, A, Campochiaro, C, Giordano, V, Panigada, M, Baldissera, E, Merlo Pich, L, Natoli, V, Ziogas, A, Domínguez-Andrés, J, De Luca, G, Mazza, D, Zambrano, S, Gnani, D, Ferrarini, M, Ferrero, E, Agresti, A, Vergani, B, Leone, B, Cenci, S, Ravelli, A, Matucci-Cerinic, M, D'Alessandro, A, Joosten, L, Dagna, L, Netea, M, Molteni, R, Cavalli, G, Cantoni, Eleonora, Merelli, Ivan, Stefanoni, Davide, Tomelleri, Alessandro, Campochiaro, Corrado, Giordano, Vito, Panigada, Maddalena, Baldissera, Elena M, Merlo Pich, Laura, Natoli, Valentina, Ziogas, Athanasios, Domínguez-Andrés, Jorge, De Luca, Giacomo, Mazza, Davide, Zambrano, Samuel, Gnani, Daniela, Ferrarini, Marina, Ferrero, Elisabetta, Agresti, Alessandra, Vergani, Barbara, Leone, Biagio Eugenio, Cenci, Simone, Ravelli, Angelo, Matucci-Cerinic, Marco, D'Alessandro, Angelo, Joosten, Leo A B, Dagna, Lorenzo, Netea, Mihai G, Molteni, Raffaella, Cavalli, Giulio, Cantoni, E, Merelli, I, Stefanoni, D, Tomelleri, A, Campochiaro, C, Giordano, V, Panigada, M, Baldissera, E, Merlo Pich, L, Natoli, V, Ziogas, A, Domínguez-Andrés, J, De Luca, G, Mazza, D, Zambrano, S, Gnani, D, Ferrarini, M, Ferrero, E, Agresti, A, Vergani, B, Leone, B, Cenci, S, Ravelli, A, Matucci-Cerinic, M, D'Alessandro, A, Joosten, L, Dagna, L, Netea, M, Molteni, R, Cavalli, G, Cantoni, Eleonora, Merelli, Ivan, Stefanoni, Davide, Tomelleri, Alessandro, Campochiaro, Corrado, Giordano, Vito, Panigada, Maddalena, Baldissera, Elena M, Merlo Pich, Laura, Natoli, Valentina, Ziogas, Athanasios, Domínguez-Andrés, Jorge, De Luca, Giacomo, Mazza, Davide, Zambrano, Samuel, Gnani, Daniela, Ferrarini, Marina, Ferrero, Elisabetta, Agresti, Alessandra, Vergani, Barbara, Leone, Biagio Eugenio, Cenci, Simone, Ravelli, Angelo, Matucci-Cerinic, Marco, D'Alessandro, Angelo, Joosten, Leo A B, Dagna, Lorenzo, Netea, Mihai G, Molteni, Raffaella, and Cavalli, Giulio

Abstract

Objective: Trained immunity (TI) is a de facto memory program of innate immune cells, characterized by immunometabolic and epigenetic changes sustaining enhanced production of cytokines. TI evolved as a protective mechanism against infections; however, inappropriate activation can cause detrimental inflammation and might be implicated in the pathogenesis of chronic inflammatory diseases. In this study, we investigated the role of TI in the pathogenesis of giant cell arteritis (GCA), a large-vessel vasculitis characterized by aberrant macrophage activation and excess cytokine production. Methods: Monocytes from GCA patients and from age- and sex-matched healthy donors were subjected to polyfunctional studies, including cytokine production assays at baseline and following stimulation, intracellular metabolomics, chromatin immunoprecipitation-qPCR, and combined ATAC/RNA sequencing. Immunometabolic activation (i.e. glycolysis) was assessed in inflamed vessels of GCA patients with FDG-PET and immunohistochemistry (IHC), and the role of this pathway in sustaining cytokine production was confirmed with selective pharmacologic inhibition in GCA monocytes. Results: GCA monocytes exhibited hallmark molecular features of TI. Specifically, these included enhanced IL-6 production upon stimulation, typical immunometabolic changes (e.g. increased glycolysis and glutaminolysis) and epigenetic changes promoting enhanced transcription of genes governing pro-inflammatory activation. Immunometabolic changes of TI (i.e. glycolysis) were a feature of myelomonocytic cells in GCA lesions and were required for enhanced cytokine production. Conclusions: Myelomonocytic cells in GCA activate TI programs sustaining enhanced inflammatory activation with excess cytokine production.

Published
2023

6. Posterior reversible encephalopathy syndrome and COVID-19: A series of 6 cases from Lombardy, Italy

Author

Colombo, A, Martinelli Boneschi, F, Beretta, S, Bresolin, N, Versino, M, Lorusso, L, Spagnoli, D, Nastasi, G, Vallauri, D, Rota, S, Repaci, M, Ferrarini, M, Pozzato, M, Princiotta Cariddi, L, Tabaee Damavandi, P, Carimati, F, Banfi, P, Clemenzi, A, Marelli, M, Giorgianni, A, Vinacci, G, Mauri, M, Melzi, P, Di Stefano, M, Tetto, A, Canesi, M, Salmaggi, A, Colombo A., Martinelli Boneschi F., Beretta S., Bresolin N., Versino M., Lorusso L., Spagnoli D., Nastasi G., Vallauri D., Rota S., Repaci M., Ferrarini M., Pozzato M., Princiotta Cariddi L., Tabaee Damavandi P., Carimati F., Banfi P., Clemenzi A., Marelli M., Giorgianni A., Vinacci G., Mauri M., Melzi P., Di Stefano M., Tetto A., Canesi M., Salmaggi A., Colombo, A, Martinelli Boneschi, F, Beretta, S, Bresolin, N, Versino, M, Lorusso, L, Spagnoli, D, Nastasi, G, Vallauri, D, Rota, S, Repaci, M, Ferrarini, M, Pozzato, M, Princiotta Cariddi, L, Tabaee Damavandi, P, Carimati, F, Banfi, P, Clemenzi, A, Marelli, M, Giorgianni, A, Vinacci, G, Mauri, M, Melzi, P, Di Stefano, M, Tetto, A, Canesi, M, Salmaggi, A, Colombo A., Martinelli Boneschi F., Beretta S., Bresolin N., Versino M., Lorusso L., Spagnoli D., Nastasi G., Vallauri D., Rota S., Repaci M., Ferrarini M., Pozzato M., Princiotta Cariddi L., Tabaee Damavandi P., Carimati F., Banfi P., Clemenzi A., Marelli M., Giorgianni A., Vinacci G., Mauri M., Melzi P., Di Stefano M., Tetto A., Canesi M., and Salmaggi A.

Abstract

Posterior reversible encephalopathy cases are increasingly being reported in patients affected by COVID-19, but the largest series so far only includes 4 patients. We present a series of 6 patients diagnosed with PRES during COVID-19 hospitalized in 5 Centers in Lombardia, Italy. 5 out of the 6 patients required intensive care assistence and seizures developed at weaning from assisted ventilation. 3 out of 6 patients underwent cerebrospinal fluid analysis which was normal in all cases, with negative PCR for Sars-CoV-2 genome search. PRES occurrence may be less rare than supposed in COVID-19 patients and a high suspicion index is warranted for prompt diagnosis and treatment.

