The Impact of Gel Parameters on the Dispersal and Fragmentation of Hyaluronic Acid Gel Fillers within an Artificial Model of Arterial Embolism.

Accidental arterial embolization of hyaluronic acid (HA) fillers can lead to severe complications, including skin ischemia, blindness, and stroke. Currently, the intra-arterial dispersal and fragmentation behavior of HA gels is unknown but critical to our understanding of the pathomechanism of these injuries. This work introduces the Pulsatile Unit for the Laboratory Simulation of Arterio-embolic Restrictions (PULSAR) and evaluates the intravascular behavior of different HA gels. The fragmentation and dispersal behaviors of four HA gels with distinct rheological properties were evaluated via high-resolution videography and ImageJ particle size and morphology analysis. The gels' elastic modulus (G'), loss modulus (G″), tan(δ), and HA concentration were subsequently correlated with their intra-arterial behaviors. This study effectively confirms the extensive fragmentation of HA gels upon arterial inoculation, with particle sizes ranging from <50 µm to >1 mm. Gel particle size and morphology correlated most significantly with tan(δ). Conversely, arterial flow rates did not significantly influence gel fragmentation behavior, though the probability of proximal, macrovascular obstruction was affected. Overall, this study validates the PULSAR model for simulation of arterial dynamics and the testing of intravascular filler kinematics. The findings demonstrate the ability of gels to microfragment and disseminate distally, as well as induce partial proximal occlusion depending on gel rheology and arterial flow parameters.

Comparative Rheology of Hyaluronic Acid Fillers, Poly-l-lactic Acid, and Varying Dilutions of Calcium Hydroxylapatite.

Background: This study examines the rheological properties of various dermal fillers, including hyaluronic acid (HA) fillers, poly-L-lactic acid (PLLA), and calcium hydroxylapatite-carboxymethylcellulose (CaHA-CMC) gels, with a particular focus on the impact of aqueous dilution on CaHA-CMC's rheology and potential clinical implications. Methods: Using standardized rheological analysis, we measured and compared the elastic modulus (G'), viscous modulus (G″), and the tan δ values of different dilutions of CaHA-CMC against published values of HA and PLLA fillers. The study aimed to determine the potential clinical use of application-specific CaHA-CMC hydrogel dilutions along a range of gel strength and cohesion for hydrogel fillers in current use. Results: The findings demonstrate that CaHA-CMC's rheological properties can be tailored across a broad spectrum of viscoelastic parameters through titrated dilution, ranging from high elasticity to low cohesion. Varying the aqueous volume allows for the rheomodulation of CaHA-CMC, potentially matching the entire rheological spectrum of HA fillers and suggesting an expanded range of clinical applications. Conclusions: The versatility of CaHA-CMC through dilution may offer a customizable approach for clinical applications, providing practitioners with the ability to fine-tune the properties of fillers to meet specific patient needs and treatment goals. This study lays the groundwork for the potential future use of filler dilutional rheomodulation in clinical practice, tailored to patient- and application-specific needs.

Hyperdiluting Calcium Hydroxylapatite With Platelet-Rich Plasma and Hyaluronidase for Improving Neck Laxity and Wrinkle Severity.

The two cases discussed in this report investigate the efficacy and safety of a novel injectable therapy for treating neck wrinkles and skin laxity, utilizing a combination of hyperdiluted calcium hydroxylapatite (CaHA), platelet-rich plasma (PRP), and hyaluronidase. Two patients presenting with moderate neck wrinkles and laxity underwent treatment and were evaluated several months later. The combined therapy demonstrated improvements in skin texture and laxity following a single treatment. The rationale behind incorporating PRP and hyaluronidase was their potential to amplify the regenerative effects of CaHA. PRP contains growth factors that stimulate collagen production and tissue regeneration while hyaluronidase facilitates the breakdown of hyaluronic acid, promoting better diffusion and more even product dispersion. The findings from these cases provide emerging preliminary evidence supporting the safety and efficacy of this innovative combination therapy for addressing neck wrinkles and laxity. This is the first documented instance of skin priming CaHA with hyaluronidase and PRP. Future investigations are warranted to explore the application of this treatment for other anatomical regions and to delineate the role of each injected component.

Improved brachial skin hydration and appearance with hyperdiluted calcium hydroxylapatite.

