85 results on '"Lalli L."'
Search Results
2. 885P Different patterns of treatment failure between p16+ and p16- patients affected by oropharyngeal carcinoma (OPC) undergoing (chemo)radiation
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Gili, R., Bossi, P., Lalli, L., Licitra, L.F.L., Maddalo, M., Cacicedo Fernandez de Bobadilla, J., facchinetti, N., Garcia Castano, A., Mesia Nin, R., Bonomo, P., Sanguineti, G., Franco, P., Argiris, A., Psyrri, A., and Orlandi, E.
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- 2024
- Full Text
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3. miR-146a-5p impairs melanoma resistance to kinase inhibitors by targeting COX2 and regulating NFkB-mediated inflammatory mediators
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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.]
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- 2020
4. Physical mechanisms associated with the soundscape: Trevi fountain case study
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Enza De Lauro, Martino, S., Falanga, M., Tedeschini Lalli, L., Velichova Daniela, de Lauro, E., de Martino, S., Falanga, M., and Tedeschini Lalli, L.
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Acoustic field ,Fountain sound ,Independent Component Analysis ,Soundscape ,Independent Component Analysi - Abstract
We investigate the soundscape around the Trevi fountain (Rome) acquired by means of several synchronized microphones with the aim to individuate the signature of the fountain from any other external disturbance. The present result is a complete separation of the sound emitted by the fountain from an external source associated with flying swallows. Thus, we introduce a methodology for the identification of medium and long-term changes in the soundscape, in order to promote suitable strategies for its conservation and protection.
- Published
- 2020
5. Math and art in prison a collaborative effort across the ocean
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Havens C., Tedeschini Lalli L., velichova Daniela, Velichova, Daniela, Havens, C., and Tedeschini Lalli, L.
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Inclusive memory ,Sierpinski triangle - Abstract
A story of inclusiveness and collaboration through mathematics and art. A inmate of a North American prison taught himself mathematics, then went on to study more and more and contacted the author. He then planned and realized together with other inmates, a piece of art reproducing a medieval pattern as studied mathematically. As the art is modular, several other inmates could collaborate. The math was necessary as a nontrivial stimulus, and so was the piece of art.
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- 2020
6. 491P Lipid-engulfed macrophages at the root of gut carcinogenesis
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Daveri, E., primary, Sorrentino, L., additional, Vergani, B., additional, Cattaneo, L., additional, Lalli, L., additional, Cosimelli, M., additional, Vitellaro, M., additional, Huber, V., additional, Cova, A., additional, Gariboldi, M., additional, Belfiore, A., additional, Leone, B.E., additional, Milione, M., additional, and Rivoltini, L., additional
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- 2021
- Full Text
- View/download PDF
7. 1901P Specific dynamic changes of peripheral blood immune profile (PBIP) associate with clinical response to nivolumab (NIVO) in patients (pts) with metastatic renal cell carcinoma (mRCC): The I-RENE trial (meet-URO 8)
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Verzoni, E., Procopio, G., Bottiglieri, A., Stellato, M., Rametta, A., Zucali, P.A., Perrucci, B., G. fornarini, Buti, S., Maruzzo, M., Cova, A., Squarcina, P., Lalli, L., Mereu, A., Cerioli, N., Agnelli, L., Todoerti, K., Busico, A., Rivoltini, L., and Huber, V.
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- 2023
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8. NUTRITIONAL STATUS IN PAEDIATRIC CANCER PATIENTS AFFECTED BY SARCOMA: A 5-YEAR RETROSPECTIVE ANALYSIS
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Della Valle, S., Armao, J., Gavazzi, C., Lalli, L., Massimino, M., Meazza, C., and Mulazzani, G.E.G.
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- 2020
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9. Nutritional status and body composition assessment in patients with a new diagnosis of advanced solid tumour: Exploratory comparison of computed tomography and bioelectrical impedance analysis
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Casirati, A., primary, Vandoni, G., additional, Della Valle, S., additional, Greco, G., additional, Platania, M., additional, Colatruglio, S., additional, Lalli, L., additional, and Gavazzi, C., additional
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- 2021
- Full Text
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10. Analysis of an aluminum single crystal with unstable initial orientation (001) [110] in channel die compression
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Becker, R., Butler, J. F., Hu, H., and Lalli, L. A.
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- 1991
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11. Experimental assessment of structure and property predictions during hot working
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Lalli, L. A. and DeArdo, A. J.
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- 1990
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12. P2.04-11 An IL-8/IFN-gammma/NLR Plasma Score to Predict Nivolumab Efficacy in Patients with NSCLC
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Passiglia, F., primary, Russo, A., additional, Ferro, S., additional, Lalli, L., additional, Cova, A., additional, Soto Parra, H., additional, Rivoltini, L., additional, and Huber, V., additional
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- 2018
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13. Potent natural killer (NK) and myeloid blood cell remodeling by cabozantinib (Cabo) in pre-treated metastatic renal cell carcinoma (mRCC) patients (pts)
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Verzoni, E., primary, Ferro, S., additional, Procopio, G., additional, Cova, A., additional, Ratta, R., additional, Raimondi, A., additional, Sepe, P., additional, Squarcina, P., additional, Lalli, L., additional, Huber, V., additional, Rinchai, D., additional, Bedognetti, D., additional, and Rivoltini, L., additional
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- 2018
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14. 882P - Potent natural killer (NK) and myeloid blood cell remodeling by cabozantinib (Cabo) in pre-treated metastatic renal cell carcinoma (mRCC) patients (pts)
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Verzoni, E., Ferro, S., Procopio, G., Cova, A., Ratta, R., Raimondi, A., Sepe, P., Squarcina, P., Lalli, L., Huber, V., Rinchai, D., Bedognetti, D., and Rivoltini, L.
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- 2018
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15. Sviluppo Di Recettori Biomimetici per la determinazione di pesticidi in matrici alimentari
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Mascini, Marcello, Sergi, Manuel, DEL CARLO, Michele, Lalli, L., Compagnone, Dario, and Year
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- 2006
16. Studio della realizzabilit... di un modello per la localizzazione di sorgenti sonore su un sistema DSP LOW COST
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Marani M., Bertini G., Lalli L., and Jacovone M.
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Acoustic source - Abstract
An abstract is not avaiable
- Published
- 1997
17. Adaptation of an Asperity Ploughing Model to Measured Roll Topographies.
- Author
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Lalli, L. A., Malkani, H. G., Sheu, S., Ghosh, S., Castro, J. C., and Lee, J. K.
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SURFACE roughness , *SURFACES (Technology) , *SIMULATION methods & models , *ALUMINUM alloys , *DEFORMATIONS (Mechanics) , *MECHANICS (Physics) - Abstract
A previously published asperity ploughing model has been adapted in order to approximate the measured as-ground roll surface topography. The model is then integrated with classical cold rolling plastic deformation equations including coupling to the lubricant film evolution through the roll bite. The friction distribution through the roll bite is thus a function of the specific details of the roll surface topography as well as the process parameters. predictions of roll force, torque and forward slip as well as sliding distance and volume of metal swept out by the asperities are then made and compared to experimental measurements for an aluminum alloy rolled on a laboratory rolling mill. © 2004 American Institute of Physics [ABSTRACT FROM AUTHOR]
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- 2004
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18. Texture Evolution in Channel-Die Compression Part II: Effects of Grains Which Shear
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Becker, R., primary and Lalli, L. A., additional
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- 1991
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19. TEXTURE EVOLUTION IN CHANNEL-DIE COMPRESSION PART II: EFFECTS OF GRAINS WHICH SHEAR.
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BECKER, R. and LALLI, L. A.
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- 1991
20. Effects of thermomechanical history on hardness of aluminium
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Sample, V. M. and Lalli, L. A.
- Abstract
A viscoplastic constitutive model with an evolving internal state variable, called hardness, has been developed for commercially pure aluminium. One application of such a constitutive model is in process modelling where hardness distributions may be predicted throughout the workpiece. This paper assesses the accuracy with which microhardness measurements of quenched specimens correlate with the hardness predicted by the constitutive model for various imposed thermomechanical histories. Using axisymmetric compression, different hardness values are achieved by various tests, both underdeveloped (increasing hardness) and overdeveloped (decreasing hardness) structures being produced during deformation. The steady state flow stress and hardness for a particular strain rate and temperature may be achieved with less strain by first deforming at a high strain rate and then decreasing the strain rate. The constitutive model accurately predicts the amount of prestrain required at the higher strain rate. Differing initial structures are achieved by using as-extruded and fully recrystallized materials. Using microhardness measurements as a method of characterizing the initial structure, the constitutive model is able to predict the subsequent flow curve and evolution of microhardness.MST/572
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- 1987
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21. An Analytical Rolling Model Including Through Thickness Shear Stress Distributions
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Lalli, L. A.
- Abstract
An extension of the slab method of analysis as applied to rolling is presented. The von Mises yield criterion, including shear stresses, is written in terms of the frictional boundary condition at the roll-metal interface. Utilizing simplifying assumptions, an expression results which can then be combined with the equilibrium equations so that analytical expressions for roll force, torque, and extrusion ratio result. Whereas the concept is based on the same physical principles inherent in Orowan’s analysis of rolling, the slab method of analysis used here is less rigorous but has the advantage that analytic expressions are obtainable. Therefore, the equations are applicable for mill control purposes. Furthermore, the analytic expressions can be inverted so that estimates of friction and flow stress may be obtained by roll force and extrusion ratio measurements. In hot rolling, the temperature of the sheet may then be inferred from this value of flow stress, if the material’s flow stress is a known function of temperature and strain rate. Thus, this provides the capability to eventually control sheet temperatures and lubrication conditions by adjusting coolant sprays. Theoretical verification is discussed by comparison with Orowan’s theory and finite element analysis. Accuracy is discussed in terms of hot continuous mill and laboratory reversing mill data.
