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Article ; Online: Sailing in deceptive calm: Navigating the undercurrents of essential thrombocythaemia.

Hashimoto, Yoshinori / Lucchesi, Alessandro

2024 Volume 204, Issue 5, Page(s) 1595–1597

Abstract: The discovery of driver mutations in myeloproliferative neoplasms has significantly contributed to the management of patients with essential thrombocythaemia (ET). High-quality evidence has started to pave the way for targeted therapy. The review by ... ...

Abstract	The discovery of driver mutations in myeloproliferative neoplasms has significantly contributed to the management of patients with essential thrombocythaemia (ET). High-quality evidence has started to pave the way for targeted therapy. The review by Ferrer-Marín et al. further advances this discussion, highlighting how molecular profiling, including non-driver gene mutations, is set to revolutionize personalized treatment approaches for ET patients. Commentary on: Ferrer-Marín et al. Essential thrombocythemia: a contemporary approach with new drugs on the horizon. Br J Haematol 2024;204:1605-1616.
MeSH term(s)	Thrombocythemia, Essential/genetics ; Humans ; Mutation ; Disease Management ; Janus Kinase 2/genetics
Chemical Substances	Janus Kinase 2 (EC 2.7.10.2)
Language	English
Publishing date	2024-04-15
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	80077-6
ISSN	1365-2141 ; 0007-1048
ISSN (online)	1365-2141
ISSN	0007-1048
DOI	10.1111/bjh.19437
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Article ; Online: Platelets beyond their count, as a key element of the innate immune system in the fight against malaria.

Lucchesi, Alessandro

British journal of haematology

2020 Volume 190, Issue 5, Page(s) 648–649

MeSH term(s)	Blood Platelets ; Burkitt Lymphoma ; Humans ; Immune System ; Kenya ; Malaria/prevention & control ; Platelet Count ; Tanzania ; Uganda
Language	English
Publishing date	2020-05-14
Publishing country	England
Document type	Journal Article ; Comment
ZDB-ID	80077-6
ISSN	1365-2141 ; 0007-1048
ISSN (online)	1365-2141
ISSN	0007-1048
DOI	10.1111/bjh.16754
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Article ; Online: Germline

Bochicchio, Maria Teresa / Micucci, Giorgia / Asioli, Silvia / Ghetti, Martina / Simonetti, Giorgia / Lucchesi, Alessandro

International journal of molecular sciences

2023 Volume 24, Issue 22

Abstract: Chronic myelomonocytic leukemia (CMML) is a hematological neoplasm characterized by monocytosis, splenomegaly, thrombocytopenia, and anemia. Moreover, it is associated ... ...

Abstract	Chronic myelomonocytic leukemia (CMML) is a hematological neoplasm characterized by monocytosis, splenomegaly, thrombocytopenia, and anemia. Moreover, it is associated with
MeSH term(s)	Humans ; Aged, 80 and over ; Leukemia, Myelomonocytic, Chronic/complications ; Leukemia, Myelomonocytic, Chronic/genetics ; Germ-Line Mutation ; Genetic Predisposition to Disease ; Mutation ; Anemia ; Germ Cells ; Receptors, Colony-Stimulating Factor/genetics
Chemical Substances	CSF3R protein, human ; Receptors, Colony-Stimulating Factor
Language	English
Publishing date	2023-11-07
Publishing country	Switzerland
Document type	Case Reports
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms242216021
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Article ; Online: Genetic regulation of iron homeostasis in sideropenic patients with mild COVID-19 disease under a new oral iron formulation: Lessons from a different perspective.

Giordano, Giulio / Bochicchio, Maria Teresa / Niro, Giovanna / Lucchesi, Alessandro / Napolitano, Mariasanta

Immunobiology

2022 Volume 227, Issue 6, Page(s) 152297

Abstract: Background: Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) needs iron to replicate itself. Coronaviruses are able to upregulate Chop/Gadd153 and Arg1 genes, consequently leading to CD8 lymphocytes decrease, degradation of asparagine and ... ...

