4 results on '"Cavalca F"'
Search Results
2. Idiopathic erythrocytosis: a germline disease?
- Author
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Elli, E, Mauri, M, D’Aliberti, D, Crespiatico, I, Fontana, D, Redaelli, S, Pelucchi, S, Spinelli, S, Manghisi, B, Cavalca, F, Aroldi, A, Ripamonti, A, Ferrari, S, Palamini, S, Mottadelli, F, Massimino, L, Ramazzotti, D, Cazzaniga, G, Piperno, A, Gambacorti-Passerini, C, Piazza, R, Elli, E. M., Mauri, M., D’Aliberti, D., Crespiatico, I., Fontana, D., Redaelli, S., Pelucchi, S., Spinelli, S., Manghisi, B., Cavalca, F., Aroldi, A., Ripamonti, A., Ferrari, S., Palamini, S., Mottadelli, F., Massimino, L., Ramazzotti, D., Cazzaniga, G., Piperno, A., Gambacorti-Passerini, C., Piazza, R., Elli, E, Mauri, M, D’Aliberti, D, Crespiatico, I, Fontana, D, Redaelli, S, Pelucchi, S, Spinelli, S, Manghisi, B, Cavalca, F, Aroldi, A, Ripamonti, A, Ferrari, S, Palamini, S, Mottadelli, F, Massimino, L, Ramazzotti, D, Cazzaniga, G, Piperno, A, Gambacorti-Passerini, C, Piazza, R, Elli, E. M., Mauri, M., D’Aliberti, D., Crespiatico, I., Fontana, D., Redaelli, S., Pelucchi, S., Spinelli, S., Manghisi, B., Cavalca, F., Aroldi, A., Ripamonti, A., Ferrari, S., Palamini, S., Mottadelli, F., Massimino, L., Ramazzotti, D., Cazzaniga, G., Piperno, A., Gambacorti-Passerini, C., and Piazza, R.
- Abstract
Polycythemia Vera (PV) is typically caused by V617F or exon 12 JAK2 mutations. Little is known about Polycythemia cases where no JAK2 variants can be detected, and no other causes identified. This condition is defined as idiopathic erythrocytosis (IE). We evaluated clinical-laboratory parameters of a cohort of 56 IE patients and we determined their molecular profile at diagnosis with paired blood/buccal-DNA exome-sequencing coupled with a high-depth targeted OncoPanel to identify a possible underling germline or somatic cause. We demonstrated that most of our cohort (40/56: 71.4%) showed no evidence of clonal hematopoiesis, suggesting that IE is, in large part, a germline disorder. We identified 20 low mutation burden somatic variants (Variant allelic fraction, VAF, < 10%) in only 14 (25%) patients, principally involving DNMT3A and TET2. Only 2 patients presented high mutation burden somatic variants, involving DNMT3A, TET2, ASXL1 and WT1. We identified recurrent germline variants in 42 (75%) patients occurring mainly in JAK/STAT, Hypoxia and Iron metabolism pathways, among them: JAK3-V722I and HIF1A-P582S; a high fraction of patients (48.2%) resulted also mutated in homeostatic iron regulatory gene HFE-H63D or C282Y. By generating cellular models, we showed that JAK3-V722I causes activation of the JAK-STAT5 axis and upregulation of EPAS1/HIF2A, while HIF1A-P582S causes suppression of hepcidin mRNA synthesis, suggesting a major role for these variants in the onset of IE.
- Published
- 2024
3. Neutrophil-to-lymphocyte ratio (NLR) at diagnosis in essential thrombocythemia: A new promising predictor of thrombotic events.
- Author
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Ripamonti A, Cavalca F, Montelisciani L, Antolini L, Gambacorti-Passerini C, and Elli EM
- Abstract
Background: Myeloproliferative neoplasms represent a heterogeneous group of acquired hematopoietic stem cell diseases in which chronic inflammation is essential for both clonal evolution and thrombotic complications. The neutrophil-to-lymphocyte ratio (NLR), reflecting the imbalance between systemic inflammation and immunity, is emerging as a prognostic biomarker in several diseases, including hematological ones., Methods: A total of 473 patients with essential thrombocythemia (ET), the relationship between NLR value at diagnosis and the risk of thrombotic events in the follow-up, in addition to conventional clinical and biological variables, were retrospectively analyzed., Results: A total of 78 thrombotic events were reported for an incidence rate of 1.8 × 100 patients/year. In multivariate analysis, NLR value ≥4 at diagnosis was associated with higher cumulative thrombotic risk (hazard ratio [HR], 2.05; 95% CI, 1.29-2.28; p = .0001) as well International Prognostic Score for Thrombosis in Essential Thrombosis score intermediate-high (HR, 2.69; 95% CI, 1.27-5.72; p = .01) and diabetes (HR, 2.49; 95% CI, 1.23-3.05; p = .010). Concerning arterial thrombotic events, in multivariate analysis, NLR value at diagnosis ≥4 was predictive for thrombosis (HR, 2.13; 95% CI, 1.31-4.04; p = .001 as well diabetes (HR, 2.44; 95% CI, 1.05-5.68; p = .04) and hypertension (HR, 2.46; 95% CI, 1.05-5.68; p = .01). About venous thrombotic events, NLR value ≥5 was a marker predictive for venous thrombosis (HR, 2.99; 95% CI, 2.45-6.48; p = .01) as well age >60 years old (HR, 2.26; 95% CI, 1.0-5.10; p = .05)., Conclusion: NLR value is a simple, cost-effective, and easy-to-obtain inflammatory marker that can predict a diagnosis the risk of thrombosis in ET. Our results suggest that NLR value could be integrated into conventional cardiovascular risk scores, to better classify high-risk patients who are candidates for cytoreductive therapy. Further larger and prospective studies are warranted., (© 2024 American Cancer Society.)
- Published
- 2024
- Full Text
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4. Evaluating the performance of large language models in haematopoietic stem cell transplantation decision-making.
- Author
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Civettini I, Zappaterra A, Granelli BM, Rindone G, Aroldi A, Bonfanti S, Colombo F, Fedele M, Grillo G, Parma M, Perfetti P, Terruzzi E, Gambacorti-Passerini C, Ramazzotti D, and Cavalca F
- Subjects
- Humans, Language, Tissue Donors, Artificial Intelligence, Hematopoietic Stem Cell Transplantation
- Abstract
In a first-of-its-kind study, we assessed the capabilities of large language models (LLMs) in making complex decisions in haematopoietic stem cell transplantation. The evaluation was conducted not only for Generative Pre-trained Transformer 4 (GPT-4) but also conducted on other artificial intelligence models: PaLm 2 and Llama-2. Using detailed haematological histories that include both clinical, molecular and donor data, we conducted a triple-blind survey to compare LLMs to haematology residents. We found that residents significantly outperformed LLMs (p = 0.02), particularly in transplant eligibility assessment (p = 0.01). Our triple-blind methodology aimed to mitigate potential biases in evaluating LLMs and revealed both their promise and limitations in deciphering complex haematological clinical scenarios., (© 2023 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)
- Published
- 2024
- Full Text
- View/download PDF
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