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- 1984
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22. Erratum: “An Analytical Rolling Model Including Through Thickness Shear Stress Distributions” (Journal of Engineering Materials and Technology, 1984, 106, pp. 1–8)
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Lalli, L. A., primary
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- 1984
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23. miR-146a-5p impairs melanoma resistance to kinase inhibitors by targeting COX2 and regulating NFkB-mediated inflammatory mediators
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Elisabetta Ferrero, Marina Ferrarini, Chiara Gargiuli, Viviana Vallacchi, Michele Del Vecchio, Macarena Gomez Lira, Eriomina Shahaj, Mara Cossa, Elena Tamborini, Barbara Vergani, Luca Lalli, Mario Santinami, Barbara Valeri, Monica Rodolfo, Gianfrancesco Gallino, Simona Frigerio, Veronica Huber, Marialuisa Sensi, Licia Rivoltini, Elisabetta Vergani, Lorenza Di Guardo, Matteo Dugo, Ilaria Mattavelli, Biagio Eugenio Leone, 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, and Vallacchi, V
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Proto-Oncogene Proteins B-raf ,BRAF/MEK inhibitors ,medicine.medical_treatment ,lcsh:Medicine ,Drug resistance ,Models, Biological ,Biochemistry ,Targeted therapy ,03 medical and health sciences ,0302 clinical medicine ,miR-146a-5p ,Cell Line, Tumor ,microRNA ,medicine ,Humans ,Epigenetics ,BRAF/MEK inhibitor ,lcsh:QH573-671 ,Extracellular Signal-Regulated MAP Kinases ,Melanoma ,Protein Kinase Inhibitors ,Molecular Biology ,030304 developmental biology ,Mitogen-Activated Protein Kinase Kinases ,0303 health sciences ,Kinase ,business.industry ,lcsh:Cytology ,Research ,lcsh:R ,NF-kappa B ,Cell Biology ,medicine.disease ,Gene Expression Regulation, Neoplastic ,Gene expression profiling ,MicroRNAs ,Cyclooxygenase 2 ,Drug Resistance, Neoplasm ,Apoptosis ,030220 oncology & carcinogenesis ,Cancer research ,Inflammation Mediators ,Melanoma resistance ,business ,Proto-Oncogene Proteins c-akt ,COX2 ,Signal Transduction - 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. Graphical Abstract
- Published
- 2020
24. The Listening of two Piazzas in Rome
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Paola Magrone, Laura Tedeschini Lalli, Magrone, P., and Tedeschini Lalli, L.
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Soundscape ,water sound ,History ,Acoustics and Ultrasonics ,soundscape ,urban spaces ,narrative documentation ,Management, Monitoring, Policy and Law ,lcsh:TD1-1066 ,Visual arts ,recorded documentation ,Urban Studies ,soundscape, recorded documentation, narrative documentation, water sound, urban spaces ,Active listening ,lcsh:Environmental technology. Sanitary engineering - Abstract
We report on the soundscape of Piazza Fontana di Trevi and Piazza Testaccio, gathering places in Rome. Soundscape is a realm of research about the interactions between cultural, cognitive and physical aspects of sound in space, still yielding interesting open questions.We performed perceptive surveys and instrument measurements, carefully spatialized in both cases. The perceptive results concern the recognizability of a particular sound in a conglomerate of sounds across an urban space and the sense of bodily orientation given by sound. They are proposed via verbal narratives and original visualizations of the place. We then use computer models to validate some of the perceived (unexpected) spatial perceptive features, by a ray-tracer simulation. The point of the paper is in fact to compare methods about sound in space, starting from perceptive evaluations, to drive objective analysis and collection of data toward new aspects, and always pursuing spatialization of data.
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- 2018
25. Astratto e materico per una matematica inclusiva. Esperienza di ricerca, didattica e museografia
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Alessandra Carlini, Laura Tedeschini Lalli, Poce, Antonella, Tedeschini Lalli, L, Carlini, A., Poce A., Carlini, Alessandra, and TEDESCHINI LALLI, Laura
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Matematica visuale, immaginario scientifico, tassellazioni in architettura , museografia, diffusione ,museografia, diffusione scientifica, allestimento, progettazione - Abstract
Esponiamo l'esperienza di un lungo percorso attraverso didattica universitaria, ricerca, elaborazione di lavori degli studenti, e poi mostre internazionali di divulgazione scientifica, didattica nelle scuole, passeggiate scientifiche in città, tutte attraverso un unico tema. Un percorso le cui tappe si sono certamente nutrite una con l'altra; tutte, vertono attorno al tema della ripetizione di pattern grafici in arabeschi o motivi ornamentali ed al suo trattamento matematico, che ha trovato un assetto completo solo agli inizi del Novecento. Ad accompagnare l'immaginario scientifico, una costante attualizzazione dell'uso e del concetto di patrimonio culturale.
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- 2021
26. Impact of baseline and on-treatment glycemia on everolimus-exemestane efficacy in patients with hormone receptor-positive advanced breast cancer (EVERMET)
- Author
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Giovanna Catania, Fabio Puglisi, Dario Trapani, Federico Nichetti, Lorenzo Gerratana, Alessandra Fabi, Marika Cinausero, Michela Palleschi, Agnese Losurdo, Filippo Montemurro, Enrico Cortesi, Rebecca Pedersini, Andrea Rocca, Carlo Alberto Giorgi, Grazia Arpino, Gaia Griguolo, Lorenzo Castagnoli, Giancarlo Pruneri, Andrea Michelotti, Giuseppe Curigliano, Valentina Guarneri, Francesca Ligorio, Giovanni Randon, Daniele Generali, Emanuela Ferraro, Luca Moscetti, A. Fabbri, Arta Ajazi, Elisa Agostinetto, Claudia De Angelis, Amelia Vantaggiato, Carmen G. Rea, Antonio Marra, Filippo de Braud, Nicla La Verde, Debora Basile, Lucia Del Mastro, Luigi Mariani, Salvatore Lo Vullo, Mariangela Ciccarese, Anna Moretti, Simone Scagnoli, Claudio Vernieri, Ottavia Bernocchi, Chiara Molinelli, Andrea Milani, Luca Lalli, Vernieri, C., Nichetti, F., Lalli, L., Moscetti, L., Giorgi, C. A., Griguolo, G., Marra, A., Randon, G., Rea, C. G., Ligorio, F., Scagnoli, S., De Angelis, C., Molinelli, C., Fabbri, A., Ferraro, E., Trapani, D., Milani, A., Agostinetto, E., Bernocchi, O., Catania, G., Vantaggiato, A., Palleschi, M., Moretti, A., Basile, D., Cinausero, M., Ajazi, A., Castagnoli, L., Vullo, S. L., Gerratana, L., Puglisi, F., La Verde, N., Arpino, G., Rocca, A., Ciccarese, M., Pedersini, R., Fabi, A., Generali, D., Losurdo, A., Montemurro, F., Curigliano, G., Del Mastro, L., Michelotti, A., Cortesi, E., Guarneri, V., Pruneri, G., Mariani, L., De Braud, F., Vernieri, Claudio, Nichetti, Federico, Lalli, Luca, Moscetti, Luca, Giorgi, Carlo Alberto, Griguolo, Gaia, Marra, Antonio, Randon, Giovanni, Rea, Carmen G, Ligorio, Francesca, Scagnoli, Simone, De Angelis, Claudia, Molinelli, Chiara, Fabbri, Agnese, Ferraro, Emanuela, Trapani, Dario, Milani, Andrea, Agostinetto, Elisa, Bernocchi, Ottavia, Catania, Giovanna, Vantaggiato, Amelia, Palleschi, Michela, Moretti, Anna, Basile, Debora, Cinausero, Marika, Ajazi, Arta, Castagnoli, Lorenzo, Lo Vullo, Salvatore, Gerratana, Lorenzo, Puglisi, Fabio, La Verde, Nicla, Arpino, Grazia, Rocca, Andrea, Ciccarese, Mariangela, Pedersini, Rebecca, Fabi, Alessandra, Generali, Daniele, Losurdo, Agnese, Montemurro, Filippo, Curigliano, Giuseppe, Del Mastro, Lucia, Michelotti, Andrea, Cortesi, Enrico, Guarneri, Valentina, Pruneri, Giancarlo, Mariani, Luigi, and de Braud, Filippo
- Subjects
0301 basic medicine ,Oncology ,Blood Glucose ,Cancer Research ,Receptor, ErbB-2 ,medicine.medical_treatment ,metabolism everolimus ,chemistry.chemical_compound ,Phosphatidylinositol 3-Kinases ,0302 clinical medicine ,ErbB-2 ,Exemestane ,Retrospective Studie ,Antineoplastic Combined Chemotherapy Protocols ,Receptors ,Hyperinsulinemia ,drug therapy breast neoplasms ,Receptors, Estrogen ,Hormone receptor ,030220 oncology & carcinogenesis ,Female ,Breast Neoplasm ,medicine.drug ,Receptor ,Human ,medicine.medical_specialty ,medicine.drug_class ,Breast Neoplasms ,genetics breast neoplasms ,03 medical and health sciences ,Diabetes mellitus ,Internal medicine ,medicine ,Humans ,Everolimus ,Retrospective Studies ,Aromatase inhibitor ,Antineoplastic Combined Chemotherapy Protocol ,blood glucose breast neoplasms ,Androstadiene ,business.industry ,Insulin ,Cancer ,medicine.disease ,Estrogen ,Androstadienes ,030104 developmental biology ,chemistry ,Phosphatidylinositol 3-Kinase ,business - Abstract
Purpose: The mTOR complex C1 (mTORC1) inhibitor everolimus in combination with the aromatase inhibitor exemestane is an effective treatment for patients with hormone receptor—positive (HR+), HER2-negative (HER2−), advanced breast cancer (HR+/HER2− aBC). However, everolimus can cause hyperglycemia and hyperinsulinemia, which could reactivate the PI3K/protein kinase B (AKT)/mTORC1 pathway and induce tumor resistance to everolimus. Experimental Design: We conducted a multicenter, retrospective, Italian study to investigate the impact of baseline and on-treatment (i.e., during first 3 months of therapy) blood glucose levels on progression-free survival (PFS) in patients with HR+/HER2− aBC treated with everolimus-exemestane. Results: We evaluated 809 patients with HR+/HER2− aBC treated with everolimus-exemestane as any line of therapy for advanced disease. When evaluated as dichotomous variables, baseline and on-treatment glycemia were not significantly associated with PFS. However, when blood glucose concentration was evaluated as a continuous variable, a multivariable model accounting for clinically relevant patient- and tumor-related variables revealed that both baseline and on-treatment glycemia are associated with PFS, and this association is largely attributable to their interaction. In particular, patients who are normoglycemic at baseline and experience on-treatment diabetes have lower PFS compared with patients who are already hyperglycemic at baseline and experience diabetes during everolimus-exemestane therapy (median PFS, 6.34 vs. 10.32 months; HR, 1.76; 95% confidence interval, 1.15–2.69; P = 0.008). Conclusions: The impact of on-treatment glycemia on the efficacy of everolimus-exemestane therapy in patients with HR+/HER2− aBC depends on baseline glycemia. This study lays the foundations for investigating novel therapeutic approaches to target the glucose/insulin axis in combination with PI3K/AKT/mTORC1 inhibitors in patients with HR+/HER2− aBC.
