Few data exist to guide treatment of anemic hemodialysis patients with high ferritin and low transferrin saturation (TSAT).The Dialysis Patients' Response to IV Iron with Elevated Ferritin (DRIVE) trial was designed to evaluate the efficacy of intravenous ferric gluconate in such patients. Inclusion criteria were hemoglobin <11 g/dl, ferritin 500 to 1200 ng/ml, TSAT <25%, and epoetin dosage >225 IU/kg per wk or >22,500 IU/wk. Patients with known infections or recent significant blood loss were excluded. Participants (n ‫؍‬ 134) were randomly assigned to no iron (control) or to ferric gluconate 125 mg intravenously with eight consecutive hemodialysis sessions (intravenous iron). At randomization, epoetin was increased 25% in both groups; further dosage changes were prohibited. At 6 wk, hemoglobin increased significantly more (P ‫؍‬ 0.028) in the intravenous iron group (1.6 ؎ 1.3 g/dl) than in the control group (1.1 ؎ 1.4 g/dl). Hemoglobin response occurred faster (P ‫؍‬ 0.035) and more patients responded after intravenous iron than in the control group (P ‫؍‬ 0.041). Ferritin <800 or >800 ng/ml had no relationship to the magnitude or likelihood of responsiveness to intravenous iron relative to the control group. Similarly, the superiority of intravenous iron compared with no iron was similar whether baseline TSAT was above or below the study median of 19%. Ferritin decreased in control subjects (؊174 ؎ 225 ng/ml) and increased after intravenous iron (173 ؎ 272 ng/ml; P < 0.001). Intravenous iron resulted in a greater increase in TSAT than in control subjects (7.5 ؎ 7.4 versus 1.8 ؎ 5.2%; P < 0.001). Reticulocyte hemoglobin content fell only in control subjects, suggesting worsening iron deficiency. Administration of ferric gluconate (125 mg for eight treatments) is superior to no iron therapy in anemic dialysis patients receiving adequate epoetin dosages and have a ferritin 500 to 1200 ng/ml and TSAT <25%.

Summary Direct measurement of the reticulocyte hemoglobin content provides useful information for the diagnosis and treatment of iron-deficient states. We have examined direct measurements of reticulocyte and red cell hemoglobin content on the Sysmex XE 2100 (Ret He and RBC He respectively) and the Bayer ADVIA 2120 (CHr and CH respectively) analyzers. patients on chronic dialysis, Ret He was compared with traditional parameters for iron deficiency (serum iron <40 lg/dl, Tsat <20%, ferritin <100 ng/ml, hemoglobin <11 g/dl) for identifying iron-deficient states. Receiver operator characteristic (ROC) curve analysis revealed values of the area under the curve for Ret He of 0.913 (P < 0.0001). With a Ret He cutoff level of 27.2 pg, iron deficiency could be diagnosed with a sensitivity of 93.3%, and a specificity of 83.2%. Ret He is a reliable marker of cellular hemoglobin content and can be used to identify the presence of iron-deficient states.Keywords CHr, reticulocyte hemoglobin content, r-HuEpo (recombinant human erythropoietin), Iron replacement therapy, Ret He (reticulocyte hemoglobin equivalent)

SummaryBackground and objectives Recurrent hemodialysis (HD)-induced ischemic cardiac injury (myocardial stunning) is common and associated with high ultrafiltration (UF) requirements, intradialytic hypotension, longterm loss of systolic function, increased likelihood of cardiovascular events, and death. More frequent HD regimens are associated with lower UF requirements and improved hemodynamic tolerability, improved cardiovascular outcomes, and reduced mortality compared with conventional thrice-weekly HD. This study investigated the hypothesis that modification of UF volume and rate with more frequent HD therapies would abrogate dialysis-induced myocardial stunning.Design, settings, participants, & measurements A cross-sectional study of 46 patients established on hemodialysis Ͼ3 months compared four groups receiving the current range of quotidian therapies: conventional thrice-weekly HD (CHD3); more-frequent HD five to six times/week in a center (CSD) and at home (HSD); and home nocturnal HD (HN). Serial echocardiography quantitatively assessed regional systolic function to identify intradialytic left ventricular regional wall motion abnormalities (RWMAs). Cardiac troponin T (cTnT), N-terminal prohormone brain natriuretic peptide (NT-proBNP), and inflammatory markers were quantified.Results More frequent HD regimens were associated with lower UF volumes and rates compared with CHD3. Intradialytic fall in systolic BP was reduced in CSD and HSD groups and abolished in HN group. Mean RWMAs per patient reduced with increasing dialysis intensity (CHD3 Ͼ CSD Ͼ HSD Ͼ HN). Homebased groups demonstrated lower high-sensitivity C-reative protein levels, with trends to lower cTnT and NT-proBNP levels in the more frequent groups.Conclusions Frequent HD regimes are associated with less dialysis-induced myocardial stunning compared with conventional HD. This may contribute to improved outcomes associated with frequent HD therapies.

