Single cell dissection of plasma cell heterogeneity in symptomatic and asymptomatic myeloma

Multiple myeloma, a plasma cell malignancy, is the second most common blood cancer. Despite extensive research, disease heterogeneity is poorly characterized, hampering efforts for early diagnosis and improved treatments. Here, we apply single cell RNA sequencing to study the heterogeneity of 40 individuals along the multiple myeloma progression spectrum, including 11 healthy controls, demonstrating high interindividual variability that can be explained by expression of known multiple myeloma drivers and additional putative factors. We identify extensive subclonal structures for 10 of 29 individuals with multiple myeloma. In asymptomatic individuals with early disease and in those with minimal residual disease post-treatment, we detect rare tumor plasma cells with molecular characteristics similar to those of active myeloma, with possible implications for personalized therapies. Single cell analysis of rare circulating tumor cells allows for accurate liquid biopsy and detection of malignant plasma cells, which reflect bone marrow disease. Our work establishes single cell RNA sequencing for dissecting blood malignancies and devising detailed molecular characterization of tumor cells in symptomatic and asymptomatic patients

Cell tracking in cardiac repair: what to image and how to image

Stem cell therapies hold the great promise and interest for cardiac regeneration among scientists, clinicians and patients. However, advancement and distillation of a standard treatment regimen are not yet finalised. Into this breach step recent developments in the imaging biosciences. Thus far, these technical and protocol refinements have played a critical role not only in the evaluation of the recovery of cardiac function but also in providing important insights into the mechanism of action of stem cells. Molecular imaging, in its many forms, has rapidly become a necessary tool for the validation and optimisation of stem cell engrafting strategies in preclinical studies. These include a suite of radionuclide, magnetic resonance and optical imaging strategies to evaluate non-invasively the fate of transplanted cells. In this review, we highlight the state-of-the-art of the various imaging techniques for cardiac stem cell presenting the strengths and limitations of each approach, with a particular focus on clinical applicability

Significance of diabetes mellitus in patients with acute myocardial infraction receiving thrombolytic theraphy

AbstractObjectives. The purpose of this study was to evaluate the risks and benefits associated with thrombolytic theraphy in patients with diabetes presenting with acute myocardial infarction.Background. Diabetes mellitus is associated with adverse risk factors and a hypercoagulable state that may adversely affect the outcome of thrombolytic therapy.Methods. Data were analyzed from 8,055 of the 8,239 patients with acute myocardial infarction who received thrombolytic therapy in the International Tissue plasminogen Activator/Streptokinase Mortality trial (diabetes history was missing for 184 patients).Results. There were 883 patients with and 8,272 patients without diabetes. Among the diabetic patients, 160 were receiving insulin therapy. Baseline risk factors were significantly worse in diabetic patients, who were older and had a higher rate of previous infarction and antecedent angina and a higher Killip grade at admission. Bleeding and hemorrhagic and ischemic stroke rates were similar among diabetic and nondiabetic patients. Hospital and 6-month mortality rates were highest among diabetic patients receiving insulin therapy (16.9% and 23.1%, respectively), followed by diabetic patients not receiving insulin therapy (11.8% and 17.8%), and lowest in nondiabetic patients (7.5% and 10.7%, p < 0.0001). Whereas diabetes of 5 years' duration was associated with a mortality rate similar to that of nondiabetic patients, a >5-year duration was associated with a relative mortality risk of 1.38 (95% cofidence interval [CI] 0.88 to 2.15) and a > 10-year duration with a relative mortality risk of 1.99 (95% CI 1.40 to 2.81). The independent relative risk for incremental mortality from discharge to 6 months was 1.74 (95% CI 1.21 to 2.50). Mortality rate among diabetic was patients lowest in patients who received both streptokinase and heparin (9.8% vs. 16.1% in patients who received streptokinase but no heparin, p < 0.05).Conclusions. The relative mortality of diabetis versus nondiabetic patients was similar to that observed in previous studies of patients with myocardial infarction not receiving thrombolytic therapy, indicating that mortality in diabetic patients receiving thrombolytic therapy is reduced to the same extent as in nondiabetic patients. In addition, risk of bleeding and stroke was not increased, indicating that diabetic patients can safely receive thrombolytic therapy for the same indications as nondiabetic patients