Emerging resistant bacteria strains in bloodstream infections of acute leukaemia patients: results of a prospective study by the Rete Ematologica Lombarda (Rel).

Multiresistant bacterial infections are a potentially life-threatening condition in acute leukaemia (AL) patients. We aimed to better define the very recent epidemiology and outcome of bloodstream infections (BSIs) in a real-life setting. We prospectively collected all consecutive febrile/infectious episodes occurring in AL patients admitted to 9 haematology units.

Primary cutaneous B-cell lymphoma other than marginal zone: clinicopathologic analysis of 161 cases: Comparison with current classification and definition of prognostic markers.

Categorization of primary cutaneous B-cell lymphomas (PCBCL) other than marginal zone (MZL) represents a diagnostic challenge with relevant prognostic implications. The 2008 WHO lymphoma classification recognizes only primary cutaneous follicular center cell lymphoma (PCFCCL) and primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT), whereas the previous 2005 WHO/EORTC classification also included an intermediate form, namely PCDLBCL, other. We conducted a retrospective, multicentric, consensus-based revision of the clinicopathologic characteristics of 161 cases of PCBCL other than MZL.

Direct oral anticoagulants and venous thromboembolism.

Venous thromboembolism (VTE), consisting of deep vein thrombosis and pulmonary embolism, is a major clinical concern associated with significant morbidity and mortality. The cornerstone of management of VTE is anticoagulation, and traditional anticoagulants include parenteral heparins and oral vitamin K antagonists. Recently, new oral anticoagulant drugs have been developed and licensed, including direct factor Xa inhibitors (e.

Porcine recombinant factor VIII: an additional weapon to handle anti-factor VIII antibodies.

This review focuses on the use of recombinant porcine factor VIII (FVIII) for the treatment of bleeding episodes in patients with severe haemophilia A complicated by inhibitors and in those with acquired haemophilia A due to the onset of anti-FVIII autoantibodies. We present the main characteristics of recombinant porcine factor VIII (FVIII) and provide a summary of the published results of the clinical studies of this novel recombinant FVIII. There is a special emphasis on how the use of recombinant porcine factor VIII (FVIII) is expected to improve the clinical management of these patients.

Von Willebrand factor (Vonvendi®): the first recombinant product licensed for the treatment of von Willebrand disease.

Introduction: Von Willebrand disease (VWD) is the most common autosomally inherited bleeding disorder, characterized by a quantitative or qualitative defect of the multimeric adhesive glycoprotein von Willebrand factor (VWF). The mainstay of treatment of bleeding in VWD involves the use of desmopressin and plasma-derived factor VIII (FVIII)-VWF concentrates. In addition, a new recombinant VWF has been recently manufactured and licensed in the USA.

Improved Outcomes With Retinoic Acid and Arsenic Trioxide Compared With Retinoic Acid and Chemotherapy in Non-High-Risk Acute Promyelocytic Leukemia: Final Results of the Randomized Italian-German APL0406 Trial.

Purpose The initial results of the APL0406 trial showed that the combination of all- trans-retinoic acid (ATRA) and arsenic trioxide (ATO) is at least not inferior to standard ATRA and chemotherapy (CHT) in first-line therapy of low- or intermediate-risk acute promyelocytic leukemia (APL). We herein report the final analysis on the complete series of patients enrolled onto this trial. Patients and Methods The APL0406 study was a prospective, randomized, multicenter, open-label, phase III noninferiority trial.

The safety of pharmacologic options for the treatment of persons with hemophilia.

Introduction: The mainstay of treatment of hemophilia A and B is the replacement of the congenitally deficient coagulation factor through the intravenous infusion of specific concentrates (factor VIII, FVIII, in hemophilia A; factor IX, FIX, in hemophilia B). Several commercial brands of FVIII or FIX products extracted from human plasma or engineered using recombinant DNA technology are available.

Areas Covered: We analyze the safety aspects of plasma-derived and recombinant FVIII and FIX products licensed in Europe, focusing on their pathogen safety and inhibitor and thrombosis risks.

Tailoring hemostatic therapies to lower inhibitor development in previously untreated patients with severe hemophilia A.

After technological progress provided safer therapeutic products for patients with hemophilia A, the development of alloantibodies (inhibitors) neutralizing the coagulant activity of infused factor VIII (FVIII) remains the most serious complication of replacement therapy, predisposing patients to greater morbidity and causing higher treatment costs. The pathogenesis of inhibitors, which develop at a high rate in previously untreated children with severe hemophilia A, is multifactorial, resulting from complex interactions between genetic and environmental factors. Among non-genetic determinants, a key role is played by treatment-related factors, including the source of FVIII product (i.