INTRODUCTION: The search for minimally invasive treatments for areas not covered by clothing, such as the arms, has increased, particularly to combat flaccidity resulting from factors such as aging and weight loss. This study evaluated the efficacy of calcium hydroxyapatite (CaHA), an injectable biostimulator, in improving flaccidity and hydration of the skin of the arms. MATERIALS AND METHODS: Six women between 40 and 50 years old with visible signs of brachial flaccidity were selected. Calcium hydroxyapatite was injected into the arms in a 1:4 dilution (1.5 mL per side), with subjective evaluation based on the GAIS score and objective hydration analysis using corneometry. RESULTS: After a single application of CaHA, there was a significant increase in skin hydration (12.2%), objectively assessed by corneometry. Patient and physician satisfaction was high, evidenced by visible improvements in photographs and by the GAIS score. No significant adverse events were reported, demonstrating the safety of the procedure. DISCUSSION: Our clinical observations confirm the ability of CaHA to visibly improve arm flaccidity. In addition, hydration measures support previous histological studies demonstrating increases in dermal proteoglycans. Compared to other studies, the increase in skin hydration with CaHA was similar to those obtained with hyaluronic acid, suggesting comparable results with a more comfortable and less invasive technique. CONCLUSION: This study demonstrates the efficacy of CaHA in improving hydration of brachial skin after a single treatment. Despite the limitations of the sample size, the research contributes to the medical literature, highlighting the utility of the 3 mL CaHA presentation for brachial treatment with objective results in skin hydration.

A morphological analysis of calcium hydroxylapatite and poly-l-lactic acid biostimulator particles.

Injectable fillers, pivotal in aesthetic medicine, have evolved significantly with recent trends favoring biostimulators like calcium hydroxylapatite (CaHA-CMC; Radiesse, Merz Aesthetics, Raleigh, NC) and poly-l-lactic acid (PLLA; Sculptra Aesthetics, Galderma, Dallas, TX). This study aims to compare the particle morphology of these two injectables and examine its potential clinical implications. Utilizing advanced light and scanning electron microscopy techniques, the physical characteristics of CaHA-CMC and PLLA particles were analyzed, including shape, size, circularity, roundness, aspect ratio, and quantity of phagocytosable particles. The findings reveal several morphological contrasts: CaHA-CMC particles exhibited a smooth, homogenous, spherical morphology with diameters predominantly ranging between 20 and 45 µm, while PLLA particles varied considerably in shape and size, appearing as micro flakes ranging from 2 to 150 µm in major axis length. The circularity and roundness of CaHA-CMC particles were significantly higher compared to PLLA, indicating a more uniform shape. Aspect ratio analysis further underscored these differences, with CaHA-CMC particles showing a closer resemblance to circles, unlike the more oblong PLLA particles. Quantification of the phagocytosable content of both injectables revealed a higher percentage of phagocytosable particles in PLLA. These morphological distinctions may influence the tissue response to each treatment. CaHA-CMC's uniform, spherical particles may result in reduced inflammatory cell recruitment, whereas PLLA's heterogeneous particle morphology may evoke a more pronounced inflammatory response.

Successful Treatment of Noninflammatory CaHA Nodules Using Focused Mechanical Vibration.

Noninflammatory nodules arising from the injection of biostimulatory fillers persist as an unwanted complication. Pathologically, noninflammatory nodules may arise from superficial injection, accidental boluses, or incorrect concentration of microparticles contained within the filler. This case report introduces a method for reversing calcium hydroxylapatite (CaHA) using focused mechanical vibration. An in situ hyperdilution was created by injecting saline into the nodule core to prepare it for resuspension. Topical microneedling was subsequently applied to generate vibrations, aiming to disperse the accumulated CaHA particles. The outcome demonstrated a significant reduction in the size and visibility of the nodule. This combined saline-microneedling approach offers a potential noninvasive, nonpharmacologic solution for managing superficial CaHA nodules.

A Structured Approach for Treating Calcium Hydroxylapatite Focal Accumulations.

BACKGROUND: Radiesse, a widely utilized calcium hydroxylapatite (CaHA) dermal filler, has shown effectiveness in soft tissue augmentation and regeneration. As with all dermal fillers, the potential for nodules may arise. Understanding the pathogenesis of these nodules and exploring effective treatment methodologies are crucial for optimizing patient outcomes. OBJECTIVES: A literature search was carried out to identify published literature documenting reversal of CaHA nodules. After identification, a consensus panel developed a structured approach, denoted by levels, for applying such reversal methods. METHODS: This concise review presents an algorithmic approach to addressing CaHA focal accumulations (noninflammatory nodules) based on invasiveness, cost, and potential risks based on published literature. RESULTS: Level 0 involves no intervention, relying on natural degradation for asymptomatic nodules. Level 1 interventions utilize mechanical dispersion techniques, including massage and in situ dispersion, which have demonstrated high success rates, cost effectiveness, and minimal invasiveness. Level 2 introduces alternative modalities such as pharmacological treatments with 5-fluorouracil and corticosteroids, lasers, and experimental approaches. Level 3 represents last-resort options, including calcium-chelating agents, manual removal, and surgical excision. CONCLUSIONS: The article offers a structured approach to managing CaHA focal accumulations.

