Acute Leukemia and Pregnancy

The combination of acute leukemia and pregnancy is infrequent. It is estimated to occur in less than 1 in 75,000 pregnancies. Maternal and fetal outcomes have improved substantially in recent years. In general, multi-agent chemotherapy is given as soon as the diagnosis of leukemia is established, even if it is in the first trimester. There are two important considerations in the management of a patient with leukemia during pregnancy, the mother who needs optimal cancer therapy and the developing fetus who could potentially be affected by the disease and/or the teratogenicity of antineoplactic agents. Vaginal delivery is preferable, and caesarian section is reserved for obstetrical indications only

The role of sclerostin/dickkopf-1 and receptor activator of nuclear factor kB ligand/osteoprotegerin signalling pathways in the development of osteoporosis in patients with haemophilia A and B: A cross-sectional study

Aim: Haemophilia A and B are associated with reduced bone mineral density (BMD). The aim of this study was to assess circulating sclerostin and dickkopf-1 (Dkk-1), (inhibitors of osteoblastic differentiation), as well as the receptor activator of nuclear factor kB ligand (RANKL)/osteoprotegerin (OPG) system (the major regulator of osteoclastogenesis), in patients with haemophilia (PWH), their possible correlations with clinical risk factors and the effect of ibandronate on these markers. Methods: Eighty-nine male PWH (mean age 45.9 ± 15.3 years) and 30 age-matched healthy male controls participated. BMD was assessed by DXA. Sclerostin, Dkk-1, RANKL and OPG were measured in serum of patients, controls, as well as in ten patients receiving oral ibandronate (150 mg/mo), at baseline and after 12 months. Results: Patients with haemophilia had lower circulating sclerostin (median ± IQR: 47.4 ± 26.93 vs 250 ± 250 pmol/L, P <.001), Dkk-1 (21.24 ± 17.18 vs 26.16 ± 15.32pg/mL, P =.04) and higher levels of RANKL (0.23 ± 0.03 vs 0.04 ± 0.03 pmol/L, P =.001), RANKL/OPG ratio (0.063 ± 0.25 vs 0.005 ± 0.11, P =.001) compared with controls. Patients with low BMD had higher OPG concentrations compared to those with normal BMD. Sclerostin and RANKL/OPG correlated positively with BMD. Patients with severe haemophilia had lower sclerostin concentrations compared with those with mild or moderate disease. The degree of arthropathy negatively correlated with sclerostin and Dkk-1 levels. PWH who received ibandronate showed a decrease in serum Dkk-1 without any significant effect on sclerostin and RANKL/OPG. Conclusions: Patients with haemophilia present increased osteoclastic activity coupled with compensatory increased osteoblastic activity. Ibandronate did not affect RANKL/OPG ratio, but it decreased Dkk-1. © 2017 John Wiley & Sons Lt

Metal Sulfide Thin Films with Tunable Nanoporosity for Photocatalytic Applications

Metal xanthates are widely used as single-source precursors for the formation of metal sulfide thin films. In this study, we explore the length of the alkyl ligand as an efficient tool to control the formation and the nanoporosity of zinc sulfide thin films. The presented approach allows us to prepare highly porous thin metal sulfide films with potential applications in photocatalysis, whereby the nanoporosity is significantly enhanced with an increasing number of carbons in the alkyl chain of the metal xanthate precursors. To gain knowledge about the mechanisms leading to the changes in the nanoporosity, the thermal conversion process toward the porous films is studied in detail by time-resolved simultaneous grazing incidence small- and wide-angle X-ray scattering measurements using synchrotron radiation and thermogravimetric analysis. Thereby, we found that the structural changes during the early stages of the conversion process, which are distinctly influenced by the decomposition temperature of the metal xanthates, different growth regimes of the nanocrystals, and a mesophase formation, governed by the properties of the decomposition products of the metal xanthates, are mainly responsible for the changes of the structural properties and the nanoporosity of the final ZnS films

U-ReSNet: Ultimate Coupling of Registration and Segmentation with Deep Nets

International audienceIn this study, we propose a 3D deep neural network called U-ReSNet, a joint framework that can accurately register and segment medical volumes. The proposed network learns to automatically generate linear and elastic deformation models, trained by minimizing the mean square error and the local cross correlation similarity metrics. In parallel, a coupled architecture is integrated, seeking to provide segmentation maps for anatomies or tissue patterns using an additional decoder part trained with the dice coefficient metric. U-ReSNet is trained in an end to end fashion, while due to this joint optimization the generated network features are more informative leading to promising results compared to other deep learning-based methods existing in the literature. We evaluated the proposed architecture using the publicly available OASIS 3 dataset, measuring the dice coefficient metric for both registration and segmentation tasks. Our promising results indicate the potentials of our method which is composed from a convolutional architecture that is extremely simple and light in terms of parameters. Our code is publicly available https://github.com/TheoEst/coupling_registration_segmentation

The Stat3/5 signaling biosignature in hematopoietic stem/progenitor cells predicts response and outcome in myelodysplastic syndrome patients treated with azacitidine

Purpose: Azacitidine is the mainstay of high-risk myelodysplastic syndromes (MDS) therapy, but molecular predictors of response and the mechanisms of resistance to azacitidine remain largely unidentified. Deregulation of signaling via Stat3 and Stat5 in acute myeloid leukemia (AML) is associated with aggressive disease. Numerous genes involved in cell signaling are aberrantly methylated inMDS, yet the alterations and the effect of azacitidine treatment on Stat3/5 signaling in high-risk MDS have not been explored. Experimental Design: We assessed longitudinally constitutive and ligand-induced phospho-Stat3/5 signaling responses by multiparametric flow cytometry in 74 patients with MDS and low blast count AML undergoing azacitidine therapy. Pretreatment Stat3/5 signaling profiles in CD34+ cells were grouped by unsupervised clustering. The differentiation stage and the molecular properties of the CD34+ G-CSF-inducible Stat3/5 double-positive subpopulation were performed by flow cytometry and quantitative real-time PCR in isolated MDS progenitors. Results: The pretreatment Stat3/5 signaling profiles in CD34+ cells correlated strongly with response and cytogenetics and independently predicted event-free survival. We further identified a CD34+ G-CSF-inducible Stat3/5 double-positive subpopulation (DP subset) whose pretreatment levels were inversely associated with treatment response and cytogenetics. The kinetics of the DP subset followed the response to azacitidine and the disease course, whereas its molecular characteristics and cellular hierarchy were consistent with a leukemia propagating cell phenotype. Conclusions: Our findings provide a novel link among Stat3/5 signaling and MDS pathobiology and suggest that the Stat3/5 signaling biosignature may serve as both a response biomarker and treatment target. © 2015 AACR