Identification of kit(M541L) somatic mutation in chronic eosinophilic leukemia, not otherwise specified and its implication in low-dose imatinib response.

Activating mutations of KIT receptor tyrosine kinase have been reported in different neoplasms. The M541L KIT substitution (KIT(M541L)) has been described to be associated with pediatric mastocytosis, to enhance growth rate of the affected cells and to confer higher sensitivity to imatinib therapy. We investigated the presence of KIT(M541L) in five males with chronic eosinophilic leukemia, not otherwise specified (CEL, NOS), all negative for Platelet-derived growth factor-alpha (PDGFR) or PDGFRbeta abnormalities, which responded to imatinib therapy.

Synchronous pleural and peritoneal malignant mesothelioma: a case report and review of literature.

The coexistence of mesothelioma and other primary malignancies has been previously reported in literature, but the finding of a pleural mesothelioma with a synchronous peritoneal mesothelioma has not been reported so far. We report a case of a 58-years-old woman that came to our attention for the incidental finding of an inguinal mass. Fine-needle biopsies of the mass and a thoracoscopy with pleural biopsies were performed, after imaging studies showed pleural thickenings suspicious for malignancy.

Prospective evaluation of early endoscopic ultrasonography for triage in suspected choledocholithiasis: results from a large single centre series.

Background: Endoscopic ultrasonography is accurate, safe, and cost-effective in diagnosing common bile duct stones, thus suggesting the possibility to avoid invasive endoscopic retrograde cholangiopancreatography.

Aim: To prospectively evaluate the diagnostic and therapeutic performance of early endoscopic ultrasonography in suspected choledocholithiasis.

Patients And Methods: All consecutive patients presenting to the Emergency Department with suspicion of choledocholithiasis between January 2010 and January 2012 were evaluated and categorized as low, moderate, or high probability of choledocholithiasis, according to accepted criteria.

Impact of HBV therapy on the incidence of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a frequent, long term complication of chronic infection with hepatitis B virus (HBV) with an annual incidence ranging from 2 to 5%, often independent from the histological stage of underlying liver disease and serological status. Nevertheless, HCC is more often seen in older patients in whom HBV has been asserting its pro-oncogenic properties through both indirect and direct mechanisms. In Europe, HBV-related HCC is associated with cirrhosis in most patients, whereas this is not true in Asia and Africa where the tumour is also common among carriers with mild hepatic fibrosis, probably because of the coexistence of environmental co-carcinogens (aflatoxin) and long standing infection that is often acquired perinatally.

Comorbidities and polypharmacy impact on complete cytogenetic response in chronic myeloid leukaemia elderly patients.

Background: In older patients comorbidity and polypharmacy can significantly influence the success of the treatment, as well as the cognitive and psycho-social aspects. A significant proportion of chronic myeloid leukaemia (CML) patients are "elderly": in the past the aim of therapy in this subset of patients was only to contain the leukaemic mass, but nowadays, with the advent of the protein-tyrosine kinase inhibitors, also elderly patients can access these treatments. We want to assess if even old CML patients, with a correct geriatric evaluation, can be successfully treated with protein-tyrosine kinase inhibitors.

Normal reference ranges of antithrombin, protein C and protein S: effect of sex, age and hormonal status.

Introduction: Antithrombin (AT), protein C (PC) and protein S (PS) deficiencies are risk factors for venous thromboembolism. Overlapping values between heterozygous carriers and normal individuals often make a correct classification of a deficiency difficult. The aim of this study was to investigate the effect of sex, age, menopause and hormone therapy on natural anticoagulant plasma levels in a large group of healthy individuals, and to evaluate the need of separate reference ranges.

Low borderline plasma levels of antithrombin, protein C and protein S are risk factors for venous thromboembolism.

Background: Inherited deficiencies of antithrombin (AT), protein C (PC) and protein S (PS) are risk factors for venous thromboembolism (VTE). They are usually defined by laboratory cut-offs (in our setting 81, 70 and 63 IU dL(-1), respectively), which give only a rough idea of the VTE risk associated with plasma levels of these proteins.

Objectives:  We investigated whether the risk of VTE associated with the plasma deficiencies of AT, PC or PS has a dose-response effect, and whether low borderline levels of these proteins are associated with an increased risk of VTE, both in the whole study population and separately in carriers of either factor V Leiden or G20210A prothrombin gene mutation.

The JAK2 V617F mutation in patients with cerebral venous thrombosis.

Background: It is currently unclear whether or not cerebral venous thrombosis, such as splanchnic venous thrombosis, can be the first manifestation of an underlying myeloproliferative neoplasm.

Objective: To determine the prevalence of the JAK2 V617F mutation in patients with a first episode of cerebral venous thrombosis.

