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1. Idiopathic erythrocytosis: a germline disease?

Author

Elli, E. M., Mauri, M., D’Aliberti, D., Crespiatico, I., Fontana, D., Redaelli, S., Pelucchi, S., Spinelli, S., Manghisi, B., Cavalca, F., Aroldi, A., Ripamonti, A., Ferrari, S., Palamini, S., Mottadelli, F., Massimino, L., Ramazzotti, D., Cazzaniga, G., Piperno, A., Gambacorti-Passerini, C., and Piazza, R.

Published
2024
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5. First-hit SETBP1 mutations cause a myeloproliferative disorder with bone marrow fibrosis

Author

Crespiatico, I, Zaghi, M, Mastini, C, D'Aliberti, D, Mauri, M, Mercado, C, Fontana, D, Spinelli, S, Crippa, V, Inzoli, E, Manghisi, B, Civettini, I, Ramazzotti, D, Sangiorgio, V, Gengotti, M, Brambilla, V, Aroldi, A, Banfi, F, Barone, C, Orsenigo, R, Riera, L, Riminucci, M, Corsi, A, Breccia, M, Morotti, A, Cilloni, D, Roccaro, A, Sacco, A, Stagno, F, Serafini, M, Mottadelli, F, Cazzaniga, G, Pagni, F, Chiarle, R, Azzoni, E, Sessa, A, Gambacorti Passerini, C, Elli, E, Mologni, L, Piazza, R, Crespiatico I., Zaghi M., Mastini C., D'Aliberti D., Mauri M., Mercado C. M., Fontana D., Spinelli S., Crippa V., Inzoli E., Manghisi B., Civettini I., Ramazzotti D., Sangiorgio V., Gengotti M., Brambilla V., Aroldi A., Banfi F., Barone C., Orsenigo R., Riera L., Riminucci M., Corsi A., Breccia M., Morotti A., Cilloni D., Roccaro A., Sacco A., Stagno F., Serafini M., Mottadelli F., Cazzaniga G., Pagni F., Chiarle R., Azzoni E., Sessa A., Gambacorti Passerini C., Elli E. M., Mologni L., Piazza R., Crespiatico, I, Zaghi, M, Mastini, C, D'Aliberti, D, Mauri, M, Mercado, C, Fontana, D, Spinelli, S, Crippa, V, Inzoli, E, Manghisi, B, Civettini, I, Ramazzotti, D, Sangiorgio, V, Gengotti, M, Brambilla, V, Aroldi, A, Banfi, F, Barone, C, Orsenigo, R, Riera, L, Riminucci, M, Corsi, A, Breccia, M, Morotti, A, Cilloni, D, Roccaro, A, Sacco, A, Stagno, F, Serafini, M, Mottadelli, F, Cazzaniga, G, Pagni, F, Chiarle, R, Azzoni, E, Sessa, A, Gambacorti Passerini, C, Elli, E, Mologni, L, Piazza, R, Crespiatico I., Zaghi M., Mastini C., D'Aliberti D., Mauri M., Mercado C. M., Fontana D., Spinelli S., Crippa V., Inzoli E., Manghisi B., Civettini I., Ramazzotti D., Sangiorgio V., Gengotti M., Brambilla V., Aroldi A., Banfi F., Barone C., Orsenigo R., Riera L., Riminucci M., Corsi A., Breccia M., Morotti A., Cilloni D., Roccaro A., Sacco A., Stagno F., Serafini M., Mottadelli F., Cazzaniga G., Pagni F., Chiarle R., Azzoni E., Sessa A., Gambacorti Passerini C., Elli E. M., Mologni L., and Piazza R.

Abstract

SETBP1 mutations are found in various clonal myeloid disorders. However, it is unclear whether they can initiate leukemia, because SETBP1 mutations typically appear as later events during oncogenesis. To answer this question, we generated a mouse model expressing mutated SETBP1 in hematopoietic tissue: this model showed profound alterations in the differentiation program of hematopoietic progenitors and developed a myeloid neoplasm with megakaryocytic dysplasia, splenomegaly, and bone marrow fibrosis, prompting us to investigate SETBP1 mutations in a cohort of 36 triple-negative primary myelofibrosis (TN-PMF) cases. We identified 2 distinct subgroups, one carrying SETBP1 mutations and the other completely devoid of somatic variants. Clinically, a striking difference in disease aggressiveness was noted, with patients with SETBP1 mutation showing a much worse clinical course. In contrast to myelodysplastic/myeloproliferative neoplasms, in which SETBP1 mutations are mostly found as a late clonal event, single-cell clonal hierarchy reconstruction in 3 patients with TN-PMF from our cohort revealed SETBP1 to be a very early event, suggesting that the phenotype of the different SETBP1+ disorders may be shaped by the opposite hierarchy of the same clonal SETBP1 variants.

Published
2024

6. Idiopathic erythrocytosis: a germline disease?

Author

Elli, E, Mauri, M, D’Aliberti, D, Crespiatico, I, Fontana, D, Redaelli, S, Pelucchi, S, Spinelli, S, Manghisi, B, Cavalca, F, Aroldi, A, Ripamonti, A, Ferrari, S, Palamini, S, Mottadelli, F, Massimino, L, Ramazzotti, D, Cazzaniga, G, Piperno, A, Gambacorti-Passerini, C, Piazza, R, Elli, E. M., Mauri, M., D’Aliberti, D., Crespiatico, I., Fontana, D., Redaelli, S., Pelucchi, S., Spinelli, S., Manghisi, B., Cavalca, F., Aroldi, A., Ripamonti, A., Ferrari, S., Palamini, S., Mottadelli, F., Massimino, L., Ramazzotti, D., Cazzaniga, G., Piperno, A., Gambacorti-Passerini, C., Piazza, R., Elli, E, Mauri, M, D’Aliberti, D, Crespiatico, I, Fontana, D, Redaelli, S, Pelucchi, S, Spinelli, S, Manghisi, B, Cavalca, F, Aroldi, A, Ripamonti, A, Ferrari, S, Palamini, S, Mottadelli, F, Massimino, L, Ramazzotti, D, Cazzaniga, G, Piperno, A, Gambacorti-Passerini, C, Piazza, R, Elli, E. M., Mauri, M., D’Aliberti, D., Crespiatico, I., Fontana, D., Redaelli, S., Pelucchi, S., Spinelli, S., Manghisi, B., Cavalca, F., Aroldi, A., Ripamonti, A., Ferrari, S., Palamini, S., Mottadelli, F., Massimino, L., Ramazzotti, D., Cazzaniga, G., Piperno, A., Gambacorti-Passerini, C., and Piazza, R.

Abstract

Polycythemia Vera (PV) is typically caused by V617F or exon 12 JAK2 mutations. Little is known about Polycythemia cases where no JAK2 variants can be detected, and no other causes identified. This condition is defined as idiopathic erythrocytosis (IE). We evaluated clinical-laboratory parameters of a cohort of 56 IE patients and we determined their molecular profile at diagnosis with paired blood/buccal-DNA exome-sequencing coupled with a high-depth targeted OncoPanel to identify a possible underling germline or somatic cause. We demonstrated that most of our cohort (40/56: 71.4%) showed no evidence of clonal hematopoiesis, suggesting that IE is, in large part, a germline disorder. We identified 20 low mutation burden somatic variants (Variant allelic fraction, VAF, < 10%) in only 14 (25%) patients, principally involving DNMT3A and TET2. Only 2 patients presented high mutation burden somatic variants, involving DNMT3A, TET2, ASXL1 and WT1. We identified recurrent germline variants in 42 (75%) patients occurring mainly in JAK/STAT, Hypoxia and Iron metabolism pathways, among them: JAK3-V722I and HIF1A-P582S; a high fraction of patients (48.2%) resulted also mutated in homeostatic iron regulatory gene HFE-H63D or C282Y. By generating cellular models, we showed that JAK3-V722I causes activation of the JAK-STAT5 axis and upregulation of EPAS1/HIF2A, while HIF1A-P582S causes suppression of hepcidin mRNA synthesis, suggesting a major role for these variants in the onset of IE.

