XIAP inhibitors induce differentiation and impair clonogenic capacity of acute myeloid leukemia stem cells.

Acute myeloid leukemia (AML) is a neoplasia characterized by the rapid expansion of immature myeloid blasts in the bone marrow, and marked by poor prognosis and frequent relapse. As such, new therapeutic approaches are required for remission induction and prevention of relapse. Due to the higher chemotherapy sensitivity and limited life span of more differentiated AML blasts, differentiation-based therapies are a promising therapeutic approach.

Cancer incidence, survival and mortality: explaining the concepts.

Cancer incidence, survival and mortality are essential population-based indicators for public health and cancer control. Confusion and misunderstanding still surround the estimation and interpretation of these indicators. Recurring controversies over the use and misuse of population-based cancer statistics in health policy suggests the need for further clarification.

High levels of global DNA methylation are an independent adverse prognostic factor in a series of 90 patients with de novo myelodysplastic syndrome.

The prognostic impact of global DNA methylation and hydroxymethylation was assessed in 90 patients with de novo myelodysplastic syndrome (MDS). DNA was isolated from bone marrow samples obtained at diagnosis and global methylation and hydroxymethylation were determined by ELISA. Patients with a percentage of methylated DNA above 2.

Rituximab, plasma exchange and intravenous immunoglobulins as a new treatment strategy for severe HLA alloimmune platelet refractoriness.

Platelet refractoriness (PR) due to HLA alloimmunization is a common and serious complication of patients receiving long-term packed red blood cell and platelet transfusions. Although most alloimmunized patients will respond to HLA-matched platelets, 20-50% of patients will remain refractory even to matched platelets. Several measures have been reported to overcome this complication, such as intravenous immunoglobulins (IVIG), plasma exchange (PE), protein A column therapy, or rituximab.

Effect of meropenem administration in extended infusion on the clinical outcome of febrile neutropenia: a retrospective observational study.

Objectives: Information on the efficacy of extended meropenem administration in neutropenic patients is scarce. Our objective was to determine whether the administration of meropenem in a 4 h extended infusion (EI) leads to a better clinical outcome in patients with febrile neutropenia than the conventional short infusion (SI).

Methods: This was a retrospective observational study.

Multilineage dysplasia is associated with a poorer prognosis in patients with de novo acute myeloid leukemia with intermediate-risk cytogenetics and wild-type NPM1.

Acute myeloid leukemia (AML) with myelodysplasia-related changes is characterized by the presence of multilineage dysplasia (MLD), frequently related to high-risk cytogenetics and poor outcome. However, the presence of MLD does not modify the favorable prognostic impact of NPM1 mutation. The prognosis of patients with AML presenting marked dysplasia lacking high-risk cytogenetics and NPM1 mutation is uncertain.

Extreme heterogeneity of myeloablative total body irradiation techniques in clinical practice: a survey of the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation.

Background: Total body irradiation (TBI) is widely used for conditioning before hematopoietic cell transplantation. Its efficacy and toxicity may depend on many methodological aspects. The goal of the current study was to explore current clinical practice in this field.

Treatment of high-risk Philadelphia chromosome-negative acute lymphoblastic leukemia in adolescents and adults according to early cytologic response and minimal residual disease after consolidation assessed by flow cytometry: final results of the PETHEMA ALL-AR-03 trial.

Purpose: Minimal residual disease (MRD) is an important prognostic factor in adults with acute lymphoblastic leukemia (ALL) and may be used for treatment decisions. The Programa Español de Tratamientos en Hematología (PETHEMA) ALL-AR-03 trial (Treatment of High Risk Adult Acute Lymphoblastic Leukemia [LAL-AR/2003]) assigned adolescent and adult patients (age 15 to 60 years) with high-risk ALL (HR-ALL) without the Philadelphia (Ph) chromosome to chemotherapy or to allogeneic hematopoietic stem-cell transplantation (allo-HSCT) according to early cytologic response (day 14) and flow-MRD level after consolidation.

Patients And Methods: Patients with good early cytologic response (< 10% blasts in bone marrow at day 14 of induction) and a flow-MRD level less than 5 × 10(-4) at the end of consolidation were assigned to delayed consolidation and maintenance therapy, and allo-HSCT was scheduled in patients with poor early cytologic response or flow-MRD level ≥ 5 × 10(-4).

Entangled states of more than 40 atoms in an optical fiber cavity.

Multiparticle entanglement enables quantum simulations, quantum computing, and quantum-enhanced metrology. Yet, there are few methods to produce and measure such entanglement while maintaining single-qubit resolution as the number of qubits is scaled up. Using atom chips and fiber-optical cavities, we have developed a method based on nondestructive collective measurement and conditional evolution to create symmetric entangled states and perform their tomography.

Tactile acuity charts: a reliable measure of spatial acuity.

For assessing tactile spatial resolution it has recently been recommended to use tactile acuity charts which follow the design principles of the Snellen letter charts for visual acuity and involve active touch. However, it is currently unknown whether acuity thresholds obtained with this newly developed psychophysical procedure are in accordance with established measures of tactile acuity that involve passive contact with fixed duration and control of contact force. Here we directly compared tactile acuity thresholds obtained with the acuity charts to traditional two-point and grating orientation thresholds in a group of young healthy adults.

Intravenous ferrous sucrose versus placebo in addition to oral iron therapy for the treatment of severe postpartum anaemia: a randomised controlled trial.

Objective: The aim of the study was to evaluate the effectiveness of intravenous iron versus placebo added to standard oral iron therapy in the treatment of severe postpartum anaemia.

Design: A randomised, double-blind, parallel-group, placebo-controlled clinical trial was performed in a single centre.

