Commentaire

Therapeutic resistance remains the principal problem in acute myeloid leukemia (AML). We used area under receiver-operating characteristic curves (AUCs) to quantify our ability to predict therapeutic resistance in individual patients, where AUC=1.0 denotes perfect prediction and AUC=0.5 denotes a coin flip, using data from 4601 patients with newly diagnosed AML given induction therapy with 3+7 or more intense standard regimens in UK Medical Research Council/National Cancer Research Institute, Dutch–Belgian Cooperative Trial Group for Hematology/Oncology/Swiss Group for Clinical Cancer Research, US cooperative group SWOG and MD Anderson Cancer Center studies. Age, performance status, white blood cell count, secondary disease, cytogenetic risk and FLT3-ITD/NPM1 mutation status were each independently associated with failure to achieve complete remission despite no early death (‘primary refractoriness’). However, the AUC of a bootstrap-corrected multivariable model predicting this outcome was only 0.78, indicating only fair predictive ability. Removal of FLT3-ITD and NPM1 information only slightly decreased the AUC (0.76). Prediction of resistance, defined as primary refractoriness or short relapse-free survival, was even more difficult. Our limited ability to forecast resistance based on routinely available pretreatment covariates provides a rationale for continued randomization between standard and new therapies and supports further examination of genetic and posttreatment data to optimize resistance prediction in AML

The polo-like kinase 1 (PLK1) inhibitor NMS-P937 is effective in a new model of disseminated primary CD56+ acute monoblastic leukaemia

CD56 is expressed in 15–20% of acute myeloid leukaemias (AML) and is associated with extramedullary diffusion, multidrug resistance and poor prognosis. We describe the establishment and characterisation of a novel disseminated model of AML (AML-NS8), generated by injection into mice of leukaemic blasts freshly isolated from a patient with an aggressive CD56+ monoblastic AML (M5a). The model reproduced typical manifestations of this leukaemia, including presence of extramedullary masses and central nervous system involvement, and the original phenotype, karyotype and genotype of leukaemic cells were retained in vivo. Recently Polo-Like Kinase 1 (PLK1) has emerged as a new candidate drug target in AML. We therefore tested our PLK1 inhibitor NMS-P937 in this model either in the engraftment or in the established disease settings. Both schedules showed good efficacy compared to standard therapies, with a significant increase in median survival time (MST) expecially in the established disease setting (MST = 28, 36, 62 days for vehicle, cytarabine and NMS-P937, respectively). Importantly, we could also demonstrate that NMS-P937 induced specific biomarker modulation in extramedullary tissues. This new in vivo model of CD56+ AML that recapitulates the human tumour lends support for the therapeutic use of PLK1 inhibitors in AML

Experiences of men with breast cancer: an exploratory focus group study

Management and care of men with breast cancer is based on that developed for women. Our study reports that men have specific issues regarding certain aspects of their breast cancer experience, including diagnosis, disclosure, support and gender-specific information, and offers suggestions for improved patient care

Network-Based Approach for Modeling and Analyzing Coronary Angiography

Significant intra-observer and inter-observer variability in the interpretation of coronary angiograms are reported. This variability is in part due to the common practices that rely on performing visual inspections by specialists (e.g., the thickness of coronaries). Quantitative Coronary Angiography (QCA) approaches are emerging to minimize observer's error and furthermore perform predictions and analysis on angiography images. However, QCA approaches suffer from the same problem as they mainly rely on performing visual inspections by utilizing image processing techniques. In this work, we propose an approach to model and analyze the entire cardiovascular tree as a complex network derived from coronary angiography images. This approach enables to analyze the graph structure of coronary arteries. We conduct the assessments of network integration, degree distribution, and controllability on a healthy and a diseased coronary angiogram. Through our discussion and assessments, we propose modeling the cardiovascular system as a complex network is an essential phase to fully automate the interpretation of coronary angiographic images. We show how network science can provide a new perspective to look at coronary angiograms

Proposed host galaxies of repeating fast radio burst sources detected by CHIME/FRB

We present a search for host galaxy associations for the third set of repeating fast radio burst (FRB) sources discovered by the CHIME/FRB Collaboration. Using the ~1 arcmin CHIME/FRB baseband localizations and probabilistic methods. We identify potential host galaxies of two FRBs, 20200223B and 20190110C at redshifts of 0.06024(2) and 0.12244(6), respectively. We also discuss the properties of a third marginal candidate host galaxy association for FRB 20191106C with a host redshift of 0.10775(1). The three putative host galaxies are all relatively massive, fall on the standard mass-metallicity relationship for nearby galaxies, and show evidence of ongoing star formation. They also all show signatures of being in a transitional regime, falling in the "green valley" which is between the bulk of star-forming and quiescent galaxies. The plausible host galaxies identified by our analysis are consistent with the overall population of repeating and non-repeating FRB hosts while increasing the fraction of massive and bright galaxies. Coupled with these previous host associations, we identify a possible excess of FRB repeaters whose host galaxies have M_u - M_r colors redder than the bulk of star-forming galaxies. Additional precise localizations are required to confirm this trend.Comment: 11 pages, submitted to AAS journal

Revealing the Dynamic Magneto-ionic Environments of Repeating Fast Radio Burst Sources through Multi-year Polarimetric Monitoring with CHIME/FRB

Fast radio bursts (FRBs) display a confounding variety of burst properties and host galaxy associations. Repeating FRBs offer insight into the FRB population by enabling spectral, temporal and polarimetric properties to be tracked over time. Here, we report on the polarized observations of 12 repeating sources using multi-year monitoring with the Canadian Hydrogen Intensity Mapping Experiment (CHIME) over 400-800 MHz. We observe significant RM variations from many sources in our sample, including RM changes of several hundred $\rm{rad\, m^{-2}}$ over month timescales from FRBs 20181119A, 20190303A and 20190417A, and more modest RM variability ($\rm{\Delta RM \lesssim}$ few tens rad m$^{-2}$) from FRBs 20181030A, 20190208A, 20190213B and 20190117A over equivalent timescales. Several repeaters display a frequency dependent degree of linear polarization that is consistent with depolarization via scattering. Combining our measurements of RM variations with equivalent constraints on DM variability, we estimate the average line-of-sight magnetic field strength in the local environment of each repeater. In general, repeating FRBs display RM variations that are more prevalent/extreme than those seen from radio pulsars in the Milky Way and the Magellanic Clouds, suggesting repeating FRBs and pulsars occupy distinct magneto-ionic environments

Chronic diarrhea associated with persistent norovirus excretion in patients with chronic lymphocytic leukemia: report of two cases

BACKGROUND: Chronic diarrhea in patients treated with immunosuppressive agents or suffering from immunosuppressive disease can represent a diagnostic and therapeutic challenge to the clinician. Norovirus infection, a major cause of acute epidemic diarrhea, has been described as a cause of chronic diarrhea in patients who are immunosuppressed, including transplant recipients and the very young. CASE PRESENTATIONS: We describe two patients, a 64 year-old man and a 59 year-old woman, both suffering from chronic lymphocytic leukemia and hypogammaglobulinemia, who developed chronic diarrhea resistant to therapy. In both cases, after months of symptoms, persistent norovirus infection--documented by repeatedly-positive high-sensitivity stool enzyme immunoassay--was found to be the cause. Both patients died with active diarrheal symptoms. CONCLUSIONS: We describe the first cases of advanced chronic lymphocytic leukemia to suffer from chronic symptomatic norovirus infection. Clinicians caring for such patients, particularly those with concomitant hypogammaglobulinema, who have chronic unexplained diarrhea, should consider norovirus infection in the differential diagnosis