Published
2024

10. Predicting a Prolonged Air Leak After Video-Assisted Thoracic Surgery, Is It Really Possible?

Author

Mancuso, M., Pernazza, F., Refai, M., Srella, F., Argnani, D., Marulli, G., De Palma, A., Bortolotti, L., Rizzardi, G., Solli, P.G., Dolci, G.P., Perkmann, R., Zaraca, F., Benvenuti, M., Gavezzoli, D., Cherchi, R., Ferrari, P., Mucilli, F., Camplese, P., Melloni, G., Mazza, F., Cavallesco, G., Maniscalco, P., Voltolini, L., Gonfiotti, A., Sollitto, F., Ardò, N., Pariscenti, G.L., Risso, C., Surrente, C., Lopez, C., Droghetti, A., Giovanardi, M., Breda, C., Giudice, Lo F., Alloisio, M., Bottoni, E., Spaggiari, L., Gasparri, R., Torre, M., Rinaldo, A., Nosotti, M., Tosi, D., Negri, G.P., Bandiera, A., Baisi, A., Raveglia, F., Stefani, A., Natali, P., Scarci, M., Pirondini, E., Curcio, C., Amore, D., Rena, O., Nicotra, S., Dell’ Amore, A., Bertani, A., Tancredi, G., Ampollini, L., Carbognani, P., Puma, F., Vinci, D., Cardillo, G., Carleo, F., Margaritora, S., Meacci, E., Luzzi, L., Ghisalberti, M., Crisci, R., Divisi, D., Lausi, P., Guerrera, F., Fontana, D., Beffa, V. Della, Morelli, A., Londero, F., Imperatori, A., Rotolo, N., Terzi, A., Viti, A., Infante, M., Benato, C., Zaraca, Francesco, Pipitone, Marco, Feil, Birgit, Perkmann, Reinhold, Bertolaccini, Luca, Curcio, Carlo, and Crisci, Roberto

Published
2021
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11. New pan-ALK inhibitor-resistant EML4::ALK mutations detected by liquid biopsy in lung cancer patients

Author

Villa, M, Malighetti, F, Sala, E, Sharma, G, Arosio, G, Gemelli, M, Manfroni, C, Fontana, D, Cordani, N, Meneveri, R, Zambon, A, Piazza, R, Pagni, F, Cortinovis, D, Mologni, L, Villa, Matteo, Malighetti, Federica, Sala, Elisa, Sharma, Geeta G., Arosio, Giulia, Gemelli, Maria, Manfroni, Chiara, Fontana, Diletta, Cordani, Nicoletta, Meneveri, Raffaella, Zambon, Alfonso, Piazza, Rocco, Pagni, Fabio, Cortinovis, Diego, Mologni, Luca, Villa, M, Malighetti, F, Sala, E, Sharma, G, Arosio, G, Gemelli, M, Manfroni, C, Fontana, D, Cordani, N, Meneveri, R, Zambon, A, Piazza, R, Pagni, F, Cortinovis, D, Mologni, L, Villa, Matteo, Malighetti, Federica, Sala, Elisa, Sharma, Geeta G., Arosio, Giulia, Gemelli, Maria, Manfroni, Chiara, Fontana, Diletta, Cordani, Nicoletta, Meneveri, Raffaella, Zambon, Alfonso, Piazza, Rocco, Pagni, Fabio, Cortinovis, Diego, and Mologni, Luca

Abstract

ALK and ROS1 fusions are effectively targeted by tyrosine kinase inhibitors (TKIs), however patients inevitably relapse after an initial response, often due to kinase domain mutations. We investigated circulating DNA from TKI-relapsed NSCLC patients by deep-sequencing. New EML4::ALK substitutions, L1198R, C1237Y and L1196P, were identified in the plasma of NSCLC ALK patients and characterized in a Ba/F3 cell model. Variants C1237Y and L1196P demonstrated pan-inhibitor resistance across 5 clinical and 2 investigational TKIs.

Published
2024

12. miR-15a targets the HSP90 co-chaperone Morgana in chronic myeloid leukemia

Author

Poggio, P, Rocca, S, Fusella, F, Ferretti, R, Ala, U, D'Anna, F, Giugliano, E, Panuzzo, C, Fontana, D, Palumbo, V, Carrà, G, Taverna, D, Gambacorti-Passerini, C, Saglio, G, Fava, C, Piazza, R, Morotti, A, Orso, F, Brancaccio, M, Poggio, Pietro, Rocca, Stefania, Fusella, Federica, Ferretti, Roberta, Ala, Ugo, D'Anna, Flora, Giugliano, Emilia, Panuzzo, Cristina, Fontana, Diletta, Palumbo, Valeria, Carrà, Giovanna, Taverna, Daniela, Gambacorti-Passerini, Carlo, Saglio, Giuseppe, Fava, Carmen, Piazza, Rocco, Morotti, Alessandro, Orso, Francesca, Brancaccio, Mara, Poggio, P, Rocca, S, Fusella, F, Ferretti, R, Ala, U, D'Anna, F, Giugliano, E, Panuzzo, C, Fontana, D, Palumbo, V, Carrà, G, Taverna, D, Gambacorti-Passerini, C, Saglio, G, Fava, C, Piazza, R, Morotti, A, Orso, F, Brancaccio, M, Poggio, Pietro, Rocca, Stefania, Fusella, Federica, Ferretti, Roberta, Ala, Ugo, D'Anna, Flora, Giugliano, Emilia, Panuzzo, Cristina, Fontana, Diletta, Palumbo, Valeria, Carrà, Giovanna, Taverna, Daniela, Gambacorti-Passerini, Carlo, Saglio, Giuseppe, Fava, Carmen, Piazza, Rocco, Morotti, Alessandro, Orso, Francesca, and Brancaccio, Mara

Abstract

Morgana is a ubiquitous HSP90 co-chaperone protein coded by the CHORDC1 gene. Morgana heterozygous mice develop with age a myeloid malignancy resembling human atypical myeloid leukemia (aCML), now renamed MDS/MPN with neutrophilia. Patients affected by this pathology exhibit low Morgana levels in the bone marrow (BM), suggesting that Morgana downregulation plays a causative role in the human malignancy. A decrease in Morgana expression levels is also evident in the BM of a subgroup of Philadelphia-positive (Ph+) chronic myeloid leukemia (CML) patients showing resistance or an incomplete response to imatinib. Despite the relevance of these data, the mechanism through which Morgana expression is downregulated in patients’ bone marrow remains unclear. In this study, we investigated the possibility that Morgana expression is regulated by miRNAs and we demonstrated that Morgana is under the control of four miRNAs (miR-15a/b and miR-26a/b) and that miR-15a may account for Morgana downregulation in CML patients.

Published
2024

13. Late relapse of chronic myeloid leukemia after allogeneic bone marrow transplantation points to KANSARL (KANSL1::ARL17A) alteration: a case report with insights on the molecular landscape

Author

Fontana, D, Zambrotta, G, Scannella, A, Piazza, R, Gambacorti-Passerini, C, Zambrotta, GPM, Fontana, D, Zambrotta, G, Scannella, A, Piazza, R, Gambacorti-Passerini, C, and Zambrotta, GPM

Abstract

Chronic myeloid leukemia is a myeloproliferative neoplasm characterized by the presence of the Philadelphia chromosome and the consequent BCR::ABL1 oncoprotein. In the era before the introduction of tyrosine kinase inhibitors (TKIs), the only potentially curative treatment was allogeneic hematopoietic stem cell transplantation (HSCT). Here, we present the case of a patient affected by CML who experienced a relapse 20 years after allogeneic HSCT. Following relapse, the patient was treated with imatinib and bosutinib, resulting in a deep molecular response and successfully discontinued treatment. Additional analysis including whole-exome sequencing and RNA sequencing provided some insights on the molecular mechanisms of the relapse: the identification of the fusion transcript KANSL1::ARL17A (KANSARL), a cancer predisposition fusion gene, could justify a condition of genomic instability which may be associated with the onset and/or probably the late relapse of his CML.

Published
2024

14. Repurposing pexmetinib as an inhibitor of TKI-resistant BCR::ABL1

Author

Fontana, D, Malighetti, F, Villa, M, Zambon, A, Gambacorti-Passerini, C, Mologni, L, Gambacorti-Passerini,C, Mologni, L., Fontana, D, Malighetti, F, Villa, M, Zambon, A, Gambacorti-Passerini, C, Mologni, L, Gambacorti-Passerini,C, and Mologni, L.

Published
2024

18. Effect of Different Methods to Synthesize Polyol-Grafted-Cellulose Nanocrystals as Inter-Active Filler in Bio-Based Polyurethane Foams

Author

Fontana, D, Recupido, F, Lama, G, Liu, J, Boggioni, L, Silvano, S, Lavorgna, M, Verdolotti, L, Fontana D., Recupido F., Lama G. C., Liu J., Boggioni L., Silvano S., Lavorgna M., Verdolotti L., Fontana, D, Recupido, F, Lama, G, Liu, J, Boggioni, L, Silvano, S, Lavorgna, M, Verdolotti, L, Fontana D., Recupido F., Lama G. C., Liu J., Boggioni L., Silvano S., Lavorgna M., and Verdolotti L.