Dilutional rheology of Radiesse: Implications for regeneration and vascular safety.

BACKGROUND: Calcium hydroxylapatite-carboxymethylcellulose (CaHA-CMC) injectables have emerged as dual-purpose fillers with bioregenerative and direct filling capabilities. AIMS: This study investigates the rheological properties of CaHA-CMC and its CMC carrier gel at various dilutions. METHODS: The storage modulus (G'), loss modulus (G″), complex viscosity (η*), loss factor (tan δ), cohesivity, and extrusion force were evaluated for a range of CaHA-CMC aqueous dilutions with an oscillatory rheometer, drop weight testing, and force analysis, respectively. RESULTS: Results revealed a significant decrease in G', η*, and increase in tan(δ) with increasing dilution, indicating a decline in the product's direct filling capabilities. Cohesivity decreased dramatically with dilution, potentially enhancing tissue biointegration and the product's biostimulatory effects. The CMC gel carrier displayed inelastic and non-resilient properties, with rheological changes differing from CaHA-CMC. Dilutional rheology was also correlated with previously published dilution-dependent biostimulatory data where hyperdiluted CaHA-CMC (>1:2) demonstrated a regenerative profile and diluted or hypodiluted mixtures retained meaningful filling properties and increased regeneration. CONCLUSIONS: These findings offer a continuum for tailoring the product's rheological profile to match specific tissue requirements. Customizable rheology allows CaHA-CMC to be tuned for either filling and contouring or optimal regenerative effects. Importantly, safety implications related to vascular occlusion suggest that dilutional rheomodulation decreases the risk of vascular events. In conclusion, this study highlights the significant impact of aqueous dilution on the rheological properties of CaHA-CMC and its carrier gel. The findings support the clinical application of tailored dilutions to achieve desired outcomes, providing versatility and safety for aesthetic applications.

Social Interest Data as a Proxy for Off-Label Performance-Enhancing Drug Use: Implications and Clinical Considerations.

Performance-enhancing drugs (PEDs) can be categorized into various classes based on the physiological mechanism of the compound, with the most popular being anabolic steroids, selective androgen receptor modulators, and growth hormones. Ancillary compounds, such as selective estrogen receptor modulators (SERMs) and selective estrogen receptor degraders, are commonly utilized alongside a PED to counterbalance any potential undesired side effects. With little clinically relevant data to support the use of these ancillary compounds, medical education and evidence-based approaches aimed at monitoring the potential adverse effects of PED use are sparse.This study aims to identify emerging trends in the interest of PEDs and related ancillary compounds, hypothesize the physiological effects of the continued respective behavior, and propose a proxy for use by clinicians to approximate off-label drug use and subsequently modify their practices accordingly. Several significant trends were identified for non-FDA-regulated compounds (i.e., selective androgen receptor modulators such as RAD-140) and off-label indications for FDA-regulated drugs (i.e., SERMs such as tamoxifen). A significant increase in interest regarding selective androgen receptor modulators, mirrored by anecdotal reports in clinical settings and online forums, is coupled with stagnant or decreasing interest in both post-cycle therapies and anabolic steroids. Ultimately, we propose a call to action for utilizing social data and/or prescription data as a proxy for clinicians to better understand trends in these compounds and thus refine their treatment protocols in a concordant manner.

Mechanically resilient hybrid aerogels containing fibers of dual-scale sizes and knotty networks for tissue regeneration.

