Search

Your search keyword '"Olimpieri, P."' showing total 30 results
Start Over Author "Olimpieri, P." Search Limiters Available in Library Collection
30 results on '"Olimpieri, P."'

1. An Indexed Linear Logic for Idempotent Intersection Types (Long version)

Author

Breuvart, Flavien and Olimpieri, Federico

Subjects
Computer Science - Logic in Computer Science
Abstract

Indexed Linear Logic has been introduced by Ehrhard and Bucciarelli, it can be seen as a logical presentation of non-idempotent intersection types extended through the relational semantics to the full linear logic. We introduce an idempotent variant of Indexed Linear Logic. We give a fine-grained reformulation of the syntax by exposing implicit parameters and by unifying several operations on formulae via the notion of base change. Idempotency is achieved by means of an appropriate subtyping relation. We carry on an in-depth study of indLL as a logic, showing how it determines a refinement of classical linear logic and establishing a terminating cut-elimination procedure. Cut-elimination is proved to be confluent up to an appropriate congruence induced by the subtyping relation.

Published
2024

2. Canonicity of Proofs in Constructive Modal Logic

Author

Acclavio, Matteo, Catta, Davide, and Olimpieri, Federico

Subjects
Computer Science - Logic in Computer Science
Abstract

In this paper we investigate the Curry-Howard correspondence for constructive modal logic in light of the gap between the proof equivalences enforced by the lambda calculi from the literature and by the recently defined winning strategies for this logic. We define a new lambda-calculus for a minimal constructive modal logic by enriching the calculus from the literature with additional reduction rules and we prove normalization and confluence for our calculus. We then provide a typing system in the style of focused proof systems allowing us to provide a unique proof for each term in normal form, and we use this result to show a one-to-one correspondence between terms in normal form and winning innocent strategies., Comment: Extended version of the TABLEAUX 2023 paper

Published
2023

3. Coherence by Normalization for Linear Multicategorical Structures

Author

Olimpieri, Federico

Subjects
Computer Science - Logic in Computer Science
Abstract

We establish a formal correspondence between resource calculi an appropriate linear multicategories. We consider the cases of (symmetric) representable, symmetric closed and autonomous multicategories. For all these structures, we prove that morphisms of the corresponding free constructions can be presented by means of typed resource terms, up to a reduction relation and a structural equivalence. Thanks to the linearity of the calculi, we can prove strong normalization of the reduction by combinatorial methods, defining appropriate decreasing measures. From this, we achieve a general coherence result: morphisms that live in the free multicategorical structures are the same whenever the normal forms of the associated terms are equal. As further application, we obtain syntactic proofs of Mac Lane's coherence theorems for (symmetric) monoidal categories.

Published
2023

4. From Thin Concurrent Games to Generalized Species of Structures (Extended Version)

Author

Clairambault, Pierre, Olimpieri, Federico, and Paquet, Hugo

Subjects
Computer Science - Logic in Computer Science
Abstract

Two families of denotational models have emerged from the semantic analysis of linear logic: dynamic models, typically presented as game semantics, and static models, typically based on a category of relations. In this paper we introduce a formal bridge between a dynamic model and a static model: the model of thin concurrent games and strategies, based on event structures, and the model of generalized species of structures, based on distributors. A special focus of this paper is the two-dimensional nature of the dynamic-static relationship, which we formalize with double categories and bicategories. In the first part of the paper, we construct a symmetric monoidal oplax functor from linear concurrent strategies to distributors. We highlight two fundamental differences between the two models: the composition mechanism, and the representation of resource symmetries. In the second part of the paper, we adapt established methods from game semantics (visible strategies, payoff structure) to enforce a tighter connection between the two models. We obtain a cartesian closed pseudofunctor, which we exploit to shed new light on recent results in the theory of the lambda-calculus., Comment: LICS 2023 version replaced with extended version, with proofs and some additional material

Published
2023

5. Shape Complementarity Optimization of Antibody-Antigen Interfaces: the Application to SARS-CoV-2 Spike Protein

Author

De Lauro, Alfredo, Di Rienzo, Lorenzo, Miotto, Mattia, Olimpieri, Pier Paolo, Milanetti, Edoardo, and Ruocco, Giancarlo