Abstract

Currently, the scientific community has spent a lot of effort in developing “green” and environmentally friendly processes and products, due the contemporary problems connected to pollution and climate change. Cellulose nanocrystals (CNCs) are at the forefront of current research due to their multifunctional characteristics of biocompatibility, high mechanical properties, specific surface area, tunable surface chemistry and renewability. However, despite these many advantages, their inherent hydrophilicity poses a substantial challenge for the application of CNCs as a reinforcing filler in polymers, as it complicates their dispersion in hydrophobic polymeric matrices, such as polyurethane foams, often resulting in aggregate structures that compromise their properties. The manipulation and fine-tuning of the interfacial properties of CNCs is a crucial step to exploit their full potential in the development of new materials. In this respect, starting from an aqueous dispersion of CNCs, two different strategies were used to properly functionalize fillers: (i) freeze drying, solubilization in DMA/LiCl media and subsequent grafting with bio-based polyols; (ii) solvent exchange and subsequent grafting with bio-based polyols. The influence of the two functionalization methods on the chemical and thermal properties of CNCs was examined. In both cases, the role of the two bio-based polyols on filler functionalization was elucidated. Afterwards, the functionalized CNCs were used at 5 wt% to produce bio-based composite polyurethane foams and their effect on the morphological, thermal and mechanical properties was examined. It was found that CNCs modified through freeze drying, solubilization and bio-polyols grafting exhibited remarkably higher thermal stability (i.e., degradation stages > 100 °C) with respect to the unmodified freeze dried-CNCs. In addition, the use of the two grafting bio-polyols influenced the functionalization process, corresponding to different amount o

Published
2023

30. Evolutionary signatures of human cancers revealed via genomic analysis of over 35,000 patients

Author

Fontana, D, Crespiatico, I, Crippa, V, Malighetti, F, Villa, M, Angaroni, F, De Sano, L, Aroldi, A, Antoniotti, M, Caravagna, G, Piazza, R, Graudenzi, A, Mologni, L, Ramazzotti, D, Fontana, D, Crespiatico, I, Crippa, V, Malighetti, F, Villa, M, Angaroni, F, De Sano, L, Aroldi, A, Antoniotti, M, Caravagna, G, Piazza, R, Graudenzi, A, Mologni, L, and Ramazzotti, D

Abstract

Recurring sequences of genomic alterations occurring across patients can highlight repeated evolutionary processes with significant implications for predicting cancer progression. Leveraging the ever-increasing availability of cancer omics data, here we unveil cancer’s evolutionary signatures tied to distinct disease outcomes, representing “favored trajectories” of acquisition of driver mutations detected in patients with similar prognosis. We present a framework named ASCETIC (Agony-baSed Cancer EvoluTion InferenCe) to extract such signatures from sequencing experiments generated by different technologies such as bulk and single-cell sequencing data. We apply ASCETIC to (i) single-cell data from 146 myeloid malignancy patients and bulk sequencing from 366 acute myeloid leukemia patients, (ii) multi-region sequencing from 100 early-stage lung cancer patients, (iii) exome/genome data from 10,000+ Pan-Cancer Atlas samples, and (iv) targeted sequencing from 25,000+ MSK-MET metastatic patients, revealing subtype-specific single-nucleotide variant signatures associated with distinct prognostic clusters. Validations on several datasets underscore the robustness and generalizability of the extracted signatures.

Published
2023

31. Myelodysplastic Syndromes/Myeloproliferative Overlap Neoplasms and Differential Diagnosis in the WHO and ICC 2022 Era: A Focused Review

Author

Fontana, D, Elli, E, Pagni, F, Piazza, R, Diletta Fontana, Elena M. Elli, Fabio Pagni, Rocco Piazza, Fontana, D, Elli, E, Pagni, F, Piazza, R, Diletta Fontana, Elena M. Elli, Fabio Pagni, and Rocco Piazza

Abstract

The myelodysplastic syndromes/myeloproliferative neoplasms (MDS/MPN) category comprises a varied group of myeloid neoplastic diseases characterized by clinical and pathologic overlapping features of both myelodysplastic and myeloproliferative neoplasms. For these reasons, these tumors are challenging in terms of diagnosis. The recent World Health Organization (WHO) 2022 classification and the International Consensus Classification (ICC) made changes in the classification of MDS/MPN compared to the previous 2016 WHO classification and improved the diagnostic criteria of these entities. The aim of this review is to describe the main entities reported in the more recent classifications, focusing on chronic myelomonocytic leukemia (CMML), MDS/MPN with neutrophilia (or atypical CML [aCML]), and MDS/MPN with SF3B1 mutation and thrombocytosis/MDS/MPN with ring sideroblasts and thrombocytosis. A particular emphasis is given to the differential diagnosis and analysis of subtle divergences and semantic differences between the WHO classification and the ICC for these entities.

Published
2023

35. Comparison of operative and postoperative characteristics and outcomes between thoracoscopic segmentectomy and lobectomy for non-small-cell lung cancer: a propensity score matching study from the Italian VATS Group Registry

Author

Dell'Amore, A., Lomangino, I., Cannone, G., Terzi, S., Pangoni, A., Lorenzoni, G., Nicotra, S., Schiavon, M., Zuin, A., Gregori, D., Crisci, R., Curcio, C., Rea, F., Mancuso, M., Pernazza, F., Refai, M., Bortolotti, L., Rizzardi, G., Solli, P., Brandolini, I., Perkmann, R., Zaraca, F., Benvenuti, M., Gavezzoli, D., Cherchi, R., Ferrari, P., Mucilli, F., Camplese, P., Melloni, G., Mazza, F., Cavallesco, G., Maniscalco, P., Voltolini, L., Gonfiotti, A., Stella, F., Argnani, D., Pariscenti, G. L., Iurilli, S., Surrente, C., Lopez, C., Droghett, A., Giovanardi, M., Breda, C., Lo Giudice, F., Alloisio, M., Bottoni, E., Spaggiari, L., Gasparri, R., Torre, M., Rinaldo, A., Nosotti, M., Rosso, L., Negri, G. P., Bandiera, A., Stefani, A., Natali, P., Scarci, M., Pirondini, E., Amore, D., Baietto, G., Casadio, C., Bertani, A., Russo, E., Ampollini, L., Carbognani, P., Puma, F., Vinci, D., Andreetti, C., Poggi, C., Cardillo, G., Margaritora, S., Meacci, E., Luzzi, L., Ghisalberti, M., Zaccagna, G., Lausi, P., Guerrera, F., Fontana, D., Della Beffa, V., Morelli, A., Londero, F., Imperatori, N., Rotolo, A., Terzi, A., Viti, A., Infante, M., and Benato, C.

Subjects
Segmentectomy, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Lung Neoplasms, medicine.medical_treatment, VATS lobectomy, Video-assisted thoracic surgery, Context (language use), Mastectomy, Segmental, Postoperative outcome, Postoperative Complications, Lobectomy, Non-small-cell lung cancer, Carcinoma, Non-Small-Cell Lung, Humans, Medicine, Registries, Thoracotomy, Pneumonectomy, Propensity Score, Lung cancer, Retrospective Studies, Thoracic Surgery, Video-Assisted, business.industry, Confounding, Postoperative complication, General Medicine, medicine.disease, Surgery, Propensity score matching, Non small cell, Cardiology and Cardiovascular Medicine, business
Abstract

OBJECTIVES Only few studies compared the surgical morbidity and mortality of thoracoscopic segmentectomy versus lobectomy for non-small-cell lung cancer, in particular, by relating the segmental resections with the corresponding anatomical lobes. METHODS We enrolled a total of 7487 patients who underwent VATS lobectomy (7269) or segmentectomy (218) from January 2014 to July 2019. A propensity score matching approach was used to account for potential confounding factors between the 2 groups. After matching, 349 lobectomies and 208 segmentectomies were included in the analysis. We analysed the operative and postoperative outcomes of video-assisted anatomical segmentectomy compared with video-assisted lobectomy and, in details, the results of segmentectomy with its corresponding lobectomy in a large cohort of patients from the Italian VATS Group Registry. RESULTS The overall conversion rate to thoracotomy was not statistically different between the groups (27 patients 8% vs 7 patients 3%, P = 0.1). The lobectomy group had a greater number of resected lymph nodes (median 11 vs 8, P = 0.006). No significant differences were detected in 30-day mortality (1.4%, 5 patients vs 0.9%, 2 patients), overall complications (18%, 62 patients vs 14%, 29 patients) and prolonged air leakage (31 patients, 9% vs 12 patients, 6%) between lobectomy and segmentectomy, respectively. No statistical differences were found regarding the median duration of drainage (3.2 days, P = 1) and the overall median length of hospital stay (6.4 days, P = 0.1) between the 2 groups. In the context of segmentectomy versus corresponding lobectomy, the right upper lobectomy compared with right upper segmentectomy showed a higher number of resected lymph nodes (P = 0.027). No statistical differences were reported in terms of conversion rate and postoperative complication and mortality. CONCLUSIONS Segmentectomy could be considered a safe procedure without significant differences compared to thoracoscopic lobectomy in terms of postoperative morbidity and mortality.

