Does the use of Blinatumomab improve the overall survival rate in adults with relapsed/refractory acute lymphoblastic leukemia?

Objective: The objective of this selective EBM review paper is to determine whether or not, “Does the use of blinatumomab improve the overall survival rate in adults with relapsed/refractory acute lymphoblastic leukemia?” Study Design: A systematic review of two RCTs and one case-based series were utilized. All studies were published between 2014-2019. Data Sources: The two RCTs were found through PubMed and the case-based series was obtained through CINAHL Plus. All the studies were published in peer-reviewed journals. Outcomes Measured: The main outcome measured in all the studies was overall survival. Both RCTs defined overall survival as the time from randomization (i.e., when patients are assigned to receive blinatumomab or standard chemotherapy) to death from any cause. The case-based series by Topp et. al defined overall survival as the time from the first dose of blinatumomab to death from any cause. Results: In the first RCT by Kantarjian et al., the median overall survival was 7.7 months in the blinatumomab group (95% CI, 5.6 to 9.6) and 4.0 months (95% CI, 2.9 to 5.3) in the chemotherapy group. The hazard ratio calculated for death was 0.71 (95% CI, 0.55 to 0.93) with a p-value of 0.01. The second RCT determined median overall survival for the first salvage group to be 11.1 months for blinatumomab (95% CI, 8.2 months-NR, not reached) and 5.5 months for chemotherapy (95% CI, 3.7–9.0 months), for a hazard ratio of 0.59 (95% CI, 0.38–0.91); p = 0.016. Median overall survival for second or later salvage was 5.1 months for blinatumomab (95% CI, 3.2–7.1 months) and 3.0 months for chemotherapy (95% CI, 2.1–4.0 months). A hazard ratio of 0.72 (95% CI, 0.52–1.01) and a p-value of 0.055 was calculated. The case-based series by Topp et al. revealed shorter overall survival (p=0.201) in patients who relapsed after previous HSCT (8.8 months) compared with those who relapsed that did not undergo a prior HSCT (14.1 months). Conclusions: All three studies in this review indicate that blinatumomab improves overall survival in patients with relapsed/refractory B cell ALL

The Effects of Metformin, Aminoguanidine, and Pyridoxamine on Methylglyoxal Induced Cardiac Myocyte Injury

Advanced glycation end (AGE) products have been under investigation for their role in cardiovascular disease in complications. Methylglyoxal, a byproduct of glucose metabolism, is elevated in the blood of diabetic patients and has shown to be an important intermediate in the production of AGEs. Due to the highly reactive structure of methylglyoxal, it can produce high levels of reactive oxygen species (ROS) within the cell via mitochondrial modification which results in a loss of cell membrane potential and possible cell death. The role of methylglyoxal in cardiac cells is not well known; in this study methylglyoxal induced cell injury and ROS generation were investigated by co-treatment of methylglyoxal with metformin, aminoguanidine hydrochloride, or pyridoxamine dihydrochloride. The effects of methylglyoxal on H9C2 myoblast viability were evaluated after incubation of drugs for 24 hours by measuring absorbance at 450 nm by using tetrazolium to differentiate metabolically active and inactive cells (e.g., CCK-8 kit). We found that methylglyoxal (1200 µM) significantly reduced cell viability to 28 ±6% when compared to the untreated control (n=4, p36 hours fluorescence was measured at excitation 488 nm and emission 527 nm (e.g., DCFDA kit). We found that methylglyoxal (1200 µM) significantly increased ROS by 205±25% when compared to the untreated control baseline (n=4,

Earth as a Tool for Astrobiology - A European Perspective

International audienceScientists use the Earth as a tool for astrobiology by analyzing planetary field analogues (i.e. terrestrial samples and field sites that resemble planetary bodies in our Solar System). In addition, they expose the selected planetary field analogues in simulation chambers to conditions that mimic the ones of planets, moons and Low Earth Orbit (LEO) space conditions, as well as the chemistry occurring in interstellar and cometary ices. This paper reviews the ways the Earth is used by astrobiologists: (i) by conducting planetary field analogue studies to investigate extant life from extreme environments, its metabolisms, adaptation strategies and modern biosignatures; (ii) by conducting planetary field analogue studies to investigate extinct life from the oldest rocks on our planet and its biosignatures; (iii) by exposing terrestrial samples to simulated space or planetary environments and producing a sample analogue to investigate changes in minerals, biosignatures and microorganisms. The European Space Agency (ESA) created a topical team in 2011 to investigate recent activities using the Earth as a tool for astrobiology and to formulate recommendations and scientific needs to improve ground-based astrobiological research. Space is an important tool for astrobiology (see Horneck et al. in Astrobiology, 16:201–243, 2016; Cottin et al., 2017), but access to space is limited. Complementing research on Earth provides fast access, more replications and higher sample throughput. The major conclusions of the topical team and suggestions for the future include more scientifically qualified calls for field campaigns with planetary analogy, and a centralized point of contact at ESA or the EU for the organization of a survey of such expeditions. An improvement of the coordinated logistics, infrastructures and funding system supporting the combination of field work with planetary simulation investigations, as well as an optimization of the scientific return and data processing, data storage and data distribution is also needed. Finally, a coordinated EU or ESA education and outreach program would improve the participation of the public in the astrobiological activities