Biological and non-biological variables unrelated to acute myeloid leukemia (AML) preclude standard therapy in many settings, with “real world” patients under-represented in clinical trials and prognostic models. Here, using a case-based format, we illustrate the impact that socioeconomic and anthropogeographical constraints can have on optimally managing AML in 4 different healthcare systems. The granular details provided, emphasize the need for the development and targeting of socioeconomic interventions that are commensurate with the changing landscape of AML therapeutics, in order to avoid worsening the disparity in outcomes between patients with biologically similar disease.

BACKGROUND AND OBJECTIVE:Increasing evidence implicates lymphocytes in pulmonary arterial hypertension (PAH) pathogenesis. Rats deficient in T-lymphocytes show increased propensity to develop PAH but when injected with endothelial progenitor cells are protected from PAH (a mechanism dependent on natural killer (NK) cells). A decreased quantity of circulating cytotoxic CD8+ T-lymphocytes and NK cells are now reported in PAH patients; however, the effect of lymphocyte depletion on disease outcome is unknown. METHODS:This prospective study analysed the lymphocyte profile and plasma brain natriuretic peptide (BNP) levels of patients with idiopathic PAH (IPAH), connective tissue disease-associated PAH (CTD-APAH) and matched healthy controls. Lymphocyte surface markers studied include: CD4+ (helper T-cell marker), CD8+ (cytotoxic T-cell marker), CD56/CD16 (NK cell marker) and CD19+ (mature B-cell marker). Lymphocyte deficiencies and plasma BNP levels were then correlated with clinical outcome. RESULTS:Fourteen patients with PAH (9 IPAH, 5CTD) were recruited. Three patients were deceased at 1-year follow-up; all had elevated CD4 : CD8 ratios and deficiencies of NK cells and cytotoxic CD8+ T-lymphocytes at recruitment. Patients with normal lymphocyte profiles at recruitment were all alive a year later, and none were on the active transplant list. As univariate markers, cytotoxic CD8+ T-cell and NK cell counts were linked to short-term survival. CONCLUSIONS:Deficiencies in NK cells and cytotoxic CD8+ T-cells may be associated with an increased risk of death in PAH patients. Further research is required in larger numbers of patients and to elucidate the mechanism of these findings.

BACKGROUND:D-dimer assays are sensitive but have poor specificity. False positive results lead to extra imaging and hospital admissions. OBJECTIVES:To make a pilot comparison of the diagnostic accuracy of the standard quantitative latex HemosIL D-dimer assay with a newer HemosIL D-dimer HS version designed to have improved specificity. PATIENTS / METHODS: Consecutive patients presenting from the community to an Emergency Department that were investigated for suspected pulmonary embolism using a D-dimer test were included in the study. Standard and D-dimer HS tests were performed. Pulmonary Embolism was diagnosed on the basis of imaging studies or post-mortem at any time from presentation to 90 days thereafter. RESULTS:The prevalence of Pulmonary Embolism was 4.5% (18/402). The sensitivity, specificity, negative predictive value, and positive predictive value for the standard quantitative D-dimer test was 100% (81.5 - 100.0), 49.2% (44.1 - 54.3),100% (98.1 - 100.0), and 8.5% (5.1 - 13.0), respectively, and 100% (81.5 - 100.0), 58.3% (53.2 - 63.3),100% (98.4 - 100.0), and 10.1% (6.1 - 15.5), for the D-dimer HS test. There were 35 (16%) fewer 'false positives' using the D-dimer HS assay compared with the standard assay. CONCLUSIONS:D-dimer HS has superior specificity to the standard quantitative D-dimer test without any loss of sensitivity. The generation of fewer false positive results should lead to less unnecessary diagnostic imaging; the use of which is associated with increased hospital admissions and length of stay. The HS assay may therefore have significant health economic benefits.