Published
2021

37. Contributi per una flora vascolare di Toscana. XIV (874-958)

Author

PERUZZI L., VICIANI D., ASTUTI G. BANDINELLI A., BETTINI D., CARTA A., CUTRONEO A., DOMINA G., FERRETTI G., FONTANA D., FRANZONI J., GAVAZZI C., GESTRI G., GIACÒ A., LASTRUCCI L., LAZZARO L., MISURI A., MO A., MUGNAI M., PIERINI B., PINZANI L., ROMA-MARZIO F., SELVI F., STINCA A., TORTA G., VANGELISTI R., BEDINI G., Peruzzi, L., Viciani, D., Astuti, G. BANDINELLI A., Bettini, D., Carta, A., Cutroneo, A., Domina, G., Ferretti, G., Fontana, D., Franzoni, J., Gavazzi, C., Gestri, G., Giacò, A., Lastrucci, L., Lazzaro, L., Misuri, A., Mo, A., Mugnai, M., Pierini, B., Pinzani, L., ROMA-MARZIO, F., Selvi, F., Stinca, A., Torta, G., Vangelisti, R., and Bedini, G.

Published
2022

38. Contributions for a vascular flora of Tuscany. XIV (874-958)

Author

Peruzzi L., Viciani D., Astuti G., Bandinelli A., Bettini D., Carta A., Cutroneo A., Domina G., Ferretti G., Fontana D., Franzoni J., Gavazzi C., Gestri G., Giacò A., Lastrucci L., Lazzaro L., Misuri A., Mo A., Mugnai M., Pierini B., Pinzani L., Roma-Marzio F., Selvi F., Stinca A., Torta G., Vangelisti R., Bedini G., Peruzzi L., Viciani D., Astuti G., Bandinelli A., Bettini D., Carta A., Cutroneo A., Domina G., Ferretti G., Fontana D., Franzoni J., Gavazzi C., Gestri G., Giacò A., Lastrucci L., Lazzaro L., Misuri A., Mo A., Mugnai M., Pierini B., Pinzani L., Roma-Marzio F., Selvi F., Stinca A., Torta G., Vangelisti R., and Bedini G.

Subjects
conservation, flora, Italy, Tuscany, Settore BIO/02 - Botanica Sistematica, Settore BIO/03 - Botanica Ambientale E Applicata
Abstract

New localities and/or confirmations concerning 85 specific and subspecific plant taxa of Tuscan vascular flora, belonging to 68 genera and 36 families are presented: Amaranthus (Amaranthaceae); Allium (Amaryllidaceae); Bifora, Bupleurum (Apiaceae); Arisarum (Araceae); Maianthemum, Ruscus (Asparagaceae); Bidens, Crepis, Galinsoga, Senecio, Taraxacum, Tolpis (Asteraceae); Anchusa, Cerinthe (Boraginaceae); Cakile, Cardamine (Brassicaceae); Butomus (Butomaceae); Campanula (Campanulaceae); Polycarpon, Silene, Stellaria (Caryophyllaceae); Convolvulus (Convolvulaceae); Phedimus (Crassulaceae); Carex, Cyperus, Schoenus (Cyperaceae); Chrozophora, Euphorbia (Euphorbiaceae); Lotus, Medicago, Ononis, Trifolium, Vicia (Fabaceae); Erodium (Geraniaceae); Myriophyllum (Haloragaceae); Philadelphus (Hydrangeaceae); Vallisneria (Hydrocharitaceae); Gladiolus (Iridaceae); Nepeta, Phlomis (Lamiaceae); Tulipa (Liliaceae); Malva (Malvaceae); Epilobium, Oenothera (Onagraceae); Orchis (Orchidaceae); Orobanche (Orobanchaceae); Passiflora (Passifloraceae); Callitriche (Plantaginaceae) Ampelodesmos, Catapodium, Cenchrus, Ceratochloa, Eragrostis, Hordeum, Melica, Nassella, Polypogon, Sclerochloa, Sporobolus (Poaceae); Aquilegia (Ranunculaceae); Rosa (Rosaceae); Asperula, Galium (Rubiaceae); Atropa (Solanaceae); Typha (Typhaceae); Parthenocissus, Vitis (Vitaceae). In the end, the conservation status of the units and eventual protection of the cited biotopes are discussed.

Published
2022

39. Clinical and Molecular features of the patients with Idiopathic Erythrocytosis

Author

Elli, E, Mauri, M, D’Aliberti, D, Crespiatico, I, Fontana, D, Redaelli, S, Pelucchi, S, Manghisi, B, Cavalca, F, Ripamonti, A, Brioschi, F, Palamini, S, Mottadelli, F, Ramazzotti, D, Piperno, A, Gambacorti Passerini, C, Piazza, R, Elli, E, Mauri, M, D’Aliberti, D, Crespiatico, I, Fontana, D, Redaelli, S, Pelucchi, S, Manghisi, B, Cavalca, F, Ripamonti, A, Brioschi, F, Palamini, S, Mottadelli, F, Ramazzotti, D, Piperno, A, Gambacorti Passerini, C, and Piazza, R

Subjects
Idiopathic Erythrocytosis
Published
2022

40. Novel ALK mutations in EML4::ALK+ NSCLC resistant to TKIs identified by liquid biopsy

Author

Villa, M, Malighetti, F, Sharma, G, Arosio, G, Sala, E, Manfroni, C, Fontana, D, Cordani, N, Meneveri, R, Zambon, A, Piazza, R, Pagni, F, Cortinovis, D, Mologni, L, Villa, M, Malighetti, F, Sharma, G, Arosio, G, Sala, E, Manfroni, C, Fontana, D, Cordani, N, Meneveri, R, Zambon, A, Piazza, R, Pagni, F, Cortinovis, D, and Mologni, L

Subjects
ctDNA, ALK+NSCLC
Abstract

SIC47-94

Published
2022

41. Characterization of the transcriptional landscape of atypical Chronic Myeloid Leukemia at single-cell resolution

Author

Fontana, D, Crippa, V, Bassi, G, D'Aliberti, D, Mauri, M, Spinelli, S, Mastini, C, Bombelli, S, Civettini, I, Guglielmana, V, Perego, R, Ramazzotti, D, Mologni, L, Piazza, R, Gambacorti Passerini, C, Fontana, D, Crippa, V, Bassi, G, D'Aliberti, D, Mauri, M, Spinelli, S, Mastini, C, Bombelli, S, Civettini, I, Guglielmana, V, Perego, R, Ramazzotti, D, Mologni, L, Piazza, R, and Gambacorti Passerini, C

Subjects
atypical Chronic Myeloid Leukemia, single-cell
Published
2022

42. Working Conditions and Health Among Italian Ageing Workers

Author

D'Errico, A., Ardito, C., Leombruni, R., Ricceri, F., Costa, G., Sacerdote, C., Odone, A., Amerio, A., Carioli, G., Fontana, D., Frascella, B., Gaetti, G., Gentile, L., Gianfredi, V., Stuckler, D., Vigezzi, G. P., Zengarini, N., D'Errico, A., Ardito, C., Leombruni, R., Ricceri, F., Costa, G., Sacerdote, C., Odone, A., Amerio, A., Carioli, G., Fontana, D., Frascella, B., Gaetti, G., Gentile, L., Gianfredi, V., Stuckler, D., Vigezzi, G. P., and Zengarini, N.

Subjects
Ageing, Retirement, Sociology and Political Science, Arts and Humanities (miscellaneous), Health, Developmental and Educational Psychology, Working conditions, General Social Sciences
Abstract

In many European countries requirements for retirement have been tightened, causing an increase in work participation of older workers, in spite their potentially poorer health may limit their work ability. This study aimed at assessing the diffusion of health problems and exposure to unfavorable working conditions among ageing workers in two Italian surveys, as well as comparing them with those observed in the same surveys conducted before the 2011 Italian pension reform tightening the normal retirement age. The 2013 National Health Survey (NHS) and Labour Force Survey (LFS) were employed to assess the prevalence of poor perceived health, health conditions and functional limitations, and of exposure to physical, psychosocial and organization factors at work, among 60–64 years workers. Poisson regression models were used to estimate Prevalence Ratios of health outcomes and unfavorable working conditions in the two surveys, compared to data from the 2005 (NHS) and 2007 (LFS) corresponding surveys, respectively. Among both men and women, approximately one quarter had at least one physical disorder or functional limitations and 15% poor mental health. Exposure to different ergonomic factors (15–30%) and working during unsocial hours (19%) were particularly diffused. A significant increase in the prevalence of functional limitations and of working at night or during unsocial hours was found in 2013, compared to corresponding data from 2005 and 2007, respectively. Our results indicate that exposure to ergonomic and organizational hazards should be reduced among ageing workers, to avoid decreased work ability, health damage or early exit from the labour market.