We investigate and characterize the magnetoencephalographic waveforms from patients during spontaneous and visually induced migraine aura. Direct current neuromagnetic fields were measured during spontaneous onset of migraine auras in 4 migraine patients, and compared with recordings from 8 migraine-with-aura patients and 6 normal controls during visual stimulation of the occipital cortex. Complex direct current magnetoencephalographic shifts, similar in waveform, were observed in spontaneous and visually induced migraine patients, but not in controls. Two-dimensional inverse imaging showed multiple cortical areas activated in spontaneous and visually induced migraine aura patients. In normal subjects, activation was only observed in the primary visual cortex. Results support a spreading, depression-like neuroelectric event occurring during migraine aura that can arise spontaneously or be visually triggered in widespread regions of hyperexcitable occipital cortex.

The Dialysis Patients Response to IV Iron with Elevated Ferritin (DRIVE) study demonstrated the efficacy of intravenous ferric gluconate to improve hemoglobin levels in anemic hemodialysis patients who were receiving adequate epoetin doses and who had ferritin levels between 500 and 1200 ng/ml and transferrin saturation (TSAT) Յ25%. The DRIVE-II study reported here was a 6-wk observational extension designed to investigate how ferric gluconate impacted epoetin dosage after DRIVE. During DRIVE-II, treating nephrologists and anemia managers adjusted doses of epoetin and intravenous iron as clinically indicated. By the end of observation, patients in the ferric gluconate group required significantly less epoetin than their DRIVE dose (mean change of Ϫ7527 Ϯ 18,021 IU/wk, P ϭ 0.003), whereas the epoetin dose essentially did not change for patients in the control group (mean change of 649 Ϯ 19,987 IU/wk, P ϭ 0.809). Mean hemoglobin, TSAT, and serum ferritin levels remained higher in the ferric gluconate group than in the control group (P ϭ 0.062, P Ͻ 0.001, and P ϭ 0.014, respectively). Over the entire 12-wk study period (DRIVE plus DRIVE-II), the control group experienced significantly more serious adverse events than the ferric gluconate group (incidence rate ratio ϭ 1.73, P ϭ 0.041). In conclusion, ferric gluconate maintains hemoglobin and allows lower epoetin doses in anemic hemodialysis patients with low TSAT and ferritin levels up to 1200 ng/ml.

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The kinetics of beta 2-microglobulin (beta 2m) were studied in five anephric or anuric hemodialysis patients. Human beta 2m was isolated from peritoneal dialysate using ion-exchange and gel chromatography and radiolabeled with 125I. Patients were injected with 10 microCi labeled beta 2m. In one study (N = 4), plasma activity was measured over 72 hours. In a second study (N = 4), patients received low-flux dialysis 24 hours after injection and high-clearance dialysis (Bellco BL655) at 48 hours. Plasma activities were fitted to a three-compartment, variable volume model. Endogenous beta 2m levels (radioimmunoassay) were 56 +/- 6 mg/liter. The beta 2m distribution volume was 12.7 +/- 2.0 liter (0.20 +/- 0.03 liter/kg) and the non-renal clearance was 3.0 +/- 0.4 ml/min. The generation rate, 9.9 +/- 1.7 mg/hr (0.16 +/- 0.04 mg/kg/hr), was similar to that measured in subjects with normal renal function. The three compartment model derived from the turnover data gave an adequate fit of the arterial concentrations of endogenous and exogenous beta 2m during low-flux (nil beta 2m clearance) and high-clearance (beta 2m clearance of 19 ml/min) dialysis. Simulations based on this model indicate that extracorporeal treatment can at best remove about 50% of weekly production. These results suggest that beta 2m production is not increased in dialysis patients, that there is substantial non-renal beta 2m clearance, and that the amount of beta 2m that can be removed by extracorporeal therapy is therefore limited.

SUMMARYPurpose: This study examines whether magnetoencephalographic (MEG) coherence imaging is more sensitive than the standard single equivalent dipole (ECD) model in lateralizing the site of epileptogenicity in patients with drug-resistant temporal lobe epilepsy (TLE). Methods: An archival review of ECD MEG analyses of 30 presurgical patients with TLE was undertaken with data extracted subsequently for coherence analysis by a blinded reviewer for comparison of accuracy of lateralization. Postoperative outcome was assessed by Engel classification. MEG coherence images were generated from 10 min of spontaneous brain activity and compared to surgically resected brain areas outlined on each subject's magnetic resonance image (MRI). Coherence values were averaged independently for each hemisphere to ascertain the laterality of the epileptic network. Reliability between runs was established by calculating the correlation between epochs. Match rates compared the results of each of the two MEG analyses with optimal postoperative outcome.Key Findings: The ECD method provided an overall match rate of 50% (13/16 cases) for Engel class I outcomes, with 37% (11/30 cases) found to be indeterminate (i.e., no spikes identified on MEG). Coherence analysis provided an overall match rate of 77% (20/26 cases). Of 19 cases without evidence of mesial temporal sclerosis, coherence analysis correctly lateralized the side of TLE in 11 cases (58%). Sensitivity of the ECD method was 41% (indeterminate cases included) and that of the coherence method 73%, with a positive predictive value of 70% for an Engel class Ia outcome. Intrasubject coherence imaging reliability was consistent from run-to-run (correlation >0.90) using three 10-min epochs. Significance: MEG coherence analysis has greater sensitivity than the ECD method for lateralizing TLE and demonstrates reliable stability from run-to-run. It, therefore, improves upon the capability of MEG in providing further information of use in clinical decisionmaking where the laterality of TLE is questioned.