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BACKGROUND: OnabotulinumtoxinA (onabotA), is assumed to achieve its therapeutic effect in migraine through blocking activation of unmyelinated meningeal nociceptors and their downstream communications with central dura-sensitive trigeminovascular neurons in the spinal trigeminal nucleus (SPV). The present study investigated the mechanism of action of onabotA by assessing its effect on activation and sensitization of dura-sensitive neurons in the SPV by cortical spreading depression (CSD). It is a follow up to our recent study on onabotA effects on activation and sensitization of peripheral trigeminovascular neurons. METHODS: In anesthetized male and female rats, single-unit recordings were used to assess effects of extracranial injections of onabotA (five injections, one unit each, diluted in 5 µl of saline were made along the lambdoid (two injection sites) and sagittal (two injection sites) suture) vs. vehicle on CSD-induced activation and sensitization of high-threshold (HT) and wide-dynamic range (WDR) dura-sensitive neurons in the SPV. RESULTS: Single cell analysis of onabotA pretreatment effects on CSD-induced activation and sensitization of central trigeminovascular neurons in the SPV revealed the ability of this neurotoxin to prevent activation and sensitization of WDR neurons (13/20 (65%) vs. 4/16 (25%) activated neurons in the control vs. treated groups, p = 0.022, Fisher's exact). By contrast, onabotA pretreatment effects on CSD-induced activation and sensitization of HT neurons had no effect on their activation (12/18 (67%) vs. 4/7 (36%) activated neurons in the control vs. treated groups, p = 0.14, Fisher's exact). Regarding sensitization, we found that onabotA pretreatment prevented the enhanced responses to mechanical stimulation of the skin (i.e. responses reflecting central sensitization) in both WDR and HT neurons. In control but not treated WDR neurons, responses to brush (p = 0.004 vs. p = 0.007), pressure (p = 0.002 vs. p = 0.79) and pinch (p = 0.007 vs. 0.79) increased significantly two hours after CSD. Similarly, in control but not treated HT neurons, responses to brush (p = 0.002 vs. p = 0.79), pressure (p = 0.002 vs. p = 0.72) and pinch (p = 0.0006 vs. p = 0.28) increased significantly two hours after CSD. Unexpectedly, onabotA pretreatment prevented the enhanced responses of both WDR and HT neurons to mechanical stimulation of the dura (commonly reflecting peripheral sensitization). In control vs. treated WDR and HT neurons, responses to dural stimulation were enhanced in 70 vs. 25% (p = 0.017) and 78 vs. 27% (p = 0.017), respectively. CONCLUSIONS: The ability of onabotA to prevent activation and sensitization of WDR neurons is attributed to its preferential inhibitory effects on unmyelinated C-fibers. The inability of onabotA to prevent activation of HT neurons is attributed to its less extensive inhibitory effects on the thinly myelinated Aδ-fibers. These findings provide further pre-clinical evidence about differences and potentially complementary mechanisms of action of onabotA and calcitonin gene-related peptide-signaling neutralizing drugs.

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Neuromuscular inhibitors have been quickly advanced from being used only for aesthetic purposes to being used as a treatment for musculoskeletal pain and muscle spasticity. This phenomenon stems from the diminished force exerted by muscles, which are essential for bone remodeling. In this context, it is hypothesized that botulinum toxin (BTX) might exert a direct influence on bone resorption. Although such treatments have the potential to provide patients with significant relief, bone loss occurring due to elective muscle paralysis has yet to be examined in clinical trials. The disuse model resulting from spinal cord injury, characterized by the absence of ground reaction and muscle forces, provides an ideal context for exploring the skeletal ramifications of intramuscular BTX injection. This approach enables an investigation into the intricate interplay between muscle and bone, encompassing the impact of spasticity on bone preservation, the potential positive and negative outcomes of BTX on bone metabolism, and the involvement of the autonomic nervous system in bone remodeling regulation. This paper presents a narrative review of research findings on the disturbance of the typical balance between muscles and bones caused by acute muscle paralysis from BTX, resulting in osteopenia and bone resorption.

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Patients presenting with large ventral abdominal wall hernias require pretreatment with injection botulinum toxin A before surgery. Currently, multipoint and multilayered botulinum injection techniques are practiced. We are describing a new ultrasound-guided, 1-point, single interfascial plane botulinum toxin A injection technique for the closure of big hernial defects.

