Resolving Concerns With the Newer Oral Anticoagulant Medications: Is Hepatotoxicity a Real Concern?

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Caval Valve Implantation for Treatment of Severe Tricuspid Regurgitation

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Etidronate for Prevention of Ectopic Mineralization in Patients With Pseudoxanthoma Elasticum

AbstractBackground

In pseudoxanthoma elasticum (PXE), low pyrophosphate levels may cause ectopic mineralization, leading to skin changes, visual impairment, and peripheral arterial disease.

Objectives

The authors hypothesized that etidronate, a pyrophosphate analog, might reduce ectopic mineralization in PXE.

Methods

In the Treatment of Ectopic Mineralization in Pseudoxanthoma Elasticum trial, adults with PXE and leg arterial calcifications (n = 74) were randomly assigned to etidronate or placebo (cyclical 20 mg/kg for 2 weeks every 12 weeks). The primary outcome was ectopic mineralization, quantified with ¹⁸fluoride positron emission tomography scans as femoral arterial wall target-to-background ratios (TBR_femoral). Secondary outcomes were computed tomography arterial calcification and ophthalmological changes. Safety outcomes were bone density, serum calcium, and phosphate.

Results

During 12 months of follow-up, the TBR_femoral increased 6% (interquartile range [IQR]: –12% to 25%) in the etidronate group and 7% (IQR: –9% to 32%) in the placebo group (p = 0.465). Arterial calcification decreased 4% (IQR: –11% to 7%) in the etidronate group and increased 8% (IQR: –1% to 20%) in the placebo group (p = 0.001). Etidronate treatment was associated with significantly fewer subretinal neovascularization events (1 vs. 9, p = 0.007). Bone density decreased 4% ± 12% in the etidronate group and 6% ± 9% in the placebo group (p = 0.374). Hypocalcemia (<2.20 mmol/l) occurred in 3 versus 1 patient (8.1% vs. 2.7%, p = 0.304). Eighteen patients (48.6%) treated with etidronate, compared with 0 patients treated with placebo (p < 0.001), experienced hyperphosphatemia (>1.5 mmol/l) and recovered spontaneously.

Conclusions

In patients with PXE, etidronate reduced arterial calcification and subretinal neovascularization events but did not lower femoral ¹⁸fluoride sodium positron emission tomography activity compared with placebo, without important safety issues. (Treatment of Ectopic Mineralization in Pseudoxanthoma elasticum; NTR5180)

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Lesion Complexity and Prolonged Antiplatelet Therapy: The Missing Variable to Complete the Puzzle

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Vascular Mineralization in Pseudoxanthoma Elasticum: Etidronate to the Rescue?

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Learning rules for aversive associative memory formation

Publication date: April 2018
Source:Current Opinion in Neurobiology, Volume 49
Author(s): Takaaki Ozawa, Joshua P Johansen
For survival, organisms need the ability to flexibly modify their behavior. To achieve this, the brain is equipped with instructive brain circuits which trigger changes in neural connectivity and adaptive changes in behavior in response to environmental/internal challenges. Recent studies using a form of aversive associative learning termed fear conditioning have shed light on the neural mechanisms of instructive signaling. These studies demonstrate that fear learning is engaged through multiple, parallel aversive signaling pathways to the amygdala. Consistent with theoretical accounts of learning, activity in these circuits and behavioral learning is tightly regulated by the predictability of the aversive experience. However, in more complex learning conditions, these emotion circuits use a form of inference to approximate the appropriate reaction to danger. This suggests a revised view of how emotional learning systems represent aversive associations and how changes in these representations are instructed during learning.



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Sex differences in the regulation of social and anxiety-related behaviors: insights from vasopressin and oxytocin brain systems

Publication date: April 2018
Source:Current Opinion in Neurobiology, Volume 49
Author(s): Remco Bredewold, Alexa H Veenema
To understand how the brain regulates behavior, many variables must be taken into account, with sex as a prominent variable. In this review, we will discuss recent human and rodent studies showing the sex-specific involvement of the neuropeptides vasopressin and oxytocin in social and anxiety-related behaviors. We discuss that sex differences can be evident at pre-pubertal ages as seen in the sex-specific regulation of social recognition, social play, and anxiety by the vasopressin system in juvenile rats. We further discuss that the oxytocin system in humans and rodents alters brain activation, anxiety, and sociosexual motivation in sex-specific ways. Finally, we propose that knowledge of vasopressin and oxytocin mediated sex-specific brain mechanisms can provide essential insights into how these neuropeptide systems contribute to sex-specific vulnerability as well as resilience to perturbations, with subsequent relevance to social and emotional disorders.



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