Published
2022

43. Molecular Pathogenesis of BCR-ABL-Negative Atypical Chronic Myeloid Leukemia

Author

Fontana, D, Gambacorti Passerini, C, Piazza, R, Fontana D., Gambacorti Passerini C., Piazza R., Fontana, D, Gambacorti Passerini, C, Piazza, R, Fontana D., Gambacorti Passerini C., and Piazza R.

Abstract

Atypical chronic myeloid leukemia is a rare disease whose pathogenesis has long been debated. It currently belongs to the group of myelodysplastic/myeloproliferative disorders. In this review, an overview on the current knowledge about diagnosis, prognosis, and genetics is presented, with a major focus on the recent molecular findings. We describe here the molecular pathogenesis of the disease, focusing on the mechanisms of action of the main mutations as well as on gene expression profiling. We also present the treatment options focusing on emerging targeted therapies.

Published
2021

44. How radical prostatectomy procedures have changed over the last 10 years in Italy: a comparative analysis based on more than 1500 patients participating in the MIRROR-SIU/LUNA and the Pros-IT CNR study

Author

Gacci, M., Artibani, W., Bassi, P., Bertoni, F., Bracarda, S., Briganti, A., Carmignani, G., Carmignani, L., Conti, G., Corvo, R., De Nunzio, C., Fusco, F., Graziotti, P., Greco, I., Maggi, S., Magrini, S. M., Mirone, V., Montironi, R., Morgia, G., Muto, G., Noale, M., Pecoraro, S., Porreca, A., Ricardi, U., Russi, E., Russo, G., Salonia, A., Simonato, A., Serni, S., Tomasini, D., Tubaro, A., Zagonel, V., Crepaldi, G., Conti, G. N., Alitto, A. R., Ambrosi, E., Antonelli, A., Aristei, C., Bardari, F., Bardoscia, L., Barra, S., Bartoncini, S., Basso, U., Becherini, C., Bellavita, R., Bergamaschi, F., Berlingheri, S., Berruti, A., Borghesi, M., Bortolus, R., Borzillo, V., Bosetti, D., Bove, G., Bove, P., Brausi, M., Bruni, A., Bruno, G., Brunocilla, E., Buffoli, A., Buglione, M., Buttigliero, C., Cacciamani, G., Caldiroli, M., Cardo, G., Carrieri, G., Castelli, E., Castrezzati, E., Catalano, G., Cattarino, S., Catucci, F., Cavallini Francolini, D., Ceccarini, O., Celia, A., Chiancone, F., Chini, T., Cianci, C., Cisternino, A., Collura, D., Corbella, F., Corinti, M., Corsi, P., Cortese, F., Corti, L., Decosimo, N., Cristiano, O., Rolando, D. A., Da Pozzo, L., D'Agostino, D., D'Elia, C., Dandrea, M., De Angelis, M., De Angelis, P., De Cobelli, O., De Concilio, B., De Lisa, A., De Luca, S., De Stefani, A., Deantoni, C. L., Degli Esposti, C., Destito, A., Detti, B., Di Muzio, N., Di Stasio, A., Di Stefano, C., Di Trapani, D., Difino, G., Falivene, S., Farullo, G., Fedelini, P., Ferrari, I., Ferrau, F., Ferro, M., Fodor, A., Fontana, F., Francesca, F., Francolini, G., Frata, P., Frezza, G., Gabriele, P., Galeandro, M., Garibaldi, E., Gennari, P. G., Gentilucci, A., Giacobbe, A., Giussani, L., Giusti, G., Gontero, P., Guarneri, A., Guida, C., Gurioli, A., Huqi, D., Imbimbo, C., Ingrosso, G., Iotti, C., Italia, C., La Mattina, P., La Rocca, R., Lamanna, E., Lastrucci, L., Lazzari, G., Liberale, F., Liguori, G., Lisi, R., Lohr, F., Lombardo, R., Lovisolo, J. A., Ludovico, G. M., Macchione, N., Maggio, F., Malizia, M., Manasse, G., Mandoliti, G., Mantini, G., Marafioti, L., Marciello, L., Marconi, A. M., Martilotta, A., Marzano, S., Masciullo, S., Maso, G., Massenzo, A., Mazzeo, E., Mearini, L., Medoro, S., Mole, R., Monesi, G., Montanari, E., Montefiore, F., Montesi, G., Moro, G., Muscas, G., Musio, D., Muto, P., Muzzonigro, G., Napodano, G., Negro, C. L. A., Nidini, M., Ntreta, M., Orsatti, M., Palazzolo, C., Palumbo, I., Parisi, A., Parma, P., Pavan, N., Pericolini, M., Pinto, F., Pistone, A., Pizzuti, V., Platania, A., Polli, C., Pomara, G., Ponti, E., Porcaro, A. B., Porpiglia, F., Pugliese, D., Pycha, A., Raguso, G., Rampini, A., Randone, D. F., Roboldi, V., Roscigno, M., Ruggieri, M. P., Ruoppo, G., Sanseverino, R., Santacaterina, A., Santarsieri, M., Santoni, R., Scagliarini, S., Scagliotti, G. V., Scanzi, M., Scarcia, M., Schiavina, R., Sciarra, A., Sciorio, C., Scolaro, T., Scuzzarella, S., Selvaggio, O., Serao, A., Signor, M. A., Silvani, M., Silvano, G., Silvestris, F., Simeone, C., Simone, V., Spagnoletti, G., Spinelli, M. G., Squillace, L., Tombolini, V., Toninelli, M., Triggiani, L., Trinchieri, A., Trodella, L., Luca, E., Trombetta, C., Tronnolone, L., Tucci, M., Urzi, D., Valdagni, R., Valeriani, M., Vanoli, M., Vitali, E., Volpe, A., Zaramella, S., Zeccolini, G., Zini, G., Acanfora, F., Aiello, E., Alchiede, S., Altieri, V., Anceschi, C., Aragona, F., Balloni, F., Barasolo, E., Barba, G., Bartoletti, R., Bigazzi, B., Belgrano, E., Salvatore, S., Battaglia, M., Bellei, L., Bettin, A., Bianchi, G., Bombieri, L., Brancato, T., Breda, G., Caggiano, S., Calabro, A., Caldironi, M., Campo, B., Capobianco, S., Capparelli, F., Carbone, A., Carlo, D., Catanzaro, F., Ciaraldi, F., Cicalese, V., Corbu, C., Cosciani Cunico, S., Cosentino, V., Crimi, A., Cucchiarale, G., Cuscuna, D., Damiano, R., D'Armiento, M., De Dominicis, C., De Grande, G., Del Boca, C., D'Elia, A., De Mayo, E., De Martin, M., Di Clemente, L., Di Meo, S., Di Monaco, G., Di Nicola, G., Di Silverio, A., Di Silverio, F., Fabri, F., Falsaperla, M., Fanciullacci, F., Ferrari, G., Fiaccavento, G., Filoni, A., Fontana, D., Fontana, G., Ghabin, H., Frea, B., Gaboardi, F., Gentile, V., Giandotti, M., Grasso, M., Grosso, G., Guazzieri, S., Isaia, A., Landi, G., Landolfi, R., Larcher, P., Laurenti, C., Lavelli, D., Leidi, G. L., Lembo, A., Leoni, S., Maffei, N., Maffezzini, M., Martinengo, C., Manieri, C., Martorana, G., Mazza, R., Medica, M., Melloni, D., Miano, L., Micheli, E., Milesi, R., Minervini, M. S., Minocci, D., Molon, A., Morello, P., Motta, M., Narcisi, F., Nicita, G., Palermo, S., Paoluzzi, M., Pompa, P., Porena, M., Raciti, G., Rizzotto, A., Rocco, F., Romano, M., Rossini, L., Russo, G. R., Salvioni, R., Sandri, S., Savoca, G., Selli, C., Selvaggi, F. P., Sercia, F., Tallarigo, C., Tanello, M., Tasca, A., Tenaglia, R., Tensi, M., Terrone, C., Tralce, L., Vagge, A., Valenti, P., Varaldo, M., Vespasiani, G., Vicentini, C., Vicirca, F., Vigano, P., Zaccone, V., Zartar, C., Gacci, M., Artibani, W., Bassi, P., Bertoni, F., Bracarda, S., Briganti, A., Carmignani, G., Carmignani, L., Conti, G., Corvo, R., De Nunzio, C., Fusco, F., Graziotti, P., Greco, I., Maggi, S., Magrini, S. M., Mirone, V., Montironi, R., Morgia, G., Muto, G., Noale, M., Pecoraro, S., Porreca, A., Ricardi, U., Russi, E., Russo, G., Salonia, A., Simonato, A., Serni, S., Tomasini, D., Tubaro, A., Zagonel, V., Crepaldi, G., Conti, G. N., Alitto, A. R., Ambrosi, E., Antonelli, A., Aristei, C., Bardari, F., Bardoscia, L., Barra, S., Bartoncini, S., Basso, U., Becherini, C., Bellavita, R., Bergamaschi, F., Berlingheri, S., Berruti, A., Borghesi, M., Bortolus, R., Borzillo, V., Bosetti, D., Bove, G., Bove, P., Brausi, M., Bruni, A., Bruno, G., Brunocilla, E., Buffoli, A., Buglione, M., Buttigliero, C., Cacciamani, G., Caldiroli, M., Cardo, G., Carrieri, G., Castelli, E., Castrezzati, E., Catalano, G., Cattarino, S., Catucci, F., Cavallini Francolini, D., Ceccarini, O., Celia, A., Chiancone, F., Chini, T., Cianci, C., Cisternino, A., Collura, D., Corbella, F., Corinti, M., Corsi, P., Cortese, F., Corti, L., Decosimo, N., Cristiano, O., Rolando, D. A., Da Pozzo, L., D'Agostino, D., D'Elia, C., Dandrea, M., De Angelis, M., De Angelis, P., De Cobelli, O., De Concilio, B., De Lisa, A., De Luca, S., De Stefani, A., Deantoni, C. L., Degli Esposti, C., Destito, A., Detti, B., Di Muzio, N., Di Stasio, A., Di Stefano, C., Di Trapani, D., Difino, G., Falivene, S., Farullo, G., Fedelini, P., Ferrari, I., Ferrau, F., Ferro, M., Fodor, A., Fontana, F., Francesca, F., Francolini, G., Frata, P., Frezza, G., Gabriele, P., Galeandro, M., Garibaldi, E., Gennari, P. G., Gentilucci, A., Giacobbe, A., Giussani, L., Giusti, G., Gontero, P., Guarneri, A., Guida, C., Gurioli, A., Huqi, D., Imbimbo, C., Ingrosso, G., Iotti, C., Italia, C., La Mattina, P., La