Publications by authors named "Guido Finazzi"

119 Publications

Increased platelet thrombus formation under flow conditions in whole blood from polycythaemia vera patients.

Blood Transfus 2021 Mar 30. Epub 2021 Mar 30.

Department of Immunohaematology and Transfusion Medicine, "Papa Giovanni XXIII" Hospital, Bergamo, Italy.

Background: Polycythaemia vera is a myeloproliferative neoplasm characterised by a high incidence of thrombosis. The contribution of platelets, key players in haemostasis, in this setting is still unclear. So far, the majority of studies have been focussed on specific platelet abnormalities but not on their actual capacity to form thrombi. The aim of this study was to characterise, ex vivo under flow conditions, the capacity of platelets from patients with polycythaemia vera to adhere to collagen and induce thrombus formation.

Materials And Methods: Thirty-nine patients and 30 healthy controls were studied. Thrombus formation was induced by perfusing whole blood over a collagen-coated surface, in a parallel-plate flow chamber coupled to a fluorescent microscope. This dynamic system enables platelet adhesion and thrombus formation to be followed in real time and also allows measurements of the extent of the thrombus and platelet surface antigen expression. Laboratory data were analysed in the light of the patients' main haematological parameters and therapies.

Results: Platelet adhesion was significantly greater in patients than in control subjects. Patient thrombi were usually larger and more complex than those formed by control platelets. A significant positive correlation was found between platelet adhesion and both the haematocrit and red blood cell count. These parameters remained significantly correlated with platelet adhesion also after multivariable analysis adjusted for gender, age, therapy and JAK2V617F allele burden. Furthermore, subjects with a haematocrit >45% had significantly greater platelet adhesion than subjects with a haematocrit <45%.

Discussion: Our data indicate that increased platelet adhesion participates in the thrombotic diathesis of patients with polycythaemia vera, and that the haematocrit level can affect the adhesive and thrombus forming capacities of platelets.
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http://dx.doi.org/10.2450/2021.0456-20DOI Listing
March 2021

Investigation and Follow-Up of a Staphylococcal Food Poisoning Outbreak Linked to the Consumption of Traditional Hand-Crafted Alm Cheese.

Pathogens 2020 Dec 19;9(12). Epub 2020 Dec 19.

Istituto Zooprofilattico Sperimentale della Lombardia e dell'Emilia Romagna, Headquarters, 25124 Brescia, Italy.

Staphylococcal food poisoning (SFP) is one of the most important foodborne diseases. This work describes a SFP event linked to the consumption of alm cheese and involved three people belonging to the same family. Leftovers of the consumed cheese, samples from the grocery store and the producing alm were collected and tested for Coagulase positive staphylococci (CPS) enumeration and for the presence of staphylococcal enterotoxins (SEs). Isolates were typed with MLST, spa typing, and tested for SEs and methicillin resistance genes. An in vitro test evaluated SEs production in relation to bacterial growth. The presence of CPS and SEs was detected in all cheese samples and all isolates belonged to the same methicillin sensitive ST8/t13296 strain harbouring , and genes. The in vitro test showed the production of enterotoxins started from 10 CFU/mL. The farmer was prescribed with corrective actions that led to eradication of the contaminating strain.
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http://dx.doi.org/10.3390/pathogens9121064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7766287PMC
December 2020

A Structural Study on the Internalin A-Human E-cadherin Interaction: A Molecular Tool to Investigate the Effects of Missense Mutations.

Toxins (Basel) 2020 01 20;12(1). Epub 2020 Jan 20.

Department of Food Control, Istituto Zooprofilattico Sperimentale della Lombardia e dell'Emilia Romagna, Via A. Bianchi 9, 25124 Brescia, Italy.

is a widespread foodborne pathogen of high concern and internalin A is an important virulence factor that mediates cell invasion upon the interaction with the host protein E-cadherin. Nonsense mutations of internalin A are known to reduce virulence. Although missense mutations are largely overlooked, they need to be investigated in respect to their effects in cell invasion processes. This work presented a computational workflow to early characterize internalin A missense mutations. The method reliably estimated the effects of a set of engineered missense mutations in terms of their effects on internalin A-E-cadherin interaction. Then, the effects of mutations of an internalin A variant from a isolate were calculated. Mutations showed impairing effects on complex stability providing a mechanistic explanation of the low cells invasion capacity previously observed. Overall, our results provided a rational approach to explain the effects of internalin A missense mutations. Moreover, our findings highlighted that the strength of interaction may not directly relate to the cell invasion capacity reflecting the non-exclusive role of internalin A in determining the virulence of . The workflow could be extended to other virulence factors providing a promising platform to support a better molecular understanding of epidemiology.
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http://dx.doi.org/10.3390/toxins12010060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7020427PMC
January 2020

Arterial thrombosis in Philadelphia-negative myeloproliferative neoplasms predicts second cancer: a case-control study.

