High-Efficiency Postdilution Online Hemodiafiltration Reduces All-Cause Mortality in Hemodialysis Patients

Retrospective studies suggest that online hemodiafiltration (OL-HDF) may reduce the risk of mortality compared with standard hemodialysis in patients with ESRD. We conducted a multicenter, open-label, randomized controlled trial in which we assigned 906 chronic hemodialysis patients either to continue hemodialysis (n=450) or to switch to high-efficiency postdilution OL-HDF (n=456). The primary outcome was all-cause mortality, and secondary outcomes included cardiovascular mortality, all-cause hospitalization, treatment tolerability, and laboratory data. Compared with patients who continued on hemodialysis, those assigned to OL-HDF had a 30% lower risk of all-cause mortality (hazard ratio [HR], 0.70; 95% confidence interval [95% CI], 0.53–0.92; P=0.01), a 33% lower risk of cardiovascular mortality (HR, 0.67; 95% CI, 0.44–1.02; P=0.06), and a 55% lower risk of infection-related mortality (HR, 0.45; 95% CI, 0.21–0.96; P=0.03). The estimated number needed to treat suggested that switching eight patients from hemodialysis to OL-HDF may prevent one annual death. The incidence rates of dialysis sessions complicated by hypotension and of all-cause hospitalization were lower in patients assigned to OL-HDF. In conclusion, high-efficiency postdilution OL-HDF reduces all-cause mortality compared with conventional hemodialysis.In the last decades, renal replacement therapy with hemodialysis has become a standard of care for patients with ESRD. Despite continuous improvement, annual mortality among these patients ranges between 15% and 25%.^1,2 Hemodialysis techniques are based on the ability of molecules to diffuse across a semipermeable membrane, which allows adequate clearance of low molecular weight particles. To increase the clearance of middle-to-large molecules, synthetic membranes with high water permeability (high-flux membranes) were introduced years ago. The anticipated benefit of high-flux over low-flux hemodialysis on patient survival was not confirmed in the Hemodialysis (HEMO) study.³ However, the Membrane Permeability Outcome (MPO) study,⁴ as well as a post hoc analysis in diabetic patients, showed that high-flux hemodialysis improved long-term survival in patients with hypoalbuminemia.Clearance of middle-to-large molecules can be increased by combining diffusive and convective transport through hemodiafiltration. The introduction of online hemodiafiltration (OL-HDF) using ultrapure dialysate as the source of the replacement fluid has allowed the convective volume to be increased and has reduced the cost of the procedure.⁵ Randomized studies with limited sample sizes and nonrandomized studies have shown that OL-HDF improves hemodynamic stability and response to erythropoietic-stimulating agents (ESAs) and reduces the incidence of hemodialysis-associated amyloidosis and chronic inflammation.^6–11 The effect of OL-HDF on patient survival is derived from noncontrolled studies. The European Dialysis Outcomes and Practice Pattern Study was associated with a mortality risk reduction of 35% in patients treated with high-efficiency hemodiafiltration compared with those treated with conventional hemodialysis.¹² These results were confirmed in other noncontrolled studies conducted in several European countries,^13–15 although two recent, randomized studies failed to show differences in patient survival^16,17In 2007, the Catalonian Health Authorities approved a specific additional reimbursement for OL-HDF to dialysis care providers and the Catalonian Society of Nephrology promoted this randomized study (On-Line Hemodiafiltration Survival Study, or Estudio de Supervivencia de Hemodiafiltración On-Line [ESHOL]) to compare the effect of OL-HDF over hemodialysis on patient survival.¹⁸     

European Species of Hebeloma Section Theobromina

This paper addresses section Theobromina within the genus Hebeloma (Agaricales). We recognise seven European species within this section, three of which are described as new: Hebeloma alboerumpens, H. griseopruinatum and H. parvicystidiatum. The first two of these species appear to be ectomycorrhizal with Cistaceae: Cistus and Helianthemum. Hebeloma parvicystidiatum is more likely to be in mycorrhizal association with Quercus spp. We also provide a key to the European species within sect. Theobromina and an updated key of known Hebeloma associates of Cistus. Molecular analyses based on multiple loci further illustrate the distinctness of the newly described taxa and provide molecular evidence, supporting the morphological evidence, for the relationship that exists among species of this section. The ITS is the only one from the sequenced loci that, alongside with morphology, distinguishes among all of the species of sect. Theobromina. The section gains most of its molecular support from the MCM7 locus, followed by RPB2.     

