Mortality and cardiovascular morbidity associated with haemoglobin levels: a pooled analysis of randomised controlled trials.

Background/aims: Several randomised controlled trials (RCTs) have raised concerns about potential harm associated with erythropoiesis-stimulating agents (ESAs) in chronic kidney disease patients, especially when haemoglobin (Hb) levels above 13 g/dl were targeted. We report the relationship between Hb levels and outcomes in the methoxy polyethylene glycol-epoetin beta RCT programme.

Methods: We assessed the association between Hb and a composite end point, as well as its components [all-cause mortality, myocardial infarction (MI) or cerebrovascular events (CVE)], in multiple post hoc analyses of 9 prospective RCTs (3,405 chronic kidney disease patients).

C.E.R.A. once every 4 weeks corrects anaemia and maintains haemoglobin in patients with chronic kidney disease not on dialysis.

Background: No previous randomized controlled studies have been reported examining de novo, once every 4 weeks (Q4W) administration of erythropoiesis-stimulating agents in chronic kidney disease (CKD) patients. We report results from a randomized multinational study that compared continuous erythropoietin receptor activator (C.E.

Maintenance treatment of renal anaemia in haemodialysis patients with methoxy polyethylene glycol-epoetin beta versus darbepoetin alfa administered monthly: a randomized comparative trial.

Background: Several studies with erythropoiesis-stimulating agents claim that maintenance therapy of renal anaemia may be possible at extended dosing intervals; however, few studies were randomized, results varied, and comparisons between agents were absent. We report results of a multi-national, randomized, prospective trial comparing haemoglobin maintenance with methoxy polyethylene glycol-epoetin beta and darbepoetin alfa administered once monthly.

Methods: Haemodialysis patients (n = 490) on stable once-weekly intravenous darbepoetin alfa were randomized to methoxy polyethylene glycol-epoetin beta once monthly or darbepoetin alfa every 2 weeks for 26 weeks, with dose adjustment for individual haemoglobin target (11-13 g/dL; maximum decrease from baseline 1 g/dL).

C.E.R.A. safety profile: a pooled analysis in patients with chronic kidney disease.

Background: C.E.R.

C.E.R.A. once every 4 weeks in patients with chronic kidney disease not on dialysis: The ARCTOS extension study.

C.E.R.

The effect of severe hepatic impairment on the pharmacokinetics and haematological response of C.E.R.A.

Aim: To examine the effect of severe hepatic impairment (HI) on the pharmacokinetics (PK) and pharmacodynamics (PD) of the continuous erythropoietin receptor activator, C.E.R.

C.E.R.A. corrects anemia in patients with chronic kidney disease not on dialysis: results of a randomized clinical trial.

Background And Objectives: This study examined the efficacy of C.E.R.

Efficacy of intravenous methoxy polyethylene glycol-epoetin beta administered every 2 weeks compared with epoetin administered 3 times weekly in patients treated by hemodialysis or peritoneal dialysis: a randomized trial.

Background: C.E.R.

Pharmacokinetic and pharmacodynamic properties of methoxy polyethylene glycol-epoetin beta are unaffected by the site of subcutaneous administration.

C.E.R.

Subcutaneous injection pain with C.E.R.A., a continuous erythropoietin receptor activator, compared with darbepoetin alfa.

Objective: This study assessed injection site pain following subcutaneous (SC) administration with a continuous erythropoietin receptor activator (C.E.R.

Pharmacokinetics and pharmacodynamics of intravenous and subcutaneous continuous erythropoietin receptor activator (C.E.R.A.) in patients with chronic kidney disease.

Continuous Erythropoietin Receptor Activator (C.E.R.

Efficacy and tolerability of intravenous continuous erythropoietin receptor activator: a 19-week, phase II, multicenter, randomized, open-label, dose-finding study with a 12-month extension phase in patients with chronic renal disease.

Background: A continuous erythropoietin receptor activator (C.E.R.

The continuous erythropoietin receptor activator (C.E.R.A.) corrects anemia at extended administration intervals in patients with chronic kidney disease not on dialysis: results of a phase II study.

Aim: This study was designed to assess the potential of the continuous erythropoietin receptor activator (C.E.R.

Effect of a continuous erythropoietin receptor activator (C.E.R.A.) on stable haemoglobin in patients with CKD on dialysis: once monthly administration.

Aims: This Phase II study aimed to determine the optimal dose and administration schedule of continuous erythropoietin receptor activator (C.E.R.