Blood 2020 01;135(5):381-386

Unit of Hematology, Department of Oncology, University of Torino, Torino, Italy.

Patients with Philadelphia-negative myeloproliferative neoplasm (MPN) are prone to the development of second cancers, but the factors associated with these events have been poorly explored. In an international nested case-control study, we recruited 647 patients with carcinoma, nonmelanoma skin cancer, hematological second cancer, and melanoma diagnosed concurrently or after MPN diagnosis. Up to 3 control patients without a history of cancer and matched with each case for center, sex, age at MPN diagnosis, date of diagnosis, and MPN disease duration were included (n = 1234). Cases were comparable to controls for MPN type, driver mutations and cardiovascular risk factors. The frequency of thrombosis preceding MPN was similar for cases and controls (P = .462). Thrombotic events after MPN and before second cancer were higher in cases than in controls (11.6% vs 8.1%; P = .013), because of a higher proportion of arterial thromboses (6.2% vs 3.7%; P = .015). After adjustment for confounders, the occurrence of arterial thrombosis remained independently associated with the risk of carcinoma (odds ratio, 1.97; 95% confidence interval, 1.14-3.41), suggesting that MPN patients experiencing arterial events after MPN diagnosis deserve careful clinical surveillance for early detection of carcinoma. This study was registered at www.clinicaltrials.gov as NCT03745378.
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http://dx.doi.org/10.1182/blood.2019002614DOI Listing
January 2020

Second cancers in MPN: Survival analysis from an international study.

Am J Hematol 2020 03 22;95(3):295-301. Epub 2019 Dec 22.

Unit of Hematology, Department of Oncology, University of Torino, Torino, Italy.

One out of ten patients with Philadelphia-negative myeloproliferative neoplasms (MPN) develop a second cancer (SC): in such patients we aimed at assessing the survival impact of SC itself and of MPN-specific therapies. Data were therefore extracted from an international nested case-control study, recruiting 798 patients with SC diagnosed concurrently or after the MPN. Overall, 2995 person-years (PYs) were accumulated and mortality rate (MR) since SC diagnosis was 5.9 (5.1-6.9) deaths for every 100 PYs. A "poor prognosis" SC (stomach, esophagus, liver, pancreas, lung, ovary, head-and-neck or nervous system, osteosarcomas, multiple myeloma, aggressive lymphoma, acute leukemia) was reported in 26.3% of the patients and was the cause of death in 65% of them (MR 11.0/100 PYs). In contrast, patients with a "non-poor prognosis" SC (NPPSC) incurred a MR of 4.6/100 PYs: 31% of the deaths were attributed to SC and 15% to MPN evolution. At multivariable analysis, death after SC diagnosis was independently predicted (HR and 95% CI) by patient age greater than 70 years (2.68; 1.88-3.81), the SC prognostic group (2.57; 1.86-3.55), SC relapse (1.53; 10.6-2.21), MPN evolution (2.72; 1.84-4.02), anemia at SC diagnosis (2.32; 1.49-3.59), exposure to hydroxyurea (1.89; 1.26-2.85) and to ruxolitinib (3.63; 1.97-6.71). Aspirin was protective for patients with a NPPSC (0.60; 0.38-0.95). In conclusion, SC is a relevant cause of death competing with MPN evolution. Prospective data are awaited to confirm the role of cytoreductive and anti-platelet drugs in modulating patient survival after the occurrence of a SC.
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http://dx.doi.org/10.1002/ajh.25700DOI Listing
March 2020

Addressing and proposing solutions for unmet clinical needs in the management of myeloproliferative neoplasm-associated thrombosis: A consensus-based position paper.

Blood Cancer J 2019 08 8;9(8):61. Epub 2019 Aug 8.

Center for the Study of Myelofibrosis, IRCCS Policlinico S. Matteo Foundation, Pavia, Italy.

This article presents the results of a group discussion among an ad hoc constituted Panel of experts aimed at highlighting unmet clinical needs (UCNs) in the management of thrombotic risk and thrombotic events associated with Philadelphia-negative myeloproliferative neoplasms (Ph-neg MPNs). With the Delphi technique, the challenges in Ph-neg MPN-associated thrombosis were selected. The most clinically relevant UCNs resulted in: (1) providing evidence of the benefits and risks of direct oral anticoagulants, (2) providing evidence of the benefits and risks of cytoreduction in patients with splanchnic vein thrombosis without hypercythemia, (3) improving knowledge of the role of the mutated endothelium in the pathogenesis of thrombosis, (4) improving aspirin dosing regimens in essential thrombocythemia, (5) improving antithrombotic management of Ph-neg MPN-associated pregnancy, (6) providing evidence for the optimal duration of anticoagulation for prophylaxis of recurrent VTE, (7) improving knowledge of the association between somatic gene mutations and risk factors for thrombosis, and (8) improving the grading system of thrombosis risk in polycythemia vera. For each of these issues, proposals for advancement in research and clinical practice were addressed. Hopefully, this comprehensive overview will serve to inform the design and implementation of new studies in the field.
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http://dx.doi.org/10.1038/s41408-019-0225-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6687826PMC
August 2019

Second cancer in Philadelphia negative myeloproliferative neoplasms (MPN-K). A nested case-control study.

