Papers by fabrizio vianello
Blood, 2012
2595 Background: Posaconazole is indicated for prophylaxis and salvage therapy of invasive fungal... more 2595 Background: Posaconazole is indicated for prophylaxis and salvage therapy of invasive fungal infections. Based on pharmacokinetic-pharmacodynamic data, a minimum serum concentration higher than 0.5 mg/L and 1.0 mg/L has been proposed for prophylaxis and therapy, respectively. While therapeutic drug monitoring (TDM) of plasma concentrations is widely accepted for triazole antifungal agents such as voriconazole, the utility of TDM for posaconazole is controversial due to debate over the relationship between posaconazole exposure in plasma and clinical response to therapy. In fact only few reports correlate posaconazole plasma concentrations (PPCs) with breakthrough infection. Methods: In this retrospective single center study we evaluated the correlation of PPCs with breakthrough invasive mould infections (IMIs) in 50 patients with acute myeloid leukaemia (AML) who underwent chemoterapy (induction or salvage therapy) between July 2009 and March 2012. To measure the posaconazole c...
L'invention concerne des procedes et des compositions permettant de moduler le mouvement de c... more L'invention concerne des procedes et des compositions permettant de moduler le mouvement de cellules eucaryotes a capacite migratoire. Plus precisement, l'invention concerne des agents anti-chimiorepulsion et leurs procedes d'utilisation pour renforcer une reponse immunitaire.
Tumori Journal, 1992
Interferon-alpha might increase triglyceride serum levels through the enhancement of hepatic lipo... more Interferon-alpha might increase triglyceride serum levels through the enhancement of hepatic lipogenesis and/or inhibition of the peripheral lipoprotein lipase. Hypertriglyceridemia during interferon-alpha therapy has been only recently described, mostly in patients with previous abnormalities of lipid metabolism. The authors report here a case of a 65-year-old male bearing advanced colon carcinoma who developed hypertriglyceridemia during long-term interferon-alpha treatment in association with 5 fluorouracil administration. Hypertriglyceridemia was maintained within acceptable levels, without adjusting the treatment plan, by an appropriate diet and gemfibrosil administration.
Infectious Diseases, 2018
Encyclopedia of Medical Genomics and Proteomics, 2004
... Alessandro Pecci3, Raffaella Scandellari1, Matteo Floris3, Alessandra Balduini2, andFabrizio ... more ... Alessandro Pecci3, Raffaella Scandellari1, Matteo Floris3, Alessandra Balduini2, andFabrizio Fabris1 1Department of Medical and Surgical Sciences University of Padua Medical School, ... Pixinamanna, Pula (CA), Italy Acknowldgments ...
PLOS ONE, 2021
Secondary antibody deficiencies (SAD) may require immunoglobulin replacement therapy (IgRT). Whil... more Secondary antibody deficiencies (SAD) may require immunoglobulin replacement therapy (IgRT). While the intravenous route (IVIG) is broadly considered effective in SAD, the use of subcutaneous immunoglobulins (SCIG) is mainly adopted from the experience in primary antibody deficiencies (PAD), where SCIG have been shown to perform as effective as IVIG. However, evidence-based data on SCIG administration in SAD patients are still insufficient. Herein we retrospectively evaluated the efficacy and safety profile of SCIG treatment in 131 SAD patients as compared to a group of 102 PAD patients. We found SCIG being equally effective in reducing annual infectious rate both in SAD and PAD patients. However, SAD patients required lower SCIG dosage and lower IgG through level to achieve similar biological effect in terms of infection burden, at the steady state. SAD patients also showed better correlation between SCIG dose and serum IgG achieved value. Furthermore, within SAD, SCIG were found t...
Blood, 2015
Background and objectives. Bendamustine in combination with rituximab has demonstrated a relevant... more Background and objectives. Bendamustine in combination with rituximab has demonstrated a relevant clinical activity and a good toxicity profile in patients with mantle cell lymphoma (MCL). Cytosine arabinoside (Ara-C) is a key drug in induction chemotherapy regimens of young patients with MCL. In vitro studies have shown that bendamustine increases the cytotoxic effect of Ara‐C in leukemic blasts and lymphoma cells, and the two drugs display high synergistic activity when used in consecutive combinations. Clinically, it has recently been demonstrated that rituximab + bendamustine + Ara‐C (R-BAC) combination has a remarkable activity and is well tolerated both in untreated and in relapsed/refractory patients with MCL (Visco C et al. J Clin Oncol 2013 31:1442-1449). In the present study, we report data from an Italian single-center experience evaluating the efficacy and tolerability of R-BAC association in previously untreated MCL patients both eligible and ineligible for transplantat...
