The anticoagulant effect of heparin during radiofrequency ablation (RFA) in patients taking apixaban or rivaroxaban.

PURPOSE: Measuring the anticoagulant effect of heparin during radiofrequency ablation (RFA) in patients taking apixaban and rivaroxaban is challenging, since the activated coagulation time (ACT) does not seem to reflect the true anticoagulant activity of these drugs. We therefore evaluated coagulation properties of apixaban and rivaroxaban during RFA by different coagulation assays to better monitor periprocedural hemostasis. METHODS: The study included 90 patients (61 ± 12 years) with atrial fibrillation who underwent RFA procedures. Patients received 20 mg rivaroxaban (n = 73) once or 5 mg apixaban (n = 17) twice daily 4 weeks prior to the procedure. During RFA, unfractionated heparin i.v. was given to maintain an ACT of 250-300 s. Blood samples were taken before and 10, 60, and 360 min after heparin administration. RESULTS: Heparin displayed a lower anti-Xa activity in rivaroxaban-treated patients compared to apixaban-treated patients. In contrast, D-dimer and prothrombin fragment F1+2 plasma levels indicated a higher activation of the coagulation cascade in apixaban/heparin than in rivaroxaban/heparin patients. This discordant coagulative state measured in vitro had no clinical impact in terms of bleeding or thromboembolic complications. CONCLUSION: We found different biochemical responses to rivaroxaban/heparin and apixaban/heparin during RFA. Precaution is necessary when monitoring periprocedural hemostasis in DOAC patients to avoid mismanagement.

Effect of the FXa inhibitors Rivaroxaban and Apixaban on platelet activation in patients with atrial fibrillation.

Rivaroxaban and Apixaban, increasingly used for stroke prevention in non-valvular atrial fibrillation (AF), might impact platelet reactivity directly or indirectly. By inhibition of Factor Xa (FXa) they preclude not only generation of relevant thrombin amounts but also block signalling of FXa via protease activated receptors. However, weather FXa-inhibition affects platelet haemostasis remains incompletely known. One hundred and twenty-eight patients with AF on chronic anticoagulation with either Rivaroxaban or Apixaban for at least 4 weeks were included in the study. In a time course group (25 on Rivaroxaban, 13 on Apixaban) venous blood samples were taken before NOAC medication intake in the morning as well as 2 and 6 h afterwards. In 90 patients (Rivaroxaban n = 73, Apixaban n = 17) blood samples were drawn during left atrial RFA procedures before as well as 10 and 60 min after the first heparin application (RFA group). Platelet reactivity analyzed by whole blood aggregometry (Multiplate Analyzer, Roche) in response to ADP, Collagen, TRAP and ASPI (arachidonic acid) was not altered by Rivaroxaban or Apixaban neither in the time course nor in the RFA group. Moreover, soluble P-selectin, Thrombospondin, von Willebrand Factor and beta thromboglobulin plasma levels, measured by ELISA, showed no statistically significant changes in both clinical settings for either FXa-inhibitor. The present study fails to demonstrate any significant changes on platelet reactivity in patients with AF under chronic Rivaroxaban or Apixaban medication, neither for trough or peak levels nor in case of a haemostatic activation in vivo as depicted by RFA procedures.

Anisotropy of electromigration-induced void and island drift.

By means of our novel self-learning kinetic Monte Carlo model (Latz et al 2012 J. Phys.: Condens. Matter 24 485005) we study the electromigration-induced drift of monolayer voids and islands on unpassivated surfaces of single crystalline Ag(111) and Ag(001) films at the atomic scale. Regarding the drift velocity, we find a non-monotonic size dependence for small voids. The drift direction is aligned with the electromigration force only along high symmetry directions, while halfway between, the angle enclosed by them is maximal. The magnitude of these directional deviations strongly depends on the system parameter, which are investigated in detail. The simulation results are in accordance with void motion observed in experiments performed on Ag(111).

Strength and failure of cemented granular matter.

Cemented granular materials (CGMs) consist of densely packed solid particles and a pore-filling solid matrix sticking to the particles. We use a sub-particle lattice discretization method to investigate the particle-scale origins of strength and failure properties of CGMs. We show that jamming of the particles leads to highly inhomogeneous stress fields. The stress probability density functions are increasingly wider for a decreasing matrix volume fraction, the stresses being more and more concentrated in the interparticle contact zones with an exponential distribution as in cohesionless granular media. Under uniaxial loading, pronounced asymmetry can occur between tension and compression both in strength and in the initial stiffness as a result of the presence of bare contacts (with no matrix interposed) between the particles. Damage growth is analyzed by considering the evolution of stiffness degradation and the number of broken bonds in the particle phase. A brutal degradation appears in tension as a consequence of brittle fracture in contrast to the more progressive nature of damage growth in compression. We also carry out a detailed parametric study in order to assess the combined influence of the matrix volume fraction and particle-matrix adherence. Three regimes of crack propagation can be distinguished corresponding to no particle damage, particle abrasion and particle fragmentation, respectively. We find that particle damage scales well with the relative toughness of the particle-matrix interface with respect to the particle toughness. This relative toughness is a function of both matrix volume fraction and particle-matrix adherence and it appears therefore to be the unique control parameter governing transition from soft to hard behavior.