Leukemia 2019 08 29;33(8):1996-2005. Epub 2019 May 29.

Unit of Hematology, Department of Oncology, University of Torino, Torino, Italy.

We conducted a large international nested case-control study including 1881 patients with Philadelphia-negative myeloproliferative neoplasms (MPN). Cases (n = 647) were patients with second cancer (SC: carcinoma, non-melanoma skin cancer, hematological second cancer, and melanoma) and controls (n = 1234) were patients without SC, matched with cases for sex, age at MPN diagnosis, date of MPN diagnosis, and MPN disease duration. The aim was to evaluate the risk of SC after exposure to cytoreductive drugs. Patients exposed to hydroxyurea (HU) (median: 3 years) had a risk of SC similar to unexposed patients (OR = 1.06, 95% CI 0.82-1.38). In contrast, in cancer-specific stratified multivariable analysis, HU had two-fold higher risk of non-melanoma (NM) skin cancer (OR = 2.28, 95% CI 1.15-4.51). A significantly higher risk of NM-skin cancer was also documented for pipobroman (OR = 3.74, 95% CI 1.00-14.01), ruxolitinib (OR = 3.87, 95% CI 1.18-12.75), and for drug combination (OR = 3.47, 95% CI 1.55-7.75). These three drugs did not show excess risk of carcinoma and hematological second cancer compared with unexposed patients. Exposure to interferon, busulfan, and anagrelide did not increase the risk. In summary, while it is reassuring that no excess of carcinoma was documented, a careful dermatologic active surveillance before and during the course of treatments is recommended.
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http://dx.doi.org/10.1038/s41375-019-0487-8DOI Listing
August 2019

Clinical outcomes under hydroxyurea treatment in polycythemia vera: a systematic review and meta-analysis.

Haematologica 2019 12 23;104(12):2391-2399. Epub 2019 May 23.

FROM Research Foundation, ASST Papa Giovanni XXIII, Bergamo

Hydroxyurea is the standard treatment in high-risk patients with polycythemia vera. However, estimates of its effect in terms of clinical outcomes (thrombosis, bleeding, hematologic transformations and mortality) are lacking. We performed a meta-analysis to determine the absolute risk of events in recent cases of patients under hydroxyurea treatment. We searched for relevant articles or abstracts in the following databases: Medline, EMBASE, clinicaltrials.gov, WHO International Clinical Trials Registry, LILACS. Sixteen studies published from 2008 to 2018 reporting number of events using World Health Organization diagnosis for polycythemia vera were selected. Through a random effect logistic model, incidences, study heterogeneity and confounder effects were estimated for each outcome at different follow ups. Overall, 3,236 patients were analyzed. While incidences of thrombosis and acute myeloid leukemia were stable over time, mortality and myelofibrosis varied depending on follow-up duration. Thrombosis rates were 1.9%, 3.6% and 6.8% persons/year at median ages 60, 70 and 80 years, respectively. Higher incidence of arterial events was predicted by previous cardiovascular complication. Leukemic transformation incidence was 0.4% persons/year. Incidence of transformation to myelofibrosis and mortality were significantly dependent on age and follow-up duration. For myelofibrosis, rates were 5.0 at five years and 33.7% at ten years; overall mortality was 12.6% and 56.2% at five and ten years, respectively. In conclusion, we provide reliable risk estimates for the main outcomes in polycythemia vera patients under hydroxyurea treatment. These findings can help design comparative clinical trials with new cytoreductive drugs and prove the feasibility of using critical end points for efficacy, such as major thrombosis.
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http://dx.doi.org/10.3324/haematol.2019.221234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6959178PMC
December 2019

Different effect of hydroxyurea and phlebotomy on prevention of arterial and venous thrombosis in Polycythemia Vera.

Blood Cancer J 2018 11 26;8(12):124. Epub 2018 Nov 26.

Department of Experimental and Clinical Medicine, Center of Research and Innovation of Myeloproliferative neoplasms (CRIMM), AOU Careggi, University of Florence, Florence, Italy.