Leukemia Research, 2017
asking difficulties in asking physicians questions. A linear regression model was used to identif... more asking difficulties in asking physicians questions. A linear regression model was used to identify the characteristics associated with the level of MDS-related distress. Results: The median age of the 301 French and Australian MDS patients was 71 years (range 19-93). The majority of patients had difficulties to understand basic health information (58.3%, functional HL) and to communicate with physicians (51.2%, communicative HL). On average three years after diagnosis, the mean IES score was 21.2 (95% Confidence Interval 19.2-23.1). Most patients (55.8%) had a high level of distress (IES score >19). Distress was not modified by gender, awareness of increased risk of developing acute myeloid leukaemia, time from MDS diagnosis or most recent treatment (Figure). Australian patients had lower level of IES score (adjusted β = −5.8, p = 0.003) compared to French patients. Satisfaction with information provided about MDS and higher health literacy level were also independently associated with less distress.
Clinical & Laboratory Haematology, 1998
We report the case of a 28-year-old woman who presented with two episodes of acute pancreatitis 3... more We report the case of a 28-year-old woman who presented with two episodes of acute pancreatitis 3 years apart both of which were complicated by the development of thrombotic thrombocytopenic purpura (TTP). On each occasion the TTP was successfully managed with plasmapheresis. Although TTP has been reported as causing acute pancreatitis, the induction of TTP by pancreatitis is rare. As far as we are aware this is the first reported case of recurrent TTP in association with acute pancreatitis. It is possible that circulating pancreatic proteases may have induced the TTP by modifying von Willebrand factor enabling spontaneous platelet membrane receptor binding resulting in intravascular platelet aggregation.
Frontiers in Oncology
About 30% of patients with diffuse large B-cell lymphoma (DLBCL) relapse or exhibit refractory di... more About 30% of patients with diffuse large B-cell lymphoma (DLBCL) relapse or exhibit refractory disease (r/r DLBCL) after first-line immunochemotherapy. Bone marrow (BM) involvement confers a dismal prognosis at diagnosis, likely due to the interaction between neoplastic cells and a complex tumor microenvironment (TME). Therefore, we developed a 3D in-vitro model from human decellularized femoral bone fragments aiming to study the role of mesenchymal stromal cells (MSC) and the extracellular matrix (ECM) in the adaptation, growth, and drug resistance of DLBCL lymphoma cells. The 3D spatial configuration of the model was studied by histological analysis and confocal and multiphoton microscopy which allowed the 3D digital reproduction of the structure. We proved that MSC adapt and expand in the 3D scaffold generating niches in which also other cell types may grow. DLBCL cell lines adhered and grew in the 3D scaffold, both in the presence and absence of MSC, suggesting an active ECM–lym...
Frontiers in Oncology, 2021
Mantle Cell Lymphoma (MCL) is still an incurable B-cell malignancy characterized by poor prognosi... more Mantle Cell Lymphoma (MCL) is still an incurable B-cell malignancy characterized by poor prognosis and frequent relapses. B Cell Receptor (BCR) signaling inhibitors, in particular of the kinases BTK and PI3Kγ/δ, have demonstrated clinically meaningful anti-proliferative effects in B cell tumors. However, refractoriness to these drugs may develop, portending a dismal prognosis. Protein kinase CK1α is an emerging pro-growth enzyme in B cell malignancies. In multiple myeloma, this kinase sustains β-catenin and AKT-dependent survival and is involved in the activation of NF-κB in B cells. In this study, we analyzed the role of CK1α on MCL cell survival and proliferation, on the regulation of BCR-related BTK, NF-κB, PI3K/AKT signaling cascades and the effects of CK1α chemical inhibition or gene silencing in association with the BTK inhibitor Ibrutinib or the PI3Kγ/δ inhibitor Duvelisib. CK1α was found highly expressed in MCL cells as compared to normal B cells. The inactivation/loss of CK...
Aging Clinical and Experimental Research, 2020
Aging is associated with a higher risk of developing malignant diseases, including myelodysplasti... more Aging is associated with a higher risk of developing malignant diseases, including myelodysplastic syndromes, clonal disorders characterised by chronic cytopenias (anaemia, neutropenia and thrombocytopenia) and abnormal cellular maturation. Myelodysplastic syndromes arising in older subjects are influenced by combinations of acquired somatic genetic lesions driving evolution from clonal haematopoiesis to myelodysplastic syndromes and from myelodysplastic syndromes to acute leukaemia. A different pattern of mutations has been identified in a small subset of myelodysplastic syndromes arising in young patients with familial syndromes. In particular, dysregulation of ANKRD26, RUNX1 and ETV6 genes plays a role in familial thrombocytopenia with predisposition to myelodysplastic syndromes and acute leukaemia. Whether these genes affect thrombopoiesis in sporadic myelodysplastic syndrome with thrombocytopenia is still undefined. Thirty-one myelodysplastic syndromes subjects and 27 controls subjects were investigated. Genomic DNA was used for mutation screening (ETV6, RUNX1, 5′UTR ANKRD26 genes). Functional studies were performed in the MEG-01-akaryoblastic cell line. We found four novel variants of RUNX1 gene, all in elderly myelodysplastic syndromes subjects with thrombocytopenia. Functional studies of the variant p.Pro103Arg showed no changes in RUNX1 expression, but the variant was associated with deregulated high transcriptional activity of ANKRD26 in MEG-01 cells. RUNX1 variant p.Pro103Arg was also associated with increased viability and reduced apoptosis of MEG-01, as well as impaired platelet production. Our findings are consistent with dysregulation of ANKRD26 in RUNX1 haploinsufficiency. Lack of repression of ANKRD26 expression may contribute to thrombocytopenia of subjects with sporadic myelodysplastic syndromes.