Patients: In this retrospective cohort study, patients with cerebral venous thrombosis were tested for the JAK2 V617F mutation and were followed until the development of a myeloproliferative neoplasm or censored at the end of follow-up.

Source and purity of factor VIII products as risk factors for inhibitor development in patients with hemophilia A.

Background: Inhibitor development is influenced by several factors and the type of factor VIII (FVIII) products may play a role.

Objectives: In order to explore such a role, we designed a cohort study whose novelty resides in the classification of products not only according to the source of FVIII (plasmatic, pd, or recombinant, r) but also to their degree of purity (expressed as specific activity).

Patients/methods: Treatment data up to inhibitor development or 150 exposure days were collected in 377 patients with hemophilia A.

Severe chronic diarrhea and maculopapular rash: a case report.

Systemic mastocytosis (SM) is a heterogeneous disease of the bone marrow characterized by abnormal growth, accumulation and activation of clonal mast cells (MCs). We report a case of SM with multi-organ involvement. A 30-year-old man presented with diarrhea, flushing, maculopapular rash with itching and weight loss.

Risk factors for postpartum hemorrhage in a cohort of 6011 Italian women.

Introduction: Postpartum hemorrhage is responsible for 25% of maternal pregnancy-related deaths and it is the first cause of maternal morbidity and mortality worldwide.

Objective: To define the prevalence of postpartum hemorrhage and associated risk factors after vaginal birth and to develop a risk model that improves postpartum hemorrhage prediction.

Patients And Methods: All women who underwent a vaginal delivery at the Obstetric Unit of a large University hospital in Milan (Italy) between July 2007 and September 2009 were enrolled.

Circulating microparticles and risk of venous thromboembolism.

Introduction: Circulating microparticles (MPs) may trigger a hypercoagulable state, leading to thrombotic complications. Data on their association with venous thromboembolism (VTE) are few and inconsistent.

Materials And Methods: To investigate whether or not high levels of MPs are associated with an increased risk of VTE, we carried out a case-control study on 186 patients with a first, objectively diagnosed, episode of VTE and 418 healthy controls.

Modeling costs and outcomes associated with a treatment algorithm for problem bleeding episodes in patients with severe hemophilia a and high-titer inhibitors.

Background: No evidence-based treatment guidelines are currently available for the treatment of problem bleedings in patients with hemophilia who develop clotting factor inhibitors. A treatment algorithm was developed previously to help providers optimize the approach to the treatment of this patient population. The algorithm provides the specific intervals between treatments; however, it does not specify dosing recommendations and does not offer insights into the likelihood of outcome improvements at each time interval.

A randomized clinical trial of prophylaxis in children with hemophilia A (the ESPRIT Study).

Background: Prevention of arthropathy is a major goal of hemophilia treatment. While studies in adults have demonstrated an impact of prophylaxis on the incidence of joint bleeds and patients' well-being in terms of improved quality of life (QoL), it is unclear whether or not prophylaxis influences the outcome and perception of well- of children with hemophilia.

Objective: This randomized controlled study compared the efficacy of prophylaxis with episodic therapy in preventing hemarthroses and image-proven joint damage in children with severe hemophilia A (factor VIII <1%) over a 10-year time period.

Development of a five-year mortality model in systemic sclerosis patients by different analytical approaches.

Objectives: Systemic sclerosis (SSc) is a multiorgan disease with high mortality rates. Several clinical features have been associated with poor survival in different populations of SSc patients, but no clear and reproducible prognostic model to assess individual survival prediction in scleroderma patients has ever been developed.

Methods: We used Cox regression and three data mining-based classifiers (Naïve Bayes Classifier [NBC], Random Forests [RND-F] and logistic regression [Log-Reg]) to develop a robust and reproducible 5-year prognostic model.

Survival dimensionality reduction (SDR): development and clinical application of an innovative approach to detect epistasis in presence of right-censored data.

Background: Epistasis is recognized as a fundamental part of the genetic architecture of individuals. Several computational approaches have been developed to model gene-gene interactions in case-control studies, however, none of them is suitable for time-dependent analysis. Herein we introduce the Survival Dimensionality Reduction (SDR) algorithm, a non-parametric method specifically designed to detect epistasis in lifetime datasets.

Incidence of thrombotic complications in patients with haematological malignancies with central venous catheters: a prospective multicentre study.

This prospective, observational and multicentre study assessed the incidence of, and risk factors for, symptomatic venous thrombotic complications after central venous catheter (CVC) positioning in patients with haematological malignancies. A total of 458 consecutive CVC insertions were registered in 416 patients (81.2% of whom had severe thrombocytopenia).