- Published
- 2021
27. Development of a Nomogram Predicting the Risk of Persistence/Recurrence of Cervical Dysplasia
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Giorgio Bogani, Luca Lalli, Francesco Sopracordevole, Andrea Ciavattini, Alessandro Ghelardi, Tommaso Simoncini, Francesco Plotti, Jvan Casarin, Maurizio Serati, Ciro Pinelli, Alice Bergamini, Barbara Gardella, Andrea Dell’Acqua, Ermelinda Monti, Paolo Vercellini, Innocenza Palaia, Giorgia Perniola, Margherita Fischetti, Giusi Santangelo, Alice Fracassi, Giovanni D’Ippolito, Lorenzo Aguzzoli, Vincenzo Dario Mandato, Luca Giannella, Cono Scaffa, Francesca Falcone, Chiara Borghi, Mario Malzoni, Andrea Giannini, Maria Giovanna Salerno, Viola Liberale, Biagio Contino, Cristina Donfrancesco, Michele Desiato, Anna Myriam Perrone, Giulia Dondi, Pierandrea De Iaco, Simone Ferrero, Giuseppe Sarpietro, Maria G. Matarazzo, Antonio Cianci, Stefano Cianci, Sara Bosio, Simona Ruisi, Lavinia Mosca, Raffaele Tinelli, Rosa De Vincenzo, Gian Franco Zannoni, Gabriella Ferrandina, Marco Petrillo, Giampiero Capobianco, Salvatore Dessiole, Annunziata Carlea, Fulvio Zullo, Barbara Muschiato, Stefano Palomba, Stefano Greggi, Arsenio Spinillo, Fabio Ghezzi, Nicola Colacurci, Roberto Angioli, Pierluigi Benedetti Panici, Ludovico Muzii, Giovanni Scambia, Francesco Raspagliesi, Violante Di Donato, Bogani, G., Lalli, L., Sopracordevole, F., Ciavattini, A., Ghelardi, A., Simoncini, T., Plotti, F., Casarin, J., Serati, M., Pinelli, C., Bergamini, A., Gardella, B., Dell'Acqua, A., Monti, E., Vercellini, P., Palaia, I., Perniola, G., Fischetti, M., Santangelo, G., Fracassi, A., D'Ippolito, G., Aguzzoli, L., Mandato, V. D., Giannella, L., Scaffa, C., Falcone, F., Borghi, C., Malzoni, M., Giannini, A., Salerno, M. G., Liberale, V., Contino, B., Donfrancesco, C., Desiato, M., Perrone, A. M., Dondi, G., De Iaco, P., Ferrero, S., Sarpietro, G., Matarazzo, M. G., Cianci, A., Cianci, S., Bosio, S., Ruisi, S., Mosca, L., Tinelli, R., De Vincenzo, R., Zannoni, G. F., Ferrandina, G., Petrillo, M., Capobianco, G., Dessiole, S., Carlea, A., Zullo, F., Muschiato, B., Palomba, S., Greggi, S., Spinillo, A., Ghezzi, F., Colacurci, N., Angioli, R., Panici, P. B., Muzii, L., Scambia, G., Raspagliesi, F., Di Donato, V., Bogani, Giorgio, Lalli, Luca, Sopracordevole, Francesco, Ciavattini, Andrea, Ghelardi, Alessandro, Simoncini, Tommaso, Plotti, Francesco, Casarin, Jvan, Serati, Maurizio, Pinelli, Ciro, Bergamini, Alice, Gardella, Barbara, Dell'Acqua, Andrea, Monti, Ermelinda, Vercellini, Paolo, Palaia, Innocenza, Perniola, Giorgia, Fischetti, Margherita, Santangelo, Giusi, Fracassi, Alice, D'Ippolito, Giovanni, Aguzzoli, Lorenzo, Mandato, Vincenzo Dario, Giannella, Luca, Scaffa, Cono, Falcone, Francesca, Borghi, Chiara, Malzoni, Mario, Giannini, Andrea, Salerno, Maria Giovanna, Liberale, Viola, Contino, Biagio, Donfrancesco, Cristina, Desiato, Michele, Perrone, Anna Myriam, Dondi, Giulia, De Iaco, Pierandrea, Ferrero, Simone, Sarpietro, Giuseppe, Matarazzo, Maria G, Cianci, Antonio, Cianci, Stefano, Bosio, Sara, Ruisi, Simona, Mosca, Lavinia, Tinelli, Raffaele, De Vincenzo, Rosa, Zannoni, Gian Franco, Ferrandina, Gabriella, Petrillo, Marco, Capobianco, Giampiero, Dessiole, Salvatore, Carlea, Annunziata, Zullo, Fulvio, Muschiato, Barbara, Palomba, Stefano, Greggi, Stefano, Spinillo, Arsenio, Ghezzi, Fabio, Colacurci, Nicola, Angioli, Roberto, Benedetti Panici, Pierluigi, Muzii, Ludovico, Scambia, Giovanni, Raspagliesi, Francesco, and Di Donato, Violante
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Pharmacology ,conization ,HPV ,Settore MED/40 - GINECOLOGIA E OSTETRICIA ,recurrence ,Infectious Diseases ,Drug Discovery ,Immunology ,LEEP ,Pharmacology (medical) ,cervical dysplasia - Abstract
Background: Cervical dysplasia persistence/recurrence has a great impact on women’s health and quality of life. In this study, we investigated whether a prognostic nomogram may improve risk assessment after primary conization. Methods: This is a retrospective multi-institutional study based on charts of consecutive patients undergoing conization between 1 January 2010 and 31 December 2014. A nomogram assessing the importance of different variables was built. A cohort of patients treated between 1 January 2015 and 30 June 2016 was used to validate the nomogram. Results: A total of 2966 patients undergoing primary conization were analyzed. The median (range) patient age was 40 (18–89) years. At 5-year of follow-up, 6% of patients (175/2966) had developed a persistent/recurrent cervical dysplasia. Median (range) recurrence-free survival was 18 (5–52) months. Diagnosis of CIN3, presence of HR-HPV types, positive endocervical margins, HPV persistence, and the omission of HPV vaccination after conization increased significantly and independently of the risk of developing cervical dysplasia persistence/recurrence. A nomogram weighting the impact of all variables was built with a C-Index of 0.809. A dataset of 549 patients was used to validate the nomogram, with a C-index of 0.809. Conclusions: The present nomogram represents a useful tool for counseling women about their risk of persistence/recurrence after primary conization. HPV vaccination after conization is associated with a reduced risk of CIN2+.
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- 2022
28. Catalogazione di manoscritti greci: l'esperienza napoletana
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FORMENTIN, MARIA ROSA, B. Cenni, C.M.F. Lalli, L. Magionami, and Formentin, MARIA ROSA
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catalogazione codici greci - Published
- 2007
29. Metamorphoses: Sudden jumps in Basin Boundaries
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James A. Yorke, Laura Tedeschini-Lalli, Kathleen T. Alligood, ALLIGOOD K., T, TEDESCHINI LALLI, L, TEDESCHINI LALLI, Laura, and Yorke, J. A.
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Plane (geometry) ,planar dissipative systems ,Mathematical analysis ,fractal basin boundary ,Boundary (topology) ,58F12 ,70K50 ,Statistical and Nonlinear Physics ,Geometry ,homoclinic tangency ,Manifold ,Attractor ,Jump ,Homoclinic orbit ,Diffeomorphism ,Physics::Atmospheric and Oceanic Physics ,Mathematical Physics ,Saddle ,Mathematics - Abstract
In some invertible maps of the plane that depend on a parameter, boundaries of basins of attraction are extremely sensitive to small changes in the parameter. A basin boundary can jump suddenly, and, as it does, change from being smooth to fractaL Such changes are called basin boundary metamorphoses. We prove (under certain non-degeneracy assumptions) that a metamorphosis occurs when the stable and unstable manifolds of a periodic saddle on the boundary undergo a homoclinic tangency.