Abstract	Background: Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) needs iron to replicate itself. Coronaviruses are able to upregulate Chop/Gadd153 and Arg1 genes, consequently leading to CD8 lymphocytes decrease, degradation of asparagine and decreased nitric oxide (NO), thus impairing immune response and antithrombotic functions. Little is known about regulation of genes involved in iron metabolism in paucisymptomatic patients with COVID-19 disease or in patients with iron deficiency treated with sucrosomial iron. Methods: Whole blood was taken from the COVID-19 patients and from patients with sideropenic anemia, treated or not (control group) with iron supplementations. Enrolled patients were: affected by COVID19 under sucrosomal iron support (group A), affected by COVID-19 not under oral iron support (group B), iron deficiency not under treatment, not affected by COVID19 (control group). After RNA extraction and complementary DNA (cDNA) synthesis of Arg1, Hepcidin and Chop/Gadd153, gene expression from the 3 groups was measured by qRT-PCR. M2 macrophages were detected by cytofluorimetry using CD163 and CD14 markers. Results: Forty patients with COVID-19 (group A), 20 patients with iron deficiency treated with sucrosomial iron (group B) and 20 patients with iron deficiency not under treatment (control group) were enrolled. In all the patients supported with oral sucrosomial iron, the gene expression of Chop, Arg1 and Hepcidin genes was lower than in sideropenic patients not supported with iron, M1 macrophages polarization and functional iron deficiency was also lower in group A and B, than observed in the control group. Conclusions: New oral iron formulations, as sucrosomial iron, are able to influence the expression of genes like Chop and Arg1 and to influence M2 macrophage polarization mainly in the early phase of COVID-19 disease.
MeSH term(s)	Humans ; COVID-19/complications ; Homeostasis ; Iron/metabolism ; Iron Deficiencies/complications ; Iron Deficiencies/drug therapy ; SARS-CoV-2 ; Ferric Compounds/therapeutic use ; Macrophages
Chemical Substances	Iron (E1UOL152H7) ; sucrosomial iron ; Ferric Compounds
Language	English
Publishing date	2022-10-26
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	563292-4
ISSN	1878-3279 ; 0171-2985
ISSN (online)	1878-3279
ISSN	0171-2985
DOI	10.1016/j.imbio.2022.152297
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Article: Use and positioning of fostamatinib in the management of primary chronic immune thrombocytopenia: an Italian expert opinion.

Lucchesi, Alessandro / Fattizzo, Bruno / De Stefano, Valerio / Ruggeri, Marco / Siragusa, Sergio / Vianelli, Nicola / Zaja, Francesco / Rodeghiero, Francesco

Therapeutic advances in hematology

2023 Volume 14, Page(s) 20406207221147777

Abstract: Fostamatinib, a spleen tyrosine kinase (Syk) inhibitor, represents a new therapeutic opportunity for patients with immune thrombocytopenia (ITP) in Europe and Italy. However, the positioning of this drug in patient's therapeutic sequence is undefined ... ...

Abstract	Fostamatinib, a spleen tyrosine kinase (Syk) inhibitor, represents a new therapeutic opportunity for patients with immune thrombocytopenia (ITP) in Europe and Italy. However, the positioning of this drug in patient's therapeutic sequence is undefined within the most recent international guidelines. The conclusions from a consensus meeting between Italian experts, whose task was to outline the profile of the ideal candidate to receive fostamatinib, are reported here. A modified Delphi methodology was used to achieve shared statements, which were reported in a narrative form. In particular, the panelists examined the strengths and weaknesses of the registration studies in terms of clinical outcomes, the safety profile of fostamatinib, the drug's impact on the quality of life of patients with chronic ITP, and the potential benefits of its use in the pandemic era. Although the experience with thrombopoietin receptor agonists (TPO-RAs) and the amount of data from real-world studies suggest the preferential use of these drugs as a second-line treatment in most patients, the absence of an increased thrombotic risk in the clinical trials could make fostamatinib a reasonable choice in patients with an increased risk of vascular events. An unstable platelet count during TPO-RAs might also justify a switch to the Syk inhibitor, which is more likely to stabilize the platelet count in responders. Fostamatinib may be preferred to immunosuppressors during the SARS-CoV-2 pandemic, in patients at infectious risk, or in case of contraindication to splenectomy. Finally, the novel mechanism of action makes it an attractive drug in multi-refractory patient.
Language	English
Publishing date	2023-02-28
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2585183-4
ISSN	2040-6215 ; 2040-6207
ISSN (online)	2040-6215
ISSN	2040-6207
DOI	10.1177/20406207221147777
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Article ; Online: Microbial profile in bile from pancreatic and extra-pancreatic biliary tract cancer.