Published
2021

7. A progression-risk score to predict treatment-free survival for early stage chronic lymphocytic leukemia patients

Author

Gentile, M, Shanafelt, T D, Cutrona, G, Molica, S, Tripepi, G, Alvarez, I, Mauro, F R, Di Renzo, N, Di Raimondo, F, Vincelli, I, Todoerti, K, Matis, S, Musolino, C, Fabris, S, Vigna, E, Levato, L, Zupo, S, Angrilli, F, Consoli, U, Festini, G, Longo, G, Cortelezzi, A, Arcari, A, Federico, M, Mannina, D, Recchia, A G, Neri, A, Kay, N E, Ferrarini, M, and Morabito, F

Published
2016
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8. miR-146a-5p impairs melanoma resistance to kinase inhibitors by targeting COX2 and regulating NFkB-mediated inflammatory mediators

Author

Vergani, E, Dugo, M, Cossa, M, Frigerio, S, Di Guardo, L, Gallino, G, Mattavelli, I, Vergani, B, Lalli, L, Tamborini, E, Valeri, B, Gargiuli, C, Shahaj, E, Ferrarini, M, Ferrero, E, Gomez Lira, M, Huber, V, Vecchio, M, Sensi, M, Leone, B, Santinami, M, Rivoltini, L, Rodolfo, M, Vallacchi, V, Vergani E., Dugo M., Cossa M., Frigerio S., Di Guardo L., Gallino G., Mattavelli I., Vergani B., Lalli L., Tamborini E., Valeri B., Gargiuli C., Shahaj E., Ferrarini M., Ferrero E., Gomez Lira M., Huber V., Vecchio M. D., Sensi M., Leone B. E., Santinami M., Rivoltini L., Rodolfo M., Vallacchi V., Vergani, E, Dugo, M, Cossa, M, Frigerio, S, Di Guardo, L, Gallino, G, Mattavelli, I, Vergani, B, Lalli, L, Tamborini, E, Valeri, B, Gargiuli, C, Shahaj, E, Ferrarini, M, Ferrero, E, Gomez Lira, M, Huber, V, Vecchio, M, Sensi, M, Leone, B, Santinami, M, Rivoltini, L, Rodolfo, M, Vallacchi, V, Vergani E., Dugo M., Cossa M., Frigerio S., Di Guardo L., Gallino G., Mattavelli I., Vergani B., Lalli L., Tamborini E., Valeri B., Gargiuli C., Shahaj E., Ferrarini M., Ferrero E., Gomez Lira M., Huber V., Vecchio M. D., Sensi M., Leone B. E., Santinami M., Rivoltini L., Rodolfo M., and Vallacchi V.

Abstract

Background: Targeted therapy with BRAF and MEK inhibitors has improved the survival of patients with BRAF-mutated metastatic melanoma, but most patients relapse upon the onset of drug resistance induced by mechanisms including genetic and epigenetic events. Among the epigenetic alterations, microRNA perturbation is associated with the development of kinase inhibitor resistance. Here, we identified and studied the role of miR-146a-5p dysregulation in melanoma drug resistance. Methods: The miR-146a-5p-regulated NFkB signaling network was identified in drug-resistant cell lines and melanoma tumor samples by expression profiling and knock-in and knock-out studies. A bioinformatic data analysis identified COX2 as a central gene regulated by miR-146a-5p and NFkB. The effects of miR-146a-5p/COX2 manipulation were studied in vitro in cell lines and with 3D cultures of treatment-resistant tumor explants from patients progressing during therapy. Results: miR-146a-5p expression was inversely correlated with drug sensitivity and COX2 expression and was reduced in BRAF and MEK inhibitor-resistant melanoma cells and tissues. Forced miR-146a-5p expression reduced COX2 activity and significantly increased drug sensitivity by hampering prosurvival NFkB signaling, leading to reduced proliferation and enhanced apoptosis. Similar effects were obtained by inhibiting COX2 by celecoxib, a clinically approved COX2 inhibitor. Conclusions: Deregulation of the miR-146a-5p/COX2 axis occurs in the development of melanoma resistance to targeted drugs in melanoma patients. This finding reveals novel targets for more effective combination treatment. [MediaObject not available: see fulltext.] Graphical Abstract: [Figure not available: see fulltext.]

Published
2020

9. Ultrasound-assisted carbon ion dosimetry and range measurement using injectable polymer-shelled phase-change nanodroplets: in vitro study

Author

UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, Toumia, Y., Pullia, M., Domenici, F., Facoetti, A., Ferrarini, M., Heymans, S.V., Carlier, B., Van Den Abeele, K., Sterpin, Edmond, D’hooge, J., D’Agostino, E., Paradossi, G., UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, Toumia, Y., Pullia, M., Domenici, F., Facoetti, A., Ferrarini, M., Heymans, S.V., Carlier, B., Van Den Abeele, K., Sterpin, Edmond, D’hooge, J., D’Agostino, E., and Paradossi, G.

Published
2022

10. Immunometabolic activation of macrophages leads to cytokine production in the pathogenesis of KRAS-mutated histiocytosis

Author

Ferrero, E, Villa, A, Stefanoni, D, Nemkov, T, D'Alessandro, A, Tengesdal, I, Belloni, D, Molteni, R, Vergani, B, De Luca, G, Grassini, G, Giulia Cangi, M, Dagna, L, Doglioni, C, Cavalli, G, Ferrarini, M, Elisabetta Ferrero, Antonello Villa, Davide Stefanoni, Travis Nemkov, Angelo D'Alessandro, Isak Tengesdal, Daniela Belloni, Raffaella Molteni, Barbara Vergani, Giacomo De Luca, Greta Grassini, Maria Giulia Cangi, Lorenzo Dagna, Claudio Doglioni, Giulio Cavalli, Marina Ferrarini, Ferrero, E, Villa, A, Stefanoni, D, Nemkov, T, D'Alessandro, A, Tengesdal, I, Belloni, D, Molteni, R, Vergani, B, De Luca, G, Grassini, G, Giulia Cangi, M, Dagna, L, Doglioni, C, Cavalli, G, Ferrarini, M, Elisabetta Ferrero, Antonello Villa, Davide Stefanoni, Travis Nemkov, Angelo D'Alessandro, Isak Tengesdal, Daniela Belloni, Raffaella Molteni, Barbara Vergani, Giacomo De Luca, Greta Grassini, Maria Giulia Cangi, Lorenzo Dagna, Claudio Doglioni, Giulio Cavalli, and Marina Ferrarini

Published
2022

12. Oncogene-induced maladaptive activation of trained immunity in the pathogenesis and treatment of Erdheim-Chester disease.

Author

Molteni, R., Biavasco, R., Stefanoni, D., Nemkov, T., Dominguez Andres, J., Arts, R.J.W., Merelli, I., Mazza, D., Zambrano, S., Panigada, M., Cantoni, E., Tengesdal, I.W., Maksud, P., Piras, F., Cesana, D., Cassina, L., Distefano, G., Loffreda, A., Gnani, D., Luca, G. De, Tomelleri, A., Campochiaro, C., Joosten, L.A.B., Dinarello, C.A., Kajaste-Rudnitski, A., Haroche, J., Cardaci, S., Cenci, S., Dagna, L., Doglioni, C., Ferrarini, M., Ferrero, E., Boletta, A., d'Alessandro, A., Montini, E., Netea, M.G., Cavalli, G.C., Molteni, R., Biavasco, R., Stefanoni, D., Nemkov, T., Dominguez Andres, J., Arts, R.J.W., Merelli, I., Mazza, D., Zambrano, S., Panigada, M., Cantoni, E., Tengesdal, I.W., Maksud, P., Piras, F., Cesana, D., Cassina, L., Distefano, G., Loffreda, A., Gnani, D., Luca, G. De, Tomelleri, A., Campochiaro, C., Joosten, L.A.B., Dinarello, C.A., Kajaste-Rudnitski, A., Haroche, J., Cardaci, S., Cenci, S., Dagna, L., Doglioni, C., Ferrarini, M., Ferrero, E., Boletta, A., d'Alessandro, A., Montini, E., Netea, M.G., and Cavalli, G.C.

Abstract

Item does not contain fulltext, Trained immunity (TI) is a proinflammatory program induced in monocyte/macrophages upon sensing of specific pathogens and is characterized by immunometabolic and epigenetic changes that enhance cytokine production. Maladaptive activation of TI (ie, in the absence of infection) may result in detrimental inflammation and development of disease; however, the exact role and extent of inappropriate activation of TI in the pathogenesis of human diseases is undetermined. In this study, we uncovered the oncogene-induced, maladaptive induction of TI in the pathogenesis of a human inflammatory myeloid neoplasm (Erdheim-Chester disease, [ECD]), characterized by the BRAFV600E oncogenic mutation in monocyte/macrophages and excess cytokine production. Mechanistically, myeloid cells expressing BRAFV600E exhibit all molecular features of TI: activation of the AKT/mammalian target of rapamycin signaling axis; increased glycolysis, glutaminolysis, and cholesterol synthesis; epigenetic changes on promoters of genes encoding cytokines; and enhanced cytokine production leading to hyperinflammatory responses. In patients with ECD, effective therapeutic strategies combat this maladaptive TI phenotype; in addition, pharmacologic inhibition of immunometabolic changes underlying TI (ie, glycolysis) effectively dampens cytokine production by myeloid cells. This study revealed the deleterious potential of inappropriate activation of TI in the pathogenesis of human inflammatory myeloid neoplasms and the opportunity for inhibition of TI in conditions characterized by maladaptive myeloid-driven inflammation.