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DAXXIFYTM (daxibotulinumtoxinA-lanm) for intramuscular injection was recently approved for temporary improvement in the appearance of the moderate to severe glabellar lines (GLs) associated with corrugator and/or procerus muscle activity in adult patients. DaxibotulinumtoxinA for Injection (DAXI) includes a purified 150-kDA botulinum toxin Type A (BoNTA) formulated with a novel peptide excipient that is positively charged and helps to bind the neurotoxin to negatively charged neuronal membrane for a longer duration. The effectiveness of DAXI was evaluated in two phase 3 trials, SAKURA 1 and SAKURA 2, using a randomized, double-blind, placebo-controlled design. The primary endpoint (treatment success) was a composite clinical outcome (investigator and subjects) of ≥2-point improvement in severity of GLs at week 4. In SAKURA 1, the treatment success was 74% (148/201) in subjects treated with DAXI and 0% in subjects treated with placebo. In SAKURA 2, the treatment success was 74% (152/205) in subjects treated with DAXI and 0% in subjects treated with placebo. An open-label study, SAKURA 3, included 2,691 participants, who underwent three consecutive treatment cycles. These individuals were recruited from either SAKURA 1 or SAKURA 2 trials, or were new to the study and received DAXI. Treatment success proportions were 73.2%, 77.7%, and 79.6% across the three consecutive treatment cycles. The recommended dose is 40 units for the Glabellar-complex divided in traditional five intramuscular injections at five injection sites (medial and lateral corrugator bilaterally and one injection in the procerus muscle).

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BACKGROUND: AbobotulinumtoxinA has become well established as a treatment option for moderate to severe glabellar lines since its first aesthetic approval in 2009. OBJECTIVE: Pivotal trials leading to regulatory approval showed that abobotulinumtoxinA treatment was associated with high responder rates when defined as achievement of none or mild glabellar lines (0 or 1 on the glabellar line severity scale) and a duration of action of up to 5 months. More recently, the goals for treatment of glabellar lines have shifted toward not only achieving a decrease in glabellar line severity but also ensuring that patients are satisfied with their experience. MATERIALS AND METHODS: Patients seek an improvement in the appearance of their glabellar lines while maintaining a "natural look," fast onset of effect, and long duration of response. RESULTS: Trial designs have evolved to meet these new targets, including expanding the definition of responders to those having at least 1-grade improvement in the glabellar line severity scale score from baseline coupled with the use of subject satisfaction and psychological well-being questionnaires. CONCLUSION: The findings demonstrate that abobotulinumtoxinA remains a well-tolerated and consistently effective treatment option associated with a rapid onset of effect, duration of efficacy lasting up to 6 months, and high, long-lasting levels of patient satisfaction.

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BACKGROUND: OnabotulinumtoxinA is an injectable product that was introduced into medicine in the 1970s and has been the subject of thousands of clinical and nonclinical publications. OBJECTIVE: To review the data related to the versatility of onabotulinumtoxinA in medical aesthetics. METHODS: PubMed was searched to identify literature evaluating the effects of onabotulinumtoxinA, with preference given to randomized, placebo-controlled trials and safety meta-analyses. RESULTS: OnabotulinumtoxinA is effective and safe across multiple facial indications, racial and ethnic groups, age groups, genders, and facial line severities. Patient-reported outcomes have been prioritized in aesthetic clinical trials and indicate high patient satisfaction and appearance-related psychological outcomes. Integrated safety meta-analysis and immunogenicity analyses have documented acceptable adverse event rates and low immunogenicity of onabotulinumtoxinA. CONCLUSION: OnabotulinumtoxinA is a versatile aesthetic product supported by a strong literature base and positive physician and patient-reported outcomes that reflect a meaningful impact on patient's quality of life.

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BACKGROUND: Millennials accept and invest in aesthetic procedures more than older generations. OBJECTIVE: To compare efficacy outcomes between millennial and nonmillennial patients after treatment of glabellar lines with prabotulinumtoxinA. MATERIALS AND METHODS: This was a post hoc analysis of 3 Phase III studies of 20 U prabotulinumtoxinA for the treatment of moderate to severe glabellar lines. Investigator- and/or subject-assessed positive responder rates in the Glabellar Line Scale, Global Aesthetic Improvement Scale, and Subject Satisfaction Scale were compared between millennials (born 1982-2000) and nonmillennials (born ≤1981). RESULTS: Aesthetic outcomes and subject satisfaction of prabotulinumtoxinA treatment were high in nonmillennials (n = 65) and even higher in millennials (n = 668) at all time points. At Days 7, 14, and 30 post-treatment, positive responder rates were >85% and >97% across all scales in nonmillennials and millennials, respectively, with statistical superiority observed in millennials at multiple time points in virtually all scales. The incidence of treatment-related adverse events was similar between groups. CONCLUSION: PrabotulinumtoxinA was highly effective in treating moderate to severe glabellar lines. The greater efficacy seen in millennials may reflect physiological differences related to aging as well as botulinum toxin-mediated effects on mood. The results align well with their aesthetic expectations.