Di Carlo, Paola / Serra, Nicola / Fasciana, Teresa Maria Assunta / Giammanco, Anna / D'Arpa, Francesco / Rea, Teresa / Napolitano, Maria Santa / Lucchesi, Alessandro / Cascio, Antonio / Sergi, Consolato Maria

PloS one

2024 Volume 19, Issue 2, Page(s) e0294049

Abstract: Background: Dysbiotic biliary bacterial profile is reported in cancer patients and is associated with survival and comorbidities, raising the question of its effect on the influence of anticancer drugs and, recently, the suggestion of perichemotherapy ... ...

Abstract	Background: Dysbiotic biliary bacterial profile is reported in cancer patients and is associated with survival and comorbidities, raising the question of its effect on the influence of anticancer drugs and, recently, the suggestion of perichemotherapy antibiotics in pancreatic cancer patients colonized by the Escherichia coli and Klebsiella pneumoniae. Objective: In this study, we investigated the microbial communities that colonize tumours and which bacteria could aid in diagnosing pancreatic and biliary cancer and managing bile-colonized patients. Methods: A retrospective study on positive bile cultures of 145 Italian patients who underwent cholangiopancreatography with PC and EPC cancer hospitalized from January 2006 to December 2020 in a QA-certified academic surgical unit were investigated for aerobic/facultative-anaerobic bacteria and fungal organisms. Results: We found that among Gram-negative bacteria, Escherichia coli and Pseudomonas spp were the most frequent in the EPC group, while Escherichia coli, Klebsiella spp, and Pseudomonas spp were the most frequent in the PC group. Enterococcus spp was the most frequent Gram-positive bacteria in both groups. Comparing the EPC and PC, we found a significant presence of patients with greater age in the PC compared to the EPC group. Regarding Candida spp, we found no significant but greater rate in the PC group compared to the EPC group (11.7% vs 1.96%). We found that Alcaligenes faecalis was the most frequent bacteria in EPC than the PC group, among Gram-negative bacterial species. Conclusions: Age differences in gut microbiota composition may affect biliary habitats in our cancer population, especially in patients with pancreatic cancer. Alcaligenes faecalis isolated in the culture of bile samples could represent potential microbial markers for a restricted follow-up to early diagnosis of extra-pancreatic cancer. Finally, the prevalence of Candida spp in pancreatic cancer seems to trigger new aspects about debate about the role of fungal microbiota into their relationship with pancreatic cancer.
MeSH term(s)	Humans ; Bile/microbiology ; Retrospective Studies ; Bacteria ; Anti-Bacterial Agents/pharmacology ; Gram-Negative Bacteria ; Biliary Tract Neoplasms/drug therapy ; Candida ; Escherichia coli ; Pancreatic Neoplasms/drug therapy ; Microbial Sensitivity Tests
Chemical Substances	Anti-Bacterial Agents
Language	English
Publishing date	2024-02-21
Publishing country	United States
Document type	Journal Article
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0294049
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Article ; Online: Oral high-dose sucrosomial iron vs intravenous iron in sideropenic anemia patients intolerant/refractory to iron sulfate: a multicentric randomized study.

Giordano, Giulio / Napolitano, Mariasanta / Di Battista, Valeria / Lucchesi, Alessandro

Annals of hematology

2020 Volume 100, Issue 9, Page(s) 2173–2179

Abstract: Iron deficiency anemia is among the most frequent causes of disability. Intravenous iron is the quickest way to correct iron deficiency, bypassing the bottleneck of iron intestinal absorption, the only true mechanism of iron balance regulation in human ... ...

