Japanese epidemiological survey with consensus statement on Japanese guidelines for treatment of iron overload in bone marrow failure syndromes

Many patients with bone marrow failure syndromes need frequent transfusions of red blood cells, and most of them eventually suffer from organ dysfunction induced by excessively accumulated iron. The only way to treat transfusion-induced iron overload is iron chelating therapy. However, most patients have not been treated effectively because daily/continuous administration of deferoxamine is difficult for outpatients. Recently, a novel oral iron chelator, deferasirox, has been developed, and introduction of the drug may help many patients benefit from iron chelation therapy. In this review, we will discuss the current status of iron overload in transfusion-dependent patients, and the development of Japanese guidelines for the treatment of iron overload in Japan, which were established by the National Research Group on Idiopathic Bone Marrow Failure Syndromes in Japan

Association of iron overload based quantitative T2* MRI technique and carotid intima-media thickness in patients with beta-thalassemia: A cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Body iron status has been implicated in atherosclerotic cardiovascular disease. The main hypothesis is that high iron status is associated with increased risk of atherosclerosis. We investigated the potential role of iron as an additional risk factor promoting atherosclerosis among beta-thalassemic patients.</p> <p>Methods</p> <p>In this cross-sectional study, the liver iron load was assessed by quantitative T2* MRI technique and intima-media thickness (IMT) of the common carotid artery by high-resolution ultrasound among 119 patients (62 male, 57 female) with beta-thalassemia (major and intermediate) whose age ranged from 10 to 50 years with a mean of 25.6 years. The patients were divided into three groups according to the severity of iron loading, obtained by T2*MRI technique: group I (normal), group II (mild) and group III (moderate and severe) iron load.</p> <p>For elimination of the effect of age on carotid IMT values, the patients also were divided into four age groups (10-19 y, 20-29 y, 30-39 y and 40-50 y). Mean carotid IMT based on the severity of iron loading were compared at different age groups, using one way ANOVA analysis for assessing the effect of iron loading on carotid IMT. Pearson's coefficient of correlation were used to assess the degree of correlation between studied variables (liver T2*, IMT, age).</p> <p>Results</p> <p>There were significant differences in mean carotid IMT based on the severity of iron loading at different age groups, with P = 0.003 at 20-29 y, P = 0.006 at 30-39 y and p = 0.037 at 40-50 y. Age (p = 0.001) and liver T2*(p = 0.003) had significant correlation with mean carotid IMT independently.</p> <p>At the age group of 10-19 years, there were not significant differences in mean carotid IMT based on the liver iron loading (p = 0.661).</p> <p>No significant differences also are seen in mean carotid IMT between male and female (p = 0.41).</p> <p>Conclusions</p> <p>This study identified a relationship between body iron status and carotid IMT. This relationship support to the hypothesis of a link between body iron load and atherosclerosis.</p

The relationship between cardiac and liver iron evaluated by MR imaging in haematological malignancies and chronic liver disease

Although iron overload is clinically significant, only limited data have been published on iron overload in haematological diseases. We investigated cardiac and liver iron accumulation by magnetic resonance imaging (MRI) in a cohort of 87 subjects who did not receive chelation, including 59 haematological patients. M-HIC (MRI-based hepatic iron concentration, normal values <36 μmol/g) is a non-invasive, liver biopsy-calibrated method to analyse iron concentration. This method, calibrated to R2 (transverse relaxation rate), was used as a reference standard (M-HIC(R2)). Transfusions and ferritin were evaluated. Mean M-HIC(R2) and cardiac R* of all patients were 142 μmol/g (95% CI, 114–170) and 36.4 1/s (95% CI, 34.2–38.5), respectively. M-HIC(R2) was higher in haematological patients than in patients with chronic liver disease or normal controls (P<0.001). Clearly elevated cardiac R2* was found in two myelodysplastic syndrome (MDS) patients with severe liver iron overload. A poor correlation was found between liver and cardiac iron (n=82, r=0.322, P=0.003), in contrast to a stronger correlation in MDS (n=7, r=0.905, P=0.005). In addition to transfusions, MDS seemed to be an independent factor in iron accumulation. In conclusion, the risk for cardiac iron overload in haematological diseases other than MDS is very low, despite the frequently found liver iron overload

Exploring Cosmic Origins with CORE: Survey requirements and mission design

Future observations of cosmic microwave background (CMB) polarisation havethe potential to answer some of the most fundamental questions of modernphysics and cosmology. In this paper, we list the requirements for a future CMBpolarisation survey addressing these scientific objectives, and discuss thedesign drivers of the CORE space mission proposed to ESA in answer to the "M5"call for a medium-sized mission. The rationale and options, and themethodologies used to assess the mission's performance, are of interest toother future CMB mission design studies. CORE is designed as a near-ultimateCMB polarisation mission which, for optimal complementarity with ground-basedobservations, will perform the observations that are known to be essential toCMB polarisation scienceand cannot be obtained by any other means than adedicated space mission

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease

Multiband variability studies and novel broadband SED modeling of Mrk 501 in 2009

