A Novel Hybrid Injectable for Soft-tissue Augmentation: Analysis of Data and Practical Experience.

Background: HA/CaHa (HArmonyCa, Allergan Aesthetics, an AbbVie Company) is a hybrid injectable filler developed for aesthetic purposes that contains calcium hydroxyapatite microspheres suspended in a hyaluronic acid gel. This review describes preclinical and clinical data, recommendations for use based on the primary author's clinical experience, and case studies that illustrate implementation of product use recommendations and patient outcomes. Methods: Preclinical data on the lift capacity and tissue integration of the HA/CaHa hybrid injectable and clinical data on its safety, efficacy, and real-world use were extracted from poster presentations, published literature, manufacturer instructions for use, and proprietary data files. Case studies were presented based on clinical experience. Results: The HA component of HA/CaHa provides an immediate and noticeable filling and lifting effect, whereas CaHa microspheres result in neocollagenesis. In preclinical studies, HA/CaHa demonstrated higher lift capacity (P < 0.05) and faster tissue integration than a CaHa filler and led to collagen I gene and protein expression. Clinical studies showed clinical safety and effectiveness with high patient satisfaction. The most common adverse event was injection-site response. Clinician recommendations for achieving desired aesthetic results while minimizing or preventing adverse events are reviewed, including patient selection and assessment, treatment approaches based on face shape, injection technique, and postprocedure care. Conclusion: The novel hybrid injectable consisting of HA with incorporated CaHa microspheres in a single marketed product may help achieve aesthetic goals by immediately restoring volume and potentially improving skin architecture and soft-tissue quality over time.

APOE4 accelerates advanced-stage vascular and neurodegenerative disorder in old Alzheimer's mice via cyclophilin A independently of amyloid-ß.

Apolipoprotein E4 (APOE4), the main susceptibility gene for Alzheimer's disease (AD), leads to vascular dysfunction, amyloid-ß pathology, neurodegeneration and dementia. How these different pathologies contribute to advanced-stage AD remains unclear. Using aged APOE knock-in mice crossed with 5xFAD mice, we show that, compared to APOE3, APOE4 accelerates blood-brain barrier (BBB) breakdown, loss of cerebral blood flow, neuronal loss and behavioral deficits independently of amyloid-ß. BBB breakdown was associated with activation of the cyclophilin A-matrix metalloproteinase-9 BBB-degrading pathway in pericytes. Suppression of this pathway improved BBB integrity and prevented further neuronal loss and behavioral deficits in APOE4;5FAD mice while having no effect on amyloid-ß pathology. Thus, APOE4 accelerates advanced-stage BBB breakdown and neurodegeneration in Alzheimer's mice via the cyclophilin A pathway in pericytes independently of amyloid-ß, which has implication for the pathogenesis and treatment of vascular and neurodegenerative disorder in AD.