Abstract	Iron deficiency anemia is among the most frequent causes of disability. Intravenous iron is the quickest way to correct iron deficiency, bypassing the bottleneck of iron intestinal absorption, the only true mechanism of iron balance regulation in human body. Intravenous iron administration is suggested in patients who are refractory/intolerant to oral iron sulfate. However, the intravenous way of iron administration requires several precautions; as the in-hospital administration requires a resuscitation service, as imposed in Europe by the European Medicine Agency, it is very expensive and negatively affects patient's perceived quality of life. A new oral iron formulation, Sucrosomial iron, bypassing the normal way of absorption, seems to be cost-effective in correcting iron deficiency anemia at doses higher than those usually effective with other oral iron formulations. In this multicentric randomized study, we analyze the cost-effectiveness of intravenous sodium ferrigluconate vs oral Sucrosomial iron in patients with iron deficiency anemia refractory/intolerant to oral iron sulfate without other interfering factors on iron absorption.
MeSH term(s)	Administration, Intravenous ; Administration, Oral ; Adult ; Aged ; Aged, 80 and over ; Anemia, Iron-Deficiency/drug therapy ; Anemia, Iron-Deficiency/economics ; Cost-Benefit Analysis ; Female ; Ferric Compounds/administration & dosage ; Ferric Compounds/economics ; Ferric Compounds/therapeutic use ; Ferrous Compounds/therapeutic use ; Hematinics/administration & dosage ; Hematinics/economics ; Hematinics/therapeutic use ; Humans ; Male ; Middle Aged ; Prospective Studies
Chemical Substances	Ferric Compounds ; Ferrous Compounds ; Hematinics ; sucrosomial iron ; ferrous sulfate (39R4TAN1VT) ; ferric gluconate (W108RK810P)
Language	English
Publishing date	2020-12-02
Publishing country	Germany
Document type	Journal Article ; Multicenter Study ; Randomized Controlled Trial
ZDB-ID	1064950-5
ISSN	1432-0584 ; 0939-5555 ; 0945-8077
ISSN (online)	1432-0584
ISSN	0939-5555 ; 0945-8077
DOI	10.1007/s00277-020-04361-3
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Article ; Online: Genetics and Pathogenetic Role of Inflammasomes in Philadelphia Negative Chronic Myeloproliferative Neoplasms: A Narrative Review.

Di Battista, Valeria / Bochicchio, Maria Teresa / Giordano, Giulio / Napolitano, Mariasanta / Lucchesi, Alessandro

International journal of molecular sciences

2021 Volume 22, Issue 2

Abstract: The last decade has been very important for the quantity of preclinical information obtained regarding chronic myeloproliferative neoplasms (MPNs) and the following will be dedicated to the translational implications of the new biological acquisitions. ... ...

Abstract	The last decade has been very important for the quantity of preclinical information obtained regarding chronic myeloproliferative neoplasms (MPNs) and the following will be dedicated to the translational implications of the new biological acquisitions. The overcoming of the mechanistic model of clonal evolution and the entry of chronic inflammation and dysimmunity into the new model are the elements on which to base a part of future therapeutic strategies. The innate immune system plays a major role in this context. Protagonists of the initiation and regulation of many pathological aspects, from cytokine storms to fibrosis, the NLRP3 and AIM2 inflammasomes guide and condition the natural history of the disease. For this reason, MPNs share many biological and clinical aspects with non-neoplastic diseases, such as autoimmune disorders. Finally, cardiovascular risk and disturbances in iron metabolism and myelopoiesis are also closely linked to the role of inflammasomes. Although targeted therapies are already being tested, an increase in knowledge on the subject is desirable and potentially translates into better care for patients with MPNs.
MeSH term(s)	Autoimmune Diseases/genetics ; Autoimmune Diseases/pathology ; Clonal Evolution ; DNA-Binding Proteins/genetics ; Humans ; Inflammasomes/genetics ; Inflammation/genetics ; Inflammation/pathology ; Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative/genetics ; Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative/pathology ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics
Chemical Substances	AIM2 protein, human ; DNA-Binding Proteins ; Inflammasomes ; NLR Family, Pyrin Domain-Containing 3 Protein ; NLRP3 protein, human
Language	English
Publishing date	2021-01-08
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms22020561
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Article ; Online: Platelets Contribution to Thrombin Generation in Philadelphia-Negative Myeloproliferative Neoplasms: The "Circulating Wound" Model.