Setting: Hospital Clinic of Barcelona, Barcelona, Spain.

Dose-intensive chemotherapy including rituximab is highly effective but toxic in human immunodeficiency virus-infected patients with Burkitt lymphoma/leukemia: parallel study of 81 patients.

The results of intensive immunochemotherapy were analyzed in human immunodeficiency virus (HIV)-related Burkitt lymphoma/leukemia (BLL) in two cohorts (Spain and Germany). Alternating cycles of chemotherapy were administered, with dose reductions for patients over 55 years. Eighty percent of patients achieved remission, 11% died during induction, 9% failed and 7% died in remission.

Comparison of direct digital mammography, computed radiography, and film-screen in the French national breast cancer screening program.

Objective: The purpose of this article was to compare the performance of digital mammography using hardcopy image reading against film-screen mammography in a French national routine population-based screening program with a decentralized organization. The French context offered the opportunity to examine separately computed radiography and direct digital mammography performances in a large cohort.

Materials And Methods: The study includes 23,423 direct digital mammography, 73,320 computed radiography, and 65,514 film-screen mammography examinations performed by 123 facilities in Bouches du Rhône, France, for women 50-74 years old between 2008 and 2010.

PTEN increases autophagy and inhibits the ubiquitin-proteasome pathway in glioma cells independently of its lipid phosphatase activity.

Two major mechanisms of intracellular protein degradation, autophagy and the ubiquitin-proteasome pathway, operate in mammalian cells. PTEN, which is frequently mutated in glioblastomas, is a tumor suppressor gene that encodes a dual specificity phosphatase that antagonizes the phosphatidylinositol 3-kinase class I/AKT/mTOR pathway, which is a key regulator of autophagy. Here, we investigated in U87MG human glioma cells the role of PTEN in the regulation of autophagy and the ubiquitin-proteasome pathway, because both are functionally linked and are relevant in cancer progression.

Barcode tagging of human oocytes and embryos to prevent mix-ups in assisted reproduction technologies.

Study Question: Is the attachment of biofunctionalized polysilicon barcodes to the outer surface of the zona pellucida an effective approach for the direct tagging and identification of human oocytes and embryos during assisted reproduction technologies (ARTs)?

Summary Answer: The direct tagging system based on lectin-biofunctionalized polysilicon barcodes of micrometric dimensions is simple, safe and highly efficient, allowing the identification of human oocytes and embryos during the various procedures typically conducted during an assisted reproduction cycle.

What Is Known Already: Measures to prevent mismatching errors (mix-ups) of the reproductive samples are currently in place in fertility clinics, but none of them are totally effective and several mix-up cases have been reported worldwide. Using a mouse model, our group has previously developed an effective direct embryo tagging system which does not interfere with the in vitro and in vivo development of the tagged embryos.

MicroRNA expression at diagnosis adds relevant prognostic information to molecular categorization in patients with intermediate-risk cytogenetic acute myeloid leukemia.

Acute myeloid leukemia (AML) is a heterogeneous disease, and optimal treatment varies according to cytogenetic risk factors and molecular markers. Several studies have demonstrated the prognostic importance of microRNAs (miRNAs) in AML. Here we report a potential association between miRNA expression and clinical outcome in 238 intermediate-risk cytogenetic AML (IR-AML) patients from 16 institutions in the CETLAM cooperative group.

Humble origins for a successful strategy: complete enrolment in early Cambrian olenellid trilobites.

Trilobites are typified by the behavioural and morphological ability to enrol their bodies, most probably as a defence mechanism against adverse environmental conditions or predators. Although most trilobites could enrol at least partially, there is uncertainty about whether olenellids-among the most phylogenetically and stratigraphically basal representatives-could perform this behaviour because of their poorly caudalized trunk and scarcity of coaptative devices. Here, we report complete-but not encapsulating-enrolment for the olenellid genus Mummaspis from the early Cambrian Mural Formation in Alberta, the earliest direct evidence of this strategy in the fossil record of polymerid trilobites.

Mifepristone versus placebo to treat uterine myoma: a double-blind, randomized clinical trial.

Objective: To evaluate the efficacy, safety, and quality of life of 5 mg mifepristone per day compared with a placebo in treating uterine fibroids.

Design: Randomized, double-blind clinical study.

Location: Eusebio Hernández Gynecology and Obstetrics Teaching Hospital, Havana, Cuba.

Core binding factor acute myeloid leukemia: the impact of age, leukocyte count, molecular findings, and minimal residual disease.

Purpose: Most patients with acute myeloid leukemia (AML) and genetic rearrangements involving the core binding factor (CBF) have favorable prognosis. In contrast, a minority of them still have a high risk of leukemia recurrence. This study investigated the adverse features of CBF AML that could justify investigational therapeutic approaches.

Prospective assessment of incidence of Tako-Tsubo cardiomyopathy in a very large urban agglomeration.

Background: Tako-Tsubo cardiomyopathy (TTC) is a recently described medical entity and the incidence of TTC in a global population is still uncertain. We sought to prospectively assess the incidence of TTC in a large urban area.

Methods And Results: We included all consecutive patients referred for coronary angiography in three hospitals located in Paris and its suburbs.

Bone marrow WT1 levels at diagnosis, post-induction and post-intensification in adult de novo AML.

We retrospectively assessed whether normalized bone marrow WT1 levels could be used for risk stratification in a consecutive series of 584 acute myeloid leukemia (AML) patients. A cutoff value of 5065 copies at diagnosis identified two prognostic groups (overall survival (OS): 44 ± 3 vs 36 ± 3%, P=0.023; leukemia-free survival (LFS): 47 ± 3 vs 36 ± 4%, P=0.