GPR68 supports AML cells through the calcium/calcineurin pro-survival pathway and confers chemoresistance by mediating glucose metabolic symbiosis.

Accumulating evidence demonstrates that the "Warburg effect" that glycolysis is enhanced even in the presence of oxygen existed in hematopoietic malignancies, contributing to extracellular acidosis. G-protein coupled receptor 68 (GPR68), as a proton sensing GPCR responding to extracellular acidosis, is expected to play a critical role in hematopoietic malignancies. In the present study, we found that GPR68 was overexpressed in acute myeloid leukemia (AML) cells, and GPR68 deficiency impaired AML cell survival in vitro and cell engraftment in vivo.

Novel Molecular Mechanism of Lenalidomide in Myeloid Malignancies Independent of Deletion of Chromosome 5q.

Lenalidomide as well as other immunomodulatory drugs (IMiDs) have achieved clinical efficacies in certain sub-types of hematologic malignancies, such as multiple myeloma, lower-risk myelodysplastic syndromes (MDS) with a single deletion of chromosome 5q (del(5q)) and others. Despite superior clinical response to lenalidomide in hematologic malignancies, relapse and resistance remains a problem in IMiD-based therapy. The last ten years have witnessed the discovery of novel molecular mechanism of IMiD-based anti-tumor therapy.

Whole body deletion of Gpr68 does not change hematopoietic stem cell function.

G protein-coupled receptor 68 (GPR68) responds to extracellular protons, thus called the proton-sensing G protein-coupled receptor (GPCR), leading to activation of the phospholipase C-β (PLCβ)/calcium (Ca) pathway or the adenylyl cyclase (AC)/cyclic AMP (cAMP) pathway. We recently found that whole body deletion of Gpr68 (Gpr68 mice) reduced the number of B lymphocytes with age and during hematopoietic regeneration, such as in response to fluorouracil (5-FU) administration. This prompted us to characterize the hematopoietic stem cell (HSC) phenotype in Gpr68 mice.

Use and effectiveness of a fixed-ratio combination of insulin degludec/liraglutide (IDegLira) in a real-world population with type 2 diabetes: Results from a European, multicentre, retrospective chart review study.

Aims: To describe the real-world use and effectiveness of IDegLira, a fixed-ratio combination of the basal insulin degludec, and the glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide.

Materials And Methods: This European, multicentre, retrospective chart review comprised adults (n = 611) with type 2 diabetes, who started IDegLira ≥6 months before data collection. Clinical characteristics were assessed at baseline (defined as the most recent recording during the 6 months before the first IDegLira prescription) and 3, 6, 9 and 12 months (± 45 days for each time point) after commencing IDegLira, where data were available.

A European, multicentre, retrospective, non-interventional study (EU-TREAT) of the effectiveness of insulin degludec after switching basal insulin in a population with type 1 or type 2 diabetes.

Aims: To evaluate the clinical effectiveness of switching to insulin degludec (IDeg) in insulin-treated patients with either type 1 diabetes (T1DM) or type 2 diabetes (T2DM) under conditions of routine clinical care.

Materials And Methods: This was a multicentre, retrospective, chart review study. In all patients, basal insulin was switched to IDeg at least 6 months before the start of data collection.

Validation in daily clinical situations of Diascope, a software developed to help healthcare professionals individualize antidiabetic treatment in type 2 diabetes.

Introduction: DiaScope is a software to help in individualized prescription of antidiabetic treatment in type 2 diabetes. This study assessed its value and acceptability by different professionals.

Material And Methods: DiaScope was developed based on the ADA-EASD 2012 algorithm and on the recommendation of 12 international diabetes experts using the RAND/UCLA appropriateness method.

A decision support tool for appropriate glucose-lowering therapy in patients with type 2 diabetes.

Background: Optimal glucose-lowering therapy in type 2 diabetes mellitus requires a patient-specific approach. Although a good framework, current guidelines are insufficiently detailed to address the different phenotypes and individual needs of patients seen in daily practice. We developed a patient-specific decision support tool based on a systematic analysis of expert opinion.

A decision tool to support appropriate referral for deep brain stimulation in Parkinson's disease.

Background And Objective: Although Deep Brain Stimulation (DBS) has been proven to be an effective treatment for patients with advanced Parkinson's disease (PD), it may be difficult for general neurologists to identify appropriate candidates for this procedure. We developed an electronic decision tool that can assist neurologists in deciding which PD patients should be referred for DBS consideration.

Methods: Using the RAND/UCLA Appropriateness Method, an international expert panel assessed the appropriateness of referral for 972 theoretical patient profiles.