Lucchesi, Alessandro / Napolitano, Roberta / Bochicchio, Maria Teresa / Giordano, Giulio / Napolitano, Mariasanta

International journal of molecular sciences

2021 Volume 22, Issue 21

Abstract: Current cytoreductive and antithrombotic strategies in MPNs are mostly based on cell counts and on patient's demographic and clinical history. Despite the numerous studies conducted on platelet function and on the role of plasma factors, an accurate and ... ...

Abstract	Current cytoreductive and antithrombotic strategies in MPNs are mostly based on cell counts and on patient's demographic and clinical history. Despite the numerous studies conducted on platelet function and on the role of plasma factors, an accurate and reliable method to dynamically quantify the hypercoagulability states of these conditions is not yet part of clinical practice. Starting from our experience, and after having sifted through the literature, we propose an in-depth narrative report on the contribution of the clonal platelets of MPNs-rich in tissue factor (TF)-in promoting a perpetual procoagulant mechanism. The whole process results in an unbalanced generation of thrombin and is self-maintained by Protease Activated Receptors (PARs). We chose to define this model as a "circulating wound", as it indisputably links the coagulation, inflammation, and fibrotic progression of the disease, in analogy with what happens in some solid tumours. The platelet contribution to thrombin generation results in triggering a vicious circle supported by the PARs/TGF-beta axis. PAR antagonists could therefore be a good option for target therapy, both to contain the risk of vascular events and to slow the progression of the disease towards end-stage forms. Both the new and old strategies, however, will require tools capable of measuring procoagulant or prohaemorrhagic states in a more extensive and dynamic way to favour a less empirical management of MPNs and their potential clinical complications.
MeSH term(s)	Animals ; Biological Assay ; Blood Platelets/metabolism ; Humans ; Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative/drug therapy ; Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative/metabolism ; Models, Biological ; Receptors, Fibrinogen/metabolism ; Thrombin/antagonists & inhibitors ; Thrombin/biosynthesis ; Thrombophilia/physiopathology
Chemical Substances	Receptors, Fibrinogen ; Thrombin (EC 3.4.21.5)
Language	English
Publishing date	2021-10-20
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms222111343
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Article: Immune Thrombocytopenia in Antiphospholipid Syndrome: Is It Primary or Secondary?

Tomasello, Riccardo / Giordano, Giulio / Romano, Francesco / Vaccarino, Federica / Siragusa, Sergio / Lucchesi, Alessandro / Napolitano, Mariasanta

Biomedicines

2021 Volume 9, Issue 9

Abstract: Antiphospholipid syndrome (APS) is frequently associated with thrombocytopenia, in most cases mild and in the absence of major bleedings. In some patients with a confirmed APS diagnosis, secondary immune thrombocytopenia (ITP) may lead to severe ... ...

Abstract	Antiphospholipid syndrome (APS) is frequently associated with thrombocytopenia, in most cases mild and in the absence of major bleedings. In some patients with a confirmed APS diagnosis, secondary immune thrombocytopenia (ITP) may lead to severe thrombocytopenia with consequent major bleeding. At the same time, the presence of antiphospholipid antibodies (aPL) in patients with a diagnosis of primary ITP has been reported in several studies, although with some specific characteristics especially related to the variety of antigenic targets. Even though it does not enter the APS defining criteria, thrombocytopenia should be regarded as a warning sign of a "high risk" APS and thus thoroughly evaluated. The presence of aPL in patients with ITP should be assessed as well to stratify the risk of paradoxical thrombosis. In detail, besides the high hemorrhagic risk in secondary thrombocytopenia, patients with a co-diagnosis of APS or only antibodies are also at risk of arterial and venous thrombosis. In this narrative review, we discuss the correlation between APS and ITP, the mechanisms behind the above-reported entities, in order to support clinicians to define the most appropriate treatment strategy in these patients, especially when anticoagulant or antiplatelet agents may be needed.
Language	English
Publishing date	2021-09-06
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines9091170
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