Aims. We present an extensive study of the BL Lac object Mrk 501 based on a data set collected during the multi-instrument campaign spanning from 2009 March 15 to 2009 August 1, which includes, among other instruments, MAGIC, VERITAS, Whipple 10 m, and Fermi-LAT to cover the gamma-ray range from 0.1 GeV to 20 TeV; RXTE and Swift to cover wavelengths from UV to hard X-rays; and GASP-WEBT, which provides coverage of radio and optical wavelengths. Optical polarization measurements were provided for a fraction of the campaign by the Steward and St. Petersburg observatories. We evaluate the variability of the source and interband correlations, the gamma-ray flaring activity occurring in May 2009, and interpret the results within two synchrotron self-Compton (SSC) scenarios.Methods. The multiband variability observed during the full campaign is addressed in terms of the fractional variability, and the possible correlations are studied by calculating the discrete correlation function for each pair of energy bands where the significance was evaluated with dedicated Monte Carlo simulations. The space of SSC model parameters is probed following a dedicated grid-scan strategy, allowing for a wide range of models to be tested and offering a study of the degeneracy of model-to-data agreement in the individual model parameters, hence providing a less biased interpretation than the "single-curve SSC model adjustment" typically reported in the literature.Results. We find an increase in the fractional variability with energy, while no significant interband correlations of flux changes are found on the basis of the acquired data set. The SSC model grid-scan shows that the flaring activity around May 22 cannot be modeled adequately with a one-zone SSC scenario (using an electron energy distribution with two breaks), while it can be suitably described within a two (independent) zone SSC scenario. Here, one zone is responsible for the quiescent emission from the averaged 4.5-month observing period, while the other one, which is spatially separated from the first, dominates the flaring emission occurring at X-rays and very-high-energy (> 100 GeV, VHE) gamma-rays. The flaring activity from May 1, which coincides with a rotation of the electric vector polarization angle (EVPA), cannot be satisfactorily reproduced by either a one-zone or a two-independent-zone SSC model, yet this is partially affected by the lack of strictly simultaneous observations and the presence of large flux changes on sub-hour timescales (detected at VHE gamma rays).Conclusions. The higher variability in the VHE emission and lack of correlation with the X-ray emission indicate that, at least during the 4.5-month observing campaign in 2009, the highest energy (and most variable) electrons that are responsible for the VHE gamma rays do not make a dominant contribution to the similar to 1 keV emission. Alternatively, there could be a very variable component contributing to the VHE gamma-ray emission in addition to that coming from the SSC scenario. The studies with our dedicated SSC grid-scan show that there is some degeneracy in both the one-zone and the two-zone SSC scenarios probed, with several combinations of model parameters yielding a similar model-to-data agreement, and some parameters better constrained than others. The observed gamma-ray flaring activity, with the EVPA rotation coincident with the first gamma-ray flare, resembles those reported previously for low frequency peaked blazars, hence suggesting that there are many similarities in the flaring mechanisms of blazars with different jet properties

Planck 2015 results I. Overview of products and scientific results

The European Space Agency's Planck satellite, which is dedicated to studying the early Universe and its subsequent evolution, was launched on 14 May 2009. It scanned the microwave and submillimetre sky continuously between 12 August 2009 and 23 October 2013. In February 2015, ESA and the Planck Collaboration released the second set of cosmology products based on data from the entire Planck mission, including both temperature and polarization, along with a set of scientific and technical papers and a web-based explanatory supplement. This paper gives an overview of the main characteristics of the data and the data products in the release, as well as the associated cosmological and astrophysical science results and papers. The data products include maps of the cosmic microwave background (CMB), the thermal Sunyaev-Zeldovich effect, diffuse foregrounds in temperature and polarization, catalogues of compact Galactic and extragalactic sources (including separate catalogues of Sunyaev-Zeldovich clusters and Galactic cold clumps), and extensive simulations of signals and noise used in assessing uncertainties and the performance of the analysis methods. The likelihood code used to assess cosmological models against the Planck data is described, along with a CMB lensing likelihood. Scientific results include cosmological parameters derived from CMB power spectra, gravitational lensing, and cluster counts, as well as constraints on inflation, non-Gaussianity, primordial magnetic fields, dark energy, and modified gravity, and new results on low-frequency Galactic foregrounds

Myocardial iron overload assessment by T2*magnetic resonance imaging in adult transfusion dependent patients with acquired anemias

Only limited data are available regarding myocardial iron overload in adult patients with transfusion dependent acquired anemias. To address this topic using MRI T2* we studied 27 consecutive chronic transfusion dependent patients with acquired anemias: (22 myelodysplastic syndrome, 5 primary myelofibrosis). Cardiac MRI T2* values obtained ranged from 5.6 to 58.7 (median value 39.8) milliseconds. Of the 24 analyzable patients, cardiac T2* correlated with transfusion burden (p=0.0002). No patient who had received less than 290 mL/kg of packed red blood cells (101 units=20 grams of iron) had a pathological cardiac T2* value (&lt; 20 ms). All patients who had received at least 24 PRBC units showed MRI T2* detectable hepatic iron (liver T2* value &lt;= 6.3 ms). Only patients with severe hepatic iron overload (T2* &lt;1.4 ms) showed cardiac T2* value indicative of dangerous myocardial iron deposition. Serum ferritin was not significantly correlated with cardiac T2* (p=0.24). Gradient echo T2* magnetic resonance imaging provides a rapid and reproducible method for detecting myocardial iron overload which developed after a heavy transfusion burden equal to or greater than 290 mL/kg of packed red blood cell units