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BACKGROUND: Botulinum toxin type A (BoNTA) is standard of care for glabellar lines ameliorization. DaxibotulinumtoxinA for Injection (DAXI) is a new BoNTA with a unique formulation representing the latest advancement in BoNTA technology. There is an unmet need for patients to understand the full potential of BoNTA treatment and new technologies. OBJECTIVE: To update clinical data supporting the use of DAXI for glabellar lines within the context of clinical experience. MATERIALS AND METHODS: A narrative review of the literature and summary of clinical experience with DAXI. RESULTS: The DAXI clinical trial program reflects clinical experience post-FDA approval, with DAXI demonstrating rapid onset, high patient response rates, and extended treatment duration versus conventional BoNTAs. Clinical observations suggest that DAXI has limited diffusion from the injection site, enabling more localized control of muscle activity and greater improvements in wrinkle severity. DAXI enables practitioners to exert greater finesse in their injections and in predicting changes to eyebrow shape and position and achieve improvement in skin quality. CONCLUSION: Advances in BoNTA technology can provide patients with greater options for treatment outcomes. The potential for enhanced localized effects with DAXI may contribute to more precise and targeted effects on muscle activity and additional aesthetic benefits to patients.

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BACKGROUND: As new aesthetic treatment techniques are developed, the understanding of botulinum toxin type A safety and treatment outcomes continues to evolve. OBJECTIVE: This article was developed to provide a comprehensive up-to-date reference for clinicians using incobotulinumtoxinA (INCO; Xeomin/Bocouture, Merz Pharmaceuticals GmbH, Frankfurt, Germany) for aesthetic treatments. PATIENTS AND METHODS/MATERIALS: A Latin American panel of 11 physicians was assembled to discuss and develop recommendations on the use of INCO for aesthetic treatment based on the literature review and their private medical practice. RESULTS: The panel found that INCO is a highly purified botulinum toxin, without other clostridial proteins (hemagglutinins and nonhemagglutinins). IncobotulinumtoxinA has proven its efficacy and duration over time, maintaining response after multiple treatment cycles. CONCLUSION: This recommendation provides up-to-date information on the use of INCO for aesthetic treatment, focusing on the differential properties of this product regarding its purity, performance, customization, and patient satisfaction.

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BACKGROUND: The use of botulinum toxins for facial rejuvenation and improvement of dynamic wrinkles has become a mainstay in the aesthetic treatment armamentarium. However, using these same neuromodulators (NMs) for lifting the structures of the face, is a newer addition to antiaging protocols. The muscles of facial animation all interplay with each other. Lifting can be accomplished by treating those muscles that are responsible for depression, leaving the elevators unopposed and resulting in a rejuvenated, lifted outcome. Brow lifting, cheek lifting, and even contouring of the lower face and jawline are all possibilities using NMs. OBJECTIVE: To review the literature and current practices in techniques for lifting the different anatomic facial zones. METHODS: The authors present and discuss the published data and personal experiences of using NM for lifting and retraining of the facial musculature. This article will discuss the effects and approaches to lifting with botulinum toxin injections, including the potential success and side effects associated with these off-label injections. RESULTS/CONCLUSIONS: The use of botulinum toxins has expanded beyond its traditional use as a reducer of dynamic wrinkles. A significant amount of published data now exists for the off-label use of botulinum toxins for lifting and shaping the face. These can be considered advanced techniques as each region has its own anatomic intricacies and side effects can occur. More placebo-controlled objective data would also help elucidate exact dosing strategies for each region.

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BACKGROUND: Botulinum toxin (BoNT) has evolved as a popular treatment for various medical and aesthetic conditions since the 1980s. The emergence of new liquid formulation BoNT products in the industry highlights the need to evaluate the value and advantages of these modern formulations. OBJECTIVE: The aim of this review was to assess and compare the expected difference in practice between liquid and powder formulation BoNT products. PAITENTS AND METHODS/MATERIALS: This article involves a review of pertinent guidelines, product information from manufacturers, available database for safety reports, and survey results. RESULTS: Guidelines and safety reports have pointed out potential risks in the reconstitution process, while medication preparation steps are simplified in liquid formulation. CONCLUSION: The shift toward ready-to-use liquid products can mitigate risks related with reconstitution errors and potentially enhancing patient care by saving time and cost associated with medication preparation.