Rocca, R., Lamanna, E., Lastrucci, L., Lazzari, G., Liberale, F., Liguori, G., Lisi, R., Lohr, F., Lombardo, R., Lovisolo, J. A., Ludovico, G. M., Macchione, N., Maggio, F., Malizia, M., Manasse, G., Mandoliti, G., Mantini, G., Marafioti, L., Marciello, L., Marconi, A. M., Martilotta, A., Marzano, S., Masciullo, S., Maso, G., Massenzo, A., Mazzeo, E., Mearini, L., Medoro, S., Mole, R., Monesi, G., Montanari, E., Montefiore, F., Montesi, G., Moro, G., Muscas, G., Musio, D., Muto, P., Muzzonigro, G., Napodano, G., Negro, C. L. A., Nidini, M., Ntreta, M., Orsatti, M., Palazzolo, C., Palumbo, I., Parisi, A., Parma, P., Pavan, N., Pericolini, M., Pinto, F., Pistone, A., Pizzuti, V., Platania, A., Polli, C., Pomara, G., Ponti, E., Porcaro, A. B., Porpiglia, F., Pugliese, D., Pycha, A., Raguso, G., Rampini, A., Randone, D. F., Roboldi, V., Roscigno, M., Ruggieri, M. P., Ruoppo, G., Sanseverino, R., Santacaterina, A., Santarsieri, M., Santoni, R., Scagliarini, S., Scagliotti, G. V., Scanzi, M., Scarcia, M., Schiavina, R., Sciarra, A., Sciorio, C., Scolaro, T., Scuzzarella, S., Selvaggio, O., Serao, A., Signor, M. A., Silvani, M., Silvano, G., Silvestris, F., Simeone, C., Simone, V., Spagnoletti, G., Spinelli, M. G., Squillace, L., Tombolini, V., Toninelli, M., Triggiani, L., Trinchieri, A., Trodella, L., Luca, E., Trombetta, C., Tronnolone, L., Tucci, M., Urzi, D., Valdagni, R., Valeriani, M., Vanoli, M., Vitali, E., Volpe, A., Zaramella, S., Zeccolini, G., Zini, G., Acanfora, F., Aiello, E., Alchiede, S., Altieri, V., Anceschi, C., Aragona, F., Balloni, F., Barasolo, E., Barba, G., Bartoletti, R., Bigazzi, B., Belgrano, E., Salvatore, S., Battaglia, M., Bellei, L., Bettin, A., Bianchi, G., Bombieri, L., Brancato, T., Breda, G., Caggiano, S., Calabro, A., Caldironi, M., Campo, B., Capobianco, S., Capparelli, F., Carbone, A., Carlo, D., Catanzaro, F., Ciaraldi, F., Cicalese, V., Corbu, C., Cosciani Cunico, S., Cosentino, V., Crimi, A., Cucchiarale, G., Cuscuna, D., Damiano, R., D'Armiento, M., De Dominicis, C., De Grande, G., Del Boca, C., D'Elia, A., De Mayo, E., De Martin, M., Di Clemente, L., Di Meo, S., Di Monaco, G., Di Nicola, G., Di Silverio, A., Di Silverio, F., Fabri, F., Falsaperla, M., Fanciullacci, F., Ferrari, G., Fiaccavento, G., Filoni, A., Fontana, D., Fontana, G., Ghabin, H., Frea, B., Gaboardi, F., Gentile, V., Giandotti, M., Grasso, M., Grosso, G., Guazzieri, S., Isaia, A., Landi, G., Landolfi, R., Larcher, P., Laurenti, C., Lavelli, D., Leidi, G. L., Lembo, A., Leoni, S., Maffei, N., Maffezzini, M., Martinengo, C., Manieri, C., Martorana, G., Mazza, R., Medica, M., Melloni, D., Miano, L., Micheli, E., Milesi, R., Minervini, M. S., Minocci, D., Molon, A., Morello, P., Motta, M., Narcisi, F., Nicita, G., Palermo, S., Paoluzzi, M., Pompa, P., Porena, M., Raciti, G., Rizzotto, A., Rocco, F., Romano, M., Rossini, L., Russo, G. R., Salvioni, R., Sandri, S., Savoca, G., Selli, C., Selvaggi, F. P., Sercia, F., Tallarigo, C., Tanello, M., Tasca, A., Tenaglia, R., Tensi, M., Terrone, C., Tralce, L., Vagge, A., Valenti, P., Varaldo, M., Vespasiani, G., Vicentini, C., Vicirca, F., Vigano, P., Zaccone, V., Zartar, C., Gacci M., Artibani W., Bassi P., Bertoni F., Bracarda S., Briganti A., Carmignani G., Carmignani L., Conti G., Corvo R., De Nunzio C., Fusco F., Graziotti P., Greco I., Maggi S., Magrini S.M., Mirone V., Montironi R., Morgia G., Muto G., Noale M., Pecoraro S., Porreca A., Ricardi U., Russi E., Russo G., Salonia A., Simonato A., Serni S., Tomasini D., Tubaro A., Zagonel V., Crepaldi G., Conti G.N., Alitto A.R., Ambrosi E., Antonelli A., Aristei C., Bardari F., Bardoscia L., Barra S., Bartoncini S., Basso U., Becherini C., Bellavita R., Bergamaschi F., Berlingheri S., Berruti A., Borghesi M., Bortolus R., Borzillo V., Bosetti D., Bove G., Bove P., Brausi M., Bruni A., Bruno G., Brunocilla E., Buffoli A., Buglione M., Buttigliero C., Cacciamani G., Caldiroli M., Cardo G., Carrieri G., Castelli E., Castrezzati E., Catalano G., Cattarino S., Catucci F., Cavallini Francolini D., Ceccarini O., Celia A., Chiancone F., Chini T., Cianci C., Cisternino A., Collura D., Corbella F., Corinti M., Corsi P., Cortese F., Corti L., deCosimo N., Cristiano O., Rolando D.A., Da Pozzo L., D'Agostino D., D'Elia C., Dandrea M., De Angelis M., De Angelis P., De Cobelli O., De Concilio B., De Lisa A., De Luca S., De Stefani A., Deantoni C.L., Degli Esposti C., Destito A., Detti B., Di Muzio N., Di Stasio A., Di Stefano C., Di Trapani D., Difino G., Falivene S., Farullo G., Fedelini P., Ferrari I., Ferrau F., Ferro M., Fodor A., Fontana F., Francesca F., Francolini G., Frata P., Frezza G., Gabriele P., Galeandro M., Garibaldi E., Gennari P.G., Gentilucci A., Giacobbe A., Giussani L., Giusti G., Gontero P., Guarneri A., Guida C., Gurioli A., Huqi D., Imbimbo C., Ingrosso G., Iotti C., Italia C., La Mattina P., La Rocca R., Lamanna E., Lastrucci L., Lazzari G., Liberale F., Liguori G., Lisi R., Lohr F., Lombardo R., Lovisolo J.A., Ludovico G.M., Macchione N., Maggio F., Malizia M., Manasse G., Mandoliti G., Mantini G., Marafioti L., Marciello L., Marconi A.M., Martilotta A., Marzano S., Masciullo S., Maso G., Massenzo A., Mazzeo E., Mearini L., Medoro S., Mole R., Monesi G., Montanari E., Montefiore F., Montesi G., Moro G., Muscas G., Musio D., Muto P., Muzzonigro G., Napodano G., Negro C.L.A., Nidini M., Ntreta M., Orsatti M., Palazzolo C., Palumbo I., Parisi A., Parma P., Pavan N., Pericolini M., Pinto F., Pistone A., Pizzuti V., Platania A., Polli C., Pomara G., Ponti E., Porcaro A.B., Porpiglia F., Pugliese D., Pycha A., Raguso G., Rampini A., Randone D.F., Roboldi V., Roscigno M., Ruggieri M.P., Ruoppo G., Sanseverino R., Santacaterina A., Santarsieri M., Santoni R., Scagliarini S., Scagliotti G.V., Scanzi M., Scarcia M., Schiavina R., Sciarra A., Sciorio C., Scolaro T., Scuzzarella S., Selvaggio O., Serao A., Signor M.A., Silvani M., Silvano G., Silvestris F., Simeone C., Simone V., Spagnoletti G., Spinelli M.G., Squillace L., Tombolini V., Toninelli M., Triggiani L., Trinchieri A., Trodella L., Luca E., Trombetta C., Tronnolone L., Tucci M., Urzi D., Valdagni R., Valeriani M., Vanoli M., Vitali E., Volpe A., Zaramella S., Zeccolini G., Zini G., Acanfora F., Aiello E., Alchiede S., Altieri V., Anceschi C., Aragona F., Balloni F., Barasolo E., Barba G., Bartoletti R., Bigazzi B., Belgrano E., Salvatore S., Battaglia M., Bellei L., Bettin A., Bianchi G., Bombieri L., Brancato T., Breda G., Caggiano S., Calabro A., Caldironi M., Campo B., Capobianco S., Capparelli F., Carbone A., Carlo D., Catanzaro F., Ciaraldi F., Cicalese V., Corbu C., Cosciani Cunico S., Cosentino V., Crimi A., Cucchiarale G., Cuscuna D., Damiano R., D'Armiento M., De Dominicis C., De Grande G., Del Boca C., D'Elia A., De Mayo E., De Martin M., Di Clemente L., Di Meo S., Di Monaco G., Di Nicola G., Di Silverio A., Di Silverio F., Fabri F., Falsaperla M., Fanciullacci F., Ferrari G., Fiaccavento G., Filoni A., Fontana D., Fontana G., Ghabin H., Frea B., Gaboardi F., Gentile V., Giandotti M., Grasso M., Grosso G., Guazzieri S., Isaia A., Landi G., Landolfi R., Larcher P., Laurenti C., Lavelli D., Leidi G.L., Lembo A., Leoni S., Maffei N., Maffezzini M., Martinengo C., Manieri C., Martorana G., Mazza R., Medica M., Melloni D., Miano L., Micheli E., Milesi R., Minervini M.S., Minocci D., Molon A., Morello P., Motta M., Narcisi F., Nicita G., Palermo S., Paoluzzi M., Pompa P., Porena M., Raciti G., Rizzotto A., Rocco F., Romano M., Rossini L., Russo G.R., Salvioni R., Sandri S., Savoca G., Selli C., Selvaggi F.P., Sercia F., Tallarigo C., Tanello M., Tasca A., Tenaglia R., Tensi M., Terrone C., Tralce L., Vagge A., Valenti P., Varaldo M., Vespasiani G., Vicentini C., Vicirca F., Vigano P., Zaccone V., Zartar C., Gacci, Mauro, Artibani, Walter, Bassi, Pierfrancesco, Bertoni, Filippo, Bracarda, Sergio, Briganti, Alberto, Carmignani, Giorgio, Carmignani, Luca, Conti, Giario, Corvò, Renzo, De Nunzio, Cosimo, Fusco, Ferdinando, Graziotti, Pierpaolo, Greco, Isabella, Maggi, Stefania, Magrini, Stefano Maria, Mirone, Vincenzo, Montironi, Rodolfo, Morgia, Giuseppe, Muto, Giovanni, Noale, Marianna, Pecoraro, Stefano, Porreca, Angelo, Ricardi, Umberto, Russi, Elvio, Russo, Giorgio, Salonia, Andrea, Simonato, Alchiede, Serni, Sergio, Tomasini, Davide, Tubaro, Andrea, Zagonel, Vittorina, and Crepaldi, Gaetano