Clinical presentation and management practice of systemic mastocytosis. A survey on 460 Italian patients.

Systemic mastocytosis is a rare heterogeneous myeloproliferative neoplasm characterized by abnormal proliferation and activation of mast cells. We describe a large multicentre series of 460 adult patients with systemic mastocytosis, with a diagnosis based on WHO 2008 criteria, in a "real-life" setting of ten Italian centers with dedicated multidisciplinary programs. We included indolent forms with (n = 255) and without (n = 165) skin lesions, smouldering (n = 20), aggressive (n = 28), associated with other hematological diseases mastocytosis (n = 21) and mast cell leukemia (n = 1).

Treating chronic lymphocytic leukemia with obinutuzumab: safety and efficacy considerations.

Introduction: Obinutuzumab is a novel glycoengineered type II anti-CD20 monoclonal antibody (MoAb) with a higher affinity for CD20 epitope. It was approved by the United States Food and Drug Administration (FDA) in November 2013 for use in combination with chlorambucil for previously untreated chronic lymphocytic leukemia (CLL).

Areas Covered: This article evaluates the safety of obinutuzumab in CLL patients, also addressing pharmacokinetics/pharmacodynamics (PK/PD), clinical use and efficacy.

Baseline factor VIII plasma levels and age at first bleeding in patients with severe forms of von Willebrand disease.

Introduction: von Willebrand disease (VWD) is the most common inherited bleeding disorder. The age of bleeding onset is highly variable, also in patients with similar degree of severity.

Aim: The primary aim of this study was to evaluate whether baseline factor VIII (FVIII) plasma levels correlate with age at first bleeding in patients with extremely low levels of VWF:RCo (<6 IU dL(-1) ).

Lack of Siglec-7 expression identifies a dysfunctional natural killer cell subset associated with liver inflammation and fibrosis in chronic HCV infection.

Objective: Sialic-acid-binding immunoglobulin-like lectin-7 (Siglec-7) is a natural killer (NK) cell inhibitory receptor associated with NK phenotypic and functional abnormalities in HIV-1 infection. We investigated the significance of NK-expressed and serum soluble Siglec-7 in relation to NK functional ability and parameters of liver necroinflammation and fibrosis in chronic HCV infection.

Design: NK-expressed and serum Siglec-7 were evaluated in 130 and 166 HCV-infected individuals by flow cytometry and ELISA, respectively.

Molecular prediction of durable remission after first-line fludarabine-cyclophosphamide-rituximab in chronic lymphocytic leukemia.

Fludarabine, cyclophosphamide, and rituximab (FCR) has represented a significant treatment advancement in chronic lymphocytic leukemia (CLL). In the new scenario of targeted agents, there is an increasing interest in identifying patients who gain the maximum benefit from FCR. In this observational multicenter retrospective analysis of 404 CLL patients receiving frontline FCR, the combination of three biomarkers that are widely tested before treatment (IGHV mutation status, 11q deletion and 17p deletion; available in 80% of the study cohort) allowed to identify a very low-risk category of patients carrying mutated IGHV genes but neither 11q or 17p deletion that accounted for 28% of all cases.

Low-dose alemtuzumab in refractory/relapsed chronic lymphocytic leukemia: Genetic profile and long-term outcome from a single center experience.

Relapsed/refractory chronic lymphocytic leukemia (CLL) represents a clinical challenge, in particular when high risk gene mutations occur. In this setting, alemtuzumab was recognized to be effective. This retrospective study evaluates long-term efficacy and tolerability of low-dose alemtuzumab in relapsed/refractory CLL and correlates clinical outcome with biological feature.

Malignant mesothelioma due to non-occupational asbestos exposure from the Italian national surveillance system (ReNaM): epidemiology and public health issues.

Introduction: Italy produced and imported a large amount of raw asbestos, up to the ban in 1992, with a peak in the period between 1976 and 1980 at about 160,000 tons/year. The National Register of Mesotheliomas (ReNaM, "Registro Nazionale dei Mesoteliomi" in Italian), a surveillance system of mesothelioma incidence, has been active since 2002, operating through a regional structure.

Methods: The Operating Regional Center (COR) actively researches cases and defines asbestos exposure on the basis of national guidelines.

Long-term prophylaxis in severe factor VII deficiency.

