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51. Humoral and cellular immune response in patients with hematological disorders after two doses of BNT162b2 mRNA COVID-19 vaccine: A single-center prospective observational study (NCT05074706)

Author

Bossi, E, Aroldi, A, Borin, L, Verga, L, Fontana, D, Cocito, F, Manghisi, B, Rindone, G, Cavalca, F, Ripamonti, A, Raggi, M, Malandrin, S, Cavallero, A, Antolini, L, Bonardi, D, Piazza, R, Gambacorti-Passerini, C, Bossi, Elisa, Aroldi, Andrea, Borin, Lorenza Maria, Verga, Luisa, Fontana, Diletta, Cocito, Federica, Manghisi, Beatrice, Rindone, Giovanni, Cavalca, Fabrizio, Ripamonti, Alessia, Raggi, Monica, Malandrin, Sergio Maria Ivano, Cavallero, Annalisa, Antolini, Laura, Bonardi, Diego, Piazza, Rocco Giovanni, Gambacorti-Passerini, Carlo, Bossi, E, Aroldi, A, Borin, L, Verga, L, Fontana, D, Cocito, F, Manghisi, B, Rindone, G, Cavalca, F, Ripamonti, A, Raggi, M, Malandrin, S, Cavallero, A, Antolini, L, Bonardi, D, Piazza, R, Gambacorti-Passerini, C, Bossi, Elisa, Aroldi, Andrea, Borin, Lorenza Maria, Verga, Luisa, Fontana, Diletta, Cocito, Federica, Manghisi, Beatrice, Rindone, Giovanni, Cavalca, Fabrizio, Ripamonti, Alessia, Raggi, Monica, Malandrin, Sergio Maria Ivano, Cavallero, Annalisa, Antolini, Laura, Bonardi, Diego, Piazza, Rocco Giovanni, and Gambacorti-Passerini, Carlo

Abstract

Hematological patients at higher risk of severe COVID-19 were excluded from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine trials. In this single-center observational prospective study (NCT05074706), we evaluate immune response in the hematological patients followed at the Hematological Division of San Gerardo Hospital, Monza (Italy) deemed to be severely immunosuppressed after vaccination with two doses of the BNT162b2 vaccine. Anti-SARS-CoV-2 immunoglobulin G titers above the cutoff value of 33.8 BAU/ml were detected in 303 (80.2%) out of the 378 patients enrolled. Patients with lymphoproliferative disorders had a significant lower probability of immunization (43.2% vs. 88.4%, p < 0.001). Patients treated with anti-CD20 showed a significantly lower probability of immunization compared to all other treatments (21.4%, p < 0.0001). Among 69 patients who failed seroconversion, 15 patients (22.7%) showed a positive T-cell response. Patients previously treated with anti-CD20 were 2.4 times more likely to test positive for T-cell responses (p = 0.014). Within a follow-up of 9 months from the second COVID-19 vaccination, symptomatic SARS-CoV-2 infections were reported by 20 patients (5.3%) and four of them required hospitalization. Successful serological or T-cell-mediated immunization conferred protection from symptomatic COVID-19. Patients treated with anti-CD20 who were not seroconverted after vaccination might still be protected from COVID-19 due to the T-cell immune response.

Published
2022

52. Caution in using second generation tyrosine kinase inhibitor, especially for first line therapy of chronic myeloid leukemia

Author

Gambacorti-Passerini, C, Nicolini, F, Larson, R, Aroldi, A, Fontana, D, Piazza, R, le Coutre, P, Antolini, L, Assouline, S, Gambacorti-Passerini, Carlo, Nicolini, Franck Emmanuel, Larson, Richard A, Aroldi, Andrea, Fontana, Diletta, Piazza, Rocco, le Coutre, Philipp, Antolini, Laura, Assouline, Sarit, Gambacorti-Passerini, C, Nicolini, F, Larson, R, Aroldi, A, Fontana, D, Piazza, R, le Coutre, P, Antolini, L, Assouline, S, Gambacorti-Passerini, Carlo, Nicolini, Franck Emmanuel, Larson, Richard A, Aroldi, Andrea, Fontana, Diletta, Piazza, Rocco, le Coutre, Philipp, Antolini, Laura, and Assouline, Sarit

Published
2022

53. Validation of a new NGS-based myeloid panel in acute myeloid leukemia: A single-center experience

Author

Steidl, C, Aroldi, A, Mologni, L, Crespiatico, I, Fontana, D, Mastini, C, Fumagalli, M, Perfetti, P, Borin, L, Valentini, C, Piazza, R, Gambacorti-Passerini, C, Steidl, Carolina, Aroldi, Andrea, Mologni, Luca, Crespiatico, Ilaria, Fontana, Diletta, Mastini, Cristina, Fumagalli, Monica, Perfetti, Paola, Borin, Lorenza, Valentini, Claudia, Piazza, Rocco, Gambacorti-Passerini, Carlo, Steidl, C, Aroldi, A, Mologni, L, Crespiatico, I, Fontana, D, Mastini, C, Fumagalli, M, Perfetti, P, Borin, L, Valentini, C, Piazza, R, Gambacorti-Passerini, C, Steidl, Carolina, Aroldi, Andrea, Mologni, Luca, Crespiatico, Ilaria, Fontana, Diletta, Mastini, Cristina, Fumagalli, Monica, Perfetti, Paola, Borin, Lorenza, Valentini, Claudia, Piazza, Rocco, and Gambacorti-Passerini, Carlo

Abstract

Acute myeloid leukemia (AML) identifies a heterogeneous group of clonal disorders, both clinically and genetically. A large number of mutations have been described in AML, although only a few are currently employed in clinical practice. Next generation sequencing (NGS) allows for better understanding of the complex genetic background in AML and may direct individualized therapies. In this study, we aim to identify molecular aberrations that are not routinely investigated in AML using an NGS-based panel encompassing 101 genes and to evaluate how their oncogenic potential correlates with survival. Forty consecutive patients with newly diagnosed AML were enrolled between January 2018 and April 2020. We performed targeted NGS and detected 96 mutations in 36 patients (90%), while 14 fusion genes were detected in 13 patients (32%). Each mutation was weighed using OncoScore, a text-mining tool ranking genes according to their oncogenic potential. An OncoScore >= 100 was associated with shorter PFS among our patients (p = 0.05). In 11 patients with no available MRD markers at diagnosis, we were able to perform NGS-based MRD monitoring using targeted deep sequencing. Overall, our study shows that NGS is a powerful tool in AML and should be employed both in routine diagnostic workup and follow up.

Published
2022

54. Large-Scale Analysis of SARS-CoV-2 Synonymous Mutations Reveals the Adaptation to the Human Codon Usage During the Virus Evolution

Author

Ramazzotti, D, Angaroni, F, Maspero, D, Mauri, M, D’Aliberti, D, Fontana, D, Antoniotti, M, Elli, E, Graudenzi, A, Piazza, R, Ramazzotti, Daniele, Angaroni, Fabrizio, Maspero, Davide, Mauri, Mario, D’Aliberti, Deborah, Fontana, Diletta, Antoniotti, Marco, Elli, Elena Maria, Graudenzi, Alex, Piazza, Rocco, Ramazzotti, D, Angaroni, F, Maspero, D, Mauri, M, D’Aliberti, D, Fontana, D, Antoniotti, M, Elli, E, Graudenzi, A, Piazza, R, Ramazzotti, Daniele, Angaroni, Fabrizio, Maspero, Davide, Mauri, Mario, D’Aliberti, Deborah, Fontana, Diletta, Antoniotti, Marco, Elli, Elena Maria, Graudenzi, Alex, and Piazza, Rocco

Abstract

Many large national and transnational studies have been dedicated to the analysis of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) genome, most of which focused on missense and nonsense mutations. However, approximately 30 per cent of the SARS-CoV-2 variants are synonymous, therefore changing the target codon without affecting the corresponding protein sequence. By performing a large-scale analysis of sequencing data generated from almost 400,000 SARS-CoV-2 samples, we show that silent mutations increasing the similarity of viral codons to the human ones tend to fixate in the viral genome overtime. This indicates that SARS-CoV-2 codon usage is adapting to the human host, likely improving its effectiveness in using the human aminoacyl-tRNA set through the accumulation of deceitfully neutral silent mutations. One-Sentence Summary. Synonymous SARS-CoV-2 mutations related to the activity of different mutational processes may positively impact viral evolution by increasing its adaptation to the human codon usage.

Published
2022

56. Transition to retirement impact on health and lifestyle habits: analysis from a nationwide Italian cohort

Author

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

Subjects
Adult, medicine.medical_specialty, Population, Health Promotion, Overweight, smoking, Habits, Self-rated health, Epidemiology, medicine, Humans, education, Life Style, Aged, Retirement, education.field_of_study, ageing, retirement, self-rated, business.industry, Physical activity, Research, Public health, Ageing, Cohort study, Health behaviour, Italy, Middle Aged, Public Health, Environmental and Occupational Health, Cohort, Propensity score matching, medicine.symptom, Public aspects of medicine, RA1-1270, business, Demography
Abstract

Background Retirement is a life-course transition likely to affect, through different mechanisms, behavioural risk factors’ patterns and, ultimately, health outcomes. We assessed the impact of transitioning to retirement on lifestyle habits and perceived health status in a nationwide cohort of Italian adults. Methods We analysed data from a large cohort of Italian adults aged 55–70, derived from linking six waves of the Participation, Labour, Unemployment Survey (PLUS), a national survey representative of the Italian workforce population, conducted between 2010 and 2018. We estimated relative-risk ratios (RRR) of transition to retirement and their corresponding 95% confidence intervals (CIs) for selected behavioural risk factors and health outcomes using multivariable logistic regression models. We used propensity score matching (PSM) to account for potential confounders. Results We included 5169 subjects in the study population, of which 1653 retired between 2010 and 2018 (exposed, 32%). Transition to retirement was associated with a 36% increased probability of practising sports (RRR 1.36, 95% CI 1.12–1.64). No statistically significant changes were reported for smoking habit (current smoker RRR: 1.18, 95% CI 0.94–1.46) and BMI (overweight/obese RRR: 0.96, 95% CI 0.81–1.15). Overall, retiring was associated with improved self-rated health status (RRR 1.26, 95% CI 1.02–1.58). Conclusion Individual data-linkage of multiple waves of the PLUS can offer great insight to inform healthy ageing policies in Italy and Europe. Transition to retirement has an independent effect on perceived health status, physical activity and selected behavioural risk factors. It should be identified as a target moment for preventive interventions, with particular reference to primary prevention so as to promote health and wellbeing in older ages.