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http://dx.doi.org/10.1038/s41408-018-0161-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6255832PMC
November 2018

Hydroxyurea prevents arterial and late venous thrombotic recurrences in patients with myeloproliferative neoplasms but fails in the splanchnic venous district. Pooled analysis of 1500 cases.

Blood Cancer J 2018 11 12;8(11):112. Epub 2018 Nov 12.

FROM Research Foundation, Papa Giovanni XXIII Hospital, Bergamo, Italy.

We collected 1500 patients with myeloproliferative neoplasms (MPN) and arterial or venous thrombosis (935/565), pooling three independent cohorts previously reported. Long-term treatment with antiplatelet drugs or vitamin K-antagonists (VKA) was given to 1391 (92.7%) patients; 975 (65%) patients received hydroxyurea (HU). We recorded 348 recurrences (venous in 142 cases) over 6075 patient-years, with an incidence rate of 5.7 per 100 pt-years (95% CI 5.1-6.4). The site of the first thrombosis predicted the site of recurrence. Independent factors influencing the rate of novel arterial thrombosis were HU (HR 0.67, 95% CI 0.46-0.98), antiplatelet treatment (HR 0.54, 95% CI 0.35-0.82), and VKA (HR 0.58, 95% CI 0.35-0.96). On the contrary, the recurrence of venous thromboses was significantly diminished only by VKA (HR 0.60, 95% CI 0.37-0.95), while HU prevented late but not early recurrences after venous thrombosis at common sites. Of note, we failed to demonstrate a positive effect of HU in the prevention of recurrent splanchnic vein thrombosis. In conclusion, in MPN patients, HU plays a role in the prevention of arterial thrombosis, together with aspirin and VKA, whereas its action in the prevention of recurrent venous thrombosis is uncertain. Such findings call for future studies to optimize and personalize secondary prophylaxis after MPN-related thrombosis.
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http://dx.doi.org/10.1038/s41408-018-0151-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6232117PMC
November 2018

Targeting myeloid cells to prevent recurrent stroke in general population: the lesson of hydroxyurea in myeloproliferative neoplasms.

Blood Cancer J 2018 11 7;8(11):103. Epub 2018 Nov 7.

Fondazione Policlinico Universitario A. Gemelli IRCCS, and Istituto di Ematologia, Università Cattolica del Sacro Cuore, Roma, Italy.

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http://dx.doi.org/10.1038/s41408-018-0143-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6221886PMC
November 2018

Prefibrotic myelofibrosis: treatment algorithm 2018.

Blood Cancer J 2018 11 7;8(11):104. Epub 2018 Nov 7.

FROM Research Foundation, ASST Papa Giovanni XXIII, Bergamo, Italy.

Prefibrotic myelofibrosis (pre-PMF) is a distinct entity among chronic myeloproliferative neoplasm diagnosed according to the revised 2016 WHO classification. The clinical picture is heterogeneous, ranging from isolated thrombocytosis, mimicking essential thrombocythemia (ET), to symptoms of high-risk PMF. Retrospective studies showed that survival of patients with pre-PMF is worse than that of ET and better than overt PMF. Whilst a specific prognostic score is lacking, the International Prognostic Scoring System is able to predict survival in pre-PMF patients, yet failing to separate intermediate-1 and -2 groups, and can be used in clinical practice. Each patient should be evaluated for, and interventions adapted to, both life-expectancy and the risk of bleeding and thrombosis. In low-risk patients with expected long survival, observation only is recommended; in cumulated intermediate-1 and -2 risk cases, whose median survival is projected at more than 10 years, treatment is based on symptoms; in high risk cases, with median survival lower than 5 years, intensive management is required. A pragmatic approach to address the risk of bleeding and thrombosis includes: no treatment or low-dose aspirin in asymptomatic patients; aspirin or oral anticoagulation if previous arterial or venous thrombosis, and hydroxyurea as first-line cytoreduction in case of thrombocytosis or leukocytosis.
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http://dx.doi.org/10.1038/s41408-018-0142-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6221891PMC
November 2018

Preparation of Powdered Infant Formula: Could Product's Safety Be Improved?

J Pediatr Gastroenterol Nutr 2018 10;67(4):543-546

Istituto Zooprofilattico Sperimentale della Lombardia e dell'Emilia Romagna "B. Ubertini," Brescia.

The recent outbreak of Salmonella Agona linked to the consumption of infant formula (powdered formula) has rekindled the attention about the correct procedures for preparation and use of these products. International guidelines have already been published so far, particularly in association with Cronobacter sakazakii in early 2000s. FAO/WHO suggested to reconstitute formula with water at no less than 70°C. We therefore contaminated powdered formula with low levels of Salmonella spp and C sakazakii to evaluate the pathogens inactivation during the formula preparation using water at 70°C. In these conditions we observed a survival of both pathogens, indicating that the suggested recommendations may be not enough to guarantee the safety of this product. Higher temperatures are needed to reduce the biological risk, even if it may be not easily realized in actual domestic conditions. Moreover, the impact on the nutritional value of reconstituted formulas should be evaluated.
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http://dx.doi.org/10.1097/MPG.0000000000002100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6155361PMC
October 2018

Splanchnic vein thrombosis in myeloproliferative neoplasms: treatment algorithm 2018.