Published
2021

13. Effectiveness of ibrutinib as first-line therapy for chronic lymphocytic leukemia patients and indirect comparison with rituximab-bendamustine: Results of study on 486 cases outside clinical trials

Author

Morabito, F., Tripepi, G., Del Poeta, G., Mauro, F. R., Reda, G., Sportoletti, P., Laurenti, L., Coscia, M., Herishanu, Y., Bossio, S., Varettoni, M., Murru, R., Chiarenza, A., Visentin, A., Condoluci, A., Moia, R., Pietrasanta, D., Loseto, G., Consoli, U., Scortechini, I., Rossi, F. M., Zucchetto, A., Al-Janazreh, H., Vigna, E., Martino, E. A., Cassin, R., D'Arrigo, G., Galimberti, S., Rago, A., Angeletti, I., Biagi, A., Del Giudice, I., Bomben, R., Neri, A., Fronza, G., Monti, P., Menichini, P., Olivieri, J., Cutrona, G., Rossi, D., Cuneo, A., Di Raimondo, F., Gaidano, G., Polliack, A., Trentin, L., Foa, R., Ferrarini, M., Gattei, V., Gentile, M., Morabito F., Laurenti L. (ORCID:0000-0002-8327-1396), Rossi F. M., Galimberti S., Monti P. (ORCID:0000-0002-2586-1881), Rossi D., Foa R., Gentile M., Morabito, F., Tripepi, G., Del Poeta, G., Mauro, F. R., Reda, G., Sportoletti, P., Laurenti, L., Coscia, M., Herishanu, Y., Bossio, S., Varettoni, M., Murru, R., Chiarenza, A., Visentin, A., Condoluci, A., Moia, R., Pietrasanta, D., Loseto, G., Consoli, U., Scortechini, I., Rossi, F. M., Zucchetto, A., Al-Janazreh, H., Vigna, E., Martino, E. A., Cassin, R., D'Arrigo, G., Galimberti, S., Rago, A., Angeletti, I., Biagi, A., Del Giudice, I., Bomben, R., Neri, A., Fronza, G., Monti, P., Menichini, P., Olivieri, J., Cutrona, G., Rossi, D., Cuneo, A., Di Raimondo, F., Gaidano, G., Polliack, A., Trentin, L., Foa, R., Ferrarini, M., Gattei, V., Gentile, M., Morabito F., Laurenti L. (ORCID:0000-0002-8327-1396), Rossi F. M., Galimberti S., Monti P. (ORCID:0000-0002-2586-1881), Rossi D., Foa R., and Gentile M.

Abstract

n/a

Published
2021

14. Comparison of ibrutinib and idelalisib plus rituximab in real-life relapsed/resistant chronic lymphocytic leukemia cases

Author

Morabito, Francesco, Tripepi, G., Del Poeta, G., Mauro, F. R., Reda, G., Sportoletti, P., Laurenti, Luca, Coscia, M., Herishanu, Y., Bossio, S., Varettoni, M., Murru, R., Chiarenza, A., Visentin, A., Condoluci, A., Moia, R., Pietrasanta, D., Loseto, G., Consoli, U., Scortechini, I., Rossi, Federica Maria, Zucchetto, A., Al-Janazreh, H., Vigna, E., Martino, E. A., Mendicino, F., Cassin, R., D'Arrigo, G., Galimberti, Sofia, Rago, A., Angeletti, I., Biagi, A., Del Giudice, I., Bomben, R., Neri, A., Fronza, G., Monti, Paolo, Menichini, P., Cutrona, G., Jaksic, O., Rossi, Dario, Di Raimondo, F., Cuneo, A., Gaidano, G., Polliack, A., Trentin, L., Foa, Robin, Ferrarini, M., Gattei, V., Gentile, Marino, Morabito F., Laurenti L. (ORCID:0000-0002-8327-1396), Rossi F. M., Galimberti S., Monti P. (ORCID:0000-0002-2586-1881), Rossi D., Foa R., Gentile M., Morabito, Francesco, Tripepi, G., Del Poeta, G., Mauro, F. R., Reda, G., Sportoletti, P., Laurenti, Luca, Coscia, M., Herishanu, Y., Bossio, S., Varettoni, M., Murru, R., Chiarenza, A., Visentin, A., Condoluci, A., Moia, R., Pietrasanta, D., Loseto, G., Consoli, U., Scortechini, I., Rossi, Federica Maria, Zucchetto, A., Al-Janazreh, H., Vigna, E., Martino, E. A., Mendicino, F., Cassin, R., D'Arrigo, G., Galimberti, Sofia, Rago, A., Angeletti, I., Biagi, A., Del Giudice, I., Bomben, R., Neri, A., Fronza, G., Monti, Paolo, Menichini, P., Cutrona, G., Jaksic, O., Rossi, Dario, Di Raimondo, F., Cuneo, A., Gaidano, G., Polliack, A., Trentin, L., Foa, Robin, Ferrarini, M., Gattei, V., Gentile, Marino, Morabito F., Laurenti L. (ORCID:0000-0002-8327-1396), Rossi F. M., Galimberti S., Monti P. (ORCID:0000-0002-2586-1881), Rossi D., Foa R., and Gentile M.

Abstract

Objectives: To compare the capacity of ibrutinib (IB) and idelalisib-rituximab (IDELA-R) of prolonging overall survival (OS) as in CLL patients, previously treated with chemotherapy only. Methods: A real-life cohort of 675 cases has been identified and investigated in the database of the groups participating in the study. Results: At an unadjusted univariate analysis, a significant death risk reduction was observed favoring IB (IDELA-R vs IB HR = 0.5, 95% CI = 0.36-0.71) although with some limitations due to the non-randomized and retrospective nature of the study and to the lower number of patients in the IDELA-R group (112 cases) related to the current prescribing practice. To overcome the potential problem of confounding by indication, we adjusted the association between the type of therapy and mortality for all variables significantly associated with OS at Cox univariate analysis. Furthermore, those variables, differently distributed between the two study groups, were introduced into the multivariate Cox model to improve the effectiveness of the analysis. By introducing all these variables into the multiple Cox regression model, we confirmed the protective effect of IB vs IDELA-R (HR = 0.67, 95% CI = 0.45-0.98, P =.04) independent of potential confounders. Conclusions: Although our analysis presents some constraints, that is, the unavailability of additional potential confounders, and the retrospective nature of the study, this observation may be of help for the daily clinical practice, particularly in the absence of randomized trials comparing the two schedules.

Published
2021

15. Assessment of the 4-factor score: Retrospective analysis of 586 CLL patients receiving ibrutinib. A campus CLL study

Author

Morabito, Francesco, Tripepi, G., Del Poeta, G., Mauro, F. R., Reda, G., Sportoletti, P., Laurenti, Luca, Coscia, M., Herishanu, Y., Varettoni, M., Murru, R., Chiarenza, A., Visentin, A., Condoluci, A., Moia, R., Pietrasanta, D., Loseto, G., Consoli, U., Scortechini, I., Rossi, Federica Maria, Zucchetto, A., Vigna, E., Martino, E. A., Mendicino, F., Botta, C., Caracciolo, D., Cassin, R., D'Arrigo, G., Galimberti, Sofia, Rago, A., Angeletti, I., Biagi, A., Del Giudice, I., Bomben, R., Neri, A., Fronza, G., Cutrona, G., Rossi, Dario, Di Raimondo, F., Cuneo, A., Gaidano, G., Polliack, A., Trentin, L., Foa, Robin, Ferrarini, M., Gattei, V., Gentile, Marino, Morabito F., Laurenti L. (ORCID:0000-0002-8327-1396), Rossi F. M., Galimberti S., Rossi D., Foa R., Gentile M., Morabito, Francesco, Tripepi, G., Del Poeta, G., Mauro, F. R., Reda, G., Sportoletti, P., Laurenti, Luca, Coscia, M., Herishanu, Y., Varettoni, M., Murru, R., Chiarenza, A., Visentin, A., Condoluci, A., Moia, R., Pietrasanta, D., Loseto, G., Consoli, U., Scortechini, I., Rossi, Federica Maria, Zucchetto, A., Vigna, E., Martino, E. A., Mendicino, F., Botta, C., Caracciolo, D., Cassin, R., D'Arrigo, G., Galimberti, Sofia, Rago, A., Angeletti, I., Biagi, A., Del Giudice, I., Bomben, R., Neri, A., Fronza, G., Cutrona, G., Rossi, Dario, Di Raimondo, F., Cuneo, A., Gaidano, G., Polliack, A., Trentin, L., Foa, Robin, Ferrarini, M., Gattei, V., Gentile, Marino, Morabito F., Laurenti L. (ORCID:0000-0002-8327-1396), Rossi F. M., Galimberti S., Rossi D., Foa R., and Gentile M.