Published
2021

57. Synergistic drug combinations preventdrug resistance in anaplastic large cell lymphomapreclinical models

Author

Sharma, G, Arosio, G, Villa, M, Mauri, M, Zappa, M, Magistroni, V, Ceccon, M, Redaelli, S, Crespiatico, I, Fontana, D, Mastini, C, Garbin, A, Lovisa, F, Mussolin, L, Piazza, R, Gambacorti Passerini, C, Mologni, L, Sharma, G, Arosio, G, Villa, M, Mauri, M, Zappa, M, Magistroni, V, Ceccon, M, Redaelli, S, Crespiatico, I, Fontana, D, Mastini, C, Garbin, A, Lovisa, F, Mussolin, L, Piazza, R, Gambacorti Passerini, C, and Mologni, L

Subjects
drug combinations, anaplastic large cell lymphoma
Published
2021

61. Phase ii study with crizotinib in patients with anaplastic lymphoma kinase (alk)-positive lymphoma relapsed/refractory to chemotherapy

Author

Bossi, E, Brioschi, F, Steidl, C, Baretta, S, Cantu, S, Verga, L, Fontana, D, Sharma, G, Mologni, L, Mussolin, L, Piazza, R, Gambacorti Passerini, C, Bossi E, Brioschi FA, Steidl C, Baretta S, Cantu S, Verga L, Fontana D, Sharma GG, Mologni L, Mussolin L, Piazza RG, Gambacorti Passerini C, Bossi, E, Brioschi, F, Steidl, C, Baretta, S, Cantu, S, Verga, L, Fontana, D, Sharma, G, Mologni, L, Mussolin, L, Piazza, R, Gambacorti Passerini, C, Bossi E, Brioschi FA, Steidl C, Baretta S, Cantu S, Verga L, Fontana D, Sharma GG, Mologni L, Mussolin L, Piazza RG, and Gambacorti Passerini C

Abstract

Crizotinib, an inhibitor of anaplastic lymphoma kinase (ALK) and cros oncogene 1 (ROS1), is approved for treatment of patients with ALKpositive or ROS1-positive advanced non-small-cell lung cancer. However, ALK rearrangements, are also implicated in anaplastic largecell lymphoma, mainly the fusion-protein NPM-ALK. ALK-positive lymphomas respond to chemotherapy, but relapses, which bear a poor prognosis, develop in more than 50% of patients. In this ongoing, single-center, single-arm, phase II study, Crizotinib was administered as monotherapy with a starting dose of 250 mg twice daily to 11 ALK+ lymphoma patients who had progression of disease after at least one line of cytotoxic therapy. Patients were enrolled at the Department of Haematology, San Gerardo Hospital, Monza (Italy) from April 2015 to October 2018. Median number of previous cytotoxic treatments was 3 (range 2-6). Median age at diagnosis was 32 years (range 18-58 years) and 5/11 patients were male. The overall response rate (ORR) was 7 of 11 (63.6%; 95% CI = 35% to 85%). All responding patients achieved complete remission and negativity for the NPM-ALK transcript by Real Time Polymerase Chain Reaction (RT-PCR). Median follow up is 10 months (range 2-48). Disease status at the latest follow up is as follows: 6 patients are in complete response under continuous crizotinib administration, 4 patients had progression of disease and died, 1 patient stopped the treatment and was in complete response after allogenic bone marrow transplantation. All relapses developed within the first 3 months of therapy. The two-years Progression Free Survival (PFS) and Overall Survival (OS, see attached Figure 1) are 65% (95% CI = 53% to 77%) and 70% (CI = 61% to 79%), respectively. The most common treatment related adverse events were diarrhea (90.9%), oedema lower legs (100%), vomiting (72.7%) and visual disorders (36.4%). All adverse events were Grade 1 or 2 and most of them were transient in nature. Crizotinib shows a good

Published
2019

62. Uniportal and three-portal video-assisted thoracic surgery lobectomy: analysis of the Italian video-assisted thoracic surgery group database

Author

Tosi, D, Nosotti, M, Bonitta, G, Mazzucco, A, Righi, I, Mendogni, P, Rosso, L, Palleschi, A, Rocco, G, Crisci, R, Mancuso, M, Pernazza, F, Refai, M, Bortolotti, L, Rizzardi, G, Gargiulo, G, Dolci, Gp, 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, Gl, Lurilli, Surrente, C, Lopez, C, Droghetti, A, Giovanardi, M, Breda, C, Lo Giudice, F, Alloisio, M, Bottoni, E, Spaggiari, L, Gasparri, R, Torre, M, Rinaldo, A, Negri, Gp, Bandiera, A, Stefani, A, Natali, P, Scarci, M, Pirondini, E, Curcio, C, Amore, D, Baietto, G, Casadio, C, Nicotra, S, Dell'Amore, A, Bertani, A, Russo, E, Ampollini, L, Carbognani, P, Puma, F, Vinci, D, Andreetti, C, Poggi, C, Cardillo, G, Margaritora, S, Meacci, Elisa, Luzzi, L, Ghisalberti, M, Zaccagna, G, Lausi, P, Guerrera, F, Fontana, D, Della Beffa, V, Morelli, A, Londero, F, Imperatori, A, Rotolo, N, Terzi, A, Viti, A, Infante, M, Benato, C, Tosi, D., Nosotti, M., Bonitta, G., Mazzucco, A., Righi, I., Mendogni, P., Rosso, L., Palleschi, A., Rocco, G., Crisci, R., Mancuso, M., Pernazza, F., Refai, M., Bortolotti, L., Rizzardi, G., Gargiulo, 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., Stella, F., Argnani, D., Pariscenti, G. L., Surrente, C., Lopez, C., Droghetti, A., Giovanardi, M., Breda, C., Lo Giudice, F., Alloisio, M., Bottoni, E., Spaggiari, L., Gasparri, R., Torre, M., Rinaldo, A., Negri, G, Bandiera, A., Stefani, A., Natali, P., Scarci, M., Pirondini, E., Curcio, C., Amore, D., Baietto, G., Casadio, C., Nicotra, S., Dell'Amore, A., 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, A., Rotolo, N., Terzi, A., Viti, A., Infante, M., Benato, C., Tosi D., Nosotti M., Bonitta G., Mazzucco A., Righi I., Mendogni P., Rosso L., Palleschi A., Rocco G., Crisci R., Mancuso M., Pernazza F., Refai M., Bortolotti L., Rizzardi G., Gargiulo 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., Stella F., Argnani D., Pariscenti G.L., Surrente C., Lopez C., Droghetti A., Giovanardi M., Breda C., Lo Giudice F., Alloisio M., Bottoni E., Spaggiari L., Gasparri R., Torre M., Rinaldo A., Negri G.P., Bandiera A., Stefani A., Natali P., Scarci M., Pirondini E., Curcio C., Amore D., Baietto G., Casadio C., Nicotra S., Dell'amore A., 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 A., Rotolo N., Terzi A., Viti A., Infante M., and Benato C.

Subjects
Male, Lung Neoplasms, Thoracic, Italian VATS Group, computer.software_genre, Postoperative pain, Settore MED/21 - CHIRURGIA TORACICA, Carcinoma, Non-Small-Cell Lung, Lobectomy, Three-portal, Uniportal, Video-assisted thoracic surgery, Aged, Equipment Design, Female, Humans, Neoplasm Staging, Operative Time, Pneumonectomy, Retrospective Studies, Thoracic Surgery, Video-Assisted, Tomography, X-Ray Computed, Stage (cooking), Non-Small-Cell Lung, Tomography, Database, Thoracic Surgery, X-Ray Computed, Cardiothoracic surgery, Cohort, Cardiology and Cardiovascular Medicine, Pulmonary and Respiratory Medicine, Italian VATS Group, Lobectomy, Postoperative pain, Three-portal, Uniportal, Video-assisted thoracic surgery, medicine.medical_specialty, VATS lobectomy, Video-Assisted, NO, medicine, Lung cancer, business.industry, Carcinoma, Odds ratio, medicine.disease, Confidence interval, Propensity score matching, Surgery, business, computer
Abstract

OBJECTIVES This study compares the uniportal with the 3-portal video-assisted thoracic surgery (VATS) by examining the data collected in the Italian VATS Group Database. The primary end point was early postoperative pain; secondary end points were intraoperative and postoperative complications, surgical time, number of dissected lymph nodes and length of stay. METHODS This was an observational, retrospective, cohort, multicentre study on data collected by 49 Italian thoracic units. Inclusion criteria were clinical stage I–II non-small-cell lung cancer, uniportal or 3-portal VATS lobectomy and R0 resection. Exclusion criteria were cT3 disease, previous thoracic malignancy, induction therapy, significant comorbidities and conversion to other techniques. The pain parameter was dichotomized: the numeric rating scale ≤3 described mild pain, whereas the numeric rating scale score >3 described moderate/severe pain. The propensity score-adjusted generalized estimating equation was used to compare the uniportal with 3-portal lobectomy. RESULTS Among 4338 patients enrolled from January 2014 to July 2017, 1980 met the inclusion criteria; 1808 patients underwent 3-portal lobectomy and 172 uniportal surgery. The adjusted generalized estimating equation regression model using the propensity score showed that over time pain decreased in both groups (P CONCLUSIONS Data from the Italian VATS Group Database showed that in clinical practice uniportal lobectomy seems to entail a higher risk of moderate/severe pain on second and third postoperative days.

