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Background: Injections of botulinum toxin type A (BoNT‐A) have been proposed as an additional treatment modality for patients suffering chronic temporomandibular disorder (TMD)‐related myofascial pain (MFP). BoNT‐A impairs muscle function, along with its analgesic effect, and a minimal effective dose should be used. The objective of this randomized placebo‐controlled crossover study was to evaluate the clinical benefit of a moderate dose (50 U) of BoNT‐A. Methods: Sixty‐six subjects were randomized into two groups, one which received BoNT‐A first and a second which received a saline solution (SS) first. Follow‐ups were performed 2, 11, and 16 weeks after the injections. Diagnostic criteria for temporomandibular disorders (DC/TMD) diagnostic algorithms were used to evaluate characteristic pain intensity (CPI) and pain‐related disability based on the Graded Chronic Pain Scale (GCPS). Electromyographic and bite force were also evaluated. Results: The within‐group analysis showed a significant improvement in pain intensity and pain‐related disability after BoNT‐A (p < 0.001, p = 0.005, p = 0.011) and SS (p = 0.003, p = 0.005, p = 0.046) injections up to week 16. The between‐group analysis of pain‐related variables revealed no differences between groups at any time. Nonetheless, BoNT‐A, but not SS, caused a significant decline in muscle performance. The number needed to treat (NNT) regarding a clinically significant pain reduction (≥30%) was 6.3, 57.0, and 19.0 at 2, 11, and 16‐week follow‐ups favoring BoNT‐A. Conclusions: Injections of 50 U of BoNT‐A might improve MFP symptoms, but the specific effect of the drug on pain compared to the placebo is not obvious. [ABSTRACT FROM AUTHOR]

Background: This pooled analysis of randomized controlled studies investigated the safety and efficacy of onabotulinumtoxinA in male and female patients with overactive bladder (OAB). Methods: Data were pooled from four similarly designed trials in North America and Europe. Adults with idiopathic OAB for ≥6 months inadequately managed by at least one anticholinergic were randomized 1:1 or 2:1 to receive onabotulinumtoxinA 100 U or matched placebo in Cycle 1 and could request open‐label retreatment with onabotulinumtoxinA 100 U at ≥12 weeks. Efficacy outcomes at Week 12 included the primary endpoint of mean urinary incontinence (UI) episodes per day and other variables, such as the proportion of patients with ≥50% reduction in daily UI episodes. Safety was assessed by monitoring treatment‐emergent adverse events (TEAEs). Analyses by sex were descriptive. Males were further analyzed by benign prostatic hyperplasia (BPH) diagnosis status. Results: In the pooled population (N = 1564), there were 194 males (12.4%) and 1370 females (87.6%). Mean number of baseline UI episodes per day was 4.9 in males and 5.5 in females. At Week 12, numerically greater mean reductions from baseline in number of daily UI episodes were observed with the onabotulinumtoxinA 100 U group (females: −3.0; males: −2.2) versus placebo (females: −1.1; males: −1.3). Achievement of ≥50% reduction in daily UI episodes was numerically greater with onabotulinumtoxinA 100 U (females: 64.8%; males: 61.2%) versus placebo (females: 30.6%; males: 44.8%), and numerically higher in males without BPH (onabotulinumtoxinA: 65.1%; placebo: 50.9%) versus with BPH (onabotulinumtoxinA: 54.3%; placebo: 36.6%). A total of 34.7% of males and 39.4% of females experienced at least one TEAE in the first 12 weeks during treatment Cycle 1. Urinary tract infection rate was 13.1% in females and 4.2% in males; incidence of hematuria was 6.8% in males and 1.1% in females. Incidence of urinary retention (defined as incomplete emptying, requiring catheterization) was 2.7% in females and 4.7% in males. Conclusion: OnabotulinumtoxinA 100 U was efficacious and well tolerated in men and women with OAB, including in males with and without BPH. No new safety findings were identified when data were analyzed by sex. [ABSTRACT FROM AUTHOR]