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- 1991
30. Response to: Correspondence on 'Predicting the risk of nodal disease with histological and molecular features in endometrial cancer: the prospective PROME trial' by Aznar et al.
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Bogani G, Lalli L, Casarin J, Ghezzi F, Chiappa V, Fanfani F, Scambia G, and Raspagliesi F
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- Humans, Female, Lymphatic Metastasis, Prospective Studies, Endometrial Neoplasms pathology, Endometrial Neoplasms genetics
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Competing Interests: Competing interests: None declared.
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- 2024
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31. Predicting the Risk of nOdal disease with histological and Molecular features in Endometrial cancer: the prospective PROME trial.
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Bogani G, Lalli L, Casarin J, Ghezzi F, Chiappa V, Fanfani F, Scambia G, and Raspagliesi F
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- Humans, Female, Middle Aged, Prospective Studies, Aged, Adult, Neoplasm Staging, Sentinel Lymph Node Biopsy, Aged, 80 and over, Lymph Nodes pathology, Lymph Nodes surgery, Carcinoma, Endometrioid pathology, Carcinoma, Endometrioid genetics, Carcinoma, Endometrioid surgery, Tumor Suppressor Protein p53 genetics, Endometrial Neoplasms pathology, Endometrial Neoplasms genetics, Endometrial Neoplasms surgery, Lymphatic Metastasis
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Objective: To assess the role of histopathological and molecular features in predicting the risk of nodal metastases in apparent early-stage endometrial cancer patients undergoing sentinel node mapping., Methods: This is a prospective trial. Consecutive patients with apparent early-stage endometrial cancer, undergoing laparoscopic hysterectomy, bilateral salpingo-oophorectomy, and sentinel node mapping, were enrolled. Histological and molecular features were used to predict the node positivity., Results: Charts of 223 apparent early-stage endometrial cancer patients were included in this study. Four (1.8%) patients were excluded from this study due to the lack of data about molecular features. Additionally, nine (4%) patients did not meet the inclusion criteria (due to the presence of peritoneal carcinomatosis or bulky nodes (the presence of p53 abnormality correlated with the presence of advanced stage disease (p<0.001)). The study population included 178 (84.8%) and 32 (15.2%) patients with endometrioid and non-endometrioid endometrial cancer, respectively. According to pathological uterine risk factors, 93 (44.3%), 45 (21.4%), 40 (19.1%), and 32 (15.2%) were classified as low, intermediate, intermediate-high, and high-risk, respectively. Using the surrogate molecular classification, 10 (4.8%), 42 (20%), 57 (27.1%), and 101 (48.1%) were included in the POLE mutated, p53 abnormal, MMRd/MSI-H, and NSMP, respectively. Overall, 41 (19.5%) patients were detected with positive nodes. Molecular features were not associated with the risk of having nodal metastases (OR 1.03, 95% CI 0.21 to 5.05, p=0.969 for POLE mutated; OR 0.788, 95% CI 0.32 to 1.98, p=0.602 for p53 abnormal; OR 1.14, 95% CI 0.53 to 2.42, p=0.733 for MMRd/MSI-H). At multivariable analysis, only deep myometrial invasion (OR 3.318, 95% CI 1.357 to 8.150, p=0.009) and lymphovascular space invasion (OR 6.584, 95% CI 2.663 to 16.279, p<0.001) correlated with the increased risk of positive nodes., Conclusion: Our data suggest that molecular classification does not seem useful to tailor the need of nodal dissection in apparent early-stage endometrial cancer. p53 abnormality predicts the risk of having advanced disease at presentation. Further external validation is needed., Clinical Trial Registration: NCT05793333., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2024. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2024
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32. Spatial distribution of tumour immune infiltrate predicts outcomes of patients with high-risk soft tissue sarcomas after neoadjuvant chemotherapy.
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Pasquali S, Vallacchi V, Lalli L, Collini P, Barisella M, Romagosa C, Bague S, Coindre JM, Dei Tos AP, Palmerini E, Quagliuolo V, Martin-Broto J, Lopez-Pousa A, Grignani G, Blay JY, Beveridge RD, Casiraghi E, Brich S, Renne SL, Bergamaschi L, Vergani B, Sbaraglia M, Casali PG, Rivoltini L, Stacchiotti S, and Gronchi A
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- Humans, Female, Male, Prognosis, Middle Aged, Adult, Aged, Treatment Outcome, Tumor Microenvironment immunology, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Biomarkers, Tumor, Immunohistochemistry, Neoadjuvant Therapy, Sarcoma drug therapy, Sarcoma mortality, Sarcoma immunology, Sarcoma pathology, Lymphocytes, Tumor-Infiltrating immunology, Lymphocytes, Tumor-Infiltrating metabolism
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Background: Anthracycline-based neoadjuvant chemotherapy (NAC) may modify tumour immune infiltrate. This study characterized immune infiltrate spatial distribution after NAC in primary high-risk soft tissue sarcomas (STS) and investigate association with prognosis., Methods: The ISG-STS 1001 trial randomized STS patients to anthracycline plus ifosfamide (AI) or a histology-tailored (HT) NAC. Four areas of tumour specimens were sampled: the area showing the highest lymphocyte infiltrate (HI) at H&E; the area with lack of post-treatment changes (highest grade, HG); the area with post-treatment changes (lowest grade, LG); and the tumour edge (TE). CD3, CD8, PD-1, CD20, FOXP3, and CD163 were analyzed at immunohistochemistry and digital pathology. A machine learning method was used to generate sarcoma immune index scores (SIS) that predict patient disease-free and overall survival (DFS and OS)., Findings: Tumour infiltrating lymphocytes and PD-1+ cells together with CD163+ cells were more represented in STS histologies with complex compared to simple karyotype, while CD20+ B-cells were detected in both these histology groups. PD-1+ cells exerted a negative prognostic value irrespectively of their spatial distribution. Enrichment in CD20+ B-cells at HI and TE areas was associated with better patient outcomes. We generated a prognostic SIS for each tumour area, having the HI-SIS the best performance. Such prognostic value was driven by treatment with AI., Interpretation: The different spatial distribution of immune populations and their different association with prognosis support NAC as a modifier of tumour immune infiltrate in STS., Funding: Pharmamar; Italian Ministry of Health [RF-2019-12370923; GR-2016-02362609]; 5 × 1000 Funds-2016, Italian Ministry of Health; AIRC Grant [ID#28546]., Competing Interests: Declaration of interests Sandro Pasquali reports institutional research funds from Pharmamar, Ikena Oncology, and ASTX Pharmaceutical. Cleofe Romagosa reports institutional research funds from Pharmamar. Angelo Paolo Dei Tos reports institutional research funds from Pharmamar. Javier Martin-Broto reports institutional research funds from Pharmamar, Adaptimmune, Amgen, AROG, Bayer, Blueprint, BMS, Celgene, Daiichi Sankyo, Deciphera, Eisai, Forma, GSK, IMMIX Biopharma, Karyopharm, Lilly, LIXTE, Nektar, Novartis, Pfizer, Roche, and PharmaMar and compensations for advisory board or consulting relationship from Tecnofarma. Jean-Yves Blay reports compensations for advisory board or consulting relationship with Merck Sharp & Dohme, Merck Serono, Daiichi-Sankyo, Astellas, Alexo Oncology, Samyang Biopharm, Hanmi, Daewoong and Amgen and has received institutional research funds from Genentech/Roche, Merck Sharp & Dohme, Merck Serono, Daiichi-Sankyo, Astellas and Amgen. Giovanni Grignani reports institutional research funds from Eli Lilly and Company, GlaxoSmithKline, Merk, Novartis, and Pharmamar. Emanuela Palmerini reports compensations for advisory boards from Daiichi Sankyo Company, Daiichi Sankyo Europe GmbH, Deciphera Pharmaceuticals Inc., EUSA Pharma (US) LLC, and SynOx Therapeutics. Paolo Casali received honoraria for speaker, consultancy, or advisory roles from: Bayer, Deciphera, Eisai, Eli Lilly, and Pfizer; his unit received funds from: Advenchen Laboratories, Amgen Dompé, AROG Pharmaceuticals, Bayer, Blueprint Medicines, Daiichi Sankyo, Deciphera, Eisai, Eli Lilly, Epizyme Inc, Glaxo, Karyopharm Pharmaceuticals, Novartis, Pfizer, and PharmaMar. Silvia Stacchiotti reports institutional research funds from: Advenchen Laboratories, Amgen Dompé, AROG Pharmaceuticals, Bayer, Blueprint Medicines, Daiichi Sankyo, Deciphera, Eisai, Eli Lilly, Epizyme Inc, Glaxo Smith Kline, Karyopharm Pharmaceuticals, Novartis, Pfizer, PharmaMar, and SpringWorks; honoraria, consultancy, or advisory role from: Bayer, Bavarian Nordic, Boehringer, Deciphera, Daiichi Sankyo Pharma, Gentili, Glaxo Smith Kline, Inhibrix, Maxivax, PharmaMar, and Servier; travel, accommodations, expenses from: PharmaMar. Alessandro Gronchi reports compensations for advisory boards from Novartis, Pfizer, Bayer, Lilly, PharmaMar, SpringWorks, and Deciphera and institutional research grants from PharmaMar and Nanobiotix. The other authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)
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- 2024
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33. Real World Analysis of Peritoneal Metastasis From Renal Cell Carcinoma. Meet-Uro27.