Hand and wrist arthralgia in systemic lupus erythematosus is associated to ultrasonographic abnormalities

ObjectiveSystemic lupus erythematosus (SLE) is an autoimmune disease which may has joint impairment. Often, SLE patients complain of hand and wrist arthralgia (HA). Usually, these patients do not show any swelling in the physical exam. Our aim was to demonstrate Power Doppler Ultrasound (PDUS) abnormalities in SLE patients with HA.MethodsWe recruited 58 consecutive SLE patients and divided them into two groups: case group (n = 28) were patients with HA, and control group (n = 30) were patients without HA. We also collected socio-demographic and disease activity data, biological markers and SLEDAI index. We evaluated disability and quality of life by mHAQ and SF-12, respectively. We performed a bilateral hand and wrist PDUS on all patients. PDUS findings were based in OMERACT-7 group criteria.ResultsWe found PDUS abnormalities in most of SLE patients who suffered HA, when compared to SLE controls (P < 0.001). The main findings in Case Group were: tenosynovitis (39.2%), synovial effusion or hypertrophy (25%) and active synovitis (14.2%). SLEDAI score and dsDNA antibodies were related to the presence of PDUS abnormalities (P < 0.05 and P < 0.001, respectively). We also found worse physical SF-12 (P < 0.05) and mHAQ (NS) scores in case group.ConclusionsSLE patients who present HA have more PDUS abnormalities. These findings are associated with a higher SLEDAI score and dsDNA antibodies. This articular affection may contribute to a worsened functional ability and a lower quality of life. PDUS seems to be a reliable tool in the assessment of SLE patients with HA.     

Use of proton pump inhibitors and risk of fragility hip fracture in a Mediterranean region

ObjectiveTo determine whether there is an increased risk of hip fracture associated with the use of proton pump inhibitors in a Mediterranean area after adjusting for other potential risk factors.MethodsRetrospective multicenter case–control study carried out in 6 primary health care centers in Catalonia, Spain. Cases were patients aged 50 years and over with a fragility hip fracture registered between January 2007 and December 2010, matched with 2 controls by sex and age. Data collected: use of proton pump inhibitors (type, dosage) in the 5 years previous to the hip fracture, socio-demographic data, body mass index, alcohol and tobacco consumption as well as health conditions and drugs associated with an increase risk of fragility hip fracture.Results358 cases were matched with 698 controls. The mean age was 82 years old in both groups. Women represented 77.1% in the case group and 76.9% in the control group. Crude association between proton pump inhibitors and hip fracture was 1.44 (95% CI, 1.09–1.89) and adjusted OR was 1.24 (95% CI, 0.93–1.65). No association was found with the continuous or discontinuous use of proton pump inhibitors, OR 1.17 (95% CI, 0.77–1.79), and OR of 1.16 (95% CI, 0.85–1.60) respectively. No association was found when restricting the analysis by sex, OR of 1.19 (95% CI, 0.27–5.14) or by age, younger or older than 80 years, OR of 0.72 (95% CI, 0.24–2.15).ConclusionThe use of proton pump inhibitors was not associated with an increased risk of hip fracture after adjusting for other risk factors in a Mediterranean area. This result suggests the existence of protective environmental factors linked to this southern area of Europe that eventually could compensate for the potential harm produced by proton pump inhibitors.     