Published
2019

67. Miocene Seep-Carbonates of the Northern Apennines (Emilia to Umbria, Italy): An Overview

Author

Conti, S, Argentino, C, Fioroni, C, Salocchi, Ac, and Fontana, D

Subjects
lcsh:Geology, VDP::Mathematics and natural science: 400::Geosciences: 450::Marine geology: 466, northern Apennines, lcsh:QE1-996.5, VDP::Matematikk og Naturvitenskap: 400::Geofag: 450::Marin geologi: 466, seep-carbonates, cold seepage, Miocene, accretionary wedge
Abstract

The natural emission of methane-rich fluids from the seafloor, known as cold seepage, is a widespread process at modern continental margins. The studies on present-day cold seepages provide high-resolution datasets regarding the fluid plumbing system, biogeochemical processes in the sediment, seafloor seepage distribution and ecosystems. However, the long-term (hundreds of thousands to millions of years) evolution of cold seepage remains elusive. The identification and study of outcrop analogous now exposed on land represent a valuable method for better understanding the effects of geological processes and climate forcing on the development of cold seepage systems. Here, we provide an overview on Miocene seep-carbonate deposits of the northern Apennines (from Emilia to the Umbria-Marchean sector, Italy), based on decades of field research integrated with detailed sedimentological and geochemical investigations. We report a total of 13 seep-carbonate outcrops, which formed in three different structural settings of the paleo-accretionary wedge corresponding to wedge-top basins, outer slope and intrabasinal highs at the deformational front. We discuss the recurring lithostratigraphic occurrence of seep deposits and the main compositional features (carbonate facies, carbon and oxygen stable isotopes) in order to interpret the seepage dynamics, duration and infer the contribution of methane-rich fluids released by paleo-gas hydrates. The datasets presented in this study represent a valuable complete record of cold seepage spanning ~12 Myr, that can be used to better understand factors controlling the regional-scale spatial and temporal evolution of cold seepage systems at modern active continental margins.

Published
2021

68. Impact of ETNK1 somatic mutations on phosphoethanolamine synthesis, ROS production and DNA damage

Author

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

Abstract

Recently we showed that Ethanolamine Kinase 1 (ETNK1) mutations cause a decreased synthesis of phosphoethanolamine, and that phosphoethanolamine is able to modulate mitochondrial activity through competition with succinate for complex II. The decreased phosphoethanolamine concentration leads to increased mitochondria activity and reactive oxygen species production, which causes the accumulation of new mutations.

Published
2021

69. Synergistic drug combinations prevent resistance in ALK+ anaplastic large cell lymphoma

Author

Arosio, G, Sharma, G, Villa, M, Mauri, M, Crespiatico, I, Fontana, D, Manfroni, C, Mastini, C, Zappa, M, Magistroni, V, Ceccon, M, Redaelli, S, Massimino, L, Garbin, A, Lovisa, F, Mussolin, L, Piazza, R, Gambacorti Passerini, C, Mologni, L, Sharma, GG, Arosio, G, Sharma, G, Villa, M, Mauri, M, Crespiatico, I, Fontana, D, Manfroni, C, Mastini, C, Zappa, M, Magistroni, V, Ceccon, M, Redaelli, S, Massimino, L, Garbin, A, Lovisa, F, Mussolin, L, Piazza, R, Gambacorti Passerini, C, Mologni, L, and Sharma, GG

Abstract

Anaplastic lymphoma kinase‐positive (ALK+) anaplastic large‐cell lymphoma (ALCL) is a subtype of non‐Hodgkin lymphoma characterized by expression of the oncogenic NPM/ALK fusion protein. When resistant or relapsed to front‐line chemotherapy, ALK+ ALCL prognosis is very poor. In these patients, the ALK inhibitor crizotinib achieves high response rates, however 30–40% of them develop further resistance to crizotinib monotherapy, indicating that new therapeutic approaches are needed in this population. We here investigated the efficacy of upfront rational drug combinations to prevent the rise of resistant ALCL, in vitro and in vivo. Different combinations of crizotinib with CHOP chemotherapy, decitabine and trametinib, or with second‐generation ALK inhibitors, were investigated. We found that in most cases combined treatments completely suppressed the emergence of resistant cells and were more effective than single drugs in the long‐term control of lymphoma cells expansion, by inducing deeper inhibition of oncogenic signaling and higher rates of apoptosis. Combinations showed strong synergism in different ALK‐dependent cell lines and better tumor growth inhibition in mice. We propose that drug combinations that include an ALK inhibitor should be considered for first‐line treatments in ALK+ ALCL.

Published
2021

74. Phase ii study with crizotinib in patients with anaplastic lymphoma kinase (alk)-positive lymphoma relapsed/refractory to chemotherapy

Author

Bossi E, Brioschi FA, Steidl C, Baretta S, Cantu S, Verga L, Fontana D, Sharma GG, Mologni L, Mussolin L, Piazza RG, Gambacorti Passerini C, Bossi, E, Brioschi, F, Steidl, C, Baretta, S, Cantu, S, Verga, L, Fontana, D, Sharma, G, Mologni, L, Mussolin, L, Piazza, R, and Gambacorti Passerini, C

Subjects
Crizotinib, anaplastic lymphoma kinase (ALK), crosoncogene 1 (ROS1), relapsed/refractory ALK+ lymphoma
Abstract

Crizotinib, an inhibitor of anaplastic lymphoma kinase (ALK) and cros oncogene 1 (ROS1), is approved for treatment of patients with ALKpositive or ROS1-positive advanced non-small-cell lung cancer. However, ALK rearrangements, are also implicated in anaplastic largecell lymphoma, mainly the fusion-protein NPM-ALK. ALK-positive lymphomas respond to chemotherapy, but relapses, which bear a poor prognosis, develop in more than 50% of patients. In this ongoing, single-center, single-arm, phase II study, Crizotinib was administered as monotherapy with a starting dose of 250 mg twice daily to 11 ALK+ lymphoma patients who had progression of disease after at least one line of cytotoxic therapy. Patients were enrolled at the Department of Haematology, San Gerardo Hospital, Monza (Italy) from April 2015 to October 2018. Median number of previous cytotoxic treatments was 3 (range 2-6). Median age at diagnosis was 32 years (range 18-58 years) and 5/11 patients were male. The overall response rate (ORR) was 7 of 11 (63.6%; 95% CI = 35% to 85%). All responding patients achieved complete remission and negativity for the NPM-ALK transcript by Real Time Polymerase Chain Reaction (RT-PCR). Median follow up is 10 months (range 2-48). Disease status at the latest follow up is as follows: 6 patients are in complete response under continuous crizotinib administration, 4 patients had progression of disease and died, 1 patient stopped the treatment and was in complete response after allogenic bone marrow transplantation. All relapses developed within the first 3 months of therapy. The two-years Progression Free Survival (PFS) and Overall Survival (OS, see attached Figure 1) are 65% (95% CI = 53% to 77%) and 70% (CI = 61% to 79%), respectively. The most common treatment related adverse events were diarrhea (90.9%), oedema lower legs (100%), vomiting (72.7%) and visual disorders (36.4%). All adverse events were Grade 1 or 2 and most of them were transient in nature. Crizotinib shows a good safety profile and carries out a potent antitumor activity with durable responses in advanced pretreated ALK+ lymphoma patients. Crizotinib should be made available for patients with relapsed/refractory ALK+ lymphoma.

Published
2019

75. What counts more: The patient, the surgical technique, or the hospital? A multivariable analysis of factors affecting perioperative complications of pulmonary lobectomy by video-assisted thoracoscopic surgery from a large nationwide registry

Author

Infante, Maurizio V, Benato, Cristiano, Silva, Ronaldo, Rocco, Gaetano, Bertani, Alessandro, Bertolaccini, Luca, Gonfiotti, Alessandro, Giovannetti, Riccardo, Bonadiman, Cinzia, Lonardoni, Alessandro, Canneto, Barbara, Falezza, Giovanni, Gandini, Paola, Curcio, Carlo, Crisci, Roberto, Alloisio, M, Amore, D, Ampollini, L, Andreetti, C, Argnani, D, Baietto, G, Bandiera, A, Benato, C, Benvenuti, M, Bertani, A, Bertolaccini, L, Bortolotti, L, Bottoni, E, Breda, C, Camplese, P, Carbognani, P, Cardillo, G, Casadio, C, Cavallesco, G, Cherchi, R, Crisci, R, Curcio, C, Dell'Amore, A, Beffa, V, Dolci, G, Droghetti, A, Ferrari, Pa, Fontana, D, Gargiulo, G, Gasparri, R, Gavezzoli, D, Ghisalberti, M, Giovanardi, M, Gonfiotti, A, Guerrera, F, Imperatori, A, Infante, M, Iurilli, L, Lausi, P, Logiudice, F, Londero, F, Lopez, C, Luzzi, L, Mancuso, M, Maniscalco, P, Margaritora, S, Meacci, E, Melloni, G, Morelli, A, Mucilli, F, Natali, P, Negri, G, Nicotra, S, Nosotti, M, Pariscenti, G, Perkmann, R, Pernazza, F, Pirondini, E, Poggi, C, Puma, F, Refai, M, Rinaldo, A, Rizzardi, G, Rosso, L, Rotolo, N, Russo, E, Sabbatini, A, Scarci, M, Spaggiari, L, Stefani, A, Solli, P, Surrente, C, Terzi, A, Torre, M, Vinci, D, Viti, A, Voltolini, L, Zaccagna, G, Zaraca, F., Infante M.V., Benato C., Silva R., Rocco G., Bertani A., Bertolaccini L., Gonfiotti A., Giovannetti R., Bonadiman C., Lonardoni A., Canneto B., Falezza G., Gandini P., Curcio C., Crisci R., Zaraca F., Alloisio M., Amore D., Ampollini L., Andreetti C., Argnani D., Baietto G., Bandiera A., Benvenuti M., Bortolotti L., Bottoni E., Breda C., Camplese P., Carbognani P., Cardillo G., Casadio C., Cavallesco G., Cherchi R., Dell'Amore A., Beffa V., Dolci G., Droghetti A., Ferrari P.A., Fontana D., Gargiulo G., Gasparri R., Gavezzoli D., Ghisalberti M., Giovanardi M., Guerrera F., Imperatori A., Iurilli L., Lausi P., Lo Giudice F., Londero F., Lopez C., Luzzi L., Mancuso M., Maniscalco P., Margaritora S., Meacci E., Melloni G., Morelli A., Mucilli F., Natali P., Negri G., Nicotra S., Nosotti M., Pariscenti G., Perkmann R., Pernazza F., Pirondini E., Poggi C., Puma F., Refai M., Rinaldo A., Rizzardi G., Rosso L., Rotolo N., Russo E., Sabbatini A., Scarci M., Spaggiari L., Stefani A., Solli P., Surrente C., Terzi A., Torre M., Vinci D., Viti A., Voltolini L., Zaccagna G., Infante, M. V., Benato, C., Silva, R., Rocco, G., Bertani, A., Bertolaccini, L., Gonfiotti, A., Giovannetti, R., Bonadiman, C., Lonardoni, A., Canneto, B., Falezza, G., Gandini, P., Curcio, C., Crisci, R., the Italian VATS group, Member, and Negri, G.