Abstract

n/a

Published
2021

18. MOOMIN - Mathematical explOration of 'Omics data on a MetabolIc Network.

Author

Pusa, T. (Taneli), Galvão Ferrarini, M. (Mariana), Andrade, R. (Ricardo), Mary, A. (Arnaud), Marchetti Spaccamela, A. (Alberto), Stougie, L. (Leen), Sagot, M.-F. (Marie-France), Pusa, T. (Taneli), Galvão Ferrarini, M. (Mariana), Andrade, R. (Ricardo), Mary, A. (Arnaud), Marchetti Spaccamela, A. (Alberto), Stougie, L. (Leen), and Sagot, M.-F. (Marie-France)

Abstract

MOTIVATION: Analysis of differential expression of genes is often performed to understand how the metabolic activity of an organism is impacted by a perturbation. However, because the system of metabolic regulation is complex and all changes are not directly reflected in the expression levels, interpreting these data can be difficult. RESULTS: In this work, we present a new algorithm and computational tool that uses a genome-scale metabolic reconstruction to infer metabolic changes from differential expression data. Using the framework of constraint-based analysis, our method produces a qualitative hypothesis of a change in metabolic activity. In other words, each reaction of the network is inferred to have increased, decreased, or remained unchanged in flux. In contrast to similar previous approaches, our method does not require a biological objective function and does not assign on/off activity states to genes. An implementation is provided and it is available online. We apply the method to three published datasets to show that it successfully accomplishes its two main goals: confirming or rejecting metabolic changes suggested by differentially expressed genes based on how well they fit in as parts of a coordinated metabolic change, as well as inferring changes in reactions whose genes did not undergo differential expression. AVAILABILITY AND IMPLEMENTATION: github.com/htpusa/moomin. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Published
2020
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19. Validation of a survival-risk score (SRS) in relapsed/refractory CLL patients treated with idelalisib–rituximab

Author

Gentile, Marino, Martino, E. A., Visentin, A., Coscia, M., Reda, G., Sportoletti, P., Mauro, F. R., Laurenti, Luca, Varettoni, M., Murru, R., Chiarenza, A., Vigna, E., Mendicino, F., Lucia, E., Bossio, S., Recchia, A. G., Moia, R., Pietrasanta, D., Loseto, G., Consoli, U., Scortechini, I., Rossi, Federica Maria, Zucchetto, A., Al-Janazreh, H., Vitale, C., Tripepi, G., D'Arrigo, G., Angeletti, I., Bomben, R., Neri, A., Cutrona, G., Fronza, G., Di Raimondo, F., Gaidano, G., Cuneo, A., Foa, Robin, Ferrarini, M., Trentin, L., Gattei, V., Morabito, Francesco, Gentile M., Laurenti L. (ORCID:0000-0002-8327-1396), Rossi F. M., Foa R., Morabito F., Gentile, Marino, Martino, E. A., Visentin, A., Coscia, M., Reda, G., Sportoletti, P., Mauro, F. R., Laurenti, Luca, Varettoni, M., Murru, R., Chiarenza, A., Vigna, E., Mendicino, F., Lucia, E., Bossio, S., Recchia, A. G., Moia, R., Pietrasanta, D., Loseto, G., Consoli, U., Scortechini, I., Rossi, Federica Maria, Zucchetto, A., Al-Janazreh, H., Vitale, C., Tripepi, G., D'Arrigo, G., Angeletti, I., Bomben, R., Neri, A., Cutrona, G., Fronza, G., Di Raimondo, F., Gaidano, G., Cuneo, A., Foa, Robin, Ferrarini, M., Trentin, L., Gattei, V., Morabito, Francesco, Gentile M., Laurenti L. (ORCID:0000-0002-8327-1396), Rossi F. M., Foa R., and Morabito F.

Abstract

N/a

Published
2020

20. Sporadic hereditary neuropathies misdiagnosed as chronic inflammatory demyelinating polyradiculoneuropathy: Pitfalls and red flags

Author

Campagnolo, M., Taioli, F., Cacciavillani, M., Ruiz, M., Luigetti, Marco, Salvalaggio, A., Castellani, F., Testi, S., Ferrarini, M., Cavallaro, T., Gasparotti, R., Fabrizi, G. M., Briani, C., Luigetti M. (ORCID:0000-0001-7539-505X), Campagnolo, M., Taioli, F., Cacciavillani, M., Ruiz, M., Luigetti, Marco, Salvalaggio, A., Castellani, F., Testi, S., Ferrarini, M., Cavallaro, T., Gasparotti, R., Fabrizi, G. M., Briani, C., and Luigetti M. (ORCID:0000-0001-7539-505X)

Abstract

Hereditary neuropathies may be misdiagnosed with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). A correct diagnosis is crucial for avoiding unnecessary therapies and access genetic counseling. We report on nine patients (seven men, mean age 49.2 ± 16.1) diagnosed with and treated as CIDP, in whom mutations or variants of unknown significance (VUS) in genes associated with hereditary neuropathies were reported. All underwent neurological and neurophysiological examination, eight also cerebrospinal fluid (CSF) analysis. In 4/9, nerve ultrasound and/or MR-neurography were performed. All the patients complained of progressive upper or lower limbs sensory-motor symptoms, with heterogeneous disease duration (1-34 years, mean 8.6 ± 10.8). Neurophysiology showed demyelinating signs in seven patients, mixed findings with predominant axonal damage in two patients. Neuroimaging disclosed diffuse abnormalities at proximal and distal segments. Molecular screening showed PMP22 duplication in two patients, mutations in the MPZ, EGR2, and GJB1 genes were reported in each of the remaining patients. The two patients with mixed neurophysiological findings had p.Val30Met mutation in the transthyretin gene. Two patients had VUS in the MARS and HSPB1 genes. Four patients had partial response to immunomodulant therapies, and CSF and neurophysiological features suggesting an inflammatory condition concomitant with the hereditary neuropathy. Hereditary neuropathy may be misdiagnosed with CIDP. The most common pitfalls are CSF (high protein levels and oligoclonal bands), incorrect interpretation of neurophysiology, and transient benefit from therapies. Neuroimaging may be helpful in cases with atypical presentations or when severe axonal damage complicate the neurophysiological interpretation.

Published
2020

21. The criminal careers of italian mafia members

Author

Weisburd, David, Savona, Ernesto U., Hasisi, Badi, Calderoni, Francesco, Savona, Ernesto Ugo, Campedelli, Gian Maria, Comunale, Tommaso, Ferrarini, M., Meneghini, Cecilia, Savona E. U., Calderoni F. (ORCID:0000-0003-2979-4599), Campedelli G. M., Comunale T., Meneghini C. (ORCID:0000-0001-9634-8367), Weisburd, David, Savona, Ernesto U., Hasisi, Badi, Calderoni, Francesco, Savona, Ernesto Ugo, Campedelli, Gian Maria, Comunale, Tommaso, Ferrarini, M., Meneghini, Cecilia, Savona E. U., Calderoni F. (ORCID:0000-0003-2979-4599), Campedelli G. M., Comunale T., and Meneghini C. (ORCID:0000-0001-9634-8367)

Abstract

This chapter provides the first analyses of the criminal career of the Italian mafias members. The analysis is based on the unique Proton Mafia Member dataset, provided by the Italian Ministry of Justice, with information on all individuals who received a final conviction for mafia offences since the 1980s. The PMM includes information on more than 11 thousand individuals and 182 thousand offences. The study explores the career of mafia members following a three-level approach, analyzing the macro, meso, and micro dimensions of the criminal careers of the mafiosi. At the macro level, Italian mafias’ member show different types of criminal trajectories, with a significant portion of the sample exhibiting a late onset and late persistence pattern. At the meso level, the four main types of mafias (the Sicilian Cosa Nostra, the Neapolitan Camorra, the Calabrian ‘Ndrangheta, and the Apulian mafias) report very similar traits although some distinctive patterns emerge. At the micro level, there are differences in the criminal career between early- and lately- recruited member, with the former showing higher frequency of violent, volume crime and the latter a more complex, white collar profile. A further exploration of the PMM data shows an escalation in both the number and the seriousness of crimes before joining the mafias, which subsequently stabilize afterwards.

