Update on Non-Interchangeability of Botulinum Neurotoxin Products.

The growing use of botulinum neurotoxins (BoNTs) for medical and aesthetic purposes has led to the development and marketing of an increasing number of BoNT products. Given that BoNTs are biological medications, their characteristics are heavily influenced by their manufacturing methods, leading to unique products with distinct clinical characteristics. The manufacturing and formulation processes for each BoNT are proprietary, including the potency determination of reference standards and other features of the assays used to measure unit potency. As a result of these differences, units of BoNT products are not interchangeable or convertible using dose ratios. The intrinsic, product-level differences among BoNTs are compounded by differences in the injected tissues, which are innervated by different nerve fiber types (e.g., motor, sensory, and/or autonomic nerves) and require unique dosing and injection sites that are particularly evident when treating complex therapeutic and aesthetic conditions. It is also difficult to compare across studies due to inherent differences in patient populations and trial methods, necessitating attention to study details underlying each outcome reported. Ultimately, each BoNT possesses a unique clinical profile for which unit doses and injection paradigms must be determined individually for each indication. This practice will help minimize unexpected adverse events and maximize efficacy, duration, and patient satisfaction. With this approach, BoNT is poised to continue as a unique tool for achieving individual goals for an increasing number of medical and aesthetic indications.

Biosimilars: From Production to Patient.

Biologic drugs are large, complex molecules produced through biotechnology. A biosimilar is a biologic product that is highly similar to an already approved biologic (reference product), with no clinically meaningful differences in purity, safety, or efficacy; as such, a biosimilar does not need to undergo the same level of study in a clinical trial program as the original reference product. Due to the potential impact of biosimilars on patient access and health care systems, the US Food and Drug Administration introduced an abbreviated pathway for approving biosimilars (351[k]) in 2009. There is strong evidence that switching from a reference product to a biosimilar does not reduce treatment effectiveness or increase the risk of adverse events. Biosimilars may reduce costs and increase patient access to biologic therapies. Biosimilar use in the United States has increased, as have the associated biosimilar cost savings, which are expected to reach $104 billion between 2020 and 2024. Yet, a need remains for increased knowledge among health care professionals and patients. Prescriber confidence is key to patient acceptance of biosimilars and minimizing the incidence of the nocebo effect. Infusion nurses are well positioned to help educate patients and to improve clinical outcomes across a range of diseases.

Infraorbital Hollow Rejuvenation: Considerations, Complications, and the Contributions of Midface Volumization.

Infraorbital hollows are one of the most common target areas for facial aesthetic treatment; however, they are often perceived to be challenging to treat due to the complex anatomy of the periorbital area, concurrent deformities, and risk of complications. Treatment options include surgical (eg, lower eyelid blepharoplasty with fat transposition or injections) and nonsurgical approaches (eg, fillers). Among these approaches, filler injections have become common practice because they are minimally invasive and provide long-term patient satisfaction. In particular, hyaluronic acid (HA) fillers have been shown to be safe and effective for infraorbital hollow rejuvenation. This review provides an overview of infraorbital hollows, including periorbital anatomy, etiology, clinical assessment, and overlapping deformities, such as malar mounds, festoons, and dark circles under the eyes. Patient and HA filler product selection, injection techniques, as well as potential adverse events, such as bruising/swelling, lower eyelid and malar edema, and vascular occlusions, are discussed. This review also highlights the importance of midfacial volumization to improve outcomes in the infraorbital region and in the overall aesthetic appearance. By selecting appropriate patients and attaining proficiency in periorbital anatomy and infraorbital hollow rejuvenation techniques, clinicians can safely and successfully perform HA filler injections that result in high patient satisfaction.

Understanding the Female Hispanic and Latino American Facial Aesthetic Patient

Background: Among the growing aesthetic patient population, Hispanic/Latinos represent the largest proportion of non-Caucasians patients. While treatment of Caucasian facial aging patterns are well documented, far less information describes the aesthetic needs of the Hispanic/Latino patient. Objective: An online study was designed to survey facial aesthetic concerns, treatment priorities, and future treatment considerations among a US-based population of Hispanic/Latino American women. Materials and Methods: A total of 401 participants ages 30 to 65 years reported their attitudes toward facial aging, current facial conditions, most bothersome facial areas, areas most/least likely to be treated first, awareness of treatment options and their consideration rates, and motives and barriers that factor into consideration of injectable treatments. Results: Most participants wanted to look good for their age and treatment interests reflected predominant conditions: facial wrinkles, periorbital signs of aging, and uneven skin tone. Most bothersome facial areas included the submental area, periorbital area, and forehead, which were also among the areas most-likely to treat first. The majority of participants would consider injectables. Cost and safety/side effects were cited as frequent concerns. Conclusion: An understanding of the facial aesthetic concerns and treatment priorities specific to Hispanic/Latino women will enhance the practitioner's patient-centric treatment approach. J Drugs Dermatol. 2019;18(7):623-632.

A Pilot, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of IncobotulinumtoxinA Injections in the Treatment of Rosacea.

BACKGROUND: Rosacea has a variable presentation. Whereas the pathophysiology may differ, erythema, and flushing are the most consistent findings in all patients.

OBJECTIVE: To evaluate the safety and efficacy of incobotulinumtoxinA in reducing the severity of rosacea symptoms.