The structure and design flexibility of aerogels make them promising for soft tissue engineering, though they tend to come with brittleness and low elasticity. While increasing crosslinking density may improve mechanics, it also imparts brittleness. In soft tissue engineering, resilience against mechanical loads from mobile tissues is paramount. We report a hybrid aerogel that consists of self-reinforcing networks of micro- and nanofibers. Nanofiber segments physically entangle microfiber pillars, allowing efficient stress distribution through the intertwined fiber networks. We show that optimized hybrid aerogels have high specific tensile moduli (~1961.3 MPa cm3 g-1) and fracture energies (~7448.8 J m-2), while exhibiting super-elastic properties with rapid shape recovery (~1.8 s). We demonstrate that these aerogels induce rapid tissue ingrowth, extracellular matrix deposition, and neovascularization after subcutaneous implants in rats. Furthermore, we can apply them for engineering soft tissues via minimally invasive procedures, and hybrid aerogels can extend their versatility to become magnetically responsive or electrically conductive, enabling pressure sensing and actuation.

Birt-Hogg-Dubé Syndrome: A Rare Genodermatosis Presenting as Skin Papillomas.

The authors present a rare case of Birt-Hogg-Dubé (BHD) syndrome that presented primarily as an aesthetic case. Previous providers failed to accurately diagnose BHD, despite the patient's history of pneumothoraces. This female patient complained of numerous recurrent, small skin-colored growths on the face and neck and patchy hypopigmentation from the multiple treatments she had to undergo for her "bumpy skin." She also suffered 4 spontaneous pneumothoraces. Following histopathologic and genetic testing, the patient was diagnosed with BHD. Computed tomography and ultrasound scans revealed multiple cysts in both lungs and an angiomyolipoma in both kidneys. This patient had undergone a variety of treatments to aesthetically remove and heal her skin bumps from several healthcare providers, all of whom had misdiagnosed her condition.

Social Data: An Underutilized Metric for Determining Participation in COVID-19 Vaccinations.

Many measures have been taken since late 2019 to combat the coronavirus disease (COVID-19) pandemic. National, state, and local governments employed precautions, including mask mandates, stay-at-home orders, and social distancing policies, to alleviate the burden on healthcare workers and slow the spread of the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) virus until an efficacious vaccine was made widely available. By early spring of 2021, three effective and well-tolerated SARS-CoV-2 vaccines emerged and underwent broad distribution. Throughout the course of the COVID-19 vaccination campaign, several key logistical and psychological issues surfaced. Of these, access to vaccines and vaccination hesitancy are cited as two substantial hindrances towards vaccination. Noting the demand for the SARS-CoV-2 vaccine and its highly sensitive storage requirements, accurate dose allocation is critical for vaccinating the population quickly and successfully. Here, we propose the use of social data as a tool to predict vaccination participation by correlating Google searches with state-level daily vaccination. We identified a temporal and regionally-ubiquitous Google search syntax that broadly captures daily vaccination trends. By correlating trends in the search syntax with daily vaccination rates, we were able to quantify the correlation and identify optimal lag periods between Google searches and daily vaccination. This work highlights the importance of analyzing social data as a metric to effectively arrange vaccination roll-outs, identify voluntary vaccination participation, and identify inflection points in vaccination participation. In addition, social data assessments can help direct dose allocation, identify geographic areas that may seek, but lack, access to the vaccines, and actively prepare for fluctuations in vaccination demands.

Analyzing Public Interest in Metabolic Health-Related Search Terms During COVID-19 Using Google Trends.

Background In late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged as a novel virus and initiated a series of events that culminated in the global coronavirus disease 2019 (COVID-19) pandemic. Throughout 2020 and the first half of 2021, massive investigational efforts towards identifying, treating, preventing, and slowing the spread of COVID-19 were carried out. Several predictors for clinical outcomes relating to metabolic health were identified. Aim and methods This study aimed to investigate how public interest in search terms associated with metabolic health has changed throughout and during the course of the COVID-19 pandemic. Google Trends was utilized as a tool to gather and compare public interest data in a variety of search phrases. The relative search values were plotted over time, compared pre-and post-COVID-19, analyzed for correlation, assessed for trend directionality, and checked for trend inclusion. Results The public interest measured by relative search volume in "metabolic health," "exercise," "home exercise," "health," and "how to improve fitness" significantly increased from pre- to post-COVID-19 pandemic onset while "diet" and "fitness" significantly decreased. The search terms "COVID" and "coronavirus" made up more than 95% of screen queries incorporating COVID-19. During the COVID-19 pandemic, "diabetes" and "weight loss" had the most significant increases in search volume. Conclusions Given the changes in public interest observed throughout the course of the COVID-19 pandemic, it is clear that the association between metabolic health and COVID-19 is being successfully disseminated to the public. However, these changes also warrant increased public education surrounding diet and fitness to align public interest with measures proven to improve the clinical outcomes of COVID-19.