Antagonistic and agonistic GnRH analogue treatment of precocious puberty: tracking gonadotropin concentrations in urine.

BACKGROUND: The pharmacodynamics of gonadotropin-releasing hormone (GnRH) agonists includes an initial 'flare-up' of the pituitary-gonadal axis, followed by reduced luteinizing hormone (LH) secretion. The question is if combining a short-acting antagonist with a long-acting agonist can diminish gonadotropin flare-up. METHODS: To achieve quick downregulation in patients with recently diagnosed central precocious puberty (CPP, 7 patients) or short stature with short predicted final height (3 patients), we combined the GnRH antagonist cetrorelix (3 subcutaneous injections every 72 h) at the beginning of GnRH agonist treatment (leuprorelin or triptorelin) in 6 patients and compared the effect to 4 patients treated solely with GnRH agonist. To monitor effects, we measured LH and FSH concentrations in urine collected from initial morning urination during the first month of treatment. RESULTS: In both treatment groups, gonadotropin flare-up could be detected in urine levels increased due to the flare-up phenomenon which was of short duration (<5 days) in the majority (5 of 6) of combined-treated patients and in the minority (1 of 4) of patients treated by agonist alone. During the first 10 days of treatment, mean LH concentration measured in urine was significantly lower in 4 CPP patients treated by the combined therapy compared to 3 CPP patients treated by the agonist only (mean LH combined therapy: 10.4 +/- 2.8 vs. 20.1 +/- 11.0 mU/ml in the agonist-only group, mean +/- SEM, p < 0.05). Significant correlations between stimulated serum LH in GnRH test prior to treatment and maximum urine LH after initiating GnRH analogue treatment (r = 0.547, p = 0.043), as well as basal serum LH and basal urine LH (r = 0.685, p = 0.014) were found. CONCLUSION: Combined GnRH agonist and antagonist treatment led to rapid gonadotropin suppression. Also, urine measurements of LH and FSH seemed suitable for monitoring gonadotropin-inhibiting or -stimulating properties of GnRH analogues in individual patients. However, a controlled trial of a larger patient cohort is required to decide which treatment is the most effective.

Elastic behavior in contact dynamics of rigid particles.

The systematic errors due to the practical implementation of the contact dynamics method for simulation of dense granular media are examined. It is shown that, using the usual iterative solver to simulate a chain of rigid particles, effective elasticity and sound propagation with a finite velocity occur. The characteristics of these phenomena are investigated analytically and numerically in order to assess the limits of applicability of this simulation method and to compare it with soft particle molecular dynamics.

The effect of human growth hormone therapy on L-(methyl-2H3)-leucine turnover and urinary pseudouridine concentration in patients with Ullrich-Turner syndrome.

UNLABELLED: The effect of daily human growth hormone (hGH) injections (3 I.U./m2/day) on tissue anabolism was determined in six patients with Ullrich-Turner syndrome (XO) (8.7-19 years of age) using novel techniques such as whole body leucine kinetics during continuous infusion of L-(Methyl-2H3)-leucine and urinary pseudouridine (5-ribosyluracil) excretion on the one hand and traditional methods like serum urea and amino acid concentrations on the other. Pseudouridine is only found in ribonucleic acid (RNA) and is neither reincorporated nor catabolically broken down and is therefore considered an ideal index of whole body RNA turnover. The mean L-(Methyl-2H3)-leucine turnover of the six XO patients before hGH was 1.90 +/- 0.15 mumoles/kg per minute. After 3 months of hGH-treatment it had increased in three patients, whereas it had decreased in the other three. The results obtained with the stable isotope technique were correlated with the urinary pseudouridine concentrations (r = 0.68; P < 0.01). The growth rates were positively correlated with leucine turnover (r = 0.63; P < 0.02) and urinary pseudouridine concentration (r = 0.73; P < 0.006) as well as negatively correlated with the serum urea concentrations r = -0.62; P < 0.03). The decrease in the individual serum urea concentrations were tightly correlated with the hGH induced change in growth rate (r = -0.90; P < 0.01). The individual bone ages were negatively correlated with the hGH induced changes in leucine turnover (r = -0.77; P < 0.003) as well as with the urinary pseudouridine concentrations (r = -0.87; P < 0.0002). The hGH effect on leucine and RNA turnover, showing effectiveness only until a developmental age between 11 and 12 years, leads the discussion of the ideal moment of oestrogen supplementation when girls with Ullrich-Turner syndrome are treated with hGH in early adolescence. CONCLUSION: The protein metabolism of patients with Ullrich-Turner syndrome is influenced by hGH in an age dependent manner. In a clinical setting, pseudouridine, an easily determined derivative of ribonucleic acids, may be able to replace the tedious work with expensive stable isotopes when questions related to tissue anabolism are to be answered.