Blood Cancer J 2018 06 26;8(7):64. Epub 2018 Jun 26.

FROM Research Foundation, ASST Papa Giovanni XXIII, Bergamo, Italy.

Myeloproliferative neoplasms (MPNs) are a leading cause of splanchnic vein thrombosis (SVT). SVT is observed in all MPNs and frequently affects young patients. Therapy should be addressed to three main goals: preventing thrombosis recurrence, managing the underlying MPN, and supporting liver dysfunction. Life-long oral anticoagulation with vitamin K antagonists is the cornerstone of the antithrombotic treatment. However, recurrences of SVT or other thrombosis may occur in 15-20% of patients. Direct oral anticoagulants can represent an alternative and preliminary data encourage comparative studies. Survival of patients with SVT in MPN is primarily influenced by the natural history of the underlying neoplasms, rather than the SVT event. An aggressive management is recommended and a treatment algorithm based on the different MPN subtypes is proposed. Hydroxyurea is the cytoreductive drug of choice in polycythemia vera and essential thrombocythemia, whereas ruxolitinib is indicated in intermediate and high-risk patients with myelofibrosis and in PV patients resistant or intolerant to hydroxyurea. The management of SVT in MPNs requires a multidisciplinary approach that may include a hematologist, a gastroenterologist, an interventional radiologist, and a surgeon. In the case of clinical deterioration despite pharmacological therapy, patients with SVT should be considered for invasive procedures or liver transplantation.
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http://dx.doi.org/10.1038/s41408-018-0100-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6018786PMC
June 2018

Antithrombotic therapy for venous thromboembolism in myeloproliferative neoplasms.

Blood Cancer J 2018 06 26;8(7):65. Epub 2018 Jun 26.

FROM Research Foundation, ASST Papa Giovanni XXIII, Bergamo, Italy.

In myeloproliferative neoplasms (MPNs) the incidence of venous thromboembolism (VTE) is 0.6-1.0 per 100 pt-years, and the rate of recurrence after VTE is 6.0-6.5 per 100 pt-yrs. Vitamin K-antagonists (VKA) reduces the risk of recurrence after VTE at usual sites (i.e., deep venous thrombosis (DVT) of the legs and pulmonary embolism (PE)) by 48-69%, with a rate of recurrent thrombosis per 100 pt-yrs of 3.4-4.7 on VKA and 8.9-9.6 off VKA; VKA discontinuation produces a 2.2-fold increased risk of novel thrombotic events with respect to continuation. However, the rate of both recurrent thrombosis and major bleeding on VKA is higher in MPN patients than in non-MPN patients, and the risk-benefit balance of long-term VKA treatment is challenging. In the absence of strong evidence, the tailored management of MPN-related VTE should operatively consider the risk categories for recurrence and bleed well established in the non-MPN setting. In summary, MPN patients with VTE are candidates for life-long VKA treatment, especially after unprovoked proximal DVT and PE. Aspirin can offer a moderate benefit in those patients who stop anticoagulation. The use of direct oral anticoagulants should be explored aiming to ameliorate the rate of bleeding.
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http://dx.doi.org/10.1038/s41408-018-0101-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6018810PMC
June 2018

The Aspirin Regimens in Essential Thrombocythemia (ARES) phase II randomized trial design: Implementation of the serum thromboxane B assay as an evaluation tool of different aspirin dosing regimens in the clinical setting.

Blood Cancer J 2018 06 1;8(6):49. Epub 2018 Jun 1.

Institute of Hematology "L. and A. Seràgnoli", S. Orsola-Malpighi Hospital, Bologna, Italy.

Once-daily (od), low-dose aspirin (75-100 mg) is recommended to reduce the thrombotic risk of patients with essential thrombocytemia (ET). This practice is based on data extrapolated from other high-risk patients and an aspirin trial in polycythemia vera, with the assumption of similar aspirin pharmacodynamics in the two settings. However, the pharmacodynamics of low-dose aspirin is impaired in ET, reflecting accelerated renewal of platelet cyclooxygenase (COX)-1. ARES is a parallel-arm, placebo-controlled, randomized, dose-finding, phase II trial enrolling 300 ET patients to address two main questions. First, whether twice or three times 100 mg aspirin daily dosing is superior to the standard od regimen in inhibiting platelet thromboxane (TX)A production, without inhibiting vascular prostacyclin biosynthesis. Second, whether long-term persistence of superior biochemical efficacy can be safely maintained with multiple vs. single dosing aspirin regimen. Considering that the primary study end point is serum TXB, a surrogate biomarker of clinical efficacy, a preliminary exercise of reproducibility and validation of this biomarker across all the 11 participating centers was implemented. The results of this preliminary phase demonstrate the importance of controlling reproducibility of biomarkers in multicenter trials and the feasibility of using serum TXB as a reliable end point for dose-finding studies of novel aspirin regimens.
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http://dx.doi.org/10.1038/s41408-018-0078-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5992153PMC
June 2018

