Syncope in the Emergency Department: A Practical Approach.

Syncope is a common condition encountered in the emergency department (ED), accounting for about 0.6-3% of all ED visits. Despite its high frequency, a widely accepted management strategy for patients with syncope in the ED is still missing.

How to recognize pulmonary embolism in syncope patients: A simple rule.

Background: Syncope can be the presenting symptom of Pulmonary Embolism (PE). It is not known wether using a standardized algorithm to rule-out PE in all patients with syncope admitted to the Emergency Departments (ED) is of value or can lead to overdiagnosis and overtreatment.

Methods: We tested if simple anamnestic and clinical parameters could be used as a rule to identify patients with syncope and PE in a multicenter observational study.

Intracellular Cholesterol Pools Regulate Oncogenic Signaling and Epigenetic Circuitries in Early T-cell Precursor Acute Lymphoblastic Leukemia.

Unlabelled: Early T-cell acute lymphoblastic leukemia (ETP-ALL) is an aggressive hematologic malignancy associated with early relapse and poor prognosis that is genetically, immunophenotypically, and transcriptionally distinct from more mature T-cell acute lymphoblastic leukemia (T-ALL) tumors. Here, we leveraged global metabolomic and transcriptomic profiling of primary ETP- and T-ALL leukemia samples to identify specific metabolic circuitries differentially active in this high-risk leukemia group. ETP-ALLs showed increased biosynthesis of phospholipids and sphingolipids and were specifically sensitive to inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase, the rate-limiting enzyme in the mevalonate pathway.

The Genetics and Mechanisms of T-Cell Acute Lymphoblastic Leukemia.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy derived from early T-cell progenitors. The recognition of clinical, genetic, transcriptional, and biological heterogeneity in this disease has already translated into new prognostic biomarkers, improved leukemia animal models, and emerging targeted therapies. This work reviews our current understanding of the molecular mechanisms of T-ALL.

GATA3-Controlled Nucleosome Eviction Drives Enhancer Activity in T-cell Development and Leukemia.

Long-range enhancers govern the temporal and spatial control of gene expression; however, the mechanisms that regulate enhancer activity during normal and malignant development remain poorly understood. Here, we demonstrate a role for aberrant chromatin accessibility in the regulation of expression in T-cell lymphoblastic leukemia (T-ALL). Central to this process, the NOTCH1- enhancer (N-Me), a long-range T cell-specific enhancer, shows dynamic changes in chromatin accessibility during T-cell specification and maturation and an aberrant high degree of chromatin accessibility in mouse and human T-ALL cells.

Neutrophils Driving Unconventional T Cells Mediate Resistance against Murine Sarcomas and Selected Human Tumors.

Neutrophils are a component of the tumor microenvironment and have been predominantly associated with cancer progression. Using a genetic approach complemented by adoptive transfer, we found that neutrophils are essential for resistance against primary 3-methylcholantrene-induced carcinogenesis. Neutrophils were essential for the activation of an interferon-γ-dependent pathway of immune resistance, associated with polarization of a subset of CD4 CD8 unconventional αβ T cells (UTC).

IL-1R8 is a checkpoint in NK cells regulating anti-tumour and anti-viral activity.

Interleukin-1 receptor 8 (IL-1R8, also known as single immunoglobulin IL-1R-related receptor, SIGIRR, or TIR8) is a member of the IL-1 receptor (ILR) family with distinct structural and functional characteristics, acting as a negative regulator of ILR and Toll-like receptor (TLR) downstream signalling pathways and inflammation. Natural killer (NK) cells are innate lymphoid cells which mediate resistance against pathogens and contribute to the activation and orientation of adaptive immune responses. NK cells mediate resistance against haematopoietic neoplasms but are generally considered to play a minor role in solid tumour carcinogenesis.

Minimal Residual Disease Assessment and Risk-based Therapy in Acute Lymphoblastic Leukemia.

The study of minimal residual disease (MRD) in adult patients with acute lymphoblastic leukemia (ALL) allows a greater refinement of the individual risk classification and is the best support for risk-specific therapy with or without allogeneic hematopoietic cell transplantation (HCT). Using case-specific sensitive molecular probes or multiparametric flow cytometry on marrow samples obtained from the end of induction until midconsolidation, MRD assays can detect up to 1 leukemic cell of 10,000 total mononuclear cells (sensitivity, 0.01%; ie, ≥10).

Genomic analyses identify recurrent MEF2D fusions in acute lymphoblastic leukaemia.

Chromosomal rearrangements are initiating events in acute lymphoblastic leukaemia (ALL). Here using RNA sequencing of 560 ALL cases, we identify rearrangements between MEF2D (myocyte enhancer factor 2D) and five genes (BCL9, CSF1R, DAZAP1, HNRNPUL1 and SS18) in 22 B progenitor ALL (B-ALL) cases with a distinct gene expression profile, the most common of which is MEF2D-BCL9. Examination of an extended cohort of 1,164 B-ALL cases identified 30 cases with MEF2D rearrangements, which include an additional fusion partner, FOXJ2; thus, MEF2D-rearranged cases comprise 5.

Achieving Molecular Remission before Allogeneic Stem Cell Transplantation in Adult Patients with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: Impact on Relapse and Long-Term Outcome.

Allogeneic stem cell transplantation (alloHSCT) in first complete remission (CR1) remains the consolidation therapy of choice in Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL). The prognostic value of measurable levels of minimal residual disease (MRD) at time of conditioning is a matter of debate. We analyzed the predictive relevance of MRD levels before transplantation on the clinical outcome of Ph+ ALL patients treated with chemotherapy and imatinib in 2 consecutive prospective clinical trials.

Colchicine is safe and effective for secondary prevention of recurrent pericarditis.

The CORP (COlchicine for Recurrent Pericarditis) trial [7]is a prospective, randomized, double-blind, placebo controlled, multicenter trial to evaluate the efficacy and safety of colchicine (1.0–2.0 mg on the first day, followed by a maintenance dose of 0.

Embryonic stem cell-derived neural stem cells improve spinal muscular atrophy phenotype in mice.

Spinal muscular atrophy, characterized by selective loss of lower motor neurons, is an incurable genetic neurological disease leading to infant mortality. We previously showed that primary neural stem cells derived from spinal cord can ameliorate the spinal muscular atrophy phenotype in mice, but this primary source has limited translational value. Here, we illustrate that pluripotent stem cells from embryonic stem cells show the same potential therapeutic effects as those derived from spinal cord and offer great promise as an unlimited source of neural stem cells for transplantation.

Motoneuron transplantation rescues the phenotype of SMARD1 (spinal muscular atrophy with respiratory distress type 1).

Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is a fatal form of infantile motoneuron disease. There is currently no effective treatment, although motor neuron replacement is a possible therapeutic strategy. We transplanted purified motor neurons into the spinal cord of nmd mice, an animal model of SMARD1.