Improved renal recovery in patients with atypical hemolytic uremic syndrome following rapid initiation of eculizimab treatment

Background: Eculizumab is approved for atypical hemolytic uremic syndrome (aHUS). Guidelines discuss the importance of prompt treatment. We report a post hoc analysis investigating the effect of baseline factors, including patient characteristics and time from the latest aHUS manifestation to eculizumab initiation, on change from baseline in estimated glomerular filtration rate (eGFR) and other outcomes. Methods: Data were pooled from four phase 2, open-label, single-arm, prospective clinical studies of eculizumab for patients with aHUS. Multivariate regressions identified predictors of eGFR change from baseline. The proportion of patients achieving sustained eGFR increase (defined: >= 15 ml/min/1.73 m(2) for >= 28 days) and platelet count normalization were evaluated 1 year post-treatment. Baseline characteristics and eGFR outcomes were summarized by time to treatment from last aHUS manifestation [ 7 days (n = 76)]. Results: Baseline eGFR were similar between groups. Multivariate regression analysis demonstrated time from aHUS manifestation to eculizumab treatment, age, baseline lactate dehydrogenase (LDH) and baseline hemoglobin were independently predictive of eGFR change from baseline. Mean eGFR change from baseline at 1 year was significantly higher in patients treated in 7 days (57 vs. 23 ml/min/1.73 m(2), p = 0.0098). After 1 year, 17/21 and 36/76 patients in the 7 day groups, respectively, achieved a sustained increase in eGFR. Mean time to platelet count normalization was similar between groups. Conclusions: Younger age, higher baseline LDH and lower baseline hemoglobin were associated with greater eGFR improvements. Early eculizumab initiation led to improved renal recovery, demonstrating the importance of rapid diagnosis and treatment of patients with aHUS

Safety and efficacy of eculizumab in pediatrics patients with aHUS, with or without baseline dialysis

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Outcomes of patients with atypical haemolytic uraemic syndrome with native and transplanted kidneys treated with eculizumab: a pooled post hoc analysis

Atypical hemolytic uremic syndrome (aHUS) often leads to end-stage renal disease (ESRD) and kidney transplantation; graft loss rates are high due to disease recurrence. A post hoc analysis of four prospective clinical trials in aHUS was performed to evaluate eculizumab, a terminal complement inhibitor, in patients with native or transplanted kidneys. The trials included 26-week treatment and extension periods. Dialysis, transplant, and graft loss were evaluated. Study endpoints included complete thrombotic microangiopathy (TMA) response, TMA event-free status, hematologic and renal parameters, and adverse events. Of 100 patients, 74 had native kidneys and 26 in the transplant subgroup had a collective history of 38 grafts. No patients lost grafts and only one with preexisting ESRD received a transplant on treatment. Efficacy endpoints were achieved similarly in both subgroups. After 26 weeks, mean absolute estimated glomerular filtration rate increased from baseline to 61 and 37 mL/min/1.73 m2 in native (n=71; P<0.0001) and transplanted kidney (n=25; P=0.0092) subgroups. Two patients (one/subgroup) developed meningococcal infections; both recovered, one continued therapy. Eculizumab was well tolerated. Eculizumab improved hematologic and renal outcomes in both subgroups. In patients with histories of multiple graft losses, eculizumab protected kidney function. (ClinicalTrials. gov numbers : NCT00844545, NCT00844844, NCT00838513, NCT00844428, NCT01193348, and NCT01194973) This article is protected by copyright. All rights reserved

SO050LONG-TERM FOLLOW-UP STUDY OF ECULIZUMAB FOR PREVENTION OF THROMBOTIC MICROANGIOPATHY IN PATIENTS WITH ATYPICAL HEMOLYTIC UREMIC SYNDROME

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LOW-FREQUENCY OBSERVATIONS OF THE MOON WITH THE MURCHISON WIDEFIELD ARRAY

A new generation of low-frequency radio telescopes is seeking to observe the redshifted 21 cm signal from the epoch of reionization (EoR), requiring innovative methods of calibration and imaging to overcome the difficulties of wide-field low-frequency radio interferometry. Precise calibration will be required to separate the expected small EoR signal from the strong foreground emission at the frequencies of interest between 80 and 300 MHz. The Moon may be useful as a calibration source for detection of the EoR signature, as it should have a smooth and predictable thermal spectrum across the frequency band of interest. Initial observations of the Moon with the Murchison Widefield Array 32 tile prototype show that the Moon does exhibit a similar trend to that expected for a cool thermally emitting body in the observed frequency range, but that the spectrum is corrupted by reflected radio emission from Earth. In particular, there is an abrupt increase in the observed flux density of the Moon within the internationally recognized frequency modulated (FM) radio band. The observations have implications for future low-frequency surveys and EoR detection experiments that will need to take this reflected emission from the Moon into account. The results also allow us to estimate the equivalent isotropic power emitted by the Earth in the FM band and to determine how bright the Earth might appear at meter wavelengths to an observer beyond our own solar system.National Science Foundation (U.S.) (Grant AST-0457585)National Science Foundation (U.S.) (Grant AST-0908884)National Science Foundation (U.S.) (Grant PHY-0835713)United States. Air Force Office of Scientific Research (Grant FA9550-0510247)Smithsonian Astrophysical ObservatoryMIT School of Scienc

The Murchison Widefield Array: The Square Kilometre Array Precursor at Low Radio Frequencies

The Murchison Widefield Array (MWA) is one of three Square Kilometre Array Precursor telescopes and is located at the Murchison Radio-astronomy Observatory in the Murchison Shire of the mid-west of Western Australia, a location chosen for its extremely low levels of radio frequency interference. The MWA operates at low radio frequencies, 80–300 MHz, with a processed bandwidth of 30.72 MHz for both linear polarisations, and consists of 128 aperture arrays (known as tiles) distributed over a ~3-km diameter area. Novel hybrid hardware/software correlation and a real-time imaging and calibration systems comprise the MWA signal processing backend. In this paper, the as-built MWA is described both at a system and sub-system level, the expected performance of the array is presented, and the science goals of the instrument are summarised.National Science Foundation (U.S.) (Grant AST CAREER-0847753)National Science Foundation (U.S.) (Grant AST-0457585)National Science Foundation (U.S.) (Grant AST-0908884)National Science Foundation (U.S.) (Grant PHY-0835713)United States. Air Force Office of Scientific Research (Grant FA9550-0510247)Smithsonian Astrophysical ObservatoryMIT School of Scienc