Benefit-risk profile of cytoreductive drugs along with antiplatelet and antithrombotic therapy after transient ischemic attack or ischemic stroke in myeloproliferative neoplasms.

Blood Cancer J 2018 02 28;8(3):25. Epub 2018 Feb 28.

Hematology Division, Papa Giovanni XXIII hospital, Bergamo, Italy.

We analyzed 597 patients with myeloproliferative neoplasms (MPN) who presented transient ischemic attacks (TIA, n = 270) or ischemic stroke (IS, n = 327). Treatment included aspirin, oral anticoagulants, and cytoreductive drugs. The composite incidence of recurrent TIA and IS, acute myocardial infarction (AMI), and cardiovascular (CV) death was 4.21 and 19.2%, respectively at one and five years after the index event, an estimate unexpectedly lower than reported in the general population. Patients tended to replicate the first clinical manifestation (hazard ratio, HR: 2.41 and 4.41 for recurrent TIA and IS, respectively); additional factors for recurrent TIA were previous TIA (HR: 3.40) and microvascular disturbances (HR: 2.30); for recurrent IS arterial hypertension (HR: 4.24) and IS occurrence after MPN diagnosis (HR: 4.47). CV mortality was predicted by age over 60 years (HR: 3.98), an index IS (HR: 3.61), and the occurrence of index events after MPN diagnosis (HR: 2.62). Cytoreductive therapy was a strong protective factor (HR: 0.24). The rate of major bleeding was similar to the general population (0.90 per 100 patient-years). In conclusion, the long-term clinical outcome after TIA and IS in MPN appears even more favorable than in the general population, suggesting an advantageous benefit-risk profile of antithrombotic and cytoreductive treatment.
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http://dx.doi.org/10.1038/s41408-018-0048-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5849668PMC
February 2018

Philadelphia chromosome-negative classical myeloproliferative neoplasms: revised management recommendations from European LeukemiaNet.

Leukemia 2018 05 27;32(5):1057-1069. Epub 2018 Feb 27.

Center for the Study of Myelofibrosis, IRCCS Policlinico S. Matteo Foundation, Pavia, Italy.

This document updates the recommendations on the management of Philadelphia chromosome-negative myeloproliferative neoplasms (Ph-neg MPNs) published in 2011 by the European LeukemiaNet (ELN) consortium. Recommendations were produced by multiple-step formalized procedures of group discussion. A critical appraisal of evidence by using Grades of Recommendation, Assessment, Development and Evaluation (GRADE) methodology was performed in the areas where at least one randomized clinical trial was published. Seven randomized controlled trials provided the evidence base; earlier phase trials also informed recommendation development. Key differences from the 2011 diagnostic recommendations included: lower threshold values for hemoglobin and hematocrit and bone marrow examination for diagnosis of polycythemia vera (PV), according to the revised WHO criteria; the search for complementary clonal markers, such as ASXL1, EZH2, IDH1/IDH2, and SRSF2 for the diagnosis of myelofibrosis (MF) in patients who test negative for JAK2V617, CALR or MPL driver mutations. Regarding key differences of therapy recommendations, both recombinant interferon alpha and the JAK1/JAK2 inhibitor ruxolitinib are recommended as second-line therapies for PV patients who are intolerant or have inadequate response to hydroxyurea. Ruxolitinib is recommended as first-line approach for MF-associated splenomegaly in patients with intermediate-2 or high-risk disease; in case of intermediate-1 disease, ruxolitinib is recommended in highly symptomatic splenomegaly. Allogeneic stem cell transplantation is recommended for transplant-eligible MF patients with high or intermediate-2 risk score. Allogeneic stem cell transplantation is also recommended for transplant-eligible MF patients with intermediate-1 risk score who present with either refractory, transfusion-dependent anemia, blasts in peripheral blood > 2%, adverse cytogenetics, or high-risk mutations. In these situations, the transplant procedure should be performed in a controlled setting.
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http://dx.doi.org/10.1038/s41375-018-0077-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5986069PMC
May 2018

Ruxolitinib in ET: not all MPN are equal.