Association of ADHD symptoms and social competence with cognitive status in preschoolers

We aimed to investigate the association of attention-deficit hyperactivity disorder (ADHD) symptoms and social competence outcomes with cognitive status in preschool children. The study population was drawn from three birth cohorts belonging to the Spanish INMA (Infancia y Medio Ambiente) project: Menorca (n = 289), Ribera d’Ebre (n = 60), and Granada (n = 108). Children were assessed at the age of 4 years for cognitive functions (McCarthy Scales of Children’s Abilities, MSCA) by psychologists and for inattention and hyperactivity symptoms (ADHD Criteria of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, ADHD-DSM-IV) and social competence (California Preschool Social Competence Scale) by their teachers. Multiple regression analyses were conducted to examine potential associations between behavioral outcomes (ADHD symptoms and social competence) and MSCA cognitive outcomes, adjusting for confounders. The presence of general ADHD symptoms (inattention, hyperactivity, or both) and poorer social competence both showed negative associations with cognitive outcomes. When we compared children according to ADHD subtypes, those with inattention symptoms alone and those with both inattention and hyperactivity symptoms showed significantly lower cognitive function scores in comparison to children with no ADHD symptoms. Behavioral dysfunctions in preschoolers may be associated with impairment of cognitive functions.     

Muscle MRI characteristic pattern for late-onset TK2 deficiency diagnosis

Journal of Neurology - TK2 deficiency (TK2d) is a rare mitochondrial disorder that manifests predominantly as a progressive myopathy with a broad spectrum of severity and age of onset. The rate of...     

Prognostic value of cutaneous reinnervation with GAP-43 in oxaliplatin-induced neuropathy

Journal of Neurology - Oxaliplatin-induced neuropathy (OIN) implies axonal damage of both small and large sensory nerve fibers. We aimed at comparing the neurophysiological changes occurred after...     

In vivo imaging of system xc- as a novel approach to monitor multiple sclerosis

Purpose

Glutamate excitotoxicity contributes to oligodendroglial and axonal damage in multiple sclerosis pathology. Extracellular glutamate concentration in the brain is controlled by cystine/glutamate antiporter (system xc-), a membrane antiporter that imports cystine and releases glutamate. Despite this, the system xc^? activity and its connection to the inflammatory reaction in multiple sclerosis (MS) is largely unknown.

Methods

Longitudinal in vivo magnetic resonance (MRI) and positron emission tomography (PET) imaging studies with 2-[¹⁸F]Fluoro-2-deoxy-D-glucose ([¹⁸F]FDG), [¹¹C]-(R)-(1-(2-chlorophenyl)-N-methyl-N-1(1-methylpropyl)-3-isoquinolinecarboxamide ([¹¹C]PK11195) and (4S)-4-(3-¹⁸F-fluoropropyl)-L-glutamate ([¹⁸F]FSPG) were carried out during the course of experimental autoimmune encephalomyelitis (EAE) induction in rats.

Results

[¹⁸F]FSPG showed a significant increase of system xc^? function in the lumbar section of the spinal cord at 14 days post immunization (dpi) that stands in agreement with the neurological symptoms and ventricle edema formation at this time point. Likewise, [¹⁸F]FDG did not show significant changes in glucose metabolism throughout central nervous system and [¹¹C]PK11195 evidenced a significant increase of microglial/macrophage activation in spinal cord and cerebellum 2 weeks after EAE induction. Therefore, [¹⁸F]FSPG showed a major capacity to discriminate regions of the central nervous system affected by the MS in comparison to [¹⁸F]FDG and [¹¹C]PK11195. Additionally, clodronate-treated rats showed a depletion in microglial population and [¹⁸F]FSPG PET signal in spinal cord confirming a link between neuroinflammatory reaction and cystine/glutamate antiporter activity in EAE rats.

Conclusions

Altogether, these results suggest that in vivo PET imaging of system xc^? could become a valuable tool for the diagnosis and treatment evaluation of MS.