Subjects
Quantitative Biology - Biomolecules
Abstract

Many factors influence biomolecules binding, and its assessment constitutes an elusive challenge in computational structural biology. In this respect, the evaluation of shape complementarity at molecular interfaces is one of the main factors to be considered. We focus on the particular case of antibody-antigen complexes to quantify the complementarities occurring at molecular interfaces. We relied on a method we recently developed, which employs the 2D Zernike descriptors, to characterize investigated regions with an ordered set of numbers summarizing the local shape properties. Collected a structural dataset of antibody-antigen complexes, we applied this method and we statistically distinguished, in terms of shape complementarity, pairs of interacting regions from non-interacting ones. Thus, we set up a novel computational strategy based on \textit{in-silico} mutagenesis of antibody binding site residues. We developed a Monte Carlo procedure to increase the shape complementarity between the antibody paratope and a given epitope on a target protein surface. We applied our protocol against several molecular targets in SARS-CoV-2 spike protein, known to be indispensable for viral cell invasion. We, therefore, optimized the shape of template antibodies for the interaction with such regions. As the last step of our procedure, we performed an independent molecular docking validation of the results of our Monte Carlo simulations., Comment: 13 pages, 4 figures

Published
2021
Full Text
View/download PDF

6. On the Taylor expansion of $\lambda$-terms and the groupoid structure of their rigid approximants

Author

Olimpieri, Federico and Auclair, Lionel Vaux

Subjects
Computer Science - Logic in Computer Science
Abstract

We show that the normal form of the Taylor expansion of a $\lambda$-term is isomorphic to its B\"ohm tree, improving Ehrhard and Regnier's original proof along three independent directions. First, we simplify the final step of the proof by following the left reduction strategy directly in the resource calculus, avoiding to introduce an abstract machine ad hoc. We also introduce a groupoid of permutations of copies of arguments in a rigid variant of the resource calculus, and relate the coefficients of Taylor expansion with this structure, while Ehrhard and Regnier worked with groups of permutations of occurrences of variables. Finally, we extend all the results to a nondeterministic setting: by contrast with previous attempts, we show that the uniformity property that was crucial in Ehrhard and Regnier's approach can be preserved in this setting.

Published
2020
Full Text
View/download PDF

9. Intersection Type Distributors

Author

Olimpieri, Federico

Subjects
Computer Science - Logic in Computer Science
Abstract

We study a family of distributors-induced bicategorical models of lambda-calculus, proving that they can be syntactically presented via intersection type systems. We first introduce a class of 2-monads whose algebras are monoidal categories modelling resource management. We lift these monads to distributors and define a parametric Kleisli bicategory, giving a sufficient condition for its cartesian closure. In this framework we define a proof-relevant semantics: the interpretation of a term associates to it the set of its typing derivations in appropriate systems. We prove that our model characterize solvability, adapting reducibility techniques to our setting. We conclude by describing two examples of our construction., Comment: Accepted paper at LICS 2021

Published
2020

10. Normalization, Taylor expansion and rigid approximation of $\lambda$-terms

Author

Olimpieri, Federico

Subjects
Computer Science - Logic in Computer Science
Abstract

The aim of this work is to characterize three fundamental normalization proprieties in lambda-calculus trough the Taylor expansion of $ \lambda$-terms. The general proof strategy consists in stating the dependence of ordinary reduction strategies on their resource counterparts and in finding a convenient resource term in the Taylor expansion that behaves well under the considered kind of reduction.

Published
2020

12. Real-life comparison of mortality in patients with SARS-CoV-2 infection at risk for clinical progression treated with molnupiravir or nirmatrelvir plus ritonavir during the Omicron era in Italy: a nationwide, cohort study