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Stellato M, Buti S, Maruzzo M, Bassanelli M, Bersanelli M, Napoli MD, Dionese M, Fanelli M, Filippi R, Fotia G, Galli L, Grillone F, Maffezzoli M, Maiorano BA, Nasso C, Rebuzzi SE, Lalli L, Roviello G, Sorarù M, Vincenzi B, Procopio G, and Verzoni E
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- Humans, Male, Female, Middle Aged, Retrospective Studies, Aged, Adult, Italy epidemiology, Aged, 80 and over, Survival Rate, Carcinoma, Renal Cell drug therapy, Carcinoma, Renal Cell secondary, Kidney Neoplasms pathology, Kidney Neoplasms drug therapy, Peritoneal Neoplasms secondary, Peritoneal Neoplasms drug therapy, Protein Kinase Inhibitors therapeutic use
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Background: Peritoneal metastases (PM) have been reported in approximately 1% of patients with metastatic Renal Cell Carcinoma (mRCC). Outcome data are limited due to the rarity of this metastatic site. Therefore, the aim of our study is to describe renal cell carcinoma (RCC) patients with PM treated as per clinical practice., Materials and Methods: Baseline characteristics and outcome data of patients with PM from RCC were retrospectively collected from 18 Italian oncological referral centers adhering to the Meet-Uro group, from January 2016 to January 2023., Results: We collect 81 RCC patients with PM. 78/81 received systemic treatment, 3/81 only best supportive care. First line treatment included tyrosine-kinase inhibitors (TKI) (46/78), ImmuneOncology (IO)-TKI (26/78) and IO-IO (6/78), with different Objective Response Rate (ORR) (43.4% in TKI monotherapy group vs 50% in IO-TKI group, respectively) and Disease Control Rate (DCR) (60.8% in TKI treated patients vs. 76.9% in IO-TKI treated patients). Median PFS was 6.4 months (95%CI 4.18-14.8) in patients treated with TKI monotherapy vs 23.7 months (95%CI 11.1-NR) in patients treated with IO-TKI (p < 0.015). The median OS (mOS) was 22.7 months (95%CI 13.32 - 64.7) in the TKI monotherapy group vs 34.5 mo (95%CI NR-NR) in the IO-TKI group with 53.8% of patients alive at 1 years in the latter group, (p < 0.16). Primary refractory patients were 36.9% for TKI and 15.3% for IO-TKI. According to International Metastatic renal cell carcinoma Database Consortium (IMDC) score, mPFS and mOS were consistent among risk categories. Median PFS was 36.6 months (95%CI 10.9-NR) for good risk patients compared to 10 months (95%CI 7.5-29.8) for intermediate risk and 2.96 months (95%CI 2.43-11.28) for poor risk population (p < 0.0005) whereas mOS was NR (95%CI 28.65-NR) for good risk patients compared to 35.3 months (95%CI 24.6-NA) and 12.4 months (95%CI 3.52-NR) for intermediate and poor risk population, respectively, (p < 0.0002). Only 34/78 (43.5%) received a second line treatment that was TKI (ORR 8.3% and DCR 41.6%) or IO (ORR 18.1% and DCR 40.9%)., Conclusion: We report one of the largest case series regarding PM from RCC. Characteristics of patients suggest a more aggressive behavior of PM from mRCC. Outcome data suggest that TKI-IO as first line treatment, and TKI as second line, confirm their activity for these patients with dismal prognosis., (Copyright © 2024 Elsevier Inc. All rights reserved.)
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- 2024
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34. Sentinel node mapping in high-intermediate and high-risk endometrial cancer: Analysis of 5-year oncologic outcomes.
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Cuccu I, Raspagliesi F, Malzoni M, Vizza E, Papadia A, Di Donato V, Giannini A, De Iaco P, Perrone AM, Plotti F, Angioli R, Casarin J, Ghezzi F, Cianci S, Vizzielli G, Restaino S, Petrillo M, Sorbi F, Multinu F, Schivardi G, De Vitis LA, Falcone F, Lalli L, Berretta R, Mueller MD, Tozzi R, Chiantera V, Benedetti Panici P, Fanfani F, Scambia G, and Bogani G
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- Female, Humans, Sentinel Lymph Node Biopsy methods, Retrospective Studies, Lymph Node Excision methods, Neoplasm Staging, Lymph Nodes surgery, Lymph Nodes pathology, Endometrial Neoplasms pathology, Sentinel Lymph Node pathology
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Objective: To assess 5-year oncologic outcomes of apparent early-stage high-intermediate and high-risk endometrial cancer undergoing sentinel node mapping versus systematic lymphadenectomy., Methods: This is a multi-institutional retrospective, propensity-matched study evaluating data of high-intermediate and high-risk endometrial cancer (according to ESGO/ESTRO/ESP guidelines) undergoing sentinel node mapping versus systematic pelvic lymphadenectomy (with and without para-aortic lymphadenectomy). Survival outcomes were assessed using Kaplan-Meier and Cox proportional hazard methods., Results: Overall, the charts of 242 patients with high-intermediate and high-risk endometrial cancer were retrieved. Data on 73 (30.1%) patients undergoing hysterectomy plus sentinel node mapping were analyzed. Forty-two (57.5%) and 31 (42.5%) patients were classified in the high-intermediate and high-risk groups, respectively. Unilateral sentinel node mapping was achieved in all patients. Bilateral mapping was achieved in 67 (91.7%) patients. Three (4.1%) patients had site-specific lymphadenectomy (two pelvic areas only and one pelvic plus para-aortic area), while adjunctive nodal dissection was omitted in the hemipelvis of the other three (4.1%) patients. Sentinel nodes were detected in the para-aortic area in eight (10.9%) patients. Twenty-four (32.8%) patients were diagnosed with nodal disease. A propensity-score matching was used to compare the aforementioned group of patients undergoing sentinel node mapping with a group of patients undergoing lymphadenectomy. Seventy patient pairs were selected (70 having sentinel node mapping vs. 70 having lymphadenectomy). Patients undergoing sentinel node mapping experienced similar 5-year disease-free survival (HR: 1.233; 95%CI: 0.6217 to 2.444; p = 0.547, log-rank test) and 5-year overall survival (HR: 1.505; 95%CI: 0.6752 to 3.355; p = 0.256, log-rank test) than patients undergoing lymphadenectomy., Conclusions: Sentinel node mapping does not negatively impact 5-year outcomes of high-intermediate and high-risk endometrial cancer. Further prospective studies are warranted., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)
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- 2024
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35. Salivary metabolomics in oral potentially malignant disorders and oral cancer patients-a systematic review with meta-analysis.
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Nazar NSBM, Ramanathan A, Ghani WMN, Rokhani FB, Jacob PS, Sabri NEB, Hassan MS, Kadir K, and Dharmarajan L
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- Humans, Acetylglucosamine, Reproducibility of Results, Mouth Neoplasms pathology, Mouth Diseases, Precancerous Conditions pathology
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Objectives: The aim of this systematic review and meta-analysis is to assess the diagnostic potential of salivary metabolomics in the detection of oral potentially malignant disorders (OPMDs) and oral cancer (OC)., Materials and Methods: A systematic review was performed in accordance with the 3rd edition of the Centre for Reviews and Dissemination (CRD) and Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Electronic searches for articles were carried out in the PubMed, Web of Science, and Scopus databases. The quality assessment of the included studies was evaluated using the Newcastle-Ottawa Quality Assessment Scale (NOS) and the new version of the QUADOMICS tool. Meta-analysis was conducted whenever possible. The effect size was presented using the Forest plot, whereas the presence of publication bias was examined through Begg's funnel plot., Results: A total of nine studies were included in the systematic review. The metabolite profiling was heterogeneous across all the studies. The expression of several salivary metabolites was found to be significantly altered in OPMDs and OCs as compared to healthy controls. Meta-analysis was able to be conducted only for N-acetylglucosamine. There was no significant difference (SMD = 0.15; 95% CI - 0.25-0.56) in the level of N-acetylglucosamine between OPMDs, OC, and the control group., Conclusion: Evidence for N-acetylglucosamine as a salivary biomarker for oral cancer is lacking. Although several salivary metabolites show changes between healthy, OPMDs, and OC, their diagnostic potential cannot be assessed in this review due to a lack of data. Therefore, further high-quality studies with detailed analysis and reporting are required to establish the diagnostic potential of the salivary metabolites in OPMDs and OC., Clinical Relevance: While some salivary metabolites exhibit significant changes in oral potentially malignant disorders (OPMDs) and oral cancer (OC) compared to healthy controls, the current evidence, especially for N-acetylglucosamine, is inadequate to confirm their reliability as diagnostic biomarkers. Additional high-quality studies are needed for a more conclusive assessment of salivary metabolites in oral disease diagnosis., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2024
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36. Peripheral blood lymphocytes predict clinical outcomes in hormone receptor-positive HER2-negative advanced breast cancer patients treated with CDK4/6 inhibitors.