Published
2020

24. Disease-biased and shared characteristics of the immunoglobulin gene repertoires in marginal zone B cell lymphoproliferations

Author

Xochelli, A. Bikos, V. Polychronidou, E. Galigalidou, C. Agathangelidis, A. Charlotte, F. Moschonas, P. Davis, Z. Colombo, M. Roumelioti, M. Sutton, L.-A. Groenen, P. van den Brand, M. Boudjoghra, M. Algara, P. Traverse-Glehen, A. Ferrer, A. Stalika, E. Karypidou, M. Kanellis, G. Kalpadakis, C. Mollejo, M. Pangalis, G. Vlamos, P. Amini, R.-M. Pospisilova, S. Gonzalez, D. Ponzoni, M. Anagnostopoulos, A. Giudicelli, V. Lefranc, M.-P. Espinet, B. Panagiotidis, P. Piris, M.A. Du, M.-Q. Rosenquist, R. Papadaki, T. Belessi, C. Ferrarini, M. Oscier, D. Tzovaras, D. Ghia, P. Davi, F. Hadzidimitriou, A. Stamatopoulos, K.

Abstract

The B cell receptor immunoglobulin (Ig) gene repertoires of marginal zone (MZ) lymphoproliferations were analyzed in order to obtain insight into their ontogenetic relationships. Our cohort included cases with MZ lymphomas (n = 488), i.e. splenic (SMZL), nodal (NMZL) and extranodal (ENMZL), as well as provisional entities (n = 76), according to the WHO classification. The most striking Ig gene repertoire skewing was observed in SMZL. However, restrictions were also identified in all other MZ lymphomas studied, particularly ENMZL, with significantly different Ig gene distributions depending on the primary site of involvement. Cross-entity comparisons of the MZ Ig sequence dataset with a large dataset of Ig sequences (MZ-related or not; n = 65 837) revealed four major clusters of cases sharing homologous (‘public’) heavy variable complementarity-determining region 3. These clusters included rearrangements from SMZL, ENMZL (gastric, salivary gland, ocular adnexa), chronic lymphocytic leukemia, but also rheumatoid factors and non-malignant splenic MZ cells. In conclusion, different MZ lymphomas display biased immunogenetic signatures indicating distinct antigen exposure histories. The existence of rare public stereotypes raises the intriguing possibility that common, pathogen-triggered, immune-mediated mechanisms may result in diverse B lymphoproliferations due to targeting versatile progenitor B cells and/or operating in particular microenvironments. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Published
2019

25. Disease-biased and shared characteristics of the immunoglobulin gene repertoires in marginal zone B cell lymphoproliferations

Author

Xochelli, A., Bikos, V., Polychronidou, E., Galigalidou, C., Agathangelidis, A., Charlotte, F., Moschonas, P., Davis, Z., Colombo, M., Roumelioti, M., Sutton, L.A., Groenen, P.J., Brand, M. van den, Boudjoghra, M., Algara, P., Traverse-Glehen, A., Ferrer, A., Stalika, E., Karypidou, M., Kanellis, G., Kalpadakis, C., Mollejo, M., Pangalis, G., Vlamos, P., Amini, R.M., Pospisilova, S., Gonzalez, D., Ponzoni, M., Anagnostopoulos, A., Giudicelli, V., Lefranc, M.P., Espinet, B., Panagiotidis, P., Piris, M.A., Du, M.Q., Rosenquist, R., Papadaki, T., Belessi, C., Ferrarini, M., Oscier, D., Tzovaras, D., Ghia, P., Davi, F., Hadzidimitriou, A., Stamatopoulos, K., Xochelli, A., Bikos, V., Polychronidou, E., Galigalidou, C., Agathangelidis, A., Charlotte, F., Moschonas, P., Davis, Z., Colombo, M., Roumelioti, M., Sutton, L.A., Groenen, P.J., Brand, M. van den, Boudjoghra, M., Algara, P., Traverse-Glehen, A., Ferrer, A., Stalika, E., Karypidou, M., Kanellis, G., Kalpadakis, C., Mollejo, M., Pangalis, G., Vlamos, P., Amini, R.M., Pospisilova, S., Gonzalez, D., Ponzoni, M., Anagnostopoulos, A., Giudicelli, V., Lefranc, M.P., Espinet, B., Panagiotidis, P., Piris, M.A., Du, M.Q., Rosenquist, R., Papadaki, T., Belessi, C., Ferrarini, M., Oscier, D., Tzovaras, D., Ghia, P., Davi, F., Hadzidimitriou, A., and Stamatopoulos, K.

Abstract

Contains fulltext : 203155.pdf (Publisher’s version ) (Closed access), The B cell receptor immunoglobulin (Ig) gene repertoires of marginal zone (MZ) lymphoproliferations were analyzed in order to obtain insight into their ontogenetic relationships. Our cohort included cases with MZ lymphomas (n = 488), i.e. splenic (SMZL), nodal (NMZL) and extranodal (ENMZL), as well as provisional entities (n = 76), according to the WHO classification. The most striking Ig gene repertoire skewing was observed in SMZL. However, restrictions were also identified in all other MZ lymphomas studied, particularly ENMZL, with significantly different Ig gene distributions depending on the primary site of involvement. Cross-entity comparisons of the MZ Ig sequence dataset with a large dataset of Ig sequences (MZ-related or not; n = 65 837) revealed four major clusters of cases sharing homologous ('public') heavy variable complementarity-determining region 3. These clusters included rearrangements from SMZL, ENMZL (gastric, salivary gland, ocular adnexa), chronic lymphocytic leukemia, but also rheumatoid factors and non-malignant splenic MZ cells. In conclusion, different MZ lymphomas display biased immunogenetic signatures indicating distinct antigen exposure histories. The existence of rare public stereotypes raises the intriguing possibility that common, pathogen-triggered, immune-mediated mechanisms may result in diverse B lymphoproliferations due to targeting versatile progenitor B cells and/or operating in particular microenvironments. Copyright (c) 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Published
2019

26. 3D culture of Erdheim-Chester disease tissues unveils histiocyte metabolism as a new therapeutic target

Author

Villa, A, Belloni, D, Vergani, B, Cenci, S, Cavalli, G, Biavasco, R, Rodolfo, M, Cangi, M, Doglioni, C, Dagna, L, Ferrero, E, Ferrarini, M, Villa, An, Cangi, MG, Villa, A, Belloni, D, Vergani, B, Cenci, S, Cavalli, G, Biavasco, R, Rodolfo, M, Cangi, M, Doglioni, C, Dagna, L, Ferrero, E, Ferrarini, M, Villa, An, and Cangi, MG

Abstract

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis, characterised by tissue infiltration by foamy CD68+ CD1a− histiocytes.1 The disease has pleomorphic clinical manifestations, including long bones and extraskeletal involvement, and may be life-threatening, particularly when heart and central nervous system are affected.1 ECD histiocytes secrete proinflammatory cytokines2 and carry activating mutations along the RAS-RAF-MEK-ERK protein kinase signalling pathway, most commonly the BRAFV600E oncogenic mutation.3 4 Accordingly, patients with ECD have been treated with cytokine inhibitors, including infliximab,⇓ 5 and, more recently, with the BRAFV600E inhibitor vemurafenib.6 The latter, however, induces sustained but partial clinical responses and recurrences on discontinuation,6 underlining the need for more effective therapeutic strategies. To identify the outcomes downstream constitutive ERK phosphorylation in ECD histiocytes and their response to small molecule-based inhibition, we performed three-dimensional (3D) culture of tissues from three BRAFV600E-mutated ECD patients in the RCCS bioreactor7 (and online supplementary methods) in the presence/absence of vemurafenib or infliximab, used as control.