Subjects
Male, Nephrology, medicine.medical_specialty, Time Factors, Urology, medicine.medical_treatment, 030232 urology & nephrology, Lymph node dissection, Logistic regression, 03 medical and health sciences, Prostate cancer, 0302 clinical medicine, Internal medicine, LUNA study, Biopsy, Humans, Medicine, Prospective Studies, Nerve sparing, Lymph node, Aged, Prostatectomy, medicine.diagnostic_test, business.industry, MIRROR SIU/LUNA study, Lymph node dissection, MIRROR SIU/LUNA study, Nerve sparing, Pros-IT CNR study, Prostate cancer, Robotic procedures, Prostatic Neoplasms, Cancer, Pros-IT CNR study, Middle Aged, medicine.disease, MIRROR SIU, Dissection, Robotic procedures, Logistic Models, medicine.anatomical_structure, Italy, 030220 oncology & carcinogenesis, business
Abstract

Purpose Therapeutic strategies for prostate cancer (PCa) have been evolving dramatically worldwide. The current article reports on the evolution of surgical management strategies for PCa in Italy. Methods The data from two independent Italian multicenter projects, the MIRROR-SIU/LUNA (started in 2007, holding data of 890 patients) and the Pros-IT-CNR project (started in 2014, with data of 692 patients), were compared. Differences in patients' characteristics were evaluated. Multivariable logistic regression models were used to identify characteristics associated with robot-assisted (RA) procedure, nerve sparing (NS) approach, and lymph node dissection (LND). Results The two cohorts did not differ in terms of age and prostate-specific antigen (PSA) levels at biopsy. Patients enrolled in the Pros-IT-CNR project more frequently were submitted to RA (58.8% vs 27.6%,p < 0.001) and NS prostatectomy (58.4% vs. 52.9%,p = 0.04), but received LND less frequently (47.7% vs. 76.7%,p < 0.001), as compared to the MIRROR-SIU/LUNA patients. At multivariate logistic models, Lower Gleason Scores (GS) and PSA levels were significantly associated with RA prostatectomy in both cohorts. As for the MIRROR-SIU/LUNA data, clinical T-stage was a predictor for NS (OR = 0.07 for T3, T4) and LND (OR = 2.41 for T2) procedures. As for Pros-IT CNR data, GS >= (4 + 3) and positive cancer cores >= 50% were decisive factors both for NS (OR 0.29 and 0.30) and LND (OR 7.53 and 2.31) strategies. Conclusions PCa management has changed over the last decade in Italian centers: RA and NS procedures without LND have become the methods of choice to treat newly medium-high risk diagnosed PCa.