Introduction: The spectrum of bleeding problems in FVII deficiency is highly variable and FVII levels and causative genetic mutations correlate poorly with the bleeding risk. Long-term prophylaxis is generally initiated in order to prevent subsequent CNS bleeding after a first event or in patients with other major/ life threatening/ frequent bleeding symptoms as gastrointestinal bleeding or hemarthrosis. However few data are available in the literature regarding FVII prophylaxis and clinical decisions cannot be based on evidence.

Interferon-free therapy for hepatitis C: The hurdles amid a golden era.

The long awaited all-oral therapy for hepatitis C virus infection has officially been inaugurated by the registration of the hepatitis C nucleotide inhibitor sofosbuvir in a combination regimen with ribavirin. More recently, the oral array to treat hepatitis C has been enriched by the arrival of the NS5A inhibitors ledipasvir (also in a single formulation with sofosbuvir, Harvoni(®)) and daclatasvir; the protease inhibitor simeprevir, and the Viekirax(®)+Exviera™ regimen based on the ritonavir boosted protease inhibitor paritaprevir; the NS5A inhibitor ombitasvir, and the non-nucleoside inhibitor dasabuvir. Owing to the budget-breaking price of the newer oral medicines, the Italian National Health System elected to restrict reimbursement of oral anti-hepatitis C therapy to patients with advanced liver disease or transplanted organs, and those who are interferon unable, only.

Epidemiological patterns of asbestos exposure and spatial clusters of incident cases of malignant mesothelioma from the Italian national registry.

Background: Previous ecological spatial studies of malignant mesothelioma cases, mostly based on mortality data, lack reliable data on individual exposure to asbestos, thus failing to assess the contribution of different occupational and environmental sources in the determination of risk excess in specific areas. This study aims to identify territorial clusters of malignant mesothelioma through a Bayesian spatial analysis and to characterize them by the integrated use of asbestos exposure information retrieved from the Italian national mesothelioma registry (ReNaM).

Methods: In the period 1993 to 2008, 15,322 incident cases of all-site malignant mesothelioma were recorded and 11,852 occupational, residential and familial histories were obtained by individual interviews.

Statins may increase the risk of liver dysfunction in patients treated with steroids for active graves' orbitopathy.

Context: Intravenous glucocorticoids (IVGC) administered at high doses for the treatment of active moderate-severe Graves' orbitopathy (GO) may induce liver toxicity. Cumulative doses should not exceed 8 g and strict monitoring of liver function is recommended to avoid potentially life-threatening side effects. The 3-hydroxy-3-methylglutaryl-coenzyme reductase inhibitors, also known as statins, are employed to prevent major cardiovascular events.

Risk factors for idiopathic sudden sensorineural hearing loss and their association with clinical outcome.

Background: Sudden sensorineural hearing loss (ISSHL) is idiopathic in 85% of cases and cochlear micro-thrombosis has been hypothesized as pathogenic mechanism. The role of thrombophilia and cardiovascular risk factors in ISSHL is controversial and whether these risk factors influence the clinical outcome of ISSHL is unknown.

Methods: and patients To investigate the role of thrombophilia and cardiovascular risk factors in ISSHL and to evaluate their influence on clinical outcome of the disease, 118 patients with a first episode of ISSHL and 415 healthy controls were investigated.

Predictors of von Willebrand disease diagnosis in individuals with borderline von Willebrand factor plasma levels.

Background: In individuals with borderline von Willebrand factor (VWF) plasma levels, second-level tests are required to confirm or exclude von Willebrand disease (VWD). These tests are time-consuming and expensive.

Objective: To assess which parameters can predict VWD diagnosis in individuals with borderline VWF levels (30-60 IU dL(-1) ).

Impact of the International Prognostic Scoring System cytogenetic risk groups on the outcome of patients with primary myelodysplastic syndromes undergoing allogeneic stem cell transplantation from human leukocyte antigen-identical siblings: a retrospective analysis of the European Society for Blood and Marrow Transplantation-Chronic Malignancies Working Party.

Acquired chromosomal abnormalities are important prognostic factors in patients with myelodysplastic syndromes treated with supportive care and with disease-modifying therapeutic interventions, including allogeneic hematopoietic stem cell transplantation. To assess the prognostic impact of cytogenetic characteristics after hematopoietic stem cell transplantation accurately, we investigated a homogeneous group of 523 patients with primary myelodysplastic syndromes who have received stem cells from human leukocyte antigen-identical siblings. Overall survival at five years from transplantation in good, intermediate, and poor cytogenetic risk groups according to the International Prognostic Scoring System was 48%, 45% and 30%, respectively (P<0.