Author

Torti, C, Olimpieri, P, Bonfanti, P, Tascini, C, Celant, S, Tacconi, D, Nicastri, E, Tacconelli, E, Cacopardo, B, Perrella, A, Buccoliero, G, Parruti, G, Bassetti, M, Biagetti, C, Giacometti, A, Erne, E, Frontuto, M, Lanzafame, M, Summa, V, Spagnoli, A, Vestri, A, Di Perri, G, Russo, P, Palù, G, Torti, Carlo, Olimpieri, Pier Paolo, Bonfanti, Paolo, Tascini, Carlo, Celant, Simone, Tacconi, Danilo, Nicastri, Emanuele, Tacconelli, Evelina, Cacopardo, Bruno, Perrella, Alessandro, Buccoliero, Giovanni Battista, Parruti, Giustino, Bassetti, Matteo, Biagetti, Carlo, Giacometti, Andrea, Erne, Elke Maria, Frontuto, Maria, Lanzafame, Massimiliano, Summa, Valentina, Spagnoli, Alessandra, Vestri, Annarita, Di Perri, Giovanni, Russo, Pierluigi, Palù, Giorgio, Torti, C, Olimpieri, P, Bonfanti, P, Tascini, C, Celant, S, Tacconi, D, Nicastri, E, Tacconelli, E, Cacopardo, B, Perrella, A, Buccoliero, G, Parruti, G, Bassetti, M, Biagetti, C, Giacometti, A, Erne, E, Frontuto, M, Lanzafame, M, Summa, V, Spagnoli, A, Vestri, A, Di Perri, G, Russo, P, Palù, G, Torti, Carlo, Olimpieri, Pier Paolo, Bonfanti, Paolo, Tascini, Carlo, Celant, Simone, Tacconi, Danilo, Nicastri, Emanuele, Tacconelli, Evelina, Cacopardo, Bruno, Perrella, Alessandro, Buccoliero, Giovanni Battista, Parruti, Giustino, Bassetti, Matteo, Biagetti, Carlo, Giacometti, Andrea, Erne, Elke Maria, Frontuto, Maria, Lanzafame, Massimiliano, Summa, Valentina, Spagnoli, Alessandra, Vestri, Annarita, Di Perri, Giovanni, Russo, Pierluigi, and Palù, Giorgio

Abstract

Background: Comparative data on mortality in COVID-19 patients treated with molnupiravir or with nirmatrelvir plus ritonavir are inconclusive. We therefore compared all-cause mortality in community-dwelling COVID-19 patients treated with these drugs during the Omicron era. Methods: Data collected in the nationwide, population-based, cohort of patients registered in the database of the Italian Medicines Agency (AIFA) were used. To increase completeness of the recorded deaths and date correctness, a cross-check with the National Death Registry provided by the Ministry of the Interior was performed. We included in this study all patients infected by SARS-CoV-2 treated within 5 days after the test date and symptom onset between February 8 and April 30, 2022. All-cause mortalities by day 28 were compared between the two treatment groups after balancing for baseline characteristics using weights obtained from a gradient boosting machine algorithm. Findings: In the considered timeframe, 17,977 patients treated with molnupiravir and 11,576 patients with nirmatrelvir plus ritonavir were included in the analysis. Most patients (25,617/29,553 = 86.7%) received a full vaccine course including the booster dose. A higher crude incidence rate of all-cause mortality was found among molnupiravir users (51.83 per 100,000 person-days), compared to nirmatrelvir plus ritonavir users (22.29 per 100,000 person-days). However, molnupiravir-treated patients were older than those treated with nirmatrelvir plus ritonavir and differences between the two populations were found as far as types of co-morbidities were concerned. For this reason, we compared the weight-adjusted cumulative incidences using the Aalen estimator and found that the adjusted cumulative incidence rates were 1.23% (95% CI 1.07%–1.38%) for molnupiravir-treated and 0.78% (95% CI 0.58%–0.98%) for nirmatrelvir plus ritonavir-treated patients (adjusted log rank p = 0.0002). Moreover, the weight-adjusted mixed-effect Cox model i

Published
2023

15. proABC-2: PRediction Of AntiBody Contacts v2 and its application to information-driven docking

Author

Ambrosetti, F, Olsen, T H, Olimpieri, P P, Jiménez-García, B, Milanetti, E, Marcatilli, P, Bonvin, A M J J, Sub NMR Spectroscopy, NMR Spectroscopy, Sub NMR Spectroscopy, and NMR Spectroscopy

Subjects
Statistics and Probability, Neural Networks, AcademicSubjects/SCI01060, Computer science, medicine.drug_class, Computational biology, Antigen-Antibody Complex, Machine learning, computer.software_genre, Monoclonal antibody, Convolutional neural network, Biochemistry, Computer, 03 medical and health sciences, 0302 clinical medicine, Antigen, medicine, Molecular Biology, Antibody, 030304 developmental biology, 0303 health sciences, Binding Sites, biology, business.industry, 030302 biochemistry & molecular biology, Binding Sites, Antibody, Software, Algorithms, Neural Networks, Computer, Rational design, Applications Notes, Structural Bioinformatics, Computer Science Applications, Computational Mathematics, Computational Theory and Mathematics, Docking (molecular), biology.protein, Paratope, Artificial intelligence, business, computer, 030217 neurology & neurosurgery
Abstract

Motivation Monoclonal antibodies are essential tools in the contemporary therapeutic armory. Understanding how these recognize their antigen is a fundamental step in their rational design and engineering. The rising amount of publicly available data is catalyzing the development of computational approaches able to offer valuable, faster and cheaper alternatives to classical experimental methodologies used for the study of antibody–antigen complexes. Results Here, we present proABC-2, an update of the original random-forest antibody paratope predictor, based on a convolutional neural network algorithm. We also demonstrate how the predictions can be fruitfully used to drive the docking in HADDOCK. Availability and implementation The proABC-2 server is freely available at: https://wenmr.science.uu.nl/proabc2/. Supplementary information Supplementary data are available at Bioinformatics online.