Authors:
Guido Finazzi

Blood 2017 10;130(17):1873-1874

OSEPEDALE PAPA GIOVANNI XXIII.

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http://dx.doi.org/10.1182/blood-2017-08-802165DOI Listing
October 2017

A reappraisal of the benefit-risk profile of hydroxyurea in polycythemia vera: A propensity-matched study.

Am J Hematol 2017 Nov 29;92(11):1131-1136. Epub 2017 Jul 29.

F.R.O.M. Research Foundation, Papa Giovanni XXIII Hospital, Bergamo, Italy.

The use of hydroxyurea (HU) as first line therapy in polycythemia vera (PV) has been criticized because no solid demonstration that this drug prevents thrombosis or prolongs survival has been so far produced. Here we present the outcomes of a large cohort of patients with PV included in the European Collaborative Low-dose Aspirin (ECLAP) study. We selected 1,042 patients who, during the follow-up, had received only phlebotomy (PHL) or HU to maintain the hematocrit level < 45%. To assure comparability, we conducted a propensity score matching analysis. The two groups (PHL n = 342 and HU n = 681) were well balanced for the parameters included in the propensity score (overall balance: χ  = 2.44, P = 0.964). Over a comparable period of follow-up (PHL = 29.9 vs. HU = 34.7 months), we documented an advantage of HU over PHL consistently significant with respect to the incidence of fatal/non-fatal cardiovascular (CV) events (5.8 vs. 3.0 per 100 person-years in PHL vs. HU group, P = 0.002) and myelofibrosis transformation that was only experienced by patients of PHL group. Evolution to acute leukemia was registered in three patients (two in PHL and one in HU group). The excess of mortality and total CV events in the PHL patients was restricted to the high-risk group, and, compared with HU cases, was significant higher in the PHL patients who failed to reach the hematocrit target < 0.45% (P = 0.000). In conclusion, this analysis provides reliable and qualified estimates of the therapeutic profile of HU and PHL treatments for future experimental studies and for the management of PV in clinical practice.
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http://dx.doi.org/10.1002/ajh.24851DOI Listing
November 2017

Safety and efficacy of ruxolitinib in splanchnic vein thrombosis associated with myeloproliferative neoplasms.

Am J Hematol 2017 Feb;92(2):187-195

CRIMM-Centro Ricerca e Innovazione per le Malattie Mieloproliferative, Azienda Ospedaliera-Universitaria Careggi, Florence, Italy.

Splanchnic vein thrombosis (SVT) is one of the vascular complications of myeloproliferative neoplasms (MPN). We designed a phase 2 clinical trial to evaluate safety and efficacy of ruxolitinib in reducing splenomegaly and improving disease-related symptoms in patients with MPN-associated SVT. Patients diagnosed with myelofibrosis (12 cases), polycythemia vera (5 cases) and essential thrombocythemia (4 cases) received ruxolitinib for 24 weeks in the core study period. Spleen volume was assessed by magnetic resonance imaging (MRI) and splanchnic vein circulation by echo-Doppler analysis. Nineteen patients carried JAK2V617F, one had MPLW515L, and one CALRL367fs*46 mutation. Eighteen patients had spleno-portal-mesenteric thrombosis, two had Budd-Chiari syndrome, and one had both sites involved; 16 patients had esophageal varices. Ruxolitinib was well tolerated with hematological toxicities consistent with those of patients without SVT and no hemorrhagic adverse events were recorded. After 24 weeks of treatment, spleen volume reduction ≥35% by MRI was achieved by 6/21 (29%) patients, and a ≥50% spleen length reduction by palpation at any time up to week 24 was obtained by 13/21 (62%) patients. At week 72, 8 of the 13 (62%) patients maintained the spleen response by palpation. No significant effect of treatment on esophageal varices or in splanchnic circulation was observed. MPN-related symptoms, evaluated by MPN-symptom assessment form (SAF) TSS questionnaire, improved significantly during the first 4 weeks and remained stable up to week 24. In conclusion, this trial shows that ruxolitinib is safe in patients with MPN-associated SVT, and effective in reducing spleen size and disease-related symptoms.
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http://dx.doi.org/10.1002/ajh.24614DOI Listing
February 2017

Seasonal Variability of Thermophilic Spp. in Raw Milk Sold by Automatic Vending Machines in Lombardy Region.

Ital J Food Saf 2016 Jun 16;5(3):5848. Epub 2016 Jun 16.

Department of Veterinary Medical Sciences, Alma Mater Studiorum-University of Bologna , Ozzano dell'Emilia (BO), Italy.