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BACKGROUND AND OBJECTIVE: Botulinum toxin treatment is gaining popularity among men for cosmetic purposes driven by workplace competition and a desire for confidence and youthfulness. Because of the unique features of male facial anatomy, careful consideration is necessary during assessment and treatment execution. METHODS: The peer-reviewed literature on male facial anatomy in relation to neuromodulator treatment was analyzed with a particular emphasis on studies involving male subjects and the use of botulinum toxin type A. RESULTS: Anatomic differences in muscle mass and contraction patterns between men and women help guide treatment. Men appear to require higher doses for effective treatment of facial wrinkles and, in the case of glabellar lines, often require double the standard dose for women. Treatment of the frontalis muscle in men, responsible for forehead creases, requires precise dosage and placement to avoid brow ptosis. The lateral canthal wrinkles are often the first area that men seek consultation for. Although FDA approval for lower face regions is lacking, off-label use can still be considered. CONCLUSION: Successful botulinum toxin treatment in men necessitates understanding facial anatomy, customized treatment plans, and appropriate dosing. Further research is warranted to refine protocols and enhance outcomes for male patients.

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BACKGROUND: Botulinum type-A toxin is a well established aesthetic and medical treatment. While the usage of type-B toxin is less common, there is a growing interest in using type-B toxin, especially in those who are treatment resistant. OBJECTIVE: To evaluate the primary FDA-approved clinical applications of rimabotulinumtoxinB, along with established and emerging off-label clinical indications. MATERIAL AND METHODS: Articles were reviewed from PubMed database and Food and Drug Adminstration guidelines. RESULTS: Facial rhytids tend to use a higher conversion ratio between type A and type B toxin, due to type B toxin's weaker affinity to muscles and higher affinity for sweat glands. Specially, a 1:100 to 1:50 ratio was utilized for glabellar rhytids, a 1:25 to 1:50 ratio for periocular rhytids, a 1:50 to 1:66.6 ratio for cervical dystonia, a 1:20 to 1:50 ratio for hyperhidrosis, and a 1:25 to 30 ratio for sialorrhea. CONCLUSION: Type B toxin has demonstrated its safety and efficacy in treating facial rhytids, cervical dystonia, sialorrhea and hyperhidrosis, with potential for novel applications under investigation. Regardless of injection location and clinical applications, dry mouth and dysphagia remained the most common side effects. Across all indications, type B toxin appeared to have a faster onset of action, a dose-dependent clinical duration, and a dose-dependent adverse effect profile.

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BACKGROUND: A successfully developed topical botulinum toxin product would overcome the disadvantages of injectable administration commonly seen with all available botulinum products, including the potential pain, bleeding, and bruising associated with injection. OBJECTIVE: Identify the disadvantages of injectable administration of botulinum products and advantages of topical administration. Identify previous attempts to develop topical products and review the only topical product candidate (ET-01, abbreviated EMX) under clinical development. MATERIALS AND METHODS: A literature review regarding injectable botulinum products and topical botulinum product candidates and an analysis of data regarding EMX development were performed. RESULTS: Multiple disadvantages of injectable administration and advantages of topical administration of botulinum toxin were identified. If available, topical botulinum products are expected to expand the clinical use of botulinum toxin. Several previous attempts to develop topical products were identified. EMX has been studied for lateral canthal line treatment in multiple controlled phase 2 clinical trials including over 700 subjects. EMX has demonstrated statistically significant positive results. CONCLUSION: The development of a topical botulinum toxin is appealing because it overcomes multiple disadvantages observed with injectable administration and would likely result in increased clinical use of botulinum toxin. The development of EMX shows promise and merits further study.

