A Novel Next-Generation Sequencing Assay for the Identification of BCR::ABL1 Transcript Type and Accurate and Sensitive Detection of TKI-Resistant Mutations.

Background: The clinical management of chronic myeloid leukemia (CML) patients requires the identification of the type of BCR::ABL1 transcript at diagnosis and the monitoring of its expression and potential tyrosine kinase inhibitor (TKI) resistance mutations during treatment. Detection of resistant mutation requires transcript type-specific amplification of BCR::ABL1 from RNA.

Methods: In this study, a custom RNA-based next-generation sequencing (NGS) assay (Dup-Seq BCR::ABL1) that enables (a) the identification of BCR::ABL1 transcript type and (b) the detection of resistance mutations from common and atypical BCR::ABL1 transcript types was developed and validated.

[New Treatment Strategies in Patients with Heart Failure with Reduced Ejection Fraction: Beyond Neurohormonal Inhibition].

Patients affected by heart failure (HF) with reduced ejection fraction (HFrEF) are prone to experience episodes of worsening symptoms and signs despite continued therapy, termed "worsening heart failure" (WHF). Although guideline-directed medical therapy is well established, worsening of chronic heart failure accounts for almost 50% of all hospital admissions for HF with consequent higher risk of death and hospitalization than patients with "stable" HF. New drugs are emerging as cornerstones to reduce residual risk of both cardiovascular mortality and readmission for heart failure.

An international multicenter study to evaluate reproducibility of automated scoring for assessment of Ki67 in breast cancer.

The nuclear proliferation biomarker Ki67 has potential prognostic, predictive, and monitoring roles in breast cancer. Unacceptable between-laboratory variability has limited its clinical value. The International Ki67 in Breast Cancer Working Group investigated whether Ki67 immunohistochemistry can be analytically validated and standardized across laboratories using automated machine-based scoring.

Activity of the fibroblast growth factor receptor inhibitors dovitinib (TKI258) and NVP-BGJ398 in human endometrial cancer cells.

The recent identification of activating fibroblast growth factor receptor 2 (FGFR2) mutations in endometrial cancer has generated an opportunity for a novel target-based therapy. Here, we explore the therapeutic potential of 2 FGFR inhibitors, the multikinase inhibitor dovitinib (TKI258) and the more selective FGFR inhibitor NVP-BGJ398 for the treatment of endometrial cancer. We examined the effects of both inhibitors on tumor cell growth, FGFR2 signaling, cell cycle, and apoptosis using a panel of 20 molecularly characterized human endometrial cancer cell lines.

[Seroconversion and immune response after anti-HBV vaccination in patients on chronic hemodialysis: comparison of two vaccines].

ESRD patients on hemodialysis (HD) have a high risk of HBV infections. Primary prevention through vaccination is a first choice to reduce the morbidity from HBV. Prevention can be accomplished by two types of vaccines.

Angiosarcoma developing after curative induction chemotherapy and radiotherapy for locally advanced squamous cell carcinoma of the larynx.

Background: Angiosarcoma arising after radiation is described in breast cancer but occurs elsewhere. Here, we present an angiosarcoma of the neck occurring after curative chemoradiation.

Methods: This is a case of angiosarcoma developing 5 years after curative therapy for T3N0 squamous cell carcinoma of the supraglottic larynx.

A half-log increase in BCR-ABL RNA predicts a higher risk of relapse in patients with chronic myeloid leukemia with an imatinib-induced complete cytogenetic response.

Purpose: Imatinib induces a complete cytogenetic response (CCR) in most chronic myeloid leukemia patients in chronic phase. Although CCR is usually durable, a minority of patients relapse. Biomarkers capable of predicting those CCR patients with a higher risk of relapse would improve therapeutic management.

Surgery versus interventional radiology in the management of thrombosed vascular access for hemodialysis.

Thrombosis is the most frequent complication occurring in vascular access (VA). The two widely used treatment strategies for thrombosed VA are surgical and endovascular. Which is the best and whether different approaches should be used on proximal versus distal VA, is still debated.

Effects of fluvastatin treatment on lipid profile, C-reactive protein trend, and renal function in dyslipidemic patients with chronic renal failure.

The purpose of this trial was to evaluate the effects of fluvastatin on the lipid pro-file and on renal function, as measured by creatinine clearance, in dyslipidemic patients with chronic renal failure. In this 8-month prospective, open-label, randomized, parallel-group trial, 130 patients (70 men and 60 women), after a 2-month washout period following previous lipid-lowering treatments, were randomly assigned to fluvastatin XL 80 mg given once daily (80 patients) or to standard treatment (50 patients). Mean total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglyceride values after 3 and 6 months of treatment with fluvastatin showed statistically significant improvement compared with standard treatment.

Inability of L22 ribosomal protein alteration to increase macrolide MICs in the absence of efflux mechanism in Haemophilus influenzae HMC-S.

Background: Haemophilus influenzae HMC-C with high-level macrolide resistance after multi-step selection by clarithromycin reverted spontaneously and became hypersusceptible to macrolides.

Objective: Determination of macrolide resistance mechanism(s) in hypersusceptible and hyperresistant strains.

Methods: The presence of macrolide efflux in the strains was studied by radioactive erythromycin accumulation.

Late symptomatic venous stenosis in three hemodialysis patients without previous central venous catheters.

It is well known that catheters placed in the subclavian or internal jugular veins may develop stenosis in the vein in which the catheter lies. Because the arteriovenous fistula (AVF) relies on good venous outflow, patients with ipsilateral central venous stenosis are subject to the malfunctioning of AVF. Until now, no data were published on patients showing central vein stenosis (CVS) without a previous central venous catheter (CVC) or a pacemaker.

Plasmapheresis in severe forms of myasthenia gravis.

In this study we introduce a new combination treatment of plasma exchange (PE) and high daily doses of prednisone for severe forms of myasthenia gravis (MG). The clinical efficacy of the combined therapy has been tested in 18 patients suffering from severe forms of MG. The protocol included 5 sessions of PE, performed in a range of 15 days, 1 session every 3 days, with concurrent administration of oral prednisone (1 mg/kg of body weight), starting at the first session of PE and given daily for at least 3 months.