Published
2020
Full Text
View/download PDF

22. The Italian Medicines Agency Prospective Registry of Bortezomib-Based Treatment in AL Amyloidosis

Author

Palladini, Giovanni, Milani, Paolo, Celant, Simone, Summa, Valentina, Affronti, Giovanni, Olimpieri, Pier Paolo, Petraglia, Sandra, Foli, Andrea, Nuvolone, Mario, Merlini, Giampaolo, and Russo, Pierluigi

Abstract

Palladini: Celgene: Other: Travel support; Jannsen Cilag: Honoraria, Other. Milani:Janssen: Other: Speaker honoraria; Celgene: Other: Travel support; Pfizer: Other: Speaker honoraria. Nuvolone:Janssen: Honoraria.Bortezomib in AL amyloidosis

Published
2020
Full Text
View/download PDF

23. Clinical Features of Idiopathic Erythrocytosis Compared to Polycythemia Vera JAK-2 V617F Positive and Negative Patients

Author

Latagliata, Roberto, Tafuri, Agostino, Spadea, Antonio, Ferretti, Antonietta, Diverio, Daniela, Breccia, Massimo, D'Andrea, Mariella, Andriani, Alessandro, Montanaro, Marco, Cedrone, Michele, Montefusco, Enrico, Rago, Angela, Olimpieri, Odoardo Maria, Bagnato, Antonino, Biondo, Francesca, Vozella, Federico, Cantonetti, Maria, Petti, Maria Concetta, and Alimena, Giuliana

Abstract

No relevant conflicts of interest to declare.

Published
2011
Full Text
View/download PDF

24. A Phase II Study of the HDAC Inhibitor Givinostat In Combination with Hydroxyurea In Patients with Polycythemia Vera Resistant to Hydroxyurea Monotherapy

Author

Rambaldi, Alessandro, Finazzi, Guido, Vannucchi, Alessandro M., Martinelli, Vincenzo, Rodeghiero, Francesco, Nobile, Francesco, Specchia, Giorgina, Pogliani, Enrico Maria, Olimpieri, Odoardo Maria, Fioritoni, Giuseppe, Musolino, Caterina, Saglio, Giuseppe, Sivera, Piera, Barosi, Giovanni, Tollo, Silvia Di, and Barbui, Tiziano