Published
2019

27. TP53 disruption as a risk factor in the era of targeted therapies: A multicenter retrospective study of 525 chronic lymphocytic leukemia cases

Author

Morabito, Francesco, Del Poeta, G., Mauro, F. R., Reda, G., Sportoletti, P., Laurenti, Luca, Coscia, M., Herishanu, Y., Bossio, S., Varettoni, M., Murru, R., Chiarenza, A., Visentin, A., Condoluci, A., Moia, R., Pietrasanta, D., Loseto, G., Consoli, U., Scortechini, I., Recchia, A. G., Rossi, Federica Maria, Zucchetto, A., Al-Janazreh, H., Martino, E. A., Vigna, E., Tripepi, G., D'Arrigo, G., Galimberti, Sofia, Rago, A., Angeletti, I., Biagi, A., Del Giudice, I., Bomben, R., Neri, A., Fronza, G., Cutrona, G., Jaksic, O., Olivieri, J., Rossi, Dario, Di Raimondo, F., Cuneo, A., Gaidano, G., Polliack, A., Trentin, L., Foa, Robin, Ferrarini, M., Gattei, V., Gentile, Marino, Morabito F., Laurenti L. (ORCID:0000-0002-8327-1396), Rossi F. M., Galimberti S., Rossi D., Foa R., Gentile M., Morabito, Francesco, Del Poeta, G., Mauro, F. R., Reda, G., Sportoletti, P., Laurenti, Luca, Coscia, M., Herishanu, Y., Bossio, S., Varettoni, M., Murru, R., Chiarenza, A., Visentin, A., Condoluci, A., Moia, R., Pietrasanta, D., Loseto, G., Consoli, U., Scortechini, I., Recchia, A. G., Rossi, Federica Maria, Zucchetto, A., Al-Janazreh, H., Martino, E. A., Vigna, E., Tripepi, G., D'Arrigo, G., Galimberti, Sofia, Rago, A., Angeletti, I., Biagi, A., Del Giudice, I., Bomben, R., Neri, A., Fronza, G., Cutrona, G., Jaksic, O., Olivieri, J., Rossi, Dario, Di Raimondo, F., Cuneo, A., Gaidano, G., Polliack, A., Trentin, L., Foa, Robin, Ferrarini, M., Gattei, V., Gentile, Marino, Morabito F., Laurenti L. (ORCID:0000-0002-8327-1396), Rossi F. M., Galimberti S., Rossi D., Foa R., and Gentile M.

Abstract

n/a

Published
2019

28. Expanding the spectrum of genes responsible for hereditary motor neuropathies

Author

Previtali, Sc, Zhao, E, Lazarevic, D, Pipitone, Gb, Fabrizi, Gm, Manganelli, F, Mazzeo, A, Pareyson, D, Schenone, A, Taroni, F, Vita, G, Bellone, E, Ferrarini, M, Garibaldi, M, Magri, S, Padua, Luca, Pennisi, E, Pisciotta, C, Riva, N, Scaioli, V, Scarlato, M, Tozza, S, Geroldi, A, Jordanova, A, Ferrari, M, Molineris, I, Reilly, Mm, Comi, G, Carrera, P, Devoto, M, Bolino, A., Padua L (ORCID:0000-0003-2570-9326), Previtali, Sc, Zhao, E, Lazarevic, D, Pipitone, Gb, Fabrizi, Gm, Manganelli, F, Mazzeo, A, Pareyson, D, Schenone, A, Taroni, F, Vita, G, Bellone, E, Ferrarini, M, Garibaldi, M, Magri, S, Padua, Luca, Pennisi, E, Pisciotta, C, Riva, N, Scaioli, V, Scarlato, M, Tozza, S, Geroldi, A, Jordanova, A, Ferrari, M, Molineris, I, Reilly, Mm, Comi, G, Carrera, P, Devoto, M, Bolino, A., and Padua L (ORCID:0000-0003-2570-9326)

Abstract

BACKGROUND: Inherited peripheral neuropathies (IPNs) represent a broad group of genetically and clinically heterogeneous disorders, including axonal Charcot-Marie-Tooth type 2 (CMT2) and hereditary motor neuropathy (HMN). Approximately 60%-70% of cases with HMN/CMT2 still remain without a genetic diagnosis. Interestingly, mutations in HMN/CMT2 genes may also be responsible for motor neuron disorders or other neuromuscular diseases, suggesting a broad phenotypic spectrum of clinically and genetically related conditions. Thus, it is of paramount importance to identify novel causative variants in HMN/CMT2 patients to better predict clinical outcome and progression. METHODS: We designed a collaborative study for the identification of variants responsible for HMN/CMT2. We collected 15 HMN/CMT2 families with evidence for autosomal recessive inheritance, who had tested negative for mutations in 94 known IPN genes, who underwent whole-exome sequencing (WES) analyses. Candidate genes identified by WES were sequenced in an additional cohort of 167 familial or sporadic HMN/CMT2 patients using next-generation sequencing (NGS) panel analysis. RESULTS: Bioinformatic analyses led to the identification of novel or very rare variants in genes, which have not been previously associated with HMN/CMT2 (ARHGEF28, KBTBD13, AGRN and GNE); in genes previously associated with HMN/CMT2 but in combination with different clinical phenotypes (VRK1 and PNKP), and in the SIGMAR1 gene, which has been linked to HMN/CMT2 in only a few cases. These findings were further validated by Sanger sequencing, segregation analyses and functional studies. CONCLUSIONS: These results demonstrate the broad spectrum of clinical phenotypes that can be associated with a specific disease gene, as well as the complexity of the pathogenesis of neuromuscular disorders.

Published
2019

30. Modeling multiple myeloma-bone marrow interactions and response to drugs in a 3d surrogate microenvironment

Author

Belloni, D, Heltai, S, Ponzoni, M, Villa, A, Vergani, B, Pecciarini, L, Marcatti, M, Girlanda, S, Tonon, G, Ciceri, F, Caligaris-Cappio, F, Ferrarini, M, Ferrero, E, Belloni, Daniela, Heltai, Silvia, Ponzoni, Maurilio, Villa, Antonello, Vergani, Barbara, Pecciarini, Lorenza, Marcatti, Magda, Girlanda, Stefania, Tonon, Giovanni, Ciceri, Fabio, Caligaris-Cappio, Federico, Ferrarini, Marina, Ferrero, Elisabetta, Belloni, D, Heltai, S, Ponzoni, M, Villa, A, Vergani, B, Pecciarini, L, Marcatti, M, Girlanda, S, Tonon, G, Ciceri, F, Caligaris-Cappio, F, Ferrarini, M, Ferrero, E, Belloni, Daniela, Heltai, Silvia, Ponzoni, Maurilio, Villa, Antonello, Vergani, Barbara, Pecciarini, Lorenza, Marcatti, Magda, Girlanda, Stefania, Tonon, Giovanni, Ciceri, Fabio, Caligaris-Cappio, Federico, Ferrarini, Marina, and Ferrero, Elisabetta

Abstract

Multiple myeloma develops primarily inside the bone marrow microenvironment, that confers pro-survival signals and drug resistance. 3D cultures that reproduce multiple myeloma-bone marrow interactions are needed to fully investigate multiple myeloma pathogenesis and response to drugs. To this purpose, we exploited the 3D Rotary Cell Culture System bioreactor technology for myelomabone marrow co-cultures in gelatin scaffolds. The model was validated with myeloma cell lines that, as assessed by histochemical and electronmicroscopic analyses, engaged contacts with stromal cells and endothelial cells. Consistently, pro-survival signaling and also cell adhesionmediated drug resistance were significantly higher in 3D than in 2D parallel co-cultures. The contribution of the VLA-4/VCAM1 pathway to resistance to bortezomib was modeled by the use of VCAM1 transfectants. Soluble factor-mediated drug resistance could be also demonstrated in both 2D and 3D co-cultures. The system was then successfully applied to co-cultures of primary myeloma cells-primary myeloma bone marrow stromal cells from patients and endothelial cells, allowing the development of functional myeloma-stroma interactions and MM cell long-term survival. Significantly, genomic analysis performed in a highrisk myeloma patient demonstrated that culture in bioreactor paralleled the expansion of the clone that ultimately dominated in vivo. Finally, the impact of bortezomib on myeloma cells and on specialized functions of the microenvironment could be evaluated. Our findings indicate that 3D dynamic culture of reconstructed human multiple myeloma microenvironments in bioreactor may represent a useful platform for drug testing and for studying tumor-stroma molecular interactions.

