New scenarios in secondary hyperparathyroidism: etelcalcetide. Position paper of working group on CKD-MBD of the Italian Society of Nephrology

Bone mineral abnormalities (defined as Chronic Kidney Disease Mineral Bone Disorder; CKD-MBD) are prevalent and associated with a substantial risk burden and poor prognosis in CKD population. Several lines of evidence support the notion that a large proportion of patients receiving maintenance dialysis experience a suboptimal biochemical control of CKD-MBD. Although no study has ever demonstrated conclusively that CKD-MBD control is associated with improved survival, an expanding therapeutic armamentarium is available to correct bone mineral abnormalities. In this position paper of Lombardy Nephrologists, a summary of the state of art of CKD-MBD as well as a summary of the unmet clinical needs will be provided. Furthermore, this position paper will focus on the potential and drawbacks of a new injectable calcimimetic, etelcalcetide, a drug available in Italy since few months ago

Collaborative research on the ecology and management of the 'Wulo' monsoon rainforest in Wunambal Gaambera Country, North Kimberley, Australia

Indigenous groups are increasingly combining traditional ecological knowledge and Western scientific approaches to inform the management of their lands. We report the outcomes of a collaborative research project focused on key ecological questions associated with monsoon vine thickets in Wunambal Gaambera country (Kimberley region, Western Australia). The study mapped monsoon rainforests and analysed the environmental correlates of their current distribution, as well as the historical drivers of patch dynamics since 1949. Remote sensing was used to chart the effectiveness of an intervention designed to re-instate Aboriginal fire regimes according to customary principles. We identified the most vulnerable patches based on size, distance from neighbouring patches, and fire frequency. More than 6000 rainforest patches were mapped. Most were small (<1 ha), occurring predominantly on nutrient-rich substrates (e.g., basalt) and fire-sheltered topographic settings (e.g., slopes and valleys). Rainforests with low fire frequency and no cattle were more likely to expand into surrounding long-unburnt savannas. Frequent fires and cattle did not cause substantial contraction, although the latter affected rainforest understories through trampling. Fire management performed by Aboriginal rangers effectively shifted fire regimes from high-intensity late dry season fires to early dry season fires, particularly in areas with clusters of vulnerable rainforests. The remote sensing methods developed in this project are applicable to the long-term monitoring of rainforest patches on Aboriginal-managed land in North Kimberley, providing tools to evaluate the impacts of fire management, feral animal control, and climate change. The study confirmed the importance of the cattle-free and rarely burnt Bougainville Peninsula as one of the most important rainforest areas in Western Australia

Effect of oral anticoagulant therapy on mortality in end-stage renal disease patients with atrial fibrillation : a prospective study

Background The aim of this study was to evaluate, in a cohort of haemodialysis patients with atrial fibrillation (AF), the relationship between oral anticoagulant therapy (OAT) and mortality, thromboembolic events and haemorrhage. Methods Two hundred and ninety patients with AF were prospectively followed for 4 years. Warfarin and antiplatelet intake, age, dialytic age, comorbidities, CHA2DS2-VASc and HAS-BLED scores were considered as predictors of risk of death, thromboembolism and bleeding events. In patients taking OAT, the international normalized ratio (INR) was assessed and the percentage time in the target therapeutic range (TTR) was calculated. Results At recruitment, 134/290 patients were taking warfarin. During follow-up there were 170 deaths, 28 thromboembolic events and 95 bleedings. After balancing for treatment propensity, intention-to-treat analysis on OAT intake at recruitment did not show differences in total mortality, thromboembolic events and bleedings, while the as-treated analysis, accounting for treatment switch, showed that patients taking OAT at recruitment had a significantly lower mortality than those not taking it [hazard ratio, HR 0.53 (95% confidence interval 0.28\u20130.90), p\u2009=\u20090.04], with a decrease of thromboembolic events [HR 0.36 (0.13\u20131.05), p\u2009=\u20090.06], and an increase of bleedings [HR 1.79 (0.72\u20134.39), p\u2009=\u20090.20], both non-significant. Among patients taking OAT at recruitment, those continuing to take warfarin had a significant reduction in the risk of total [HR 0.28 (0.14\u20130.53), p\u2009<\u20090.001] and cardiovascular [HR 0.21 (0.11\u20130.40), p\u2009<\u20090.001] mortality compared to patients stopping OAT. Conclusions In haemodialysis patients with AF, continuously taking warfarin is associated with a reduction of the risk of total and cardiovascular mortality