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Zattarin E, Mariani L, Menichetti A, Leporati R, Provenzano L, Ligorio F, Fucà G, Lobefaro R, Lalli L, Vingiani A, Nichetti F, Griguolo G, Sirico M, Bernocchi O, Marra A, Corti C, Zagami P, Agostinetto E, Jacobs F, Di Mauro P, Presti D, Sposetti C, Giorgi CA, Guarneri V, Pedersini R, Losurdo A, Generali D, Curigliano G, Pruneri G, de Braud F, Dieci MV, and Vernieri C
- Abstract
Background: Cyclin-Dependent Kinase 4/6 inhibitors (CDK4/6i) combined with Endocrine Therapy (ET) are the standard treatment for patients with Hormone Receptor-positive/HER2-negative advanced breast cancer (HR+/HER2- aBC)., Objectives: While CDK4/6i are known to reduce several peripheral blood cells, such as neutrophils, lymphocytes and platelets, the impact of these modulations on clinical outcomes is unknown., Design: A multicenter, retrospective-prospective Italian study., Methods: We investigated the association between baseline peripheral blood cells, or their early modifications (i.e. 2 weeks after treatment initiation), and the progression-free survival (PFS) of HR+/HER2- aBC patients treated with ETs plus CDK4/6i. Random Forest models were used to select covariates associated with patient PFS among a large list of patient- and tumor-related variables., Results: We evaluated 638 HR+/HER2- aBC patients treated with ET plus CDK4/6i at six Italian Institutions between January 2017 and May 2021. High baseline lymphocyte counts were independently associated with longer PFS [median PFS (mPFS) 20.1 versus 13.2 months in high versus low lymphocyte patients, respectively; adjusted Hazard Ratio (aHR): 0.78; 95% confidence interval (CI): 0.66-0.92; p = 0.0144]. Moreover, patients experiencing a lower early reduction of lymphocyte counts had significantly longer PFS when compared to patients undergoing higher lymphocyte decrease (mPFS 18.1 versus 14.5 months; aHR: 0.82; 95% CI: 0.73-0.93; p = 0.0037). Patients with high baseline lymphocytes and undergoing a lower reduction, or even an increase, of lymphocyte counts during CDK4/6i therapy experienced the longest PFS, while patients with lower baseline lymphocytes and undergoing a higher decrease of lymphocytes had the lowest PFS (mPFS 21.4 versus 11 months, respectively)., Conclusion: Baseline and on-treatment modifications of peripheral blood lymphocytes have independent prognostic value in HR+/HER2- aBC patients. This study supports the implementation of clinical strategies to boost antitumor immunity in patients with HR+/HER2- aBC treated with ETs plus CDK4/6i., (© The Author(s), 2023.)
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- 2023
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37. Reporting Quality of the Abstracts for Randomized Controlled Trials in Pediatric Dentistry.
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Gopinath VK, Shetty RM, Renugalakshmi A, Dharmarajan L, Prakash PSG, and Jayaraman J
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Objectives: The purpose of this study is to systematically appraise the reporting quality of abstracts for randomized controlled trials (RCT) published in pediatric dentistry using Consolidated Standards of Reporting Trials (CONSORT) for abstracts and to analyze the relationship between the characteristics of the RCT to the quality of abstracts., Materials and Methods: RCTs published in Pediatric Dentistry were retrieved from the PubMed database from 2016 to 2021. The quality of abstracts was appraised using CONSORT for abstracts checklist by two independent reviewers., Statistical Analysis: In descriptive statistics, frequency and percentage analysis were used for categorical variables, whereas mean and standard deviation were used for continuous variables. To find the significant difference between the bivariate samples in independent groups, Mann-Whitney U test was employed. Multivariate analysis was performed using Kruskal-Wallis test and Mann-Whitney U tests. Probability value of p -value less than 0.05 was considered as statistically significant., Results: Two hundred abstracts were included in the study. All the abstracts adequately reported the "objective" item, whereas only 2 and 4% of abstracts adequately addressed "randomization" and "harms" items, respectively. A significant relationship was observed between the continent of first author/corresponding author, number of authors, impact factor, adherence to CONSORT guidelines, word count, focus of study, and a priori protocol registration to the quality of abstracts ( p < 0.05)., Conclusion: The abstracts of the RCT included in the study did not adequately follow the CONSORT for abstract guidelines. Adherence to the reporting guidelines would improve the overall reporting quality of abstracts of RCT published in Pediatric Dentistry. The overall mean score of the abstracts was 6.80 out of 15 indicating that the abstracts did not adequately follow the CONSORT for abstract reporting guidelines., Competing Interests: None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)
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- 2023
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38. Reporting quality of systematic reviews with network meta-analyses in Endodontics.
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Nagendrababu V, Narasimhan S, Faggion CM Jr, Dharmarajan L, Jacob PS, Gopinath VK, and Dummer PMH
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- Humans, Network Meta-Analysis, Checklist, Dental Care, Endodontics
- Abstract
Objectives: To evaluate the reporting quality of systematic reviews with network meta-analyses (NMAs) in Endodontics using the the Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) for NMA checklist., Methods: The current investigation extends a recently published study in the International Endodontic Journal (Nagendrababu V, Faggion Jr CM, Pulikkotil SJ, Alatta A, Dummer PM Methodological assessment and overall confidence in the results of systematic reviews with network meta-analyses in Endodontics. International Endodontic Journal 2022;55:393-404) that assessed the methodological quality of systematic reviews with NMAs in Endodontics using the A MeaSurement Tool to Assess systematic Reviews (AMSTAR 2) tool. In the present study, the PRISMA for NMA checklist with 32 items was used to assess the reporting quality of the systematic reviews with NMAs (n = 12). Two independent assessors assigned '1' when an item was completely addressed, '0.5' when it was partially addressed, and '0' when it was not addressed. Disagreements were resolved through reviewer discussion until consensus was reached. If conflicts persisted, a third reviewer made the final decision. The PRISMA for NMA scores were shared with the relevant authors of the individual reviews to reduce the likelihood of misinterpretation and verify the scores assigned. The results for each individual item of the PRISMA-NMA items were calculated by summing the individual scores awarded; the maximum score for each item was 12., Results: All the systematic reviews with NMAs adequately reported the following items: Title, Introduction section (Objectives), Methods section (Eligibility criteria and Information sources), Results section (Study selection, Study characteristics and Risk of bias within studies), and Discussion section (Summary of evidence). The items that were reported least often were the "geometry of the network" and "the summary of network geometry" with only 2 manuscripts (17%) including these items., Conclusion: A number of the items in the PRISMA-NMA checklist were adequately addressed in the NMAs; however, none adequately reported all the PRISMA-NMA items. The inadequacies of published NMAs that have been identified should be taken into consideration by authors of NMAs in Endodontics and by editors when managing the peer review process. In future, researchers who are writing systematic reviews with NMAs should comply with the PRISMA-NMA checklist., Clinical Relevance: None of the included systematic reviews with NMA adequately reported all the PRISMA-NMA items. Inadequate reporting of a systematic review with NMA increases the possibility that it will provide invalid results. Therefore, authors should follow the PRISMA-NMA guidelines when reporting systematic reviews with NMA in Endodontics., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2023
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39. COVID-19 hospitalisations and all-cause mortality by risk group in Finland.
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Summanen M, Kosunen M, Kainu V, Cansel A, Niskanen S, Nurmi L, Leskelä RL, and Isomeri O
- Subjects
- Aged, Humans, Adolescent, Finland, SARS-CoV-2, Hospitalization, Risk Factors, COVID-19
- Abstract
Ever since COVID-19 was announced as a global pandemic in March 2020, healthcare systems around the world have struggled with the burden of the disease. Vaccinations and other preventive measures have decreased this burden, but severe forms of COVID-19 leading to hospitalizations and even deaths still effect certain risk groups, such as the elderly and patients with multiple comorbidities. The objective of this retrospective observational study was to identify which risk groups are at the highest risk for a severe COVID-19 infection in Finland using national registry data ranging from January 2021 to June 2022. The data was analysed in three time periods, enabling comparisons in high-risk groups between epidemiological waves caused by different variants of SARS-CoV-2. The summary level data were stratified according to predefined groups based on two criteria: age (≥18 years, 18-59 years, and ≥60 years) and risk group. The results include analysis of infection hospitalisation rate (IHR), case fatality rate (CFR) and average length of stay (LOS) in both primary and specialty care for each risk group and age group. Our results confirm that despite the decrease in COVID-19 hospitalisations and deaths observed during the study period, a significant proportion of patients are still hospitalised, and deaths occur especially in the 60+ population. Also, even though the average length of stay of hospitalised COVID-19 patients has decreased, it is still long compared to specialty care hospitalisations in general. Old age is a significant risk factor for severe COVID-19 in all patient groups and certain risk factors such as chronic kidney disease clearly increase the risk for severe COVID-19 outcomes. Early treatment should be considered with a low threshold for risk group patients and for elderly patients in order to avoid severe disease courses, and to ease the burden on hospitals where resources are currently very strained., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Summanen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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- 2023
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40. Oral Health of Patients Undergoing Percutaneous Coronary Intervention-A Possible Link between Periodontal Disease and In-Stent Restenosis.
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Nagy FT, Gheorghita D, Dharmarajan L, Braunitzer G, Achim A, Ruzsa Z, and Antal MÁ
- Abstract
Introduction: There is a well-documented association between coronary artery disease (CHD) and periodontal disease (PD) mediated by common inflammatory pathways. This association, however, has not been investigated extensively in the special context of in-stent restenosis. This study aimed to investigate the periodontal status of patients undergoing percutaneous coronary intervention (PCI) for restenotic lesions. Methods and Results : We enrolled 90 patients undergoing percutaneous coronary intervention and 90 age- and gender-matched healthy controls in the present study. All subjects received a full-mouth examination by a periodontist. Plaque index, periodontal status, and tooth loss were determined. The periodontal state was significantly worse ( p < 0.0001) in the PCI group, and each periodontal stage increased the odds of belonging to the PCI group. This effect of PD was independent of diabetes mellitus, another strong risk factor for CAD. The PCI group was further divided into two subgroups: PCI for restenotic lesions ( n = 39) and PCI for de novo lesions ( n = 51). Baseline clinical and procedural characteristics were comparable between the two PCI subgroups. A significant ( p < 0.001) association was found between the PCI subgroup and the severity of periodontal disease, with the incidence of severe PD reaching 64.1%. Conclusions: Patients undergoing PCI for in-stent restenosis exhibit more severe forms of periodontal disease not only as compared to healthy controls but also as compared to patients stented for de novo lesions. The potential causality between PD and restenosis must be studied in larger prospective studies., Competing Interests: The authors declare no conflict of interest.