Abstract

Several agents inhibiting the JAK2V617F mutation are actively investigated in patients with polycythemia vera (PV) and other chronic myeloproliferative neoplasms (MPN) with promising results. Givinostat, an HDAC inhibitor, specifically inhibits proliferation of cells bearing the JAK2V617F mutation and has shown significant activity with good tolerability in clinical studies in MPN patients. The aim of the present study was to evaluate safety and efficacy of two oral doses of Givinostat (50 or 100 mg daily) in combination with hydroxyurea (HU) in PV patients.In this multicenter, randomized, open-label, phase II study, we treated 44 patients with JAK2V617F positive PV, non-responders (NR) to the maximum tolerated doses of HU monotherapy for at least 3 months. The clinical -hematological response criteria developed by the European LeukemiaNet (ELN) consensus conference (complete and partial response) were used to assess the primary endpoint after 12 weeks of treatment. Recruited patients were randomly assigned to receive Givinostat (50 or 100 mg/die) in combination with the maximum tolerated dose of HU. After week 12, NR patients increased the initial daily dose of Givinostat by 50 mg, while responders continued Givinostat at the initial daily dose. Overall, the treatment lasted up to a maximum of 24 cumulative weeks of drug administration.Baseline demographic and hematological parameters were balanced between the two randomized groups. The mean weekly dose of HU at baseline was 6.75 (range 1.75–14) and 6.25 (1–14) grams and was reduced during the study to 6.25 (range 1.75–14) and 5.75 (0.75-12.25) grams, in the 50 (group A) and 100 mg (group B) Givinostat groups, respectively.The combination of Givinostat and HU was well tolerated. Only five out of 44 evaluable patients dropped-out before week 12, respectively 2 in group A and 3 in group B. Reasons for treatment discontinuation were grade 2 thrombocytopenia and iperkalemia in group A and panic attack, withdrawal of consent and investigator decision due to safety reason (detection of familiar cardiac disorder unknown at recruitment) in group B. Only two grade 3 not drug related adverse events (AEs) were observed (hyperkalemia and platelet count increase), both occurring in group B. The most frequent grade 2 AEs were thrombocytopenia (4 cases, two in each group), leukopenia (2 cases both in group B) and diarrhea (2 cases, one in each group).Complete (CR) plus partial (PR) response according to ELN response criteria was observed in 50% and 45% of patients in group A and B respectively. Moreover, a notable control of itching was observed at week 12 in most of the 21 evaluable patients affected by severe itching (grade ≥ 2) at baseline. Seven out of 11 (64%) and 8 out of 10 (80%) patients had a complete itching relief, in group A and B respectively.The combined use of Givinostat and HU is well tolerated and about 50% of patients resistant to HU monotherapy achieved an overall ELN response (PR or CR). At week 12 no differences were found in the two randomized arms in term of hematological responses and itching relief. Givinostat confirms to be active in PV through the control of myeloproliferation and of some specific clinical needs, such as severe itching. Completed clinical and molecular data (after 24 cumulative weeks of treatment) will be presented at the meeting.Rambaldi: Italfarmaco S.p.A.: Consultancy, Honoraria. Vannucchi:Italfarmaco S.p.A.: Consultancy, Honoraria. Barbui:Italfarmaco S.p.A.: Consultancy, Honoraria.

Published
2011
Full Text
View/download PDF

25. Physiologic Inhibitors of Coagulation, Thrombophilic Acquired Factors and Venous Thromboembolism in Gastrointestinal Cancer Patients.

Author

Schiavon, Gaia, Olimpieri, Odoardo M., Giannetti, Barbara, Tirindelli, Maria C., La Cesa, Annalisa, Borzomati, Domenico, Vincenzi, Bruno, Coppola, Roberto, Tonini, Giuseppe, and Avvisati, Giuseppe

Abstract

Venous Thromboembolism (VTE) in cancer patients recognizes a multifactorial pathogenesis, depending on endogeous and esogenous factors. However, the relationship among VTE and laboratoristic thrombophilic alterations in cancer patients is not clearly known. Aim of our trial has been to evaluate changes in the levels of physiological coagulation inhibitors and some thrombophilic acquired factors in a cohort of gastrointestinal tumours patients considering four timepoints of their medical history. All patients over 18 years with a new diagnosis of malignant gastrointestinal neoplasm observed in the Surgery department of the University Hospital “Campus Bio-Medico” from October 2002 to June 2004 have been included in this trial. Patients with antineoplastic previous treatment, anticoagulant current therapies, autoimmune or hematological diseases were not included. The following physiological coagulation inhibitors have been tested: Protein C, Protein S, Antithrombin III. Moreover, we tested also the presence of Lupus Anticoagulant by mean of Silica Clotting Time (SCT), Diluted Russel Viper Venom Test (DRVVT) and Anticardiolipin Antibodies of IgG type (ACA IgG). Furthermore, we investigated also the levels of homocysteine and annexin V as well as the presence of activated Protein C resistance. Tests were performed on samples taken just before and after surgery as well as before and at the end of the chemotherapeutic protocols. In addiction, VTE’s prevalence has been evaluated. A total of 102 patients (60 males and 42 females) have been included; median age was 67 years (range 28–92). A significant modification in the values of DRVVT, ACA IgG, PS, ATIII has been observed in the samples taken just after surgery (P <.001) and just before chemotherapy (P <.004). Moreover, PC levels were significantly reduced only after surgery (P <.000); SCT was significantly prolonged before starting chemotherapy (P <.003) while homocysteine levels were significantly reduced (P <.001) just after the end of the chemotherapeutic protocols. In this cohort of patients, VTE’s prevalence has been 7,8% (8/102) of these, 5/8 (62,5%) were treated with FU-based therapies and 3/8 (37,5%) had a Central Venous Catheter. None of the thrombophilic parameters tested was correlated with the development of VTE, while an advanced disease (P<.024) was strongly correlated to VTE. These preliminar results agree with other published trials as for the reduction in physiological coagulation inhibitors after surgery and VTE’s prevalence in cancer patients. Moreover, as expected, patients with advanced inoperable disease experience more easily VTE. Surprisingly, FU-based therapies reduce the levels of homocysteine in this cohort of patients. Increasing the number of studied patients may better clarify which are, in addiction to advanced disease, the more useful parameters for identifying those patients with gastrointestinal cancers at risk of VTE who may, therefore, benefit of a correct VTE prophylaxis.