Warfarin use, mortality, bleeding and stroke in haemodialysis patients with atrial fibrillation

OBACKGROUND: Oral anticoagulation therapy (OAT) is the choice treatment for thromboembolism prevention in atrial fibrillation (AF), although data about OAT use in haemodialysis (HD) patients with AF are contradictory. METHODS: The effect of OAT on the risk of mortality, stroke and bleeding was prospectively evaluated in a population of HD patients with AF. All the patients of 10 HD Italian centres alive on 31 October 2010 with documented AF episode(s) were recruited and followed-up for 2 years. OAT and antiplatelet intake, age, dialytic age, comorbidities and percentage time in the target international normalized ratio (INR) range (target therapeutic range; TTR) were considered as predictors of hazard of death, thromboembolic and bleeding events. RESULTS: At recruitment, 134 patients out of 290 were taking OAT. During the follow-up, 115 patients died (4 strokes, 3 haemorrhagic and 1 thromboembolic). Antiplatelet therapy, but not OAT, was associated with increased mortality (HR 1.71, CI 1.10-2.64, P = 0.02). The estimated survival of patients always taking OAT tended to be higher than that of patients who stopped taking (68.6 versus 49.6%, P = 0.07). OAT was not correlated to a significant decreased risk of thromboembolic events (HR 0.12, CI 0.00-3.59, P = 0.20), while it was associated with an increased risk of bleeding (HR 3.96, CI 1.15-13.68, P = 0.03). Higher TTR was associated with a reduced bleeding risk (HR 0.09, CI 0.01-0.76, P = 0.03), while previous haemorrhagic events were associated with higher haemorrhagic risk (HR 2.17, CI 1.09-4.35, P = 0.03). CONCLUSIONS: In our population of HD patients with AF, the mortality is very high. OAT is not associated with increased mortality, while antiplatelet drugs are. OAT seems, on the contrary, associated with a better survival; however, it does not decrease the incidence of ischaemic stroke, whereas it increases the incidence of bleeding. Bleeding risk is lower in subjects in whom the INR is kept within the therapeutic range

New scenarios in secondary hyperparathyroidism: etelcalcetide. Position paper of working group on CKD-MBD of the Italian Society of Nephrology

Bone mineral abnormalities (defined as Chronic Kidney Disease Mineral Bone Disorder; CKD-MBD) are prevalent and associated with a substantial risk burden and poor prognosis in CKD population. Several lines of evidence support the notion that a large proportion of patients receiving maintenance dialysis experience a suboptimal biochemical control of CKD-MBD. Although no study has ever demonstrated conclusively that CKD-MBD control is associated with improved survival, an expanding therapeutic armamentarium is available to correct bone mineral abnormalities. In this position paper of Lombardy Nephrologists, a summary of the state of art of CKD-MBD as well as a summary of the unmet clinical needs will be provided. Furthermore, this position paper will focus on the potential and drawbacks of a new injectable calcimimetic, etelcalcetide, a drug available in Italy since few months ago

Measuring and Estimating GFR and Treatment Effect in ADPKD Patients: Results and Implications of a Longitudinal Cohort Study

Trials failed to demonstrate protective effects of investigational treatments on glomerular filtration rate (GFR) reduction in Autosomal Dominant Polycystic Kidney Disease (ADPKD). To assess whether above findings were explained by unreliable GFR estimates, in this academic study we compared GFR values centrally measured by iohexol plasma clearance with corresponding values estimated by Chronic Kidney Disease Epidemiology Collaboration (CKD-Epi) and abbreviated Modification of Diet in Renal Disease (aMDRD) formulas in ADPKD patients retrieved from four clinical trials run by a Clinical Research Center and five Nephrology Units in Italy. Measured baseline GFRs and one-year GFR changes averaged 78.6±26.7 and 8.4±10.3 mL/min/1.73 m2 in 111 and 71 ADPKD patients, respectively. CKD-Epi significantly overestimated and aMDRD underestimated baseline GFRs. Less than half estimates deviated by <10% from measured values. One-year estimated GFR changes did not detect measured changes. Both formulas underestimated GFR changes by 50%. Less than 9% of estimates deviated <10% from measured changes. Extent of deviations even exceeded that of measured one-year GFR changes. In ADPKD, prediction formulas unreliably estimate actual GFR values and fail to detect their changes over time. Direct kidney function measurements by appropriate techniques are needed to adequately evaluate treatment effects in clinics and research