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- 2023
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41. Prognostic significance of HER2-low status in HR-positive/HER2-negative advanced breast cancer treated with CDK4/6 inhibitors.
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Zattarin E, Presti D, Mariani L, Sposetti C, Leporati R, Menichetti A, Corti C, Benvenuti C, Fucà G, Lobefaro R, Ligorio F, Provenzano L, Vingiani A, Del Vecchio M, Griguolo G, Sirico M, Bernocchi O, Marra A, Zagami P, Agostinetto E, Jacobs F, Di Mauro P, Esposito A, Giorgi CA, Lalli L, Boldrini L, Giacchetti PPB, Schianca AC, Guarneri V, Pedersini R, Losurdo A, Zambelli A, Generali D, Criscitiello C, Curigliano G, Pruneri G, de Braud F, Dieci MV, and Vernieri C
- Abstract
Whether Human Epidermal growth factor Receptor 2 (HER2)-low status has prognostic significance in HR + /HER2- advanced Breast Cancer (aBC) patients treated with first-line Endocrine Therapy plus CDK 4/6 inhibitors remains unclear. In 428 patients evaluated, HER2-low status was independently associated with significantly worse PFS and OS when compared with HER2-0 status. Based on our findings, HER2-low status could become a new prognostic biomarker in this clinical setting., (© 2023. The Author(s).)
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- 2023
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42. Metagenomic insights into the plasma virome of Brazilian patients with prostate cancer.
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Luciola Zanette D, Andrade Coelho KBC, de Carvalho E, Aoki MN, Nardin JM, Araújo Lalli L, Dos Santos Bezerra R, Giovanetti M, Simionatto Zucherato V, Montenegro de Campos G, de Souza Todão Bernardino J, Louis Viala V, Ciccozzi M, Junior Alcantara LC, Coccuzzo Sampaio S, Elias MC, Kashima S, Tadeu Covas D, and Nanev Slavov S
- Abstract
Growing evidence suggests that metavirome changes could be associated increased risk for malignant cell transformation. Considering Viruses have been proposed as factors for prostate cancer induction. The objective of this study was to examine the composition of the plasma metavirome of patients with prostate cancer. Blood samples were obtained from 49 male patients with primary prostate adenocarcinoma. Thirty blood donors were included as a control group. The obtained next-generation sequencing data were analyzed using a bioinformatic pipeline for virus metagenomics. Viral reads with higher abundance were assembled in contigs and analyzed taxonomically. Viral agents of interest were also confirmed by qPCR. Anelloviruses and the Human Pegivirus-1 (HPgV-1) were the most abundant component of plasma metavirome. Clinically important viruses like hepatitis C virus (HCV), cytomegalovirus and human adenovirus type C were also identified. In comparison, the blood donor virome was exclusively composed of torque teno virus types (TTV) types. The performed HPgV-1 and HCV phylogeny revealed that these viruses belong to commonly detected in Brazil genotypes. Our study sheds light on the plasma viral abundance in patients with prostatic cancer. The obtained viral diversity allowed us to separate the patients and controls, probably suggesting that malignant processes may influence virome composition. More complex and multiple approach investigations are necessary to examine the likely causal relationship between metavirome and its nvolvement in prostate cancer., Competing Interests: No potential conflict of interest was reported by the authors., (© 2023 The Author(s). Published with license by Taylor & Francis Group, LLC.)
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- 2023
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43. Y 90 -radioembolisation in hepatocellular carcinoma induces immune responses calling for early treatment with multiple checkpoint blockers.
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Rivoltini L, Bhoori S, Camisaschi C, Bergamaschi L, Lalli L, Frati P, Citterio D, Castelli C, and Mazzaferro V
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- Humans, Immunotherapy, Carcinoma, Hepatocellular radiotherapy, Liver Neoplasms radiotherapy, Embolization, Therapeutic
- Abstract
Competing Interests: Competing interests: None declared.
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- 2023
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44. COMPARING THE CLINICAL AND RADIOGRAPHIC OUTCOMES OF PULPOTOMIES IN PRIMARY MOLARS USING BIOACTIVE ENDODONTIC MATERIALS AND FERRIC SULFATE - A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED CLINICAL TRIALS.
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Gopinath VK, Pulikkotil SJ, Veettil SK, Dharmarajan L, Prakash PSG, Dhar V, and Jayaraman J
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- Child, Humans, Randomized Controlled Trials as Topic, Pulpotomy, Treatment Outcome, Tooth, Deciduous, Molar diagnostic imaging, Molar surgery
- Abstract
Objective: To compare the clinical and radiographic outcomes of pulpotomies in primary molars using bioactive endodontic materials and ferric sulfate., Design: The search was conducted in PubMed, Ebscohost, ProQuest, and Scopus databases till June 2021. Children undergoing pulpotomy therapy in primary molars treated with ferric sulfate (FS) and bioactive endodontic materials were evaluated for clinical and radiographic success. Meta-analysis was performed on a random-effects model to assess the success at 6,12,18, and 24 months. The quality of studies was evaluated using the Cochrane risk of bias tool for randomized trials RESULTS: No significant difference was observed between Mineral trioxide aggregate (MTA) and FS at 24 months for both clinical [RR0.98 (95%CI 0.15,6.34), I
2 = 0%] and radiographic [RR0.74 (95%CI: 0.23,2.43), I2 = 0%] success. At 6 months [RR1.36 (95%CI: 0.10,19.34), I2 = 33%], no difference was observed in the clinical [RR1.00 (95%CI: 0.95,1.05), I2 = 0%] and radiographic success [RR0.99 (95%CI: 0.88,1.11), I2 = 51%] between Biodentine (BD), FS and radiographic success of calcium enriched cement and FS [RR0.25 (95%CI: 0.03, 2.22), I2 = 0%]., Conclusion: Amongst bioactive materials, MTA and FS demonstrated equal success rates in both clinical and radiographic outcomes with follow-up periods of up to 24 months. Future, high-quality trials are required to verify the result of the current review., (Copyright © 2022 Elsevier Inc. All rights reserved.)- Published
- 2022
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45. Genetic Layout of Melanoma Lesions Is Associated with BRAF/MEK-Targeted Therapy Resistance and Transcriptional Profiles.
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Vergani E, Busico A, Dugo M, Devecchi A, Valeri B, Cossa M, Di Guardo L, De Cecco L, Feltrin E, Valle G, Deho P, Frigerio S, Lalli L, Gallino G, Del Vecchio M, Santinami M, Pruneri G, Tamborini E, Rivoltini L, Sensi M, Vallacchi V, and Rodolfo M
- Subjects
- Humans, Vemurafenib therapeutic use, Antineoplastic Combined Chemotherapy Protocols therapeutic use, MAP Kinase Kinase Kinases genetics, MAP Kinase Kinase Kinases therapeutic use, Mutation, Chromatin, Mechanistic Target of Rapamycin Complex 1, Mitogen-Activated Protein Kinase Kinases, Protein Kinase Inhibitors pharmacology, Protein Kinase Inhibitors therapeutic use, Proto-Oncogene Proteins B-raf genetics, Melanoma drug therapy, Melanoma genetics, Melanoma pathology
- Abstract
The genetic landscape of melanoma resistance to targeted therapy with small molecules inhibiting BRAF and MEK kinases is still largely undefined. In this study, we portrayed in detail the somatic alterations of resistant melanoma and explored the associated biological processes and their integration with transcriptional profiles. By targeted next-generation sequencing and whole-exome sequencing analyses, a list of 101 genes showing imbalance in metastatic tumors from patients with a complete/durable response or disease progression during therapy with vemurafenib or with dabrafenib and trametinib was defined. Classification of altered genes in functional categories indicated that the mutational pattern of both resistant tumors and melanoma cell lines was enriched in gene families involved in oncogenic signaling pathways and in DNA repair. Integration of genomic and transcriptomic features showed that the enrichment of mutations in gene sets associated with anabolic processes, chromatin alterations, and IFN-α response determined a significant positive modulation of the same gene signatures at the transcriptional level. In particular, MTORC1 signaling was enriched in tumors from poorly responsive patients and in resistant tumors excised from treated patients. Results indicate that genetic patterns are associated with melanoma resistance to targeted therapy and disclose the underlying key molecular pathways to define drug combinations for improved personalized therapies., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2022
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46. Extracellular vesicles in anti-tumor immunity.
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Vergani E, Daveri E, Vallacchi V, Bergamaschi L, Lalli L, Castelli C, Rodolfo M, Rivoltini L, and Huber V
- Subjects
- Humans, Immunotherapy, Immunity, Cell Line, Tumor, Extracellular Vesicles metabolism
- Abstract
To what extent extracellular vesicles (EVs) can impact anti-tumor immune responses has only started to get unraveled. Their nanometer dimensions, their growing number of subtypes together with the difficulties in defining their origin hamper their investigation. The existence of tumor cell lines facilitated advance in cancer EV understanding, while capturing information about phenotypes and functions of immune cell EVs in this context is more complex. The advent of immunotherapy with immune checkpoint inhibitors has further deepened the need to dissect the impact of EVs during immune activation and response, not least to contribute unraveling and preventing the generation of resistance occurring in the majority of patients. Here we discuss the factors that influence anddrive the immune response in cancer patients in the context of cancer therapeutics and the roles or possible functions that EVs can have in this scenario. With immune cell-derived EVs as leitmotiv, we will journey from EV discovery and subtypes through physiological and pathological functions, from similarities with tumor EVs to measures to revert detrimental consequences on immune responses to cancer., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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- 2022
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47. The Effect of Laser Micro Grooved Platform Switched Implants and Abutments on Early Crestal Bone Levels and Peri-Implant Soft Tissues Post 1 Year Loading among Diabetic Patients-A Controlled Clinical Trial.