Subjects
Male, Registrie, Conversion, Morbidity, Postoperative complications, Video-assisted thoracoscopic surgery lobectomy, Lung Neoplasms, Intraoperative Complication, Aged, Female, Hospitals, Humans, Intraoperative Complications, Lung, Middle Aged, Pneumonectomy, Postoperative Complications, Registries, Retrospective Studies, Risk Factors, Thoracic Surgery, Video-Assisted, medicine.medical_treatment, Interquartile range, Retrospective Studie, Settore MED/21 - CHIRURGIA TORACICA, Conversion, Morbidity, Postoperative complications, Video-assisted thoracoscopic surgery lobectomy, Thoracic Surgery, General Medicine, Video-assisted thoracoscopic surgery, Cardiology and Cardiovascular Medicine, Human, Pulmonary and Respiratory Medicine, medicine.medical_specialty, VATS lobectomy, Video-Assisted, NO, Hospital, medicine, business.industry, Risk Factor, Retrospective cohort study, Perioperative, medicine.disease, Comorbidity, Surgery, Postoperative complication, Lung Neoplasm, Complication, business
Abstract

OBJECTIVESInherent technical aspects of pulmonary lobectomy by video-assisted thoracoscopic surgery (VATS) may limit surgeons’ ability to deal with factors predisposing to complications. We analysed complication rates after VATS lobectomy in a prospectively maintained nationwide registry.METHODSThe registry was queried for all consecutive VATS lobectomy procedures from 49 Italian Thoracic Units. Baseline condition, tumour features, surgical techniques, devices, postoperative care, complications, conversions and the reasons thereof were detailed. Univariable and multivariable regressions were used to assess factors potentially linked to complications.RESULTSFour thousand one hundred and ninety-one VATS lobectomies in 4156 patients (2480 men, 1676 women) were analysed. The median age-adjusted Charlson index of the patients was 4 (interquartile range 3–6). Grade 1 and 2 and Grade 3–5 complications were observed in 20.1% and in 5.8%, respectively. Ninety-day mortality was 0.55%. The overall conversion rate was 9.2% and significantly higher in low-volume centres (CONCLUSIONSVATS lobectomy is a safe procedure even in medically compromised patients. An improved classification system for conversions is proposed and prevention strategies are suggested to reduce conversion rates and possibly complications in less-experienced centres.

Published
2019

76. Recent advances on hydrometallurgical recovery of critical and precious elements from end of life electronic wastes - a review

Author

Sethurajan M., van Hullebusch E. D., Fontana D., Akcil A., Deveci H., Batinic B., Leal J. P., Gasche T. A., Ali Kucuker M., Kuchta K., Neto I. F. F., Soares H. M. V. M., Chmielarz A., Sethurajan, M., van Hullebusch, E. D., Fontana, D., Akcil, A., Deveci, H., Batinic, B., Leal, J. P., Gasche, T. A., Ali Kucuker, M., Kuchta, K., Neto, I. F. F., Soares, H. M. V. M., and Chmielarz, A.

Subjects
Critical raw materials, WEEEs, Critical and precious metals, E-Wastes, Hydrometallurgy, Metal selective recovery, Rare earth elements, Critical and precious metal, Rare earth element, E-Waste, Critical raw material
Abstract

Waste electrical and electronic equipment (WEEE) contains economically significant levels of precious, critical metals and rare earth elements, apart from base metals and other toxic compounds. Recycling and recovery of critical elements from WEEEs using a cost-effective technology are now one of the top priorities in metallurgy due to the rapid depletion of their natural resources. More than 150 publications on WEEE management, leaching and recovery of metals from WEEE were reviewed in this work, with special emphasize on the recent research (2015–2018). This paper summarizes the recent progress regarding various hydrometallurgical processes for the leaching of critical elements from WEEEs. Various methodologies and techniques for critical elements selective recovery (using ionic liquids, solvent extraction, electrowinning, adsorption, and precipitation) from the WEEEs leachates are discussed. Future prospects regarding the use of WEEEs as secondary resources for critical raw materials and its techno-economical and commercial beneficiaries are discussed. AbbreviationsE-Waste Electronic wasteWEEE Waste electrical and electronic equipmentCRM Critical raw materialsPCB Printed circuit boardLCD Liquid crystal displayCRT Cathode ray tubeFl. Lamp Fluorescent lampHDD Hard disk drivesLED Light emitting diodeEU European UnionUNEP United Nations Environmental ProgramREE Rare earth elementITO Indium-tin oxidePM Precious metalNiMH battery Nickel-hydride batteryCPU Central processing unitRAM Random access memoryLiBs Li-ion batteriesSFL Spent fluorescent lamps.

Published
2019

77. Paired Exome Sequencing Reveals Recurrent Germline Variants in Patients with Idiopathic Erythrocytosis

Author

Mauri, M, Elli, E, D'Aliberti, D, Crespiatico, I, Nava, M, Massimino, L, Sharma, G, Fontana, D, Redaelli, S, Bombelli, S, Pelucchi, S, Perego, R, Piperno, A, Gambacorti Passerini, C, Piazza, R, Mauri, M, Elli, E, D'Aliberti, D, Crespiatico, I, Nava, M, Massimino, L, Sharma, G, Fontana, D, Redaelli, S, Bombelli, S, Pelucchi, S, Perego, R, Piperno, A, Gambacorti Passerini, C, and Piazza, R

Subjects
Idiopathic Erythrocytosis
Published
2019

78. Erratum: Identification of 4-Phenoxyquinoline Based Inhibitors for L1196M Mutant of Anaplastic Lymphoma Kinase by Structure-Based Design (Journal of Medicinal Chemistry (2017) 60:22 (9205-9221) DOI: 10.1021/acs.jmedchem.7b01039)

Author

Mah, S, Park, J, Jung, H, Ahn, K, Choi, S, Tae, H, Jung, K, Rho, J, Lee, J, Passerini, C, Fontana, D, Hong, S, Mah S, Park JH, Jung HY, Ahn K, Choi S, Tae HS, Jung KH, Rho JK, Lee JC, Passerini CG, Fontana D, Hong SS, Hong S, Mah, S, Park, J, Jung, H, Ahn, K, Choi, S, Tae, H, Jung, K, Rho, J, Lee, J, Passerini, C, Fontana, D, Hong, S, Mah S, Park JH, Jung HY, Ahn K, Choi S, Tae HS, Jung KH, Rho JK, Lee JC, Passerini CG, Fontana D, Hong SS, and Hong S

Abstract

Page 9205. We are adding two authors (Carlo Gambacorti Passerini and Diletta Fontana) and their affiliation (Department of Health Science, University of Milano-Bicocca, via Cadore, 48, 20900 Monza, Italy). Page 9219. In the Acknowledgments, the sentence needs to be added that “All Ba/F3 ALK WT and mutant cell lines were kindly provided by University of Milano-Bicocca (UNIMIB)”.

Published
2018

79. Erratum: Identification of 4-Phenoxyquinoline Based Inhibitors for L1196M Mutant of Anaplastic Lymphoma Kinase by Structure-Based Design (Journal of Medicinal Chemistry (2017) 60:22 (9205-9221) DOI: 10.1021/acs.jmedchem.7b01039)

Author

Mah S, Mah, S, Park, J, Jung, H, Ahn, K, Choi, S, Tae, H, Jung, K, Rho, J, Lee, J, Passerini, C, Fontana, D, Hong, S, Mah S, Park JH, Jung HY, Ahn K, Choi S, Tae HS, Jung KH, Rho JK, Lee JC, Passerini CG, Fontana D, Hong SS, Hong S, Mah S, Mah, S, Park, J, Jung, H, Ahn, K, Choi, S, Tae, H, Jung, K, Rho, J, Lee, J, Passerini, C, Fontana, D, Hong, S, Mah S, Park JH, Jung HY, Ahn K, Choi S, Tae HS, Jung KH, Rho JK, Lee JC, Passerini CG, Fontana D, Hong SS, and Hong S

Abstract

Page 9205. We are adding two authors (Carlo Gambacorti Passerini and Diletta Fontana) and their affiliation (Department of Health Science, University of Milano-Bicocca, via Cadore, 48, 20900 Monza, Italy). Page 9219. In the Acknowledgments, the sentence needs to be added that “All Ba/F3 ALK WT and mutant cell lines were kindly provided by University of Milano-Bicocca (UNIMIB)”.