Published
2018

31. A new mechanism shapes the naïve CD8+ T cell repertoire: the selection for full diversity

Author

Goncalves, P, Ferrarini, M, Molina-Paris, C, Lythe, G, Vasseur, F, Lim, A, Rocha, B, and Azogui, O

Abstract

During thymic T cell differentiation, TCR repertoires are shaped by negative, positive and agonist selection. In the thymus and in the periphery, repertoires are also shaped by strong inter-clonal and intra-clonal competition to survive death by neglect. Understanding the impact of these events on the T cell repertoire requires direct evaluation of TCR expression in peripheral naïve T cells. Several studies have evaluated TCR diversity, with contradictory results. Some of these studies had intrinsic technical limitations since they used material obtained from T cell pools, preventing the direct evaluation of clone sizes. Indeed with these approaches, identical TCRs may correspond to different cells expressing the same receptor, or to several amplicons from the same T cell. We here overcame this limitation by evaluating TCRB expression in individual naïve CD8+ T cells. Of the 2269 Tcrb sequences we obtained from 13 mice, 99% were unique. Mathematical analysis of this data showed that the average number of naïve peripheral CD8+ T cells expressing the same TCRB is 1.1 cell. Since TCRA co-expression studies could only increase repertoire diversity, these results reveal that the number of naïve T cells with unique TCRs approaches the number of naïve cells. Since thymocytes undergo multiple rounds of divisions after TCRB rearrangement; and 3–5% of thymocytes survive thymic selection events; the number of cells expressing the same TCRB was expected to be much higher. Thus, these results suggest a new repertoire selection mechanism, which strongly selects for full TCRB diversity.

Published
2017

32. Cardiovascular manifestations of Erdheim-Chester disease

Author

Berti, A., Ferrarini, M., Elisabetta Ferrero, Dagna, L., Berti, A, Ferrarini, M, Ferrero, E., and Dagna, Lorenzo

Subjects
Erdheim-Chester Disease, Heart Diseases, Cardiovascular Diseases, Aortic Diseases, Humans, Magnetic Resonance Imaging, Cine, Pericardial Effusion
Abstract

Erdheim-Chester disease (ECD) is a rare inflammatory disorder of unknown etiology, characterised by diffuse organ infiltration of CD68-positive, CD1a-negative, S100-low/negative foamy histiocytes. It is a non-Langerhans cell histiocytosis which invariably involves bones (96% of cases). Extraskeletal involvement is observed in about 50% of cases. Cardiovascular involvement affects more than 20% of patients and associates with poor prognosis, conferring a reduced response to treatment. Frequent findings are pericardial effusion (24% of patients), "coated aorta", a perivascular circumferential thickening of the aorta, and pericardial thickening. Other typical features include right atrial mass with pseudo-tumoural appearance and histiocytes' infiltration of right atrial walls, atrioventricular sulcus and interatrial septum. After the recent introduction of cardiac cine MRI in the clinical assessment of patients affected by ECD, a growing body of case reports and retrospective data showed that cardiovascular involvement is present more frequently than previously thought and that it is relatively often asymptomatic. Hence, clinicians should systematically screen ECD patients for occult cardiovascular involvement by means of highly sensitive imaging tools. Despite these recent novelties, comprehensive literature reviews focusing on ECD cardiovascular involvement and its imaging assessment in the last decade are lacking.

Published
2014

34. A GLOBAL PROGRESSION RISK SCORE FOR EARLY STAGE CHRONIC LYMPHOCYTIC LEUKEMIA PATIENTS: THE NEVER-ENDING STORY

Author

Gentile, M., Shanafelt, T. D., Giovanna Cutrona, Molica, S., Tripepi, G., Ilariucci, F., Mauro, F. R., Di Renzo, N., Di Raimondo, F., Vincelli, I., Todoerti, K., Matis, S., Musolino, C., Maura, F., Fabris, S., Lionetti, M., Levato, L., Zupo, S., Angrilli, F., Consoli, U., Festini, G., Longo, G., Cortelezzi, A., Musto, P., Federico, M., Mannina, D., Neri, A., Kay, N. E., Ferrarini, M., and Morabito, F.

Published
2015

36. Prospective validation of a risk score based on biological markers for predicting progression free survival in Binet stage A chronic lymphocytic leukemia patients: results of the multicenter O-CLL1-GISL study

Author

Gentile, M, Cutrona, G, Mosca, L, Matis, S, Fabris, S, Lionetti, M, Ilariucci, F, Zupo, S, Musolino, C, Levato, L, Molica, S, DI RAIMONDO, Francesco, Vincelli, I, Di Rienzo, N, Pesce, Ea, Angrilli, F, Federico, M, Neri, A, Ferrarini, M, and Morabito, F.

Subjects
Male, Gene Expression Profiling, Reproducibility of Results, Biological markers, chronic lymphocytic leukemia, early stage, gene expression profiles, prognosis, Middle Aged, Prognosis, Leukemia, Lymphocytic, Chronic, B-Cell, Risk Assessment, biological markers, Disease-Free Survival, Cohort Studies, Predictive Value of Tests, Biomarkers, Tumor, Disease Progression, Humans, Female, Prospective Studies
Abstract

A risk score based on three biological features (CD38, ZAP-70, and IGHV mutational status) was previously developed to predict progression-free survival (PFS) in untreated Binet A CLL patients. Here we perform a score validation analysis in a prospective and independent cohort of patients. Biological markers (CD38, ZAP-70, and IGHV mutational status) and gene expression profiles (GEP) of leukemic cells from CLL patients included in a prospective multicenter observational study (O-CLL1-GISL protocol, clinicaltrial.gov ID:NCT00917549) were used to assess the value and reproducibility of this score. To date, 468 Binet A patients were classified as low- (0 positive marker), intermediate- (1 positive marker), or high-risk (2 or 3 positive markers) using the progression risk score. The 3-year PFS probability was 91.7%, 82.9%, and 57.4% for low-, intermediate-, and high-risk (P 0.0001) cases, respectively. These values were similar to those found in the original cohort. At Cox multivariate analysis, Rai stage, absolute lymphocyte count, progression risk score, and β-2 microglobulin maintained an independent prognostic impact on PFS. This score remained a predictor of progression when analysis was limited to 371 Rai 0 cases (P 0.0001). Finally, the cells from the different CLL risk groups showed differences in their gene expression patterns. These results confirm the ability of this progression risk score to predict PFS among Binet A patients. The utility of the score was also extended by demonstrating that it retains prognostic value when applied exclusively to Rai 0 patients. Specific transcriptional patterns were significantly associated with risk groups.

Published
2014

37. Ig V Gene Mutation Status and CD38 Expression As Novel Prognostic Indicators in Chronic Lymphocytic Leukemia

Author

Damle, R. N., Wasil, T., Fais, F., Fabio Ghiotto, Valetto, A., Allen, S. L., Buchbinder, A., Budman, D., Dittmar, K., Kolitz, J., Lichtman, S. M., Schulman, P., Vinciguerra, V. P., Rai, K. R., Ferrarini, M., and Chiorazzi, N.

Subjects
Male, B-Lymphocytes, Time Factors, Genes, Immunoglobulin, Immunology, Immunoglobulin Variable Region, Cell Biology, Hematology, CD5 Antigens, Prognosis, Leukemia, Lymphocytic, Chronic, B-Cell, Survival Analysis, Biochemistry, Immunophenotyping, Cohort Studies, Antigens, CD, immune system diseases, hemic and lymphatic diseases, Mutation, Humans, Female, Immunoglobulin Light Chains, Follow-Up Studies
Abstract

Cellular immunophenotypic studies were performed on a cohort of randomly selected IgM+ B-chronic lymphocytic leukemia (B-CLL) cases for which Ig VH and VL gene sequences were available. The cases were categorized based on V gene mutation status and CD38 expression and analyzed for treatment history and survival. The B-CLL cases could be divided into 2 groups. Those patients with unmutated V genes displayed higher percentages of CD38+ B-CLL cells (≥30%) than those with mutated V genes that had lower percentages of CD38+ cells (

Published
1999

38. Sostituzione valvolare aortica in pazienti con grave disfunzione ventricolare sinistra

Author

Bevilacqua, S, Paradossi, U, Ferrarini, M, Gamba, A, Glauber, M, Tasca, G, Senni, M, Quaini, E, Ferrazzi, P, Bevilacqua S, Paradossi U, Ferrarini M, Gamba A, Glauber M, Tasca G, Senni M, Quaini E, Ferrazzi P, Bevilacqua, S, Paradossi, U, Ferrarini, M, Gamba, A, Glauber, M, Tasca, G, Senni, M, Quaini, E, Ferrazzi, P, Bevilacqua S, Paradossi U, Ferrarini M, Gamba A, Glauber M, Tasca G, Senni M, Quaini E, and Ferrazzi P