Published
2004
Full Text
View/download PDF

26. Thrombophilic Genetic Mutations Have No Impact in the Pathogenesis of Thromboembolism in Gastro-Intestinal Cancer Patients.

Author

Olimpieri, Odoardo M., Schiavon, Gaia, Giannetti, Barbara, Tirindelli, Maria C., Santini, Daniele, Valeri, Sergio, Vincenzi, Bruno, Coppola, Roberto, Tonini, Giuseppe, and Avvisati, Giuseppe

Abstract

Deep venous thrombosis and pulmonary embolism are well recognized and feared complications in cancer patients, with a considerable impact on the overall survival and the quality of life. During the last years many prothrombotic genetic mutations have been described, of these the most common are: Factor V Leiden, prothrombin G20210A gene mutation and the C677T mutation in the 5,10 methylenetetrahydrofolate reductase (MTHFR) gene. Aim of this study was to asses the impact of these thrombophilic gene mutations on the development of VTE (Venous ThromboEmbolism) in patients with gastro-intestinal neoplasms. Moreover, we have tried to determine whether or not the C677T polymorphism of the MTHFR gene was associated with a higher toxicity during chemotherapy with antimetabolites such as 5-FU. From October 2002 to June 2004 48 patients (aged more than 18 years) not assuming anticoagulant therapy, with a new histopathologic diagnosis of gastro-intestinal cancer and no known hematologic or immunologic diseases were investigated by standard polymerase chain reaction techniques for the presence of the above thrombophilic gene mutations. Of the 48 tested patients, a homozygous or heterozygous Factor V Leiden was present respectively in 1 and 3, while the G20210A Factor II mutation was observed in 6 patients (all heterozygous). The C677T mutation in the MTHFR gene allelic frequency in the studied population was 46%. A VTE was observed in 7/48 patients (14.5%) and none of these patients had Factor V Leiden or G20210A Factor II mutations while 4 had a C677T MTHFR mutation. Therefore, none of the thrombophilic genetic mutations studied was associated to the development of VTE in the cohort of gastro-intestinal cancer patients. On the contrary chemotherapy (P=0.007) and advanced inoperable disease (P=0.009) were the only risk factors statistically significant for the development of VTE. As for toxicity during chemotherapy with antimetabolites, it was present in 25% of patients with the C677T polymorphism of the MTHFR while none of the patients without mutation had a toxicity (P=0.06). In conclusion, thrombophilic genetic mutations have no effect on the development of VTE in gastro-intestinal cancer patients. Moreover, we confirm that chemotherapy and an advanced disease play an important role in the pathogenesis of VTE in cancer patients. Furthermore, patients carrier of the C677T mutation in the MTHFR gene have a higher risk (OR: 1.4; C.I. 95%: 0.88–2.24) of toxicity during an antimetabolites-based chemotherapy.

Published
2004
Full Text
View/download PDF

27. How many chronic myeloid leukemia patients who started a frontline second-generation tyrosine kinase inhibitor have to switch to a second-line treatment? A retrospective analysis from the monitoring registries of the italian medicines agency (AIFA)

Author

Massimo Breccia, Pier Paolo Olimpieri, Odoardo Olimpieri, Fabrizio Pane, Alessandra Iurlo, Paolo Foggi, Alessia Cirilli, Antonietta Colatrella, Marcello Cuomo, Lucia Gozzo, Valentina Summa, Paolo Corradini, Pierluigi Russo, the AIFA’s Monitoring Registries Group, Breccia, M., Olimpieri, P. P., Olimpieri, O., Pane, F., Iurlo, A., Foggi, P., Cirilli, A., Colatrella, A., Cuomo, M., Gozzo, L., Summa, V., Corradini, P., and Russo, P.

Subjects
0301 basic medicine, Male, Cancer Research, Drug Resistance, Tyrosine-kinase inhibitor, chemistry.chemical_compound, 0302 clinical medicine, hemic and lymphatic diseases, 80 and over, Registries, Chronic, Original Research, Aged, 80 and over, Family Characteristics, Leukemia, Ponatinib, Myeloid leukemia, Middle Aged, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Prognosis, failure, Dasatinib, Survival Rate, Oncology, Italy, second‐generation TKIs, second-generation TKIs, 030220 oncology & carcinogenesis, Cohort, Female, intolerance, medicine.drug, Adult, medicine.medical_specialty, medicine.drug_class, Decision Making, lcsh:RC254-282, 03 medical and health sciences, Young Adult, chronic myeloid leukemia, Internal medicine, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, medicine, Humans, Radiology, Nuclear Medicine and imaging, Protein Kinase Inhibitors, Aged, Retrospective Studies, Salvage Therapy, Second line treatment, business.industry, Clinical Cancer Research, Discontinuation, 030104 developmental biology, Nilotinib, chemistry, Drug Resistance, Neoplasm, Neoplasm, BCR-ABL Positive, business, Myelogenous, Follow-Up Studies
Abstract

The frequency of patients who switch to a second‐line therapy from a frontline second‐generation (2gen) tyrosine kinase inhibitor (TKI) such as dasatinib and nilotinib, is still substantially unknown. We retrospectively investigated a large series of chronic phase chronic myeloid leukemia (CP‐CML) patients initially treated with 2gen TKIs monitored through the Italian Medicines Agency (AIFA Agenzia Italiana del farmaco) registries. Overall, 2420 patients were analyzed over a period of 6 years. One hundred and fifty‐seven patients (16.3%) treated with dasatinib and 164 treated with nilotinib (11.3%) have switched to another drug, with an overall frequency of 13.2%. In the dasatinib cohort, 39.4% of patients changed treatment for failure and 36.3% for intolerance as compared to 45.7% and 27.4% respectively in the nilotinib cohort. Overall, the median time to switch due to resistance was 293 days, whereas it was 317 days in case of intolerance. Resistance was observed mainly in younger male patients with high‐risk features, while intolerance was not related to any baseline parameter. After resistance/intolerance to nilotinib, the majority of patients switched to dasatinib (53.8%) whereas in case of frontline dasatinib to ponatinib (43.2%). To the best of our knowledge these data provide the first report on the frequency of discontinuation of frontline 2gen TKIs and on the main causes and pattern of choice to a second‐line therapy in the real‐life setting., Overall, 2420 patients were analyzed over a period of 6 years. One hundred and fifty‐seven patients (16.3%) treated with dasatinib and 164 treated with nilotinib (11.3%) have switched to another drug, with an overall frequency of 13.2%. In the dasatinib cohort, 39.4% of patients changed treatment for failure and 36.3% for intolerance as compared to 45.7% and 27.4% respectively in the nilotinib cohort. Resistance was observed mainly in younger male patients with high‐risk features, while intolerance was not related to any baseline parameter. To the best of our knowledge these data provide the first report on the frequency of discontinuation of frontline 2gen TKIs and on the main causes and pattern of choice to a second‐line therapy in the real‐life setting.

Published
2020

28. Pazopanib in the real-world setting in soft tissue sarcomas: data from the Italian national registry.

Author

Vincenzi B, Olimpieri PP, Celant S, Mazzocca A, Cortellini A, Comandone A, Tomassini L, Di Segni S, Russo P, and Casali PG

Subjects
Humans, Male, Female, Italy, Middle Aged, Aged, Adult, Angiogenesis Inhibitors therapeutic use, Angiogenesis Inhibitors pharmacology, Aged, 80 and over, Prospective Studies, Treatment Outcome, Soft Tissue Neoplasms drug therapy, Indazoles therapeutic use, Sulfonamides therapeutic use, Sulfonamides pharmacology, Pyrimidines therapeutic use, Pyrimidines pharmacology, Registries, Sarcoma drug therapy
Abstract

Background: Pazopanib is part of the therapeutic armamentarium for the treatment of patients with advanced non-adipocytic soft tissue sarcomas (STS) who have received prior chemotherapy, but its optimal use in STS histologies is still left to be further defined., Design and Methods: Data on STS patients treated with pazopanib in Italy have been prospectively collected from July 2013 to December 2019 through a drug monitoring registry managed by the Italian Medicines Agency (AIFA). This nationwide observational cohort study included patients with advanced STS who received pazopanib. Clinicians were mandatorily requested to fill in the AIFA monitoring registry in order to prescribe pazopanib. Patients were recorded on the basis of their clinical characteristics, histological subtype captured at the time of treatment start, and clinical outcome. Primary outcome was time to treatment discontinuation (TTD). Secondary outcomes recorded were frequency of dose reduction and time to first dose reduction., Results: We analyzed data from 1964 sarcoma patients. The most represented histological subtypes were leiomyosarcoma (44.7%), undifferentiated sarcomas/not otherwise specified (11.5%), and synovial sarcoma (8.1%). Overall, the median TTD was 106 days. The variables significantly associated to shorter TTD were Eastern Cooperative Oncology Group performance status (1-2 versus 0), the number of previous lines of treatment (2-4 versus 0-1) and prescribed dose (200 mg or 400 mg versus 800 mg, all once daily). Among the most represented (>20 patients) histological subtypes, we also observed longer TTD in patients with histological diagnosis of malignant solitary fibrous tumor if compared with undifferentiated sarcoma not otherwise specified., Conclusions: In this nationwide observational real-world study, the outcomes are similar to those reported in the pivotal trial (PALETTE study). Our study includes a significant number of patients with rare/ultra-rare sarcoma subtypes and underlines possible differences in treatment duration among these histologies., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Published
2024
Full Text
View/download PDF

29. Production in Bacteria and Characterization of Engineered Humanized Fab Fragment against the Nodal Protein.

Author

Sivaccumar JP, Iaccarino E, Oliver A, Cantile M, Olimpieri P, Leonardi A, Ruvo M, and Sandomenico A

Abstract

Drug development in recent years is increasingly focused on developing personalized treatments based on blocking molecules selective for therapeutic targets specifically present in individual patients. In this perspective, the specificity of therapeutic targets and blocking agents plays a crucial role. Monoclonal antibodies (mAbs) and their surrogates are increasingly used in this context thanks to their ability to bind therapeutic targets and to inhibit their activity or to transport bioactive molecules into the compartments in which the targets are expressed. Small antibody-like molecules, such as Fabs, are often used in certain clinical settings where small size and better tissue penetration are required. In the wake of this research trend, we developed a murine mAb (3D1) neutralizing the activity of Nodal, an oncofetal protein that is attracting an ever-increasing interest as a selective therapeutic target for several cancer types. Here, we report the preparation of a recombinant Fab of 3D1 that has been humanized through a computational approach starting from the sequence of the murine antibody. The Fab has been expressed in bacterial cells (1 mg/L bacterial culture), biochemically characterized in terms of stability and binding properties by circular dichroism and bio-layer interferometry techniques and tested in vitro on Nodal-positive cancer cells.

Published
2023
Full Text
View/download PDF

30. Non-vitamin K antagonist oral anticoagulation agents in patients with atrial fibrillation: Insights from Italian monitoring registries.

Author

Olimpieri PP, Di Lenarda A, Mammarella F, Gozzo L, Cirilli A, Cuomo M, Gulizia MM, Colivicchi F, Murri G, Gabrielli D, and Trotta F

Abstract

Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia associated with an increased risk of stroke and thromboembolism. Anticoagulation with Vitamin K antagonists (VKAs) or with novel oral anti-coagulants (NOACs) represents the cornerstone of the pharmacological treatment to reduce the risk of thromboembolism. This study aims to provide real-world data from a whole large European country about NOAC use in "non-valvular atrial fibrillation" (NVAF)., Methods: We analysed the Italian Medicines Agency (AIFA) monitoring registries collecting data of a nationwide cohort of patients with "NVAF" treated with NOACs. Using logistic regression analysis, baseline characteristics and treatment discontinuation information were compared among initiators of the 4 NOACs., Results: In the reference period, the NOAC database collected data for 683,172 patients. The median age was 78 years with 19.5% aged 85 or older. Overall, the treatments were in accordance with guidelines. About 1/3 of patients switched from a prior VKA treatment; in the 72.3% of cases, these patients had a labile International Normalized Ratio (INR) at first prescription. The most prescribed NOAC was rivaroxaban, followed by apixaban, dabigatran and edoxaban., Conclusions: This study is the largest European real-world study ever published on NOACs. It includes all Italian patients treated with NOACs since 2013 accounting for about 1/3 of subjects with AF. The enrolled population consisted of very elderly patients, at high risk of ischemic adverse events. The AIFA registries are consolidated tools that guarantee the appropriateness of prescription and provide important information for the governance of National Health System by collecting real-world data., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2019 Published by Elsevier B.V.)

Published
2020
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results