Published
2018

80. Predictors of nodal upstaging in patients with cT1-3N0 non-small cell lung cancer (NSCLC): results from the Italian VATS Group Registry

Author

Marulli, G., Faccioli, E., Mammana, M., Nicotra, S., Comacchio, G., Verderi, E., De Palma, A., Curcio, C., Rea, F., Bertani, A., Russo, E., Voltolini, L., Gonfiotti, A., Nosotti, M., Rosso, L., Muriana, G., Droghetti, A., Crisci, R., Zaccagna, G., Amore, D., di Rienzo, G., Lopez, C., Morelli, A., Londero, F., Spaggiari, L., Gasparri, R., Baietto, G., Casadio, C., Infante, M., Benato, C, Alloisio, M., Bottoni, E, Cardillo, G., Carleo, F., Stella, F., Dolci, G., Puma, F., Vinci, D., Cavallesco, G., Maniscalco, P., Ampollini, L., Carbognani, P., Terzi, A., Viti, A, Negri, G., Bandiera, A., Perkmann, R., Zaraca, F., Andreetti, C., Poggi, C., Mucilli, F., Camplese, P., Luzzi, L., Ghisalberti, M., Imperatori, A., Rotolo, N., Bortolotti, L., Rizzardi, G., Torre, M., Rinaldo, A., Sabbatini, A., Refai, M., Benvenuti, M. R., Benetti, D., Stefani, A., Natali, P., Lausi, P., Guerrera, F., Melloni, G., Mazza, F., Argnani, D., Sanna, S., Fontana, D., Beffa, V. D., Meda, S., Pernazza, F. a, and Italian VATS Group

Subjects
Oncology, Male, Lung Neoplasms, medicine.medical_treatment, non-small cell lung cancer (NSCLC), Nodal upstaging, VATS lobectomy, 0302 clinical medicine, Risk Factors, Carcinoma, Non-Small-Cell Lung, 80 and over, Registries, Non-Small-Cell Lung, Child, Pneumonectomy, GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries), Aged, 80 and over, Thoracic Surgery, Video-Assisted, Thoracic Surgery, General Medicine, Middle Aged, Lymph node dissection, Mediastinal staging, Predictive risk factors, Adolescent, Adult, Aged, Disease Progression, Female, Humans, Italy, Lymph Node Excision, Neoplasm Staging, Predictive Value of Tests, Young Adult, 030220 oncology & carcinogenesis, Predictive value of tests, 030211 gastroenterology & hepatology, Lymph node dissection, Mediastinal staging, Nodal upstaging, Predictive risk factors, VATS lobectomy, medicine.medical_specialty, Video-Assisted, NO, 03 medical and health sciences, Internal medicine, medicine, In patient, business.industry, Disease progression, Carcinoma, medicine.disease, Surgery, Neoplasm staging, business
Abstract

Accurate staging of early non-small cell lung cancer is fundamental for selecting the best treatment. The aim of this study was to identify risk factors for nodal upstaging after video-assisted thoracoscopic lobectomy for clinical T1-3N0 tumors.From 2014 to 2017, 3276 thoracoscopic lobectomies were recorded in the prospective database "Italian VATS Group". Linear and multiple logistic regression models were adapted to identify independent predictors of nodal upstaging and factors associated with progression in postoperative N status.Nodal upstaging was found in 417 cases (12.7%), including 206 cases (6.2%) of N1-positive nodes, 81 cases of N2 nodes (2.4%), and 130 cases (4%) of involvement of both N1 + N2 nodes. A total of 241 (7.3%) patients had single-station nodal involvement, whereas 176 (5.3%) had multiple-station involvement. In the final regression model, the tumor grade, histology, pathologic T status, and 12 resected nodes were independent predictors of nodal upstaging.The number of resected lymph nodes seems to predict nodal upstaging better than the type of intraoperative lymph node management. Other preoperative risk factors correspond to those for which the current guidelines of the European Society of Thoracic Surgery recommend more extensive preoperative mediastinal staging.

Published
2020

81. Correction to: Predictors of nodal upstaging in patients with cT1-3N0 non-small cell lung cancer (NSCLC): results from the Italian VATS Group Registry (Surgery Today, (2020), 50, 7, (711-718), 10.1007/s00595-019-01939-x)

Author

Marulli, G., Faccioli, E., Mammana, M., Nicotra, S., Comacchio, G., Verderi, E., De Palma, A., Curcio, C., Rea, F., Bertani, A., Russo, E., Voltolini, L., Gonfiotti, A., Nosotti, M., Rosso, L., Muriana, G., Droghetti, A., Crisci, R., Zaccagna, G., Amore, D., di Rienzo, G., Lopez, C., Morelli, A., Londero, F., Spaggiari, L., Gasparri, R., Baietto, G., Casadio, C., Infante, M., Benato, C., Alloisio, M., Bottoni, E., Cardillo, G., Carleo, F., Stella, F., Dolci, G., Puma, F., Vinci, D., Cavallesco, G., Maniscalco, P., Ampollini, L., Carbognani, P., Terzi, A., Viti, A., Negri, G., Bandiera, A., Perkmann, R., Zaraca, F., Andreetti, C., Poggi, C., Mucilli, F., Camplese, P., Luzzi, L., Ghisalberti, M., Imperatori, A., Rotolo, N., Bortolotti, L., Rizzardi, G., Torre, M., Rinaldo, A., Sabbatini, A., Refai, M., Benvenuti, M. R., Benetti, D., Stefani, A., Natali, P., Lausi, P., Guerrera, F., Melloni, G., Mazza, F., Argnani, D., Sanna, S., Fontana, D., Beffa, V. D., Meda, S., and Pernazza, F.

Subjects
NO
Published
2020

83. Integrated Genomic, Functional, and Prognostic Characterization of Atypical Chronic Myeloid Leukemia

Author

Fontana, D, Ramazzotti, D, Aroldi, A, Redaelli, S, Magistroni, V, Pirola, A, Niro, A, Massimino, L, Mastini, C, Brambilla, V, Bombelli, S, Bungaro, S, Morotti, A, Rea, D, Stagno, F, Martino, B, Campiotti, L, Caocci, G, Usala, E, Merli, M, Onida, F, Bregni, M, Elli, E, Fumagalli, M, Ciceri, F, Perego, R, Pagni, F, Mologni, L, Piazza, R, Gambacorti-Passerini, C, Fontana, Diletta, Ramazzotti, Daniele, Aroldi, Andrea, Redaelli, Sara, Magistroni, Vera, Pirola, Alessandra, Niro, Antonio, Massimino, Luca, Mastini, Cristina, Brambilla, Virginia, Bombelli, Silvia, Bungaro, Silvia, Morotti, Alessandro, Rea, Delphine, Stagno, Fabio, Martino, Bruno, Campiotti, Leonardo, Caocci, Giovanni, Usala, Emilio, Merli, Michele, Onida, Francesco, Bregni, Marco, Elli, Elena Maria, Fumagalli, Monica, Ciceri, Fabio, Perego, Roberto A, Pagni, Fabio, Mologni, Luca, Piazza, Rocco, Gambacorti-Passerini, Carlo, Fontana, D, Ramazzotti, D, Aroldi, A, Redaelli, S, Magistroni, V, Pirola, A, Niro, A, Massimino, L, Mastini, C, Brambilla, V, Bombelli, S, Bungaro, S, Morotti, A, Rea, D, Stagno, F, Martino, B, Campiotti, L, Caocci, G, Usala, E, Merli, M, Onida, F, Bregni, M, Elli, E, Fumagalli, M, Ciceri, F, Perego, R, Pagni, F, Mologni, L, Piazza, R, Gambacorti-Passerini, C, Fontana, Diletta, Ramazzotti, Daniele, Aroldi, Andrea, Redaelli, Sara, Magistroni, Vera, Pirola, Alessandra, Niro, Antonio, Massimino, Luca, Mastini, Cristina, Brambilla, Virginia, Bombelli, Silvia, Bungaro, Silvia, Morotti, Alessandro, Rea, Delphine, Stagno, Fabio, Martino, Bruno, Campiotti, Leonardo, Caocci, Giovanni, Usala, Emilio, Merli, Michele, Onida, Francesco, Bregni, Marco, Elli, Elena Maria, Fumagalli, Monica, Ciceri, Fabio, Perego, Roberto A, Pagni, Fabio, Mologni, Luca, Piazza, Rocco, and Gambacorti-Passerini, Carlo

Abstract

Atypical chronic myeloid leukemia (aCML) is a BCR-ABL1-negative clonal disorder, which belongs to the myelodysplastic/myeloproliferative group. This disease is characterized by recurrent somatic mutations in SETBP1, ASXL1 and ETNK1 genes, as well as high genetic heterogeneity, thus posing a great therapeutic challenge. To provide a comprehensive genomic characterization of aCML we applied a high-throughput sequencing strategy to 43 aCML samples, including both whole-exome and RNA-sequencing data. Our dataset identifies ASXL1, SETBP1, and ETNK1 as the most frequently mutated genes with a total of 43.2%, 29.7 and 16.2%, respectively. We characterized the clonal architecture of 7 aCML patients by means of colony assays and targeted resequencing. The results indicate that ETNK1 variants occur early in the clonal evolution history of aCML, while SETBP1 mutations often represent a late event. The presence of actionable mutations conferred both ex vivo and in vivo sensitivity to specific inhibitors with evidence of strong in vitro synergism in case of multiple targeting. In one patient, a clinical response was obtained. Stratification based on RNA-sequencing identified two different populations in terms of overall survival, and differential gene expression analysis identified 38 significantly overexpressed genes in the worse outcome group. Three genes correctly classified patients for overall survival.

Published
2020

84. Germ-Line TP53 Mutation in an Adolescent With CMML/Atypical CML and Familiar Cancer Predisposition

Author

Nucera, S, Fazio, G, Piazza, R, Rigamonti, S, Fontana, D, Gambacorti Passerini, C, Maitz, S, Rovelli, A, Biondi, A, Cazzaniga, G, Balduzzi, A, Nucera, Silvia, Fazio, Grazia, Piazza, Rocco, Rigamonti, Silvia, Fontana, Diletta, Gambacorti Passerini, Carlo, Maitz, Silvia, Rovelli, Attilio, Biondi, Andrea, Cazzaniga, Giovauni, Balduzzi, Adriana, Nucera, S, Fazio, G, Piazza, R, Rigamonti, S, Fontana, D, Gambacorti Passerini, C, Maitz, S, Rovelli, A, Biondi, A, Cazzaniga, G, Balduzzi, A, Nucera, Silvia, Fazio, Grazia, Piazza, Rocco, Rigamonti, Silvia, Fontana, Diletta, Gambacorti Passerini, Carlo, Maitz, Silvia, Rovelli, Attilio, Biondi, Andrea, Cazzaniga, Giovauni, and Balduzzi, Adriana

Published
2020

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

Author

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

Published
2021
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91. P-01-4 A New Tool to Explore Brain Functional Basis of Gender Disphoria: Validation of a Functional MRI Protocol to Investigate Patterns of Brain Activation Related to Body Image and Gender Identity

Author

Ceruti, C., primary, D'Agata, F., additional, Bergui, M., additional, Sibona, M., additional, Preto, M., additional, Gualerzi, A., additional, Crespi, C., additional, Cicerale, A., additional, Diano, M., additional, Timpano, M., additional, Falcone, M., additional, Sedigh, O., additional, Fontana, D., additional, Rolle, L., additional, Motta, G., additional, Manieri, C., additional, Lanfranco, F., additional, Gontero, P., additional, and Molo, M.T., additional

Published
2020
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93. Glomerular filtration rate: A prognostic marker in atrial fibrillation—A subanalysis of the AntiThrombotic Agents Atrial Fibrillation

Author

Proietti, Riccardo, Gonzini, Lucio, Pizzimenti, Giovanni, Ledda, Antonietta, Sanna, Pietro, Alturki, Ahmed, Russo, Vincenzo, Lencioni, Mauro, Siciliano, R., Boffa, M., Bazzanini, F., Di Nucci, G., Fonti, S., De Franceschi, T., Davio, P., Alagna, G., Cipollini, F., Arma, P., Gunnellini, M. G., Dottori, M., Paulillo, D., Giudice, M., Sicuro, M., Lenti, S., Iannelli, G., Notarstefano, P., Galiotto, M., Apolloni, Enzo, Molini, G., Massarelli, L., Di Iorio, P., Scandurra, F., Candelmo, F., Iodice, P., Laureano, R., Perlangeli, S., Praticò, A., Lucchesi, Q., Conese, V., Scalera, G., Palma, F., De Antoni, M. E., Beltramello, G., Carbonella, M., Capone, A., Bianchi, V., Zerella, F., Masina, M., Boggian, G., Pancaldi, L. G., Brucato, A. L., Scialfa, S., Ferrari, P., Gavazzi, A., Santoro, E., Bertinieri, G., Caragnano, V., Zaccaroni, S., Marchetti, G., Urbinati, S., Belmonte, G., Giannoni, C., Panuccio, D., Pedone, V., Colletta, M., Di Pasquale, G., Cemin, R., Paffoni, P. R. C., Pezzotti, Chiara, Capretti, M., Lamari, A. L., Maugeri, S., Moretti, R., Ganga, R., Mascia, P., Caddori, A., Cusumano, S., Alletto, M., DE VINCENZO, Ciro, Musacchio, E., Stendardo, A., Cantarella, SALVATORE ALFREDO, Ferrari, V., Bassano, F., PERRONE CAPANO, Carla, Piccinni, G. C., Catanzaro, M., Vinciguerra, A., Lusiani, L., De Caro, G., Scarcia, M., Scarcia, Aurora, Losi, E., Gaddi, O., Lo Sciuto, A., Cascio Ingurgio, N., Vignai, E., Romano, M., Borzì, V., Bellanuova, I. A., Felis, S., Gulizia, M. M., Francese, G. M., Artale, S., Mazzuca, S., Perticone, F., Tirotta, D., Talini, E., Ventrella, F., Iosa, G., Cuccurullo, O., Bertello, P. D., Benemio, G., Garognoli, O., Arcelli, G., Prosciutti, L., De Matthaeis, G., Quattrini, C., Calcagno, S., Canestrini, S., Franco, A., Pastorelli, R., Acquati, F., Botto, G. L., Sitta, N., Migliacci, R., Cosmi, F., Tarquini, B., Chiappetta, P., Sprovieri, M. F., Macrì, G., Bertolazzi, S., Spotti, Alessia, Pirelli, S., Marasco, M. F., Elia, Martina, Gambino, G. M., Fenoglio, L., Gelmini, G. P., Ziacchi, V., Rigon, N., Petix, N. R., Zipoli, A., Caiolo, A., Marino, E., Scattolin, G., Gerini, S., Parisi, G., Tavernese, G., Conti, Alessandro, Ferrante, Federico, Morettini, A., Alterini, B., Rocchi, Federico, Nozzoli, C., Goedecke, L., Seravalle, C., Cuomo, A., Panettieri, I., Pellegrino, P., Di Biase, M., Savarese, G., Patriarchi, F., Bondì, Giuseppina, Rossini, Elena, Nello, S., Ranieri, A. T., Gelonesi, F. N., Costantini, M., Dugnani, M., Ria, L., Mussardo, V., Zanini, G., Morgante, O., Fazio, G., Lo, G., Castello, C., Moroni, L. A., Costa, S., Domenicucci, S., Venzano, C., Loiacono, L., Ortuso, R., Esposito, L., Cuzzucrea, D. G., Fiammengo, F., Selva, E., Gestra, R., Alessandri, M., Nuzzi, G., Porrino, L., Parise, P., Capponi, E. A., Mandorla, S., Politi, Caterina, Olivieri, Claudia, Gurioli, L., Agostinelli, P., Striuli, R., Petrarca, Massimo, Corsini, Francesca, Orlandini, F., Badolati, S., Colarusso, D., Vertullo, V., Pelaggi, P., Campagna, G., Haupt, E., Parente, F., Milanese, G., Magliari, F., Morando, G., Guarise, P., Mazzone, A., Palumbo, G., Lambelet, P., Camaiti, A., Pasquinelli, P., Frediani, L., Vituliano, A., Brunelleschi, G., Lisi, C., La Torre, P. P. A., Villella, A., Rimoldi, A., Russo, V., Di Summa, F., Reggiani, A., Raimondo, F. C., Disalvo, D., Borrello, V. M., Magnante, A., Stellitano, E., Procopio, L., Franculli, F., Serafini, Filippo, Tondo, C., Fiorentini, C., Manfredini, R., Robbiolo, L., Pizzimenti, G., VASQUEZ LOPEZ, LUIDER FERNEY, Piangiamore, A., Tosi, P., Donà, G., Bacchiega, E., Malavasi, V., Modena, M. G., Divella, C., Marengo, C., Montanari, P., Manicardi, V., Abate, L., Cuccuini, A., Magni, S., Vincenti, A., Spinelli, M., Mortara, A., Specchia, G., Silvestri, N., Silvestri, Oriana, Piscopo, G., Muscherà, R., Gallucci, F., Cannavale, A., Bresciani, A., Perrone Filardi, P., Fontanella, Andrea, Iannuzzo, D., Lucà, S., Zuccoli, A., Rinaldi, P., Ferri, G., Barbieri, E., Grasselli, S., Rossi, A., Agosti, S., Sanna, GIAN PAOLO, Casu, G., Orecchioni, G., Da Silva Carvalho, P. C., POZZI MUCELLI, Roberto, Salvati, Fabio, Bendini, M. G., Giordano, G., Pellegrini, F., Pighini, G., Tremolada, F., Zanin, L., Ledda, A., Floresta, A. M., Enia, F., Nicolosi, G., Ingrillì, F., D'Angelo, A., Musacchio, D., Savastano, Silvia, Magnani, Leonardo, Capitelli, M., Cioni, Giovanni, Aloisi, B., De Finis, A., Vacri, A., Costantini, V., Guercini, F., Zingarini, G., Nardoni, M. C., Teghini, L., Panigada, G., Di Marco, S., Vergoni, W., Paonessa, K., Artom, A., Bigliardi, M., Riccardi, R., Riva, L., Marandino, A., Barsotti, L., Ginocchio, G., Marchese, Dario, Tintori, G., Annese, M., Breschi, R., Manini, M., Scopelliti, Giulia, Pastore, A., Spirito, G., Amato, A., Del Bianco, F., Ongari, M., Fiorencis, R., Querci, F., Martone, V. D., Molero, U., Fiusti, R., Giovannini, T., D'Arienzo, E., Cellamare, G., Placci, A., Gulli, G., Ruggeri, A., Pulitanò, G., Iori, I., Ingianni, N., Saporito, D., Marconi, GIAN MARIA, Grossi, Alice, Grosseto, D., Ciamei, M., Mete, F., Russo, F., Bianchi, C., Costantino, S., Manfellotto, D., Risa, M. P., Azzolini, P., Conversano, L., Santini, M., Macchiusi, A., Francia, P., Pietrantonio, F., Biscione, F., Magliano, G., Fedele, Francesca, Salituri, S., Salituri, F., Zamboni, S., Rossetti, C., Roncon, Leonora, Delucchi, M., De Benedictis, M., Vitolo, A., Anselmi, Michela, Celino, T., Moretti, V., Cuccurullo, M., Castelli, G., Martino, G., Pierandrei, G., Carella, A. M., Tonizzo, M., Nassi, R., Tarducci, R., Fronticelli Baldelli, M., Commisso, B., Lazzarini, D., Matarazzo, M. M., Novati, P., Petacchi, R., Maninchedda, P., Melandri, F., Bellesi, P., Sacchetti, C., Grandi, M., Cattana, A., Tassara, R., Menardo, G., Aykut, V., Chesi, G., Reverzani, A., Galgano, Angela, Bartone, B., Stornello, M., Muscio, G., Gemmiti, M. P., Alfonsi, F., Fontana, D., Astarita, C., Gaspardo, G., La Brocca, A., Rillo, M., Pascente, T., Pirozzi, M. R., Addis, L., De Siati, P., Beato, E., Iannaccone, V., Barabani, M., Castronuovo, M., Battaia, L., Biscottini, B., Boccali, A., Marengo, S., Dallerba, R., Diana, A., Coser, Alessandra, Pauletto, P., Calzolari, V., Olivari, Z., De Masi De Luca, G., Accogli, M., Gerloni, R., Cattin, Laura, Vitali Serdoz, L., Sinagra, G., Bulfoni, A., DE BIASIO, Melissa, Proclemer, A., Miserocchi, F., Marazzi, R., SALERNO URIARTE, JORGE ANTONIO, Levantesi, G., Olivetti, P., Capuano, A., Bertoncelli, M. C., Molinaro, N., Anastasio, L., Teti, G., Vescovo, G. A., Muriago, M., Incao, F., Lettica, G. V., Nieswandt, V., Osti, R., Tafi, A., Proietti, Riccardo, Gonzini, Lucio, Pizzimenti, Giovanni, Ledda, Antonietta, Sanna, Pietro, Alturki, Ahmed, Russo, Vincenzo, Lencioni, Mauro, Siciliano, R., Boffa, M., Bazzanini, F., Di Nucci, G., Fonti, S., De Franceschi, T., Davio, P., Alagna, G., Cipollini, F., Arma, P., Gunnellini, M. G., Dottori, M., Paulillo, D., Giudice, M., Sicuro, M., Lenti, S., Iannelli, G., Notarstefano, P., Galiotto, M., Apolloni, E., Molini, G., Massarelli, L., Di Iorio, P., Scandurra, F., Candelmo, F., Iodice, P., Laureano, R., Perlangeli, S., Praticò, A., Lucchesi, Q., Conese, V., Scalera, G., Palma, F., De Antoni, M. E., Beltramello, G., Carbonella, M., Capone, A., Bianchi, V., Zerella, F., Masina, M., Boggian, G., Pancaldi, L. G., Brucato, A. L., Scialfa, S., Ferrari, P., Gavazzi, A., Santoro, E., Bertinieri, G., Caragnano, V., Zaccaroni, S., Marchetti, G., Urbinati, S., Belmonte, G., Giannoni, C., Panuccio, D., Pedone, V., Colletta, M., Di Pasquale, G., Cemin, R., Paffoni, P. R. C., Pezzotti, C., Capretti, M., Lamari, A. L., Maugeri, S., Moretti, R., Ganga, R., Mascia, P., Caddori, A., Cusumano, S., Alletto, M., De Vincenzo, C., Musacchio, E., Stendardo, A., Cantarella, S. A., Ferrari, V., Bassano, F., Perrone, C., Piccinni, G. C., Catanzaro, M., Vinciguerra, A., Lusiani, L., De Caro, G., Scarcia, M., Scarcia, A., Losi, E., Gaddi, O., Lo Sciuto, A., Cascio Ingurgio, N., Vignai, E., Romano, M., Borzì, V., Bellanuova, I. A., Felis, S., Gulizia, M. M., Francese, G. M., Artale, S., Mazzuca, S., Perticone, F., Tirotta, D., Talini, E., Ventrella, F., Iosa, G., Cuccurullo, O., Bertello, P. D., Benemio, G., Garognoli, O., Arcelli, G., Prosciutti, L., De Matthaeis, G., Quattrini, C., Calcagno, S., Canestrini, S., Franco, A., Pastorelli, R., Acquati, F., Botto, G. L., Sitta, N., Migliacci, R., Cosmi, F., Tarquini, B., Chiappetta, P., Sprovieri, M. F., Macrì, G., Bertolazzi, S., Spotti, A., Pirelli, S., Marasco, M. F., Elia, M., Gambino, G. M., Fenoglio, L., Gelmini, G. P., Ziacchi, V., Rigon, N., Petix, N. R., Zipoli, A., Caiolo, A., Marino, E., Scattolin, G., Gerini, S., Parisi, G., Tavernese, G., Conti, A., Ferrante, F., Morettini, A., Alterini, B., Rocchi, F., Nozzoli, C., Goedecke, L., Seravalle, C., Cuomo, A., Panettieri, I., Pellegrino, P., Di Biase, M., Savarese, G., Patriarchi, F., Bondi, G., Rossini, E., Nello, S., Ranieri, A. T., Gelonesi, F. N., Costantini, M., Dugnani, M., Ria, L., Mussardo, V., Zanini, G., Morgante, O., Fazio, G., Lo, G., Castello, C., Moroni, L. A., Costa, S., Domenicucci, S., Venzano, C., Loiacono, L., Ortuso, R., Esposito, L., Cuzzucrea, D. G., Fiammengo, F., Selva, E., Gestra, R., Alessandri, M., Nuzzi, G., Porrino, L., Parise, P., Capponi, E. A., Mandorla, S., Politi, C., Olivieri, C., Gurioli, L., Agostinelli, P., Striuli, R., Petrarca, M., Corsini, F., Orlandini, F., Badolati, S., Colarusso, D., Vertullo, V., Pelaggi, P., Campagna, G., Haupt, E., Parente, F., Milanese, G., Magliari, F., Morando, G., Guarise, P., Mazzone, A., Palumbo, G., Lambelet, P., Camaiti, A., Pasquinelli, P., Frediani, L., Vituliano, A., Brunelleschi, G., Lisi, C., La Torre, P. P. A., Villella, A., Rimoldi, A., Russo, V., Di Summa, F., Reggiani, A., Raimondo, F. C., Disalvo, D., Borrello, V. M., Magnante, A., Stellitano, E., Procopio, L., Franculli, F., Serafini, F., Tondo, C., Fiorentini, C., Manfredini, R., Robbiolo, L., Pizzimenti, G., Vasquez, L., Piangiamore, A., Tosi, P., Donà, G., Bacchiega, E., Malavasi, V., Modena, M. G., Divella, C., Marengo, C., Montanari, P., Manicardi, V., Abate, L., Cuccuini, A., Magni, S., Vincenti, A., Spinelli, M., Mortara, A., Specchia, G., Silvestri, N., Silvestri, O., Piscopo, G., Muscherà, R., Gallucci, F., Cannavale, A., Bresciani, A., Perrone Filardi, P., Fontanella, A., Iannuzzo, D., Lucà, S., Zuccoli, A., Rinaldi, P., Ferri, G., Barbieri, E., Grasselli, S., Rossi, A., Agosti, S., Sanna, P., Casu, G., Orecchioni, G., Da Silva Carvalho, P. C., Pozzi, R., Salvati, F., Bendini, M. G., Giordano, G., Pellegrini, F., Pighini, G., Tremolada, F., Zanin, L., Ledda, A., Floresta, A. M., Enia, F., Nicolosi, G., Ingrillì, F., D'Angelo, A., Musacchio, D., Savastano, S., Magnani, L., Capitelli, M., Cioni, G., Aloisi, B., De Finis, A., Vacri, A., Costantini, V., Guercini, F., Zingarini, G., Nardoni, M. C., Teghini, L., Panigada, G., Di Marco, S., Vergoni, W., Paonessa, K., Artom, A., Bigliardi, M., Riccardi, R., Riva, L., Marandino, A., Barsotti, L., Ginocchio, G., Marchese, D., Tintori, G., Annese, M., Breschi, R., Manini, M., Scopelliti, G., Pastore, A., Spirito, G., Amato, A., Del Bianco, F., Ongari, M., Fiorencis, R., Querci, F., Martone, V. D., Molero, U., Fiusti, R., Giovannini, T., D'Arienzo, E., Cellamare, G., Placci, A., Gulli, G., Ruggeri, A., Pulitanò, G., Iori, I., Ingianni, N., Saporito, D., Marconi, M., Grossi, A., Grosseto, D., Ciamei, M., Mete, F., Russo, F., Bianchi, C., Costantino, S., Manfellotto, D., Risa, M. P., Azzolini, P., Conversano, L., Santini, M., Macchiusi, A., Francia, P., Pietrantonio, F., Biscione, F., Magliano, G., Fedele, F., Salituri, S., Salituri, F., Zamboni, S., Rossetti, C., Roncon, L., Delucchi, M., De Benedictis, M., Vitolo, A., Anselmi, M., Celino, T., Moretti, V., Cuccurullo, M., Castelli, G., Martino, G., Pierandrei, G., Carella, A. M., Tonizzo, M., Nassi, R., Tarducci, R., Fronticelli Baldelli, M., Commisso, B., Lazzarini, D., Matarazzo, M. M., Novati, P., Petacchi, R., Maninchedda, P., Melandri, F., Bellesi, P., Sacchetti, C., Grandi, M., Cattana, A., Tassara, R., Menardo, G., Aykut, V., Chesi, G., Reverzani, A., Galgano, A., Bartone, B., Stornello, M., Muscio, G., Gemmiti, M. P., Alfonsi, F., Fontana, D., Astarita, C., Gaspardo, G., La Brocca, A., Rillo, M., Pascente, T., Pirozzi, M. R., Addis, L., De Siati, P., Beato, E., Iannaccone, V., Barabani, M., Castronuovo, M., Battaia, L., Biscottini, B., Boccali, A., Marengo, S., Dallerba, R., Diana, A., Coser, A., Pauletto, P., Calzolari, V., Olivari, Z., De Masi De Luca, G., Accogli, M., Gerloni, R., Cattin, L., Vitali Serdoz, L., Sinagra, G., Bulfoni, A., De Biasio, M., Proclemer, A., Miserocchi, F., Marazzi, R., Salerno Uriarte, J. A., Levantesi, G., Olivetti, P., Capuano, A., Bertoncelli, M. C., Molinaro, N., Anastasio, L., Teti, G., Vescovo, G. A., Muriago, M., Incao, F., Lettica, G. V., Nieswandt, V., Osti, R., and Tafi, A.

Subjects
Male, medicine.medical_specialty, Time Factors, Clinical Investigations, Renal function, 030204 cardiovascular system & hematology, Risk Assessment, 03 medical and health sciences, 0302 clinical medicine, Fibrinolytic Agents, Risk Factors, atrial fibrillation, glomerular filtration rate, mortality, Cardiology and Cardiovascular Medicine, Internal medicine, Antithrombotic, medicine, Humans, In patient, 030212 general & internal medicine, Renal Insufficiency, Cardiovascular mortality, Aged, Retrospective Studies, business.industry, Incidence, Atrial fibrillation, General Medicine, medicine.disease, Prognosis, Survival Rate, Italy, Hospital admission, Atrial Fibrillation, Female, Follow-Up Studies, Glomerular Filtration Rate, Morbidity, Cardiology, business
Abstract

OBJECTIVE: An increased cardiovascular mortality and morbidity has been widely reported in patients with atrial fibrillation (AF). In this study, a subanalysis of the AntiThrombotic Agents Atrial Fibrillation (ATA‐AF) is performed with the aim to evaluate estimated glomerular filtration rate (eGFR) as an independent prognostic marker of cardiovascular mortality and morbidity in patients with AF. METHODS AND RESULTS: The ATA‐AF study enrolled 7148 patients with AF, in 360 Italian centers. The eGFR was calculated from data reported in patient notes or hospital database. This post‐hoc analysis included 1097 AF patients with eGFR data available and 1‐year clinical follow‐up. The endpoint was assessed as cardiovascular mortality and/or hospital admission for cardiovascular causes at follow‐up. Patients were also divided in two groups according to the eGFR (