Sudden Death in End Stage Renal Disease : Comparing Hemodialysis versus Peritoneal Dialysis

Background/Aims: This study aimed to evaluate total and sudden death (SD) in a cohort of dialysis patients, comparing hemodialysis (HD) vs. peritoneal dialysis (PD). Methods: This is a multicenter retrospective cohort study. Results: Deaths were 626 out of 1,823 in HD and 62 of 249 in PD patients. HD patients had a greater number of comorbidities (p < 0.05). PD patients had a lower risk of death than HD patients (p < 0.001); however, the advantage decreased with time (p < 0.001). Mortality predictors were left ventricular ejection fraction (LVEF) \ue2\u89\ua435%, older age, ischemic heart disease, diabetes mellitus, previous stroke, and atrial fibrillation (p < 0.03). SDs were 84:71 in HD and 13 in PD population (12.1 and 22.8% of all causes of death, respectively). A non-significant risk of SD among PD compared to HD patients was detected. SD predictors were older age, ischemic heart disease, and LVEF \ue2\u89\ua435% (p < 0.05). Conclusions: HD patients showed a greater presence of comorbidities and reduced survival compared to PD patients; however, the incidence of SD does not differ in the 2 populations. Video Journal Club "Cappuccino with Claudio Ronco" at http://www.karger.com/?doi=464347

Micromechanical Properties of Injection-Molded Starch–Wood Particle Composites

The micromechanical properties of injection molded starch–wood particle composites were investigated as a function of particle content and humidity conditions. The composite materials were characterized by scanning electron microscopy and X-ray diffraction methods. The microhardness of the composites was shown to increase notably with the concentration of the wood particles. In addition,creep behavior under the indenter and temperature dependence were evaluated in terms of the independent contribution of the starch matrix and the wood microparticles to the hardness value. The influence of drying time on the density and weight uptake of the injection-molded composites was highlighted. The results revealed the role of the mechanism of water evaporation, showing that the dependence of water uptake and temperature was greater for the starch–wood composites than for the pure starch sample. Experiments performed during the drying process at 70°C indicated that the wood in the starch composites did not prevent water loss from the samples.Peer reviewe

Evaluation of HPFH and δβ-thalassemia mutations in a Brazilian group with high Hb F levels.

Fetal hemoglobin (Hb F) is characteristic of the fetal development period. However, in some genetic conditions, such as hereditary persistence of fetal hemoglobin (HPFH) and delta-beta thalassemia (δβ-thalassemia), Hb F continues to be produced in adulthood. We evaluated the frequency of two mutations of HPFH, HPFH-1 and HPFH-2 African, and two mutations in δβ-thalassemia, Sicilian and Spanish, in a Brazilian population. Peripheral blood samples were collected from adults from hospitals and blood centers in southeast and northeast Brazil. These individuals were healthy and without complaints of anemia, but had increased Hb F. Samples were submitted to electrophoretic and chromatographic analyses to quantify Hb F values and, subsequently, to molecular analyses to verify the mutations. In the molecular analysis, 16 of the 60 samples showed a heterozygous profile for the HPFH mutations, two for HPFH-1 and 14 for HPFH-2. In the same sample set, three were heterozygous for Spanish δβ-thalassemia and none were heterozygous for Sicilian δβ- thalassemia. The Hb F values in the HPFH-2 heterozygotes differed from those previously reported for this mutation. In this group, the HPFH mutations were more frequent than the δβ-thalassemia mutations. The finding of these mutations in this Brazilian population reflects the mixing process that occurred during its formation