Published
2001

40. Cardiopatia Dilatativa Post-Ischemica: Risultati a Medio Termine dell’Intervento di Rimodellamento del Ventricolo Sinistro

Author

Fino, C, Senni, M, Matteucci, S, Scuri, M, Ferrarini, M, Bevilacqua, S, Gavazzi, A, Ferrazzi, P, Fino C, Senni M, Matteucci S, Scuri M, Ferrarini M, Bevilacqua S, Gavazzi A, Ferrazzi P, Fino, C, Senni, M, Matteucci, S, Scuri, M, Ferrarini, M, Bevilacqua, S, Gavazzi, A, Ferrazzi, P, Fino C, Senni M, Matteucci S, Scuri M, Ferrarini M, Bevilacqua S, Gavazzi A, and Ferrazzi P

Published
2001

41. lncRNA profiling in early-stage chronic lymphocytic leukemia identifies transcriptional fingerprints with relevance in clinical outcome

Author

Ronchetti, D, primary, Manzoni, M, additional, Agnelli, L, additional, Vinci, C, additional, Fabris, S, additional, Cutrona, G, additional, Matis, S, additional, Colombo, M, additional, Galletti, S, additional, Taiana, E, additional, Recchia, A G, additional, Bossio, S, additional, Gentile, M, additional, Musolino, C, additional, Di Raimondo, F, additional, Grilli, A, additional, Bicciato, S, additional, Cortelezzi, A, additional, Tassone, P, additional, Morabito, F, additional, Ferrarini, M, additional, and Neri, A, additional

Published
2016
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42. Alliance Against Cancer, the network of Italian cancer centers bridging research and care

Author

De Paoli, P, Ciliberto, G, Ferrarini, M, Pelicci, P, Dellabona, P, De Lorenzo, F, Mantovani, A, Musto, P, Opocher, G, Picci, P, Ricciardi, Walter, De Maria Marchiano, Ruggero, Ricciardi W (ORCID:0000-0002-5655-688X), De Maria Marchiano (ORCID:0000-0003-2255-0583), De Paoli, P, Ciliberto, G, Ferrarini, M, Pelicci, P, Dellabona, P, De Lorenzo, F, Mantovani, A, Musto, P, Opocher, G, Picci, P, Ricciardi, Walter, De Maria Marchiano, Ruggero, Ricciardi W (ORCID:0000-0002-5655-688X), and De Maria Marchiano (ORCID:0000-0003-2255-0583)

Abstract

Alliance Against Cancer (ACC) was established in Rome in 2002 as a consortium of six Italian comprehensive cancer centers (Founders). The aims of ACC were to promote a network among Italian oncologic institutions in order to develop speci c, advanced projects in clinical and translational research. During the following years, many additional full and associate members joined ACC, that presently includes the National Institute of Health, 17 research-oriented hospitals, scienti c and patient organizations. Furthermore, in the last three years ACC underwent a reorganiza- tion process that redesigned the structure, governance and major activities. The present goal of ACC is to achieve high standards of care across Italy, to implement and harmonize principles of modern personalized and precision medicine, by developing cost e ective processes and to provide tailored information to cancer patients. We herein summarize some of the major initiatives that ACC is currently developing to reach its goal, including tumor genetic screening programs, establishment of clinical trial programs for cancer patients treated in Italian cancer centers, facili- tate their access to innovative drugs under development, improve quality through an European accreditation process (European Organization of Cancer Institutes), and develop international partnerships. In conclusion, ACC is a growing organization, trying to respond to the need of networking in Italy and may contribute signi cantly to improve the way we face cancer in Europe.

Published
2015

43. A progression-risk score to predict treatment-free survival for early stage chronic lymphocytic leukemia patients

Author

Gentile, M, primary, Shanafelt, T D, additional, Cutrona, G, additional, Molica, S, additional, Tripepi, G, additional, Alvarez, I, additional, Mauro, F R, additional, Di Renzo, N, additional, Di Raimondo, F, additional, Vincelli, I, additional, Todoerti, K, additional, Matis, S, additional, Musolino, C, additional, Fabris, S, additional, Vigna, E, additional, Levato, L, additional, Zupo, S, additional, Angrilli, F, additional, Consoli, U, additional, Festini, G, additional, Longo, G, additional, Cortelezzi, A, additional, Arcari, A, additional, Federico, M, additional, Mannina, D, additional, Recchia, A G, additional, Neri, A, additional, Kay, N E, additional, Ferrarini, M, additional, and Morabito, F, additional

Published
2015
Full Text
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44. Brief report: Inherited perforin and Fas mutations in a patient with autoimmune lymphoproliferative syndrome and lymphoma

Author

Clementi R, Dianzani U, Dupre L, Dianzani I, Cometa A, Chiocchetti A, Sabbadini MG, Rugarli C, Maccario R, Locatelli F, Danesino C, Ferrarini M, Bregni M., DAGNA , LORENZO, PONZONI , MAURILIO, CICERI , FABIO, Clementi, R, Dagna, Lorenzo, Dianzani, U, Dupre, L, Dianzani, I, Ponzoni, Maurilio, Cometa, A, Chiocchetti, A, Sabbadini, Mg, Rugarli, C, Ciceri, Fabio, Maccario, R, Locatelli, F, Danesino, C, Ferrarini, M, and Bregni, M.

Abstract

27-year-old man with the autoimmune lymphoproliferative syndrome and a large-B-cell lymphoma had heterozygous mutations in the Fas and perforin (Prf1) genes. The Fas mutation was inherited from his healthy father and was also carried by his healthy brother, whereas the Prf1 mutation was inherited from his healthy mother. The combined effect of the two mutant genes may have contributed to the development of the autoimmune lymphoproliferative syndrome and lymphoma in this patient. A 27-year-old man with the autoimmune lymphoproliferative syndrome and a large-B-cell lymphoma had heterozygous mutations in the Fas and perforin (Prf1) genes. The Fas mutation was inherited from his healthy father and was also carried by his healthy brother, whereas the Prf1 mutation was inherited from his healthy mother. The combined effect of the two mutant genes may have contributed to the development of the autoimmune lymphoproliferative syndrome and lymphoma in this patient.

Published
2004

46. The LUPIN detector: supporting least intrusive beam monitoring technique through neutron detection

Author

Manessi, G P, Silari, M, Welsch, C, Caresana, M, and Ferrarini, M

Subjects
Physics::Accelerator Physics, Accelerators and Storage Rings
Abstract

The Long interval, Ultra-wide dynamic Pile-up free Neutron rem counter (LUPIN) is a novel detector initially developed for radiation protection purposes, specifically conceived for applications in pulsed neutron fields. The detector has a measurement capability varying over many orders of neutron burst intensity, from a single neutron up to thousands of interactions for each burst, without showing any saturation effect. Whilst LUPIN has been developed for applications in the radiation protection fields, its unique properties make it also well suited to support other beam instrumentation. In this contribution, the design of LUPIN is presented in detail and results from measurements carried out in different facilities summarize its main characteristics. Its potential use as beam loss monitor (BLM) and complementary detector for non-invasive beam monitoring purposes (e.g. to complement a monitor based on proton beam “halo” detection) in medical accelerators is then examined. In the context of its application as a beam loss monitor for hadrontherapy accelerators, results of measurements performed at the Italian National Centre of Hadrontherapy (CNAO) are presented and analysed.

Published
2013

49. Pathologic findings in lymph nodes in a patient with autoimmune lymphoproliferative syndrome (ALPS) who developed a histiocyte-rich/T-cell-rich B cell lymphoma: Evolution during a 20-year follow-up

Author

DAGNA , LORENZO, PONZONI , MAURILIO, Tantardini F, Dianzani U, Dianzani I, Baldissera E, Sanvito F, Freschi M, Sabbadini MG, Rugarli C, Ferrarini M., Dagna, Lorenzo, Ponzoni, Maurilio, Tantardini, F, Dianzani, U, Dianzani, I, Baldissera, E, Sanvito, F, Freschi, M, Sabbadini, Mg, Rugarli, C, and Ferrarini, M.

Published
2002

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