Background: Botulinum toxin A (BoNT‐A) is widely utilized in the management of hypertrophic and keloid scars. One proposed mechanism for scar prevention involves the inhibition of fibroblast migration in scars by BoNT‐A. However, the data regarding the effect of BoNT‐A on the migration of normal human dermal fibroblasts (NHDF) is limited. Objectives: The aim of this study was to investigate the inhibitory effect of different types and dilutions of BoNT‐A on the migration of NHDF. Methods: In vitro scratch wound assay, NHDF cells were cultured, incubated, and subjected to scratching using a sterile tip. Subsequently, the scratched NHDF monolayer was treated with different types of BoNT‐A, including onabotulinumtoxinA (ONA), incobotulinumtoxinA (INCO), prabotulinumtoxinA (PRABO), or letibotulinumtoxinA (LETI), at varying concentrations of 10, 20, 25, 40, 50, and 100 units/milliliter (U/mL). Additionally, abobotulinumtoxinA (ABO) was administered at concentrations of 33, 50, 66, 71, 100, 150, 300, and 500 U/mL. Normal saline solution (NSS) served as a negative control. The extent of NHDF migration was evaluated by comparing each dilution of BoNT‐A with the controls using high‐content imaging at the 48‐h time point. Furthermore, the viability of the of NHDF was assessed. Results: The concentrations of 25, 40, and 50 U/mL of ONA (p < 0.001) and 25 U/mL of LETI (p < 0.05) demonstrated significantly inhibited NHDF migration in comparison to the control group. Conversely, all dilutions of PRABO, INCO, and ABO exhibited comparable NHDF migration to that of the control group. Regarding NHDF viability, no significant decrease was observed across any of the BoNT‐A types and dilutions. Conclusion: Different types and dilutions of BoNT‐A demonstrated variable inhibitory effects on NHDF migration in vitro. The selection of BoNT‐A formulation may significantly impact the clinical outcome of scar prevention related to fibroblast migration. [ABSTRACT FROM AUTHOR]

Background: Patients with hypertrophic scarring tend to experience recurrence after treatment, which often occurs in areas of the body with high skin tension. Aims: To evaluate better treatments aimed at reducing the risk of scar recurrence in areas of high skin tension. Methods: Patients were randomly divided into the following three treatment groups: botulinum toxin type A (BTA) via dual‐plane micro‐drop injections, triamcinolone acetonide (TAC) suspension, and CO2 via fractional CO2 laser. Interventions were implemented in all three groups once a month for three consecutive sessions. After the final treatment, scarring was evaluated at 1, 3, 6, 12, and 24 months using the Patient and Observer Scar Assessment Scale (POSAS). Results: The 3‐month POSAS score for each scar indicator in the treatment groups was significantly lower than that in the preoperative groups (p < 0.001). The scar score in the TAC group decreased at 3 months and increased thereafter. For other groups, the scar score continually decreased at all time points according to the Patient Scar Assessment Scale. Based on the Observer Scar Assessment Scale, the scar score continuously decreased at all time points in the BTA group; in the TAC group, it decreased at 1 month and increased thereafter; and in the CO2 group, the scar score decreased at 3 months and subsequently stabilized. Conclusions: All three treatment methods were effective. However, the BTA group experienced a reduced risk of scar recurrence and maintained long‐term treatment effects. [ABSTRACT FROM AUTHOR]

Objective: To characterize the long‐term (56‐week) benefits of continuous onabotulinumtoxinA treatment response in individuals with chronic migraine (CM) who achieved reduction to <15 headache days/month with treatment. Background: There are limited data exploring reductions in monthly headache days to levels consistent with episodic migraine among those experiencing CM. Understanding the impact of sustained preventive treatment response in CM can provide important information about the impact of successful therapy. Methods: The two Phase 3 REsearch Evaluating Migraine Prophylaxis Therapy trials of onabotulinumtoxinA in adults included a 24‐week, randomized, