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  1. Article: Management of Trastuzumab Deruxtecan-related nausea and vomiting in real-world practice.

    Notini, Giulia / Naldini, Matteo Maria / Sica, Lorenzo / Viale, Giulia / Rognone, Alessia / Zambelli, Stefania / Zucchinelli, Patrizia / Piras, Marta / Bosi, Carlo / Mariani, Marco / Aldrighetti, Daniela / Bianchini, Giampaolo / Licata, Luca

    Frontiers in oncology

    2024  Volume 14, Page(s) 1374547

    Abstract: Background: Nausea and vomiting are common side effects of Trastuzumab Deruxtecan (T-DXd), but guidelines for optimal management were not initially available. This retrospective single-center study aimed at evaluating the efficacy of two antiemetic ... ...

    Abstract Background: Nausea and vomiting are common side effects of Trastuzumab Deruxtecan (T-DXd), but guidelines for optimal management were not initially available. This retrospective single-center study aimed at evaluating the efficacy of two antiemetic regimens in patients receiving T-DXd.
    Methods: Data from metastatic breast cancer patients receiving T-DXd were collected. Two groups were defined: patients treated with 5-HT3 receptor antagonists (RA) ± dexamethasone (5-HT3-group) and patients treated with a fixed oral combination of netupitant (NK1RA) and palonosetron ± dexamethasone (NK1 group). Physicians preferentially offered the NK1 regimen to patients at higher risk of nausea and vomiting based on internal recommendations. Only nausea and vomiting during cycles 1 and 2 were considered. Comparisons of nausea and vomiting by the antiemetic prophylaxis group were assessed using chi-square.
    Results: A total of 53 patients were included in the analysis. At cycle 1, 72% and 28% of patients received the 5-HT3 and NK1 prophylaxis, respectively. Overall, 58% reported nausea, with no differences between groups (58% vs. 60%;
    Conclusions: The NK1 regimen improved vomiting control at cycle 1 and, when introduced at cycle 2, significantly improved both nausea and vomiting. The biased NK1 selection for higher-risk patients may have dampened the differences between groups at cycle 1. These findings support enhanced control of T-DXd-related nausea and vomiting with NK1RA.
    Language English
    Publishing date 2024-03-11
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2649216-7
    ISSN 2234-943X
    ISSN 2234-943X
    DOI 10.3389/fonc.2024.1374547
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Author Correction: Genotoxic effects of base and prime editing in human hematopoietic stem cells.

    Fiumara, Martina / Ferrari, Samuele / Omer-Javed, Attya / Beretta, Stefano / Albano, Luisa / Canarutto, Daniele / Varesi, Angelica / Gaddoni, Chiara / Brombin, Chiara / Cugnata, Federica / Zonari, Erika / Naldini, Matteo Maria / Barcella, Matteo / Gentner, Bernhard / Merelli, Ivan / Naldini, Luigi

    Nature biotechnology

    2024  

    Language English
    Publishing date 2024-01-25
    Publishing country United States
    Document type Published Erratum
    ZDB-ID 1311932-1
    ISSN 1546-1696 ; 1087-0156
    ISSN (online) 1546-1696
    ISSN 1087-0156
    DOI 10.1038/s41587-024-02142-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Tissue- and liquid biopsy-based biomarkers for immunotherapy in breast cancer.

    Licata, Luca / Mariani, Marco / Rossari, Federico / Viale, Giulia / Notini, Giulia / Naldini, Matteo Maria / Bosi, Carlo / Piras, Marta / Dugo, Matteo / Bianchini, Giampaolo

    Breast (Edinburgh, Scotland)

    2023  Volume 69, Page(s) 330–341

    Abstract: Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy and now represent the mainstay of treatment for many tumor types, including triple-negative breast cancer and two agnostic registrations. However, despite impressive durable responses ...

    Abstract Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy and now represent the mainstay of treatment for many tumor types, including triple-negative breast cancer and two agnostic registrations. However, despite impressive durable responses suggestive of an even curative potential in some cases, most patients receiving ICIs do not derive a substantial benefit, highlighting the need for more precise patient selection and stratification. The identification of predictive biomarkers of response to ICIs may play a pivotal role in optimizing the therapeutic use of such compounds. In this Review, we describe the current landscape of tissue and blood biomarkers that could serve as predictive factors for ICI treatment in breast cancer. The integration of these biomarkers in a "holistic" perspective aimed at developing comprehensive panels of multiple predictive factors will be a major step forward towards precision immune-oncology.
    MeSH term(s) Humans ; Breast ; Immunotherapy ; Triple Negative Breast Neoplasms/drug therapy ; Biomarkers ; Liquid Biopsy ; Biomarkers, Tumor
    Chemical Substances Biomarkers ; Biomarkers, Tumor
    Language English
    Publishing date 2023-03-27
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 1143210-x
    ISSN 1532-3080 ; 0960-9776
    ISSN (online) 1532-3080
    ISSN 0960-9776
    DOI 10.1016/j.breast.2023.03.014
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  4. Article ; Online: Genotoxic effects of base and prime editing in human hematopoietic stem cells.

    Fiumara, Martina / Ferrari, Samuele / Omer-Javed, Attya / Beretta, Stefano / Albano, Luisa / Canarutto, Daniele / Varesi, Angelica / Gaddoni, Chiara / Brombin, Chiara / Cugnata, Federica / Zonari, Erika / Naldini, Matteo Maria / Barcella, Matteo / Gentner, Bernhard / Merelli, Ivan / Naldini, Luigi

    Nature biotechnology

    2023  

    Abstract: Base and prime editors (BEs and PEs) may provide more precise genetic engineering than nuclease-based approaches because they bypass the dependence on DNA double-strand breaks. However, little is known about their cellular responses and genotoxicity. ... ...

    Abstract Base and prime editors (BEs and PEs) may provide more precise genetic engineering than nuclease-based approaches because they bypass the dependence on DNA double-strand breaks. However, little is known about their cellular responses and genotoxicity. Here, we compared state-of-the-art BEs and PEs and Cas9 in human hematopoietic stem and progenitor cells with respect to editing efficiency, cytotoxicity, transcriptomic changes and on-target and genome-wide genotoxicity. BEs and PEs induced detrimental transcriptional responses that reduced editing efficiency and hematopoietic repopulation in xenotransplants and also generated DNA double-strand breaks and genotoxic byproducts, including deletions and translocations, at a lower frequency than Cas9. These effects were strongest for cytidine BEs due to suboptimal inhibition of base excision repair and were mitigated by tailoring delivery timing and editor expression through optimized mRNA design. However, BEs altered the mutational landscape of hematopoietic stem and progenitor cells across the genome by increasing the load and relative proportions of nucleotide variants. These findings raise concerns about the genotoxicity of BEs and PEs and warrant further investigation in view of their clinical application.
    Language English
    Publishing date 2023-09-07
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1311932-1
    ISSN 1546-1696 ; 1087-0156
    ISSN (online) 1546-1696
    ISSN 1087-0156
    DOI 10.1038/s41587-023-01915-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Artificial intelligence-based prediction of transfusion in the intensive care unit in patients with gastrointestinal bleeding.

    Levi, Riccardo / Carli, Francesco / Arévalo, Aldo Robles / Altinel, Yuksel / Stein, Daniel J / Naldini, Matteo Maria / Grassi, Federica / Zanoni, Andrea / Finkelstein, Stan / Vieira, Susana M / Sousa, João / Barbieri, Riccardo / Celi, Leo Anthony

    BMJ health & care informatics

    2021  Volume 28, Issue 1

    Abstract: Objective: Gastrointestinal (GI) bleeding commonly requires intensive care unit (ICU) in cases of potentialhaemodynamiccompromise or likely urgent intervention. However, manypatientsadmitted to the ICU stop bleeding and do not require further ... ...

    Abstract Objective: Gastrointestinal (GI) bleeding commonly requires intensive care unit (ICU) in cases of potentialhaemodynamiccompromise or likely urgent intervention. However, manypatientsadmitted to the ICU stop bleeding and do not require further intervention, including blood transfusion. The present work proposes an artificial intelligence (AI) solution for the prediction of rebleeding in patients with GI bleeding admitted to ICU.
    Methods: A machine learning algorithm was trained and tested using two publicly available ICU databases, the Medical Information Mart for Intensive Care V.1.4 database and eICU Collaborative Research Database using freedom from transfusion as a proxy for patients who potentially did not require ICU-level care. Multiple initial observation time frames were explored using readily available data including labs, demographics and clinical parameters for a total of 20 covariates.
    Results: The optimal model used a 5-hour observation period to achieve an area under the curve of the receiving operating curve (ROC-AUC) of greater than 0.80. The model was robust when tested against both ICU databases with a similar ROC-AUC for all.
    Conclusions: The potential disruptive impact of AI in healthcare innovation is acknowledge, but awareness of AI-related risk on healthcare applications and current limitations should be considered before implementation and deployment. The proposed algorithm is not meant to replace but to inform clinical decision making. Prospective clinical trial validation as a triage tool is warranted.
    MeSH term(s) Artificial Intelligence ; Blood Transfusion/statistics & numerical data ; Female ; Gastrointestinal Hemorrhage/therapy ; Humans ; Intensive Care Units/statistics & numerical data ; Male ; Prospective Studies ; ROC Curve
    Language English
    Publishing date 2021-01-14
    Publishing country England
    Document type Journal Article
    ISSN 2632-1009
    ISSN (online) 2632-1009
    DOI 10.1136/bmjhci-2020-100245
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Circulating hematopoietic stem/progenitor cell subsets contribute to human hematopoietic homeostasis.

    Quaranta, Pamela / Basso-Ricci, Luca / Jofra Hernandez, Raisa / Pacini, Guido / Naldini, Matteo Maria / Barcella, Matteo / Seffin, Luca / Pais, Giulia / Spinozzi, Giulio / Benedicenti, Fabrizio / Pietrasanta, Carlo / Cheong, Jin Gyu / Ronchi, Andrea / Pugni, Lorenza / Dionisio, Francesca / Monti, Ilaria / Giannelli, Stefania / Darin, Silvia / Fraschetta, Federico /
    Barera, Graziano / Ferrua, Francesca / Calbi, Valeria / Ometti, Marco / Di Micco, Raffaella / Mosca, Fabio / Josefowicz, Steven Zvi / Montini, Eugenio / Calabria, Andrea / Bernardo, Maria Ester / Cicalese, Maria Pia / Gentner, Bernhard / Merelli, Ivan / Aiuti, Alessandro / Scala, Serena

    Blood

    2024  Volume 143, Issue 19, Page(s) 1937–1952

    Abstract: Abstract: In physiological conditions, few circulating hematopoietic stem/progenitor cells (cHSPCs) are present in the peripheral blood, but their contribution to human hematopoiesis remain unsolved. By integrating advanced immunophenotyping, single- ... ...

    Abstract Abstract: In physiological conditions, few circulating hematopoietic stem/progenitor cells (cHSPCs) are present in the peripheral blood, but their contribution to human hematopoiesis remain unsolved. By integrating advanced immunophenotyping, single-cell transcriptional and functional profiling, and integration site (IS) clonal tracking, we unveiled the biological properties and the transcriptional features of human cHSPC subpopulations in relationship to their bone marrow (BM) counterpart. We found that cHSPCs reduced in cell count over aging and are enriched for primitive, lymphoid, and erythroid subpopulations, showing preactivated transcriptional and functional state. Moreover, cHSPCs have low expression of multiple BM-retention molecules but maintain their homing potential after xenotransplantation. By generating a comprehensive human organ-resident HSPC data set based on single-cell RNA sequencing data, we detected organ-specific seeding properties of the distinct trafficking HSPC subpopulations. Notably, circulating multi-lymphoid progenitors are primed for seeding the thymus and actively contribute to T-cell production. Human clonal tracking data from patients receiving gene therapy (GT) also showed that cHSPCs connect distant BM niches and participate in steady-state hematopoietic production, with primitive cHSPCs having the highest recirculation capability to travel in and out of the BM. Finally, in case of hematopoietic impairment, cHSPCs composition reflects the BM-HSPC content and might represent a biomarker of the BM state for clinical and research purposes. Overall, our comprehensive work unveiled fundamental insights into the in vivo dynamics of human HSPC trafficking and its role in sustaining hematopoietic homeostasis. GT patients' clinical trials were registered at ClinicalTrials.gov (NCT01515462 and NCT03837483) and EudraCT (2009-017346-32 and 2018-003842-18).
    MeSH term(s) Animals ; Humans ; Mice ; Hematopoiesis ; Hematopoietic Stem Cells/cytology ; Hematopoietic Stem Cells/metabolism ; Homeostasis ; Single-Cell Analysis
    Language English
    Publishing date 2024-03-06
    Publishing country United States
    Document type Clinical Trial ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80069-7
    ISSN 1528-0020 ; 0006-4971
    ISSN (online) 1528-0020
    ISSN 0006-4971
    DOI 10.1182/blood.2023022666
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  7. Article ; Online: Longitudinal single-cell profiling of chemotherapy response in acute myeloid leukemia.

    Naldini, Matteo Maria / Casirati, Gabriele / Barcella, Matteo / Rancoita, Paola Maria Vittoria / Cosentino, Andrea / Caserta, Carolina / Pavesi, Francesca / Zonari, Erika / Desantis, Giacomo / Gilioli, Diego / Carrabba, Matteo Giovanni / Vago, Luca / Bernardi, Massimo / Di Micco, Raffaella / Di Serio, Clelia / Merelli, Ivan / Volpin, Monica / Montini, Eugenio / Ciceri, Fabio /
    Gentner, Bernhard

    Nature communications

    2023  Volume 14, Issue 1, Page(s) 1285

    Abstract: Acute myeloid leukemia may be characterized by a fraction of leukemia stem cells (LSCs) that sustain disease propagation eventually leading to relapse. Yet, the contribution of LSCs to early therapy resistance and AML regeneration remains controversial. ... ...

    Abstract Acute myeloid leukemia may be characterized by a fraction of leukemia stem cells (LSCs) that sustain disease propagation eventually leading to relapse. Yet, the contribution of LSCs to early therapy resistance and AML regeneration remains controversial. We prospectively identify LSCs in AML patients and xenografts by single-cell RNA sequencing coupled with functional validation by a microRNA-126 reporter enriching for LSCs. Through nucleophosmin 1 (NPM1) mutation calling or chromosomal monosomy detection in single-cell transcriptomes, we discriminate LSCs from regenerating hematopoiesis, and assess their longitudinal response to chemotherapy. Chemotherapy induced a generalized inflammatory and senescence-associated response. Moreover, we observe heterogeneity within progenitor AML cells, some of which proliferate and differentiate with expression of oxidative-phosphorylation (OxPhos) signatures, while others are OxPhos (low) miR-126 (high) and display enforced stemness and quiescence features. miR-126 (high) LSCs are enriched at diagnosis in chemotherapy-refractory AML and at relapse, and their transcriptional signature robustly stratifies patients for survival in large AML cohorts.
    MeSH term(s) Humans ; Neoplastic Stem Cells/metabolism ; Leukemia, Myeloid, Acute/drug therapy ; Leukemia, Myeloid, Acute/genetics ; Leukemia, Myeloid, Acute/metabolism ; MicroRNAs/metabolism ; Recurrence
    Chemical Substances MicroRNAs ; MIRN126 microRNA, human
    Language English
    Publishing date 2023-03-08
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-023-36969-0
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  8. Article ; Online: Sex dimorphism and cancer immunotherapy: May pregnancy solve the puzzle?

    Venanzi, Francesco Maria / Bini, Marta / Nuccio, Antonio / De Toma, Alessandro / Lambertini, Matteo / Ogliari, Francesca Rita / Oresti, Sara / Viganò, Maria Grazia / Brioschi, Elena / Polignano, Maggie / Naldini, Matteo Maria / Riva, Silvia / Ferrara, Michele / Fogale, Nicola / Damiano, Giuseppe / Russo, Vincenzo / Reni, Michele / Veronesi, Giulia / Foggetti, Giorgia /
    Conforti, Fabio / Bulotta, Alessandra / Ferrara, Roberto

    Cancer treatment reviews

    2023  Volume 121, Page(s) 102648

    Abstract: In the immunoncology era, growing evidence has shown a clear sex dimorphism in antitumor immune response with a potential impact on outcomes upon immunecheckpoint blockade (ICI) in patients with cancer. Sex dimorphism could affect tumor microenvironment ... ...

    Abstract In the immunoncology era, growing evidence has shown a clear sex dimorphism in antitumor immune response with a potential impact on outcomes upon immunecheckpoint blockade (ICI) in patients with cancer. Sex dimorphism could affect tumor microenvironment composition and systemic anticancer immunity; however, the modifications induced by sex are heterogeneous. From a clinical perspective, six metanalyses have explored the role of sex in cancer patients receiving ICI with conflicting results. Environmental and reproductive factors may further jeopardize the sex-related heterogeneity in anticancer immune response. In particular, pregnancy is characterized by orchestrated changes in the immune system, some of which could be long lasting. A persistence of memory T-cells with a potential fetal-antigen specificity has been reported both in human and mice, suggesting that a previous pregnancy may positively impact cancer development or response to ICI, in case of fetal-antigen sharing from tumor cells. On the other hand, a previous pregnancy may also be associated with a regulatory memory characterized by increased tolerance and anergy towards cancer-fetal common antigens. Finally, fetal-maternal microchimerism could represent an additional source of chronic exposure to fetal antigens and may have important immunological implications on cancer development and ICI activity. So far, the role of pregnancy dimorphism (nulliparous vs parous) in women and the impact of pregnancy-related variables remain largely underexplored in cancer patients. In this review, we summarize the evidence regarding sex and pregnancy dimorphism in the context of immune response and anticancer immunotherapy and advocate the importance of analyzing pregnancy variables on ICIs clinical trials.
    MeSH term(s) Pregnancy ; Humans ; Female ; Animals ; Mice ; Sex Characteristics ; Immunotherapy ; Antibody Specificity ; Tumor Microenvironment ; Neoplasms/therapy
    Language English
    Publishing date 2023-10-26
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 125102-8
    ISSN 1532-1967 ; 0305-7372
    ISSN (online) 1532-1967
    ISSN 0305-7372
    DOI 10.1016/j.ctrv.2023.102648
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  9. Article ; Online: miR-126 identifies a quiescent and chemo-resistant human B-ALL cell subset that correlates with minimal residual disease.