Published
2021

47. Phase two study of crizotinib in patients with anaplastic lymphoma kinase (ALK) positive anaplastic large cell lymphoma relapsed/refractory to chemotherapy

Author

Bossi, E, Aroldi, A, Brioschi, F, Steidl, C, Baretta, S, Renso, R, Verga, L, Fontana, D, Sharma, G, Mologni, L, Mussolin, L, Piazza, R, Gambacorti Passerini, C, Bossi E., Aroldi A., Brioschi F. A., Steidl C., Baretta S., Renso R., Verga L., Fontana D., Sharma G. G., Mologni L., Mussolin L., Piazza R., Gambacorti Passerini C., Bossi, E, Aroldi, A, Brioschi, F, Steidl, C, Baretta, S, Renso, R, Verga, L, Fontana, D, Sharma, G, Mologni, L, Mussolin, L, Piazza, R, Gambacorti Passerini, C, Bossi E., Aroldi A., Brioschi F. A., Steidl C., Baretta S., Renso R., Verga L., Fontana D., Sharma G. G., Mologni L., Mussolin L., Piazza R., and Gambacorti Passerini C.

Published
2020

48. Increased tumor burden in patients with chronic myeloid leukemia after 36 months of imatinib discontinuation

Author

Diral, E, Mori, S, Antolini, L, Abruzzese, E, Le Coutre, P, Martino, B, Pungolino, E, Elena, C, Bergamaschi, M, Assouline, S, Di Bona, E, Gozzini, A, Andrade-Campos, M, Stagno, F, Iurlo, A, Pirola, A, Fontana, D, Petiti, J, Bonanomi, M, Crivori, P, Piazza, R, Fava, C, Gambacorti Passerini, C, Diral E., Mori S., Antolini L., Abruzzese E., Le Coutre P., Martino B., Pungolino E., Elena C., Bergamaschi M., Assouline S., Di Bona E., Gozzini A., Andrade-Campos M., Stagno F., Iurlo A., Pirola A., Fontana D., Petiti J., Bonanomi M. L., Crivori P., Piazza R., Fava C., Gambacorti Passerini C., Diral, E, Mori, S, Antolini, L, Abruzzese, E, Le Coutre, P, Martino, B, Pungolino, E, Elena, C, Bergamaschi, M, Assouline, S, Di Bona, E, Gozzini, A, Andrade-Campos, M, Stagno, F, Iurlo, A, Pirola, A, Fontana, D, Petiti, J, Bonanomi, M, Crivori, P, Piazza, R, Fava, C, Gambacorti Passerini, C, Diral E., Mori S., Antolini L., Abruzzese E., Le Coutre P., Martino B., Pungolino E., Elena C., Bergamaschi M., Assouline S., Di Bona E., Gozzini A., Andrade-Campos M., Stagno F., Iurlo A., Pirola A., Fontana D., Petiti J., Bonanomi M. L., Crivori P., Piazza R., Fava C., and Gambacorti Passerini C.

Abstract

TO THE EDITOR: The Imatinib Suspension and Validation (ISAV) study1 is a multicenter trial of imatinib discontinuation (ID) among patients with chronic myeloid leukemia (CML) in undetectable deep molecular remission (U-DMR). After 12 months of follow-up, 48% of patients relapsed (total n = 107), with the majority of relapses occurring within the first 9 months. An inverse relationship between patient age and risk of relapse was also observed at this timepoint. Here we report the final results of ISAV after a median follow-up of 49 months, as well as the dynamics of leukemic tumor load as determined by digital polymerase chain reaction (dPCR) in nonrelapsed patients. This trial is registered at www.clinicaltrials.gov (NCT01578213). Eligible patients were 18 years and older and had CML, either in chronic or accelerated phase, with U-DMR of at least 18 months’ duration and at least...

Published
2020

49. ETNK1 mutations induce a mutator phenotype that can be reverted with phosphoethanolamine

Author

Fontana, D, Mauri, M, Renso, R, Docci, M, Crespiatico, I, Rost, L, Jang, M, Niro, A, D'Aliberti, D, Massimino, L, Bertagna, M, Zambrotta, G, Bossi, M, Citterio, S, Crescenzi, B, Fanelli, F, Cassina, V, Corti, R, Salerno, D, Nardo, L, Chinello, C, Mantegazza, F, Mecucci, C, Magni, F, Cavaletti, G, Bruheim, P, Rea, D, Larsen, S, Gambacorti-Passerini, C, Piazza, R, Fontana D., Mauri M., Renso R., Docci M., Crespiatico I., Rost L. M., Jang M., Niro A., D'Aliberti D., Massimino L., Bertagna M., Zambrotta G., Bossi M., Citterio S., Crescenzi B., Fanelli F., Cassina V., Corti R., Salerno D., Nardo L., Chinello C., Mantegazza F., Mecucci C., Magni F., Cavaletti G., Bruheim P., Rea D., Larsen S., Gambacorti-Passerini C., Piazza R., Fontana, D, Mauri, M, Renso, R, Docci, M, Crespiatico, I, Rost, L, Jang, M, Niro, A, D'Aliberti, D, Massimino, L, Bertagna, M, Zambrotta, G, Bossi, M, Citterio, S, Crescenzi, B, Fanelli, F, Cassina, V, Corti, R, Salerno, D, Nardo, L, Chinello, C, Mantegazza, F, Mecucci, C, Magni, F, Cavaletti, G, Bruheim, P, Rea, D, Larsen, S, Gambacorti-Passerini, C, Piazza, R, Fontana D., Mauri M., Renso R., Docci M., Crespiatico I., Rost L. M., Jang M., Niro A., D'Aliberti D., Massimino L., Bertagna M., Zambrotta G., Bossi M., Citterio S., Crescenzi B., Fanelli F., Cassina V., Corti R., Salerno D., Nardo L., Chinello C., Mantegazza F., Mecucci C., Magni F., Cavaletti G., Bruheim P., Rea D., Larsen S., Gambacorti-Passerini C., and Piazza R.

Abstract

Recurrent somatic mutations in ETNK1 (Ethanolamine-Kinase-1) were identified in several myeloid malignancies and are responsible for a reduced enzymatic activity. Here, we demonstrate in primary leukemic cells and in cell lines that mutated ETNK1 causes a significant increase in mitochondrial activity, ROS production, and Histone H2AX phosphorylation, ultimately driving the increased accumulation of new mutations. We also show that phosphoethanolamine, the metabolic product of ETNK1, negatively controls mitochondrial activity through a direct competition with succinate at mitochondrial complex II. Hence, reduced intracellular phosphoethanolamine causes mitochondria hyperactivation, ROS production, and DNA damage. Treatment with phosphoethanolamine is able to counteract complex II hyperactivation and to restore a normal phenotype.

Published
2020

50. ETNK1 mutations in atypical chronic myeloid leukemia induce a mutator phenotype that can be reverted with phosphoethanolamine

Author

Fontana, D, Mauri, M, Renso, R, Docci, M, Crespiatico, I, Rost, L, Jang, M, Niro, A, D'Aliberti, D, Massimino, L, Bertagna, M, Zambrotta, G, Bossi, M, Citterio, S, Crescenzi, B, Fanelli, F, Cassina, V, Corti, R, Salerno, D, Nardo, L, Chinello, C, Mantegazza, F, Mecucci, C, Magni, F, Cavaletti, G, Bruheim, P, Rea, D, Larsen, S, Piazza, R, Gambacorti-Passerini, C, Fontana D., Mauri M., Renso R., Docci M., Crespiatico I., Rost L. M., Jang M., Niro A., D'Aliberti D., Massimino L., Bertagna M., Zambrotta G., Bossi M., Citterio S., Crescenzi B., Fanelli F., Cassina V., Corti R., Salerno D., Nardo L., Chinello C., Mantegazza F., Mecucci C., Magni F., Cavaletti G., Bruheim P., Rea D., Larsen S., Piazza R., Gambacorti-Passerini C., Fontana, D, Mauri, M, Renso, R, Docci, M, Crespiatico, I, Rost, L, Jang, M, Niro, A, D'Aliberti, D, Massimino, L, Bertagna, M, Zambrotta, G, Bossi, M, Citterio, S, Crescenzi, B, Fanelli, F, Cassina, V, Corti, R, Salerno, D, Nardo, L, Chinello, C, Mantegazza, F, Mecucci, C, Magni, F, Cavaletti, G, Bruheim, P, Rea, D, Larsen, S, Piazza, R, Gambacorti-Passerini, C, Fontana D., Mauri M., Renso R., Docci M., Crespiatico I., Rost L. M., Jang M., Niro A., D'Aliberti D., Massimino L., Bertagna M., Zambrotta G., Bossi M., Citterio S., Crescenzi B., Fanelli F., Cassina V., Corti R., Salerno D., Nardo L., Chinello C., Mantegazza F., Mecucci C., Magni F., Cavaletti G., Bruheim P., Rea D., Larsen S., Piazza R., and Gambacorti-Passerini C.

Published
2020

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