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BACKGROUND: Facial aging involves multilevel changes, extending from the skin to deep support structures. A comprehensive treatment approach targeting the many aspects of facial dynamics and architecture is often necessary to achieve optimal correction, prevent changes before they occur, and/or help highlight inherited features. OBJECTIVE: To explore the integration of botulinum toxin type A (BoNT-A) into multimodal aesthetic treatment plans. MATERIALS AND METHODS: This article reviews evidence supporting the combination of BoNT-A with other minimally invasive cosmetic therapies, including dermal fillers, lasers, and energy-based devices as well as with plastic and reconstructive surgeries for more controlled healing and improved scar cosmesis. RESULTS: Combination treatment protocols including BoNT-A demonstrate higher patient satisfaction and retention rates compared to monotherapy or sequential treatments. Some guidelines for sequencing of treatments exist, but evidence is scant with certain combinations. CONCLUSION: Integrating BoNT-A into a larger aesthetic treatment plan is crucial for achieving natural and satisfying results in facial rejuvenation. Evidence supports better outcomes when incorporating with both surgical and nonsurgical modalities. Understanding how to address anatomy over time through different aesthetic therapies together allows for individually tailored, more deeply impactful treatment plans.

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BACKGROUND AND OBJECTIVE: Botulinum toxins, originally used for facial rejuvenation, have emerged as a promising tool for sculpting and refining contours for both the face and body. METHODS: The peer-reviewed literature on neuromodulator contouring treatments was analyzed, with a particular emphasis on studies and case reports involving the use of botulinum toxin type A. RESULTS: Modification of face, neck, shoulder, arm, and calf contour has been reported. Treatment and dosing protocols vary with the strength and depth of the target muscle. Regional effects of neuromodulator treatment begin to appear approximately 2 weeks after injection and are often most prominent at the 70- to 90-day time point. Although treatments are generally well tolerated, short-term muscle weakness and other side effects may occur. CONCLUSION: The use of neuromodulators to enhance facial and body contours has demonstrated efficacy, but further research is needed to validate their use and explore the full potential of this intervention through larger randomized controlled trials. The application of neuromodulators as a minimally invasive tool to address the rising demand for nonsurgical body sculpting represents a promising frontier in aesthetics.

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The application of Botulinum toxin (Masport) in urology has a long history. We aimed to assess the effect of local Masport on improvement in patients with urethral stricture by reducing the recurrence of urethral stricture. This pilot study conducted was a double-blind randomized clinical trial with code IRCT20191222045852N1 on patients suffering from urethral stricture. Finally, 28 patients were allocated to intervention and control groups. Twelve patients received intralesional injection with Masport in addition to internal urethrotomy, while 16 patients underwent internal urethrotomy with normal saline. The Cox regression hazard model was used to evaluate the effect of treatment status on recurrence time adjusted for the age, length, and location of the stenosis, cause of the stenosis, and history of previous operations. The effect of treatment type was significant at the .05 level. The past medical history and cause of urethral stricture had a significant impact on relapse-free survival. Also, the improvement in the mean score of the EuroQol Visual Analogue Scale (EQ-VAS), International Prostate Symptom Score (IPSS), and Q-max in the group with Masport was significantly different from the group with normal saline. The internal urethrotomy with intralesional injection of Masport has a better survival prognosis than internal urethrotomy with normal saline group. Therefore, the authors suggest that, given this successful initial clinical trial, consideration be given to future studies involving the use of botox in the management of urethral strictures in conjunction with internal urethrotomy.

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OBJECTIVE: This systematic review aims to summarize and synthesize the evidence that investigates the secondary effects of the application of botulinum toxin (BT) into the masticatory muscles and its effects on bone density. MATERIALS AND METHODS: Database searches were conducted until March 19th, 2024. The quality of the studies was assessed by the Cochrane tool risk of bias for the randomized controlled trials and the ROBINS-I tool for non-randomized studies. The Cochrane Grading of Recommendations Assessment Development and Evaluation (GRADE) was used to evaluate the confidence in the overall evidence. RESULTS: Five studies looking at the effects of botulinum toxin on bone density and resorption when applied to masticatory muscles were found. No significant changes were observed in most of the studies when looking at the effects of botulinum toxin on mandibular condyle volume, density, mandibular angle thickness, and coronoid process volume. The only finding that was statistically and clinically relevant was the difference between patients who received a double application of BT when compared with patients who received a single application (SMD: -0.99 [95%CI: -1.94,-0.05]) on the volume of the mandibular angle. CONCLUSIONS: There is no clear pattern on whether the application of botulinum toxin is associated with bone resorption or not. Although some studies show statistical significance of the findings, the magnitude of the changes in bone density and their clinical significance are not completely clear. CLINICAL RELEVANCE: To understand the effectiveness of the use of botulinum toxin into the masticatory muscles and its possible secondary adverse effects on the density of the mandible.

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