Published
2018

94. ETNK1 mutations promote ROS production and DNA damage through increased mitochondrial activity

Author

Fontana, D, Mauri, M, Niro, A, Massimino, L, Bertagna, M, Zambrotta, G, Bossi, M, CITTERIO, STEFANIA, Crescenzi, B, Signore, G, Piazza, V, Mecucci, C, Cavaletti, G, Rea, D, Gambacorti-Passerini, C, Piazza, R, Fontana, D, Mauri, M, Niro, A, Massimino, L, Bertagna, M, Zambrotta, G, Bossi, M, Citterio, S, Crescenzi, B, Signore, G, Piazza, V, Mecucci, C, Cavaletti, G, Rea, D, Gambacorti-Passerini, C, and Piazza, R

Subjects
ETNK1, ROS
Abstract

Atypical chronic myeloid leukemia (aCML) is a clonal disorder belonging to the myelodysplastic/myeloproliferative syndromes. About 13% of aCML cases carry somatic mutations in ETNK1 gene, encoding for H243Y, N244S, and G245V substitutions. We previously showed that ETNK1 mutations cause a decreased catalytic activity of the enzyme. Despite this evidence however, their oncogenic role remained largely unexplained. Since ETNK1 activity is essential for the synthesis of phosphatidylethanolamine (PE) and given that PE is one of the most abundant phospholipids in the inner membrane of mitochondria, we focused our attention on mitochondrial activity. In order to characterize the oncogenic effect of ETNK1 variants we generated CRISPR/Cas9 clones carrying heterozygous N244S mutation and homozygous ETNK1 deletion (KO cells) on the 293 Flp-In™ cell-line. Both N244S and KO cells showed a significant increase in mitochondrial activity (1.78 and 2.13 fold increase, respectively; p= 0.0096 and p=0.0050) compared to WT, as assessed by MitoTracker™ Red. In line with this finding, electron microscopy revealed a significant modification in mitochondria morphology for N244S and KO cells, changing from an elongated, tubular shape to a round, swollen one. ATP (1.67 and 1.68 fold; p

Published
2018

95. ETNK1 mutations increase mitochondrial activity and promote DNA damage through ROS production

Author

Fontana, D, Mauri, M, Niro, A, Massimino, L, Bertagna, M, Zambrotta, G, Bossi, M, Citterio, S, Crescenzi, B, Signore, G, Piazza, V, Fanelli, F, Mecucci, C, Cavaletti, G, Rea, D, Gambacorti Passerini, C, Piazza, R, Fontana, D, Mauri, M, Niro, A, Massimino, L, Bertagna, M, Zambrotta, G, Bossi, M, Citterio, S, Crescenzi, B, Signore, G, Piazza, V, Fanelli, F, Mecucci, C, Cavaletti, G, Rea, D, Gambacorti Passerini, C, and Piazza, R

Subjects
atypical chronic myeloid leukemia, mitochondrial activity
Published
2018

99. Corrigendum to: What counts more: The patient, the surgical technique, or the hospital? A multivariable analysis of factors affecting perioperative complications of pulmonary lobectomy by video-assisted thoracoscopic surgery from a large nationwide registry (European Journal of Cardio-thoracic Surgery (2019) DOI: 10.1093/ejcts/ezz187)

Author

Infante, M. V., Benato, C., Silva, R., Rocco, G., Bertani, A., Bertolaccini, L., Gonfiotti, A., Giovannetti, R., Bonadiman, C., Lonardoni, A., Canneto, B., Falezza, G., Gandini, P., Curcio, C., Crisci, R., Zaraca, F., Alloisio, M., Amore, D., Ampollini, L., Andreetti, C., Argnani, D., Baietto, G., Bandiera, A., Benvenuti, M., Bortolotti, L., Bottoni, E., Breda, C., Camplese, P., Carbognani, P., Cardillo, G., Casadio, C., Cavallesco, G., Cherchi, R., Dell'Amore, A., Beffa, V., Dolci, G, Droghetti, A, Ferrari, P. A., Fontana, D., Gargiulo, G., Gasparri, R., Gavezzoli, D., Ghisalberti, M., Giovanardi, M., Guerrera, F., Imperatori, A., Iurilli, L., Lausi, P., Lo Giudice, F., Londero, F., Lopez, C., Luzzi, L., Mancuso, M., Maniscalco, P., Margaritora, S., Meacci, E., Melloni, G., Morelli, A., Mucilli, F., Natali, P., Negri, G., Nicotra, S., Nosotti, M., Pariscenti, G., Perkmann, R., Pernazza, F., Pirondini, E., Poggi, C., Puma, F., Refai, M., Rinaldo, A., Rizzardi, G, Rosso, L., Rotolo, N., Russo, E., Sabbatini, A., Scarci, M., Spaggiari, L., Stefani, A., Solli, P., Surrente, C., Terzi, A., Torre, M., Vinci, D., Viti, A., Voltolini, L., Zaccagna, G., and the Italian VATS group members

Subjects
Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Lung Neoplasms, Thoracic, medicine.medical_treatment, MEDLINE, NO, Postoperative Complications, Risk Factors, Pulmonary lobectomy, Humans, Medicine, Registries, Intraoperative Complications, Pneumonectomy, Lung, Aged, Retrospective Studies, Thoracic Surgery, Video-Assisted, business.industry, General surgery, General Medicine, Perioperative, Middle Aged, Corrigenda, Hospitals, Video-assisted thoracoscopic surgery, Female, Surgery, Cardiology and Cardiovascular Medicine, business
Abstract

OBJECTIVES: Inherent technical aspects of pulmonary lobectomy by video-assisted thoracoscopic surgery (VATS) may limit surgeons’ ability to deal with factors predisposing to complications. We analysed complication rates after VATS lobectomy in a prospectively maintained nationwide registry. METHODS: The registry was queried for all consecutive VATS lobectomy procedures from 49 Italian Thoracic Units. Baseline condition, tumour features, surgical techniques, devices, postoperative care, complications, conversions and the reasons thereof were detailed. Univariable and multivariable regressions were used to assess factors potentially linked to complications. RESULTS: Four thousand one hundred and ninety-one VATS lobectomies in 4156 patients (2480 men, 1676 women) were analysed. The median age-adjusted Charlson index of the patients was 4 (interquartile range 3–6). Grade 1 and 2 and Grade 3–5 complications were observed in 20.1% and in 5.8%, respectively. Ninety-day mortality was 0.55%. The overall conversion rate was 9.2% and significantly higher in low-volume centres (

Published
2019

100. Análise espectro-temporal de NDVI e área da soja cultivada frente ao La Niña de 2012

Author

RODIGHERI, G., FONTANA, D. C., SCHAPARINI, L. P., MENDES, A. P. da S. F., DALMAGO, G. A., Grazieli Rodigheri, Universidade Federal do Rio Grande do Sul, Programa de Pós-Graduação em Sensoriamento Remoto – PPGSR, Centro Estadual de Pesquisa em Senso-riamento Remoto e Meteorologia – CEPSRM. Av. Bento Gonçalves, 9500 – Campus do Vale– Caixa Postal: 15044, CEP 91501, GENEI ANTONIO DALMAGO, CNPT., Laura Pigatto Schaparini, Universidade Federal do Rio Grande do Sul - Faculdade de Agronomia. Avenida Bento Gonçalves 7712, Caixa Postal 15096, CEP 91501.970. Porto Alegre, RS. E-mails: dfontana@ufrgs.br e laura_pigatto@yahoo.com.br, Denise Cybis Fontana, Universidade Federal do Rio Grande do Sul, Programa de Pós-Graduação em Sensoriamento Remoto – PPGSR, Centro Estadual de Pesquisa em Senso-riamento Remoto e Meteorologia – CEPSRM. Av. Bento Gonçalves, 9500 – Campus do Vale– Caixa Postal: 15044, CEP 91501, and Alan Pereira da Silva Falcão Mendes, Universidade Federal do Rio Grande do Sul, Programa de Pós-Graduação em Sensoriamento Remoto – PPGSR, Centro Estadual de Pesquisa em Senso-riamento Remoto e Meteorologia – CEPSRM. Av. Bento Gonçalves, 9500 – Campus do Vale– Caixa Postal: 15044, CEP 91501

Subjects
NDVI, Soja, Déficit hídrico, Estresses hídricos, Máscara de cultivo, Balanço Hídrico, Sensoriamento Remoto
Abstract

O cultivo da soja é bastante vulnerável à estresses hídricos, podendo acarretar em prejuízos no rendimento de grãos e na produção final da cultura, principalmente quando exposto a eventos meteorológicos severos. O uso do sensoriamento remoto, através de índices de vegetação, pode propiciar análises sobre o status da cultura sob restrições hídricas. Assim, o objetivo do trabalho foi comparar os padrões espectro-temporal de NDVI e das áreas de cultivo da soja na microrregião de Passo Fundo, RS, utilizando dados MODIS, em um evento de La Niña. Foram utilizadas imagens do produto MOD13Q1, que retorna o máximo NDVI, de um ano neutro (2013/2014) e um ano de anomalia climática La Niña (2011/2012). Para as duas safras foram gerados perfis de NDVI e, então, feita uma comparação destes com variáveis meteorológicas. Os resultados mostram que o evento de La Niña foi fortemente associado a reduções no rendimento de grãos da soja, em consequência das deficiências hídricas ocorridas durante o evento. Através do perfil espectro-temporal de NDVI, nota-se que o déficit hídrico afeta o desenvolvimento da cultura. Made available in DSpace on 2020-03-13T01:07:42Z (GMT). No. of bitstreams: 1 AnaliseespectrotemporaldeNDVIeareadasojacultivada.pdf: 7323891 bytes, checksum: d8d266ed100389b589f11bb0d68ee6a1 (MD5) Previous issue date: 2019

Published
2019

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