In temperate climates, a seasonal trend was observed in the incidence of human campylobacteriosis cases, with peaks reported in spring and autumn in some countries, or in summer in others; a similar trend was observed in spp. dairy cattle faecal shedding, suggesting that cattle may play a role in the seasonal peak of human infection. The objectives of this study were to assess if a seasonal trend in thermophilic spp. contamination of raw milk exists and to evaluate a possible relation between this and the increase of human campylobacteriosis incidence in summer months. The results showed a mean prevalence of 1.6% of milk samples positive for thermophilic spp. with a wide range (0.0-3.1%) in different months during the three years considered. The statistical analysis showed a significant difference (P<0.01) of the prevalence of positive samples for thermophilic spp. between warmer and cooler months (2.3 0.6%). The evidence of a seasonal trend in thermophilic spp. contamination of raw milk sold for direct consumption, with an increase of the prevalence in warmer months, may represent one of the possible links between seasonal trend in cattle faecal shedding and seasonal trend in human campylobacteriosis.
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http://dx.doi.org/10.4081/ijfs.2016.5848DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5090118PMC
June 2016

FLOQSwab™: Optimisation of Procedures for the Recovery of Microbiological Samples from Surfaces.

Ital J Food Saf 2016 Jun 3;5(3):5756. Epub 2016 Aug 3.

Institute for Experimental Veterinary Medicine of Lombardy and Emilia Romagna , Brescia, Italy.

The FLOQSwab™ is a specimen collection device worldwide recognised for its superior performance in the clinical diagnostics. The aim of this work was to evaluate FLOQSwab™ for the recovery of microbiological samples from surfaces compared to the traditional swab (rayon tipped swab) as per ISO 18593:2004 standard. The FLOQSwab™, thanks to its innovative manufacturing technology, allows improving the efficiency of recovery and release of analyte. The study has been divided into two experiments. In the first experiment the two swabs were evaluated for their capacity to recover and release the analyte (three different bacterial loads of ). In the second experiment, the two swabs were evaluated for their capacity to recover three different bacterial loads of from two different surface materials (stainless steel and polypropylene). In all experiments the flocked swab demonstrated a higher recovery rate compared to the traditional rayon tipped swab. The data obtained from this preliminary study demonstrated that the FLOQSwab™ could be a good food surfaces collection device, which improves the recovery of the analyte and thus produces accurate results. Based on the outcomes of the study, a larger field study is in progress using the FLOQSwab™ for samples collection to improve both environmental monitoring and the efficacy of the hygiene controls for food safety.
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http://dx.doi.org/10.4081/ijfs.2016.5756DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5090112PMC
June 2016

The potential role of hematocrit control on symptom burden among polycythemia vera patients: Insights from the CYTO-PV and MPN-SAF patient cohorts.

Leuk Lymphoma 2017 06 10;58(6):1481-1487. Epub 2016 Nov 10.

e Unit of Hematology, Ospedale Papa Giovanni XXIII , Foundation for Research (FROM) , Bergamo , Italy.

Current guidelines suggest that polycythemia vera (PV) patients maintain a strict hematocrit less than 45%. However, to date, little is known about the relationship between HCT control and PV- related symptom burden. In this study, PV patient data was analyzed from the CYTO PV trial (n = 224) and the MPN-SAF study cohort (n = 645). No significant differences in symptom burden were seen at the 6 and 12 month follow-up when evaluating prospective hematocrit control in the CYTO PV cohort. Patients in the MPN-SAF cohort with a worst item score of greater than 5/10 on the Myeloproliferative Neoplasm Symptom Total Symptom Score had a significantly lower mean hematocrit (p = .0376). These findings suggest a relationship between traditional aggressive therapy for PV and increased symptom burden with prolonged therapy. Thus, symptom burden should be considered when contemplating the choice of therapy in the second-line setting for PV.
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http://dx.doi.org/10.1080/10428194.2016.1246733DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8148875PMC
June 2017

Direct oral anticoagulants in rare venous thrombosis.

Intern Emerg Med 2016 Mar 13;11(2):167-70. Epub 2016 Feb 13.

Dipartimento di Medicina Clinica e Sperimentale, Università degli Studi dell'Insubria, Varese, Italy.

The direct inhibitors of thrombin (dabigatran) or factor Xa (rivaroxaban, apixaban) are currently used in patients with venous thrombosis of the lower or upper limbs or with pulmonary embolism. However, the use of these direct oral anticoagulants (DOACs) in subjects with abdominal or cerebral venous thrombosis is more contentious due to the paucity of available data. In a few case reports and small series of patients hitherto published, the DOACs showed good efficacy and safety, supporting an extension of their use to these rare conditions. Thus, prospective cohort studies and randomized controlled trials have been set up. In this article, we review the published clinical experience with DOACs in rare venous thrombosis, and provide updated information on ongoing clinical trials.
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http://dx.doi.org/10.1007/s11739-016-1398-6DOI Listing
March 2016