METHODS: Nine subjects with erythematotelangiectactic or papulopustular rosacea were randomized in 2 groups. Subjects in Group 1 (n=4) received up to a total of 20 U of incobotulinumtoxinA in the affected area (across both cheeks). Subjects in Group 2 (n=5) were injected with equal volumes of a saline solution. Rosacea Clinical Scores and subject satisfaction were evaluated at baseline and at 1, 4, 12, and 16 weeks post-treatment. At week 16, both groups were injected with incobotulinumtoxinA. Follow-up visits were performed at 1 and 4 weeks post-retreatment.

RESULTS: Patients in Group 1 exhibited reduction in the primary features of rosacea within 4 weeks of treatment with incobotulinumtoxinA. Consistent with this observation, patients in Group 2 (who had received the placebo in the first arm without significant changes to their symptoms) exhibited reductions in all of the primary and some of the secondary features upon treatment with incobotulinumtoxinA.

CONCLUSIONS: IncobotulinumtoxinA may be a safe and effective agent to reduce the severity of rosacea symptoms and increase patient satisfaction.

J Drugs Dermatol. 2017;16(6):549-554.

Polydioxanone Absorbable Plate for Cartilaginous Grafting in Endonasal Rhinoplasty: A Randomized Clinical Trial.

IMPORTANCE: The caudal septal extension (CSE) graft maneuver commonly is used to adjust the nasal tip projection. It can, however, be difficult to stabilize and straighten the CSE graft, especially when the procedure is performed through an endonasal approach. Because the stabilization and correct positioning of the CSE graft are vital for achievement of the desired outcome, new approaches must be found that facilitate the technical ease of this procedure. OBJECTIVE: To assess the safety and efficacy of the polydioxanone (PDS) absorbable plate in CSE graft procedures performed via an endonasal approach. DESIGN, SETTING, AND PARTICIPANTS: In an open-label, 2-arm parallel trial, 30 patients who requested a surgical nasal correction and required a CSE graft performed via an endonasal approach were randomized into 2 groups of 15 patients each. All patients underwent endonasal rhinoplasty at a single center from February 17, 2011, to December 26, 2013. Depending on their treatment group, patients received a CSE graft with or without a PDS plate. Data were collected and evaluated from November 24, 2010, to January 19, 2015, when final follow-up occurred. Data were analyzed based on an evaluable population. INTERVENTIONS: Endonasal rhinoplasty with or without the use of a PDS plate. MAIN OUTCOMES AND MEASURES: Technical difficulty assessed using a visual analog scale (range, 0-100; higher scores indicate increased difficulty of use), surgeon and blinded evaluator satisfaction with the graft assessed using a 4-point categorical scale (1 indicates highly satisfied; 4, unsatisfied), change in nasal tip projection, and complications at 30, 60, 180, and 365 days after surgery. RESULTS: Twenty-seven patients (13 in the PDS group and 14 in the non-PDS group) completed their 6-month postoperative visit, and 19 patients (10 in the PDS group and 9 in the non-PDS group) completed the entire study (12 months). The mean (SD; range) surgeon-assessed visual analog scale score for ease of use was 46 (13; 25-64) mm for the 15 patients in the non-PDS treatment group and 17 (10; 7-48) mm for the 15 patients in the PDS group (P < .001). The surgeon's satisfaction with the graft did not differ significantly between the PDS and the non-PDS groups (P = .34), and the nontreating blinded evaluator's assessment of standardized photographs taken at the time of the graft placement and at postoperative days 30, 60, 180, and 365 did not establish any significant differences between the 2 groups (P > .99). Postoperative change in the nasal tip projection at 365 postoperative days compared with 30 postoperative days was significantly lower in the PDS group compared with the non-PDS group (-0.31% vs -6.5%; P = .04), thus increasing the long-term stability of the graft in the PDS group. A single incident of infection was observed in each group along with no episodes of rejection or extrusion. CONCLUSIONS AND RELEVANCE: In this study, use of a PDS plate in CSE graft procedures was associated with less technical difficulty than CSE graft procedures without use of a PDS plate and with reduced long-term variations in the nasal tip projection after the graft placement. LEVEL OF EVIDENCE: 1. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01225250.

Large-scale chromatin structure of inducible genes: transcription on a condensed, linear template.

The structure of interphase chromosomes, and in particular the changes in large-scale chromatin structure accompanying transcriptional activation, remain poorly characterized. Here we use light microscopy and in vivo immunogold labeling to directly visualize the interphase chromosome conformation of 1-2 Mbp chromatin domains formed by multi-copy BAC transgenes containing 130-220 kb of genomic DNA surrounding the DHFR, Hsp70, or MT gene loci. We demonstrate near-endogenous transcription levels in the context of large-scale chromatin fibers compacted nonuniformly well above the 30-nm chromatin fiber. An approximately 1.5-3-fold extension of these large-scale chromatin fibers accompanies transcriptional induction and active genes remain mobile. Heat shock-induced Hsp70 transgenes associate with the exterior of nuclear speckles, with Hsp70 transcripts accumulating within the speckle. Live-cell imaging reveals distinct dynamic events, with Hsp70 transgenes associating with adjacent speckles, nucleating new speckles, or moving to preexisting speckles. Our results call for reexamination of classical models of interphase chromosome organization.