    Caserta, Carolina / Nucera, Silvia / Barcella, Matteo / Fazio, Grazia / Naldini, Matteo Maria / Pagani, Riccardo / Pavesi, Francesca / Desantis, Giacomo / Zonari, Erika / D'Angiò, Mariella / Capasso, Paola / Lombardo, Angelo / Merelli, Ivan / Spinelli, Orietta / Rambaldi, Alessandro / Ciceri, Fabio / Silvestri, Daniela / Valsecchi, Maria Grazia / Biondi, Andrea /
    Cazzaniga, Giovanni / Gentner, Bernhard

    Leukemia

    2023  Volume 37, Issue 10, Page(s) 1994–2005

    Abstract: Complete elimination of B-cell acute lymphoblastic leukemia (B-ALL) by a risk-adapted primary treatment approach remains a clinical key objective, which fails in up to a third of patients. Recent evidence has implicated subpopulations of B-ALL cells with ...

    Abstract Complete elimination of B-cell acute lymphoblastic leukemia (B-ALL) by a risk-adapted primary treatment approach remains a clinical key objective, which fails in up to a third of patients. Recent evidence has implicated subpopulations of B-ALL cells with stem-like features in disease persistence. We hypothesized that microRNA-126, a core regulator of hematopoietic and leukemic stem cells, may resolve intratumor heterogeneity in B-ALL and uncover therapy-resistant subpopulations. We exploited patient-derived xenograft (PDX) models with B-ALL cells transduced with a miR-126 reporter allowing the prospective isolation of miR-126(high) cells for their functional and transcriptional characterization. Discrete miR-126(high) populations, often characterized by MIR126 locus demethylation, were identified in 8/9 PDX models and showed increased repopulation potential, in vivo chemotherapy resistance and hallmarks of quiescence, inflammation and stress-response pathway activation. Cells with a miR-126(high) transcriptional profile were identified as distinct disease subpopulations by single-cell RNA sequencing in diagnosis samples from adult and pediatric B-ALL. Expression of miR-126 and locus methylation were tested in several pediatric and adult B-ALL cohorts, which received standardized treatment. High microRNA-126 levels and locus demethylation at diagnosis associate with suboptimal response to induction chemotherapy (MRD > 0.05% at day +33 or MRD+ at day +78).
    MeSH term(s) Adult ; Humans ; Child ; Neoplasm, Residual/genetics ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/genetics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy ; Burkitt Lymphoma ; MicroRNAs/genetics ; MicroRNAs/metabolism
    Chemical Substances MicroRNAs ; MIRN126 microRNA, human
    Language English
    Publishing date 2023-08-28
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 807030-1
    ISSN 1476-5551 ; 0887-6924
    ISSN (online) 1476-5551
    ISSN 0887-6924
    DOI 10.1038/s41375-023-02009-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Clinical management of a Nigerian patient affected by sickle cell disease with rare blood group and persistent SARS-CoV-2 positivity.

    Quaresima, Micol / Quaresima, Virginia / Naldini, Matteo Maria / Cirillo, Daniela Maria / Ferrari, Angela / Mazzi, Angela / Tesini, Ester Maria Carla / Leone, Maria Cristina / Merli, Francesco

    EJHaem

    2020  Volume 1, Issue 1, Page(s) 384–387

    Keywords covid19
    Language English
    Publishing date 2020-07-04
    Publishing country United States
    Document type Case Reports
    ISSN 2688-6146
    ISSN (online) 2688-6146
    DOI 10.1002/jha2.53
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