Continuous Erythropoietin Receptor Activator (C.E.R.A.) administered at extended administration intervals corrects anaemia in patients with chronic kidney disease on dialysis: a randomised, multicentre, multiple-dose, phase II study.

This dose-finding, open-label study examined the potential of subcutaneous Continuous Erythropoietin Receptor Activator (C.E.R.

Harmonic analysis of perfusion pumps.

The controversy over the use of nonpulsatile versus pulsatile pumps for maintenance of normal organ function during ex vivo perfusion has continued for many years, but resolution has been limited by lack of a congruent mathematical definition of pulsatility. We hypothesized that the waveform frequency and amplitude, as well as the underlying mean distending pressure are all key parameters controlling vascular function. Using discrete Fourier Analysis, our data demonstrate the complexity of the pulmonary arterial pressure waveform in vivo and the failure of commonly available perfusion pumps to mimic in vivo dynamics.

MLYCD mutation analysis: evidence for protein mistargeting as a cause of MLYCD deficiency.

Malonyl-CoA decarboxylase (MLYCD) deficiency is an autosomal recessive disorder characterized by malonic aciduria, developmental delay, seizure disorder, hypoglycemia, and cardiomyopathy. Genomic sequencing of MLYCD in nine unrelated patients identified 16 of 18 pathogenic alleles, which are documented in the newly created Human MLYCD Allelic Variant Database (http://mlycd.hgu.

Predictors of 90-day outcome in patients stabilized after acute coronary syndromes.

Aims: We investigated predictors of 90-day risk among patients surviving the early period after an acute coronary syndrome (ACS).

Methods And Results: The study population included 15 904 stabilized ST-segment elevation or non-ST-segment elevation ACS patients randomized in SYMPHONY and 2nd SYMPHONY. We developed risk models for death, death or myocardial infarction (MI), and death, MI, or severe recurrent ischaemia (SRI) using Cox proportional-hazards techniques.

Rod photoreceptor function in children with mitochondrial disorders.

Objective: To test the hypothesis that function of the rod photoreceptors is abnormal in pediatric patients with mitochondrial disorders.

Methods: Patients (n = 22; median age, 5 years) with a deficiency of 1 or more of the mitochondrial enzyme complexes, or a mutation in mitochondrial DNA, were studied by means of scotopic, full-field electroretinography (ERG). The conditions of ERG testing allowed derivation of the parameters of the activation of rod phototransduction from the ERG a-wave, and postreceptoral function from b-wave and P(2) stimulus-response functions.

Metabolic testing in mitochondrial disease.

Mitochondrial oxidative phosphorylation (OXPHOS) disorders are a heterogeneous group of diseases with variable expression that often pose diagnostic dilemmas. Although definitive diagnosis of these disorders usually requires a muscle biopsy and mtDNA and enzymatic testing, standard metabolic studies including organic acid and amino acid analysis often provide useful findings that support an OXPHOS disease and the need for more invasive studies. In addition, the detection of possible metabolic derangements, such as elevated lactate levels, may lead to improved long-term outcomes for affected patients through the use of various treatment regimens.

Attenuation of histamine-induced endothelial permeability responses after pacing-induced heart failure: role for endogenous catecholamines.

Objective: After congestive heart failure (CHF), lung endothelial permeability responses to a number of perturbations, including acute barotrauma, angiotensin II, and thapsigargin are blunted. Our hypothesis was that similar attenuation of permeability responses occurs in peripheral vascular beds after CHF. We compared peripheral microvascular permeability responses to the autacoid histamine in control dogs and in dogs paced to heart failure (245 bpm for approximately 36 days).

Spectrum of phenotypic variability in Niemann-Pick type C disease: A cause of delayed diagnosis.

Background: Niemann-Pick type C (NP-C) disease exhibits marked heterogeneity in its phenotype. This can pose diagnostic dilemmas and even delayed recognition of this condition.

Objective: To highlight the phenotypic variations and distinctive pathological and biochemical findings in this disorder.

Familial recurrence of atypical symptoms in an extended pedigree with the syndrome of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS).

We report a clinically heterogeneous, multigenerational pedigree with the syndrome of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) associated with a mutation at nucleotide 3243 in the mitochondrial DNA tRNA(Leu)(UUR) gene. Our findings suggest that the mutation at nucleotide 3243 is not always associated with the classic MELAS phenotype and that other symptoms (notably cardiac and gastrointestinal abnormalities) should raise the suspicion of a mitochondrial disorder.