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Dharmarajan L, Prakash PSG, Appukuttan D, Crena J, Subramanian S, Alzahrani KJ, Alsharif KF, Halawani IF, Alnfiai MM, Alamoudi A, Kamil MA, Balaji TM, and Patil S
- Subjects
- Humans, Lasers, Prostheses and Implants, Alveolar Bone Loss, Mouth, Edentulous, Diabetes Mellitus
- Abstract
Background and Objectives: The study aimed to compare the mean crestal bone level (CBL) and peri-implant soft tissue parameters in laser micro-grooved (LMG) platform switched implants and abutments (I&A) post 1 year of functional loading among non-diabetic and type II diabetic individuals. Materials and methods: Patients with an edentulous site having minimum bone height and width of ≥13 mm and ≥6 mm, respectively, were divided into two groups: (i) Non-diabetic-8 (control) and (ii) diabetic-8 (test). LMG Implants were placed and loaded immediately with a provisional prosthesis. Mean crestal bone level (MCBL) was evaluated radiographically at baseline and at 1 year. Peri-implant attachment level (PIAL) and relative position of the gingival margin (R-PGM) were recorded. Implant stability quotient (ISQ) level and implant survival rate (ISR) were evaluated at 1 year. Results: Early MCBL within the groups 1 year postloading was similar both mesially and distally (control-0.00 to 0.16 mm and 0.00 to 0.17 mm, respectively; test-0.00 to 0.21 mm and 0.00 to 0.22 mm, respectively) with statistical significance ( p ≤ 0.003, p ≤ 0.001 and p ≤ 0.001, p ≤ 0.001, respectively). However, intergroup comparison showed no significant difference statistically in the MCBL in 1 year post functional loading. The peri-implant soft tissue parameters showed no significant difference between the groups. ISQ level between both groups did not reveal any significant changes ( p ≤ 0.92), and ISR was 100%. Conclusions: LMG Implants resulted in minimal and comparable early crestal bone loss and soft tissue changes post 1 year of functional loading in moderately controlled diabetic and non-diabetic individuals, suggesting that this could be a reliable system for use in systemically compromised individuals.
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- 2022
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48. Low baseline neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios predict increased overall survival in locally recurrent rectal cancer despite R1 margins.
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Daveri E, Sorrentino L, Lalli L, Guaglio M, Battaglia L, Cattaneo L, Sabella G, Milione M, Rivoltini L, Cosimelli M, and Belli F
- Subjects
- Blood Platelets, Humans, Lymphocytes, Margins of Excision, Neoplasm Recurrence, Local, Prognosis, Retrospective Studies, Neutrophils, Rectal Neoplasms
- Abstract
Background: Prognostic features in locally recurrent rectal cancer (LRRC), beyond R0 surgery, are unknown., Aims: Aim of the present study was to evaluate the prognostic role of peripheral immune estimators, such as neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), on survival outcomes in LRRC patients., Methods: 184 LRRC patients treated at the National Cancer Institute of Milan (Italy) were included. Optimal cut-off values for NLR and PLR were determined. Kaplan-Meier curves and multivariate Cox analyses were used to assess the 5-yr overall survival (OS) according to NLR and PLR, also considering margins status., Results: NLR >3.9 (hazard ratio [HR] 3.96, P = 0.049), PLR >275 (HR 5.39, P = 0.002) and size on imaging (HR 1.36, P = 0.044) were associated to worse OS. R+ patients with NLR >3.9 showed a significantly lower 5-yr OS compared to NLR ≤3.9 (13.5% vs. 36.7%, P < 0.0001). Also PLR >275 was related with a lower 5-yr OS compared to PLR ≤275 in R+ patients (6.4% vs. 36.8%, P = 0.0003). Conversely, NLR and PLR were irrelevant in case of R0 surgery., Conclusion: NLR and PLR predict 5-yr OS in LRRC, also identifying a subset of R+ patients with a similar expected survival compared to R0 cases., Competing Interests: Conflict of interest None declared., (Copyright © 2022. Published by Elsevier Ltd.)
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- 2022
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49. Cabozantinib as First-line Treatment in Patients With Metastatic Collecting Duct Renal Cell Carcinoma: Results of the BONSAI Trial for the Italian Network for Research in Urologic-Oncology (Meet-URO 2 Study).
- Author
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Procopio G, Sepe P, Claps M, Buti S, Colecchia M, Giannatempo P, Guadalupi V, Mariani L, Lalli L, Fucà G, de Braud F, and Verzoni E
- Subjects
- Aged, Anilides adverse effects, Fatigue, Humans, Pyridines, Retrospective Studies, Carcinoma, Renal Cell pathology, Kidney Neoplasms pathology
- Abstract
Importance: Metastatic collecting duct carcinoma (mCDC) is a rare type of non-clear cell renal cell carcinoma (ncRCC) with poor prognosis and no standard treatments. Despite retrospective series that have documented the benefit of cabozantinib in ncRCC, no prospective trials have evaluated this treatment in mCDC., Objective: To determine whether cabozantinib is an active treatment in patients with mCDC., Design, Setting, and Participants: The caBozantinib in cOllectiNg ductS Renal Cell cArcInoma (BONSAI) trial was an open-label, single-arm, phase 2 clinical trial carried out between January 2018 and November 2020 at a single academic center with data cut off in September 2021 on behalf of the the Italian Network for Research in Urologic-Oncology (Meet-URO 2). Eligible patients had histologic diagnosis of centrally confirmed mCDC with measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST; version 1.1). In total, 25 patients were screened., Interventions: Patients received cabozantinib, 60 mg orally once daily, until disease progression, unacceptable toxic effects, or withdrawal of consent., Main Outcomes and Measures: The primary end point was objective response rate (ORR) per RECIST, version 1.1., Results: At data cut off, of 25 patients enrolled, 23 started treatment because 2 were excluded after failing the screening process at pathologic review. The median follow-up cannot be estimated using the reverse Kaplan-Meier estimator. The median time to censoring was 11 months (95% CI, 0-22 months). Median (range) age was 66 (53-74) years. As best overall response, 3 patients presented stable disease, 1 patient achieved a complete response, and 7 a partial response. The ORR was 35% (95% CI, 16%-57%). The median progression-free survival was 4 months (95% CI, 3-13 months). The median OS was 7 months (95% CI, 3-31 months). All patients reported at least 1 grade (G) 1 to 2 adverse event (AE). The most common G1 to G2 AEs were fatigue (14 [60%]), anorexia (9 [39%]), hand-foot syndrome (7 [30%]), hypothyroidism (7 [30%]), mucositis (7 [30%]), diarrhea (5 [22%]), and hypertension (3 [13%]). Six G3 AEs were reported: 2 arterial hyperthension, 1 pulmonary thromboembolism, 1 bleeding, and 2 fatigue. There were no permanent discontinuations from the study owing to AEs. Four patients (17%) required dose reduction to 40 mg, and 4 (17%) required a transitory interruption to manage toxic effects., Conclusions and Relevance: The study met the ORR primary end point, showing encouraging efficacy of cabozantinib in untreated patients with mCDC. Further investigations to advance the molecular understanding of this tumor are ongoing., Trial Registration: ClinicalTrials.gov Identifier: NCT03354884.
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- 2022
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50. Development of a Nomogram Predicting the Risk of Persistence/Recurrence of Cervical Dysplasia.
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Bogani G, Lalli L, Sopracordevole F, Ciavattini A, Ghelardi A, Simoncini T, Plotti F, Casarin J, Serati M, Pinelli C, Bergamini A, Gardella B, Dell'Acqua A, Monti E, Vercellini P, Palaia I, Perniola G, Fischetti M, Santangelo G, Fracassi A, D'Ippolito G, Aguzzoli L, Mandato VD, Giannella L, Scaffa C, Falcone F, Borghi C, Malzoni M, Giannini A, Salerno MG, Liberale V, Contino B, Donfrancesco C, Desiato M, Perrone AM, Dondi G, De Iaco P, Ferrero S, Sarpietro G, Matarazzo MG, Cianci A, Cianci S, Bosio S, Ruisi S, Mosca L, Tinelli R, De Vincenzo R, Zannoni GF, Ferrandina G, Petrillo M, Capobianco G, Dessiole S, Carlea A, Zullo F, Muschiato B, Palomba S, Greggi S, Spinillo A, Ghezzi F, Colacurci N, Angioli R, Benedetti Panici P, Muzii L, Scambia G, Raspagliesi F, and Di Donato V
- Abstract
Background: Cervical dysplasia persistence/recurrence has a great impact on women's health and quality of life. In this study, we investigated whether a prognostic nomogram may improve risk assessment after primary conization. Methods: This is a retrospective multi-institutional study based on charts of consecutive patients undergoing conization between 1 January 2010 and 31 December 2014. A nomogram assessing the importance of different variables was built. A cohort of patients treated between 1 January 2015 and 30 June 2016 was used to validate the nomogram. Results: A total of 2966 patients undergoing primary conization were analyzed. The median (range) patient age was 40 (18-89) years. At 5-year of follow-up, 6% of patients (175/2966) had developed a persistent/recurrent cervical dysplasia. Median (range) recurrence-free survival was 18 (5-52) months. Diagnosis of CIN3, presence of HR-HPV types, positive endocervical margins, HPV persistence, and the omission of HPV vaccination after conization increased significantly and independently of the risk of developing cervical dysplasia persistence/recurrence. A nomogram weighting the impact of all variables was built with a C-Index of 0.809. A dataset of 549 patients was used to validate the nomogram, with a C-index of 0.809. Conclusions: The present nomogram represents a useful tool for counseling women about their risk of persistence/recurrence after primary conization. HPV vaccination after conization is associated with a reduced risk of CIN2+.
- Published
- 2022
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