Internal and Emergency Medicine, 2019
, a 29-yearold Moldovan woman was referred to our center with a platelet count of 4 × 10 9 /L and... more , a 29-yearold Moldovan woman was referred to our center with a platelet count of 4 × 10 9 /L and bleeding symptoms such as epistaxis and petechiae. She had been diagnosed with immunethrombocytopenia (ITP) in 2002. Ever since her childhood, her thrombocytopenia had been associated with hemolytic anemia (Evans syndrome) requiring blood transfusions, and complicated by HCV-related hepatitis (anti-HCV antibodies, HCV-RNA 1257491 IU/ml, genotype 1b). Previous therapy for ITP, based on prednisone, intravenous immunoglobulin (IVIg) and azathioprine had been ineffective. In 2006, she underwent splenectomy, and achieved a stable complete remission (CR), maintained with a low daily dose of prednisone (2.5 mg). She also suffered from Sjögren's syndrome, with severe dry eyes, positive ANA and ENA anti-SSA titers, and monoclonal gammopathy of undetermined significance IgGK without Bence-Jones proteinuria. Definitive diagnosis Dr. Vianello: We performed a bone marrow examination, which was normal; platelet-associated autoantibodies against GpIIb/IIIa and GpIb were identified. An abdominal CT scan performed during hospitalization at our center was negative for accessory spleen. A definitive diagnosis of secondary and refractory ITP was established.
Blood cells, molecules & diseases, May 24, 2017
A novel germ-line mutation of c-mpl gene in a sporadic case of essential thrombocythemia Editor: ... more A novel germ-line mutation of c-mpl gene in a sporadic case of essential thrombocythemia Editor: Mohandas Narla To the Editor, Hereditary thrombocytosis (HT) as well as myeloproliferative neoplasms (MPN) such as essential thrombocythemia (ET) and primary myelofibrosis (PMF), have been described as associated to germ-line mutations of the thrombopoietin receptor c-mpl gene (MPL) [1]. Among the most frequent mutations, MPL S505 has been found both in a somatic and germ-line pattern [2]. Mutations of this residue are responsible for transmembrane domain movement, that altering the conformation of the nearby intracellular domain, which eventually leads to constitutive activation of MPL's kinase partner, JAK2. Computational modelling has demonstrated that residues 486 to 512 form the transmembrane domain (TM) of MPL protein. Therefore, mutations in this region likely affect the TM conformation by inducing changes in its angle along the membrane axis [3]. We report a novel germ-line mutation of the TM MPL protein (p.H500delinsG; p.V502delinsS) in a subject with MPN. A 52-years old asymptomatic man with thrombocytosis was referred to this hematology unit in 2012. His blood count showed WBC 11.4 × 10 9 / L, neutrophils 7.9 × 10 9 /L, hemoglobin 143 g/L, platelets 995 × 10 9 /L. His past medical history and physical examination was unremarkable. JAK2 gene analysis did not find V617F or exon 12 mutation. Bone marrow biopsy performed at diagnosis, showed slight increase in cellularity, increased numbers of large mature megakaryocytes with hyperlobulated nuclei, no increase in reticulin fibers, a pattern consistent with ET. He was put on regular follow up and no therapy was recommended. On August 2015, immature cells appeared at the complete blood count (CBC). Physical examination disclosed enlarged spleen (about 5 cm below the left costal margin on deep inspiration) and a bone marrow re-evaluation was recommended. The histological pattern showed slight increase reticulin fibrosis, consistent with MF-1 (DIPSS Plus Score 1) [4,5]. No further clinical changes were reported at the more recent follow-up visit. Genomic DNA was isolated using standard procedures from peripheral blood or buccal swab samples, after informed consent. Exon 10 including the intron/exon boundaries of the MPL gene was sequenced on an Applied Biosystem 3130 XL DNA sequencer (Applied Biosystems, Foster City, CA, USA). Genomic DNA was amplified by PCR using the following primers: ex10fw 5′-GACGCTGGGCTATCGAAG-3′ and ex10rw 5′-CCAAGAATGCCTGTTTACA-3′. The PCR was also performed using amplification sub-cloning kit (NEB PCR Cloning Kit New England Biolabs) according to the manufacturer's instructions and confirmed with sequencing. Both DNA analysis from buccal swabs and from peripheral blood cells showed a previously not described deletion/insertion at position c.1537-1545delinsGGCCTCAGC in exon 10 (http://www.HGVS.org/varnomen) in a heterozygous pattern (Fig.1). This mutation was not found in buccal nor peripheral blood DNA from patient's mother, sister and patient's two children, all with a normal CBC. Historical laboratory data of patient's father did not show MPN phenotype. All subjects were enrolled after informed consent. Gene analysis of 100 healthy subjects was negative for the mutation. In silico analysis carried out using Mutation T@ster software confirmed the pathogenic effect of this novel mutation. Replacement of histidine 500 with glycine and of valine 502 with serine (p.H500delinsG; p.V502delinsS) in the TM domain changes the side chain polarity of the original amino acid, thereby potentially affecting the polar contribution of the TM. Germline MPL mutations have been reported in cases of HT or ET, which share similar clinical features. In particular, the mutation MPL p.S505N of the TM domain, more frequently found in the germ line inheritance pattern of hereditary thrombocytosis, [6] is characterized by a progressive increase of spleen volume and a bone marrow pattern resembling that of primary myelofibrosis in adult and elderly patients. In our case, lack of MPL mutation or family history of MPN in relatives is more consistent with sporadic ET, although this diagnosis should rely on demonstration of bone marrow clonal hematopoiesis. In summary, this is the first report of a germ-line MPL gene mutation in a sporadic case of ET. Further investigations are required to demonstrate the specific mechanism underlying the mutation. All authors declare no conflict of interest. Acknowledgment We wish to express our gratitude to "Associazione Emofilia ed altre Coagulopatie delle tre Venezie" for the kind contribution to the realization of this study.
British Journal of Haematology
Frontiers in Molecular Biosciences, 2021
Idiopathic pulmonary fibrosis (IPF) is mainly characterized by aberrant extracellular matrix depo... more Idiopathic pulmonary fibrosis (IPF) is mainly characterized by aberrant extracellular matrix deposition, consequent to epithelial lung injury and myofibroblast activation, and inflammatory response. Glycogen synthase kinase 3 (GSK-3) is a serine–threonine kinase involved in several pathways, and its inhibition has been already suggested as a therapeutic strategy for IPF patients. There is evidence that GSK-3 is able to induce matrix metalloproteinase (MMP) expression and that its inhibition modulates MMP expression in the tissues. The aim of our study was to investigate the role of GSK-3 and its inhibition in the modulation of MMP-9 and -2 in an in vivo mouse model of lung fibrosis and in vitro using different cell lines exposed to pro-inflammatory or pro-fibrotic stimuli. We found that GSK-3 inhibition down-modulates gene expression and protein levels of MMP-9, MMP-2, and their inhibitors TIMP-1 and TIMP-2 in inflammatory cells harvested from bronchoalveolar lavage fluid (BALF) of ...
Clinical Immunology, 2022
Many patients with immunodeficiencies require lifelong immunoglobulin replacement therapy (IgRT).... more Many patients with immunodeficiencies require lifelong immunoglobulin replacement therapy (IgRT). In a multicenter, randomized, open-label, crossover, non-inferiority 3-month-trial, we compared the impact of the subcutaneous immunoglobulin Gammanorm® administered via pump or syringe (rapid push). Primary endpoint was the life quality index (LQI), secondary endpoints were QoL (SF36v2), satisfaction (TSQM-11), disease and treatment burden (PRISM), incidence of infections and adverse events (AE), treatment costs, and IgG levels. 28/30 patients completed the study. Most of the endpoints were comparable. Drug administrations with rapid push were more frequent, but reduced total time expenditure and some costs. Of the TSQM-11/LQI/SF36 components only "treatment interference with daily activities" was superior with pump and two QoL domains with rapid push. Both delivery devices showed favorable safety. Rapid push was preferred by 34.5% of patients. It proved to be an efficacious and cost-effective alternative to pumps adding to patient choice and increasing flexibility during long-term IgRT.
European Journal of Haematology, 2020
This study describes previously unreported histological patterns of ITP spleens, suggesting possi... more This study describes previously unreported histological patterns of ITP spleens, suggesting possible correlations with disease pathogenesis and splenectomy outcome.-Clinical and pathological correlations may predict response to splenectomy.-Clinical predictors of splenectomy outcome may help select ITP patients, who would likely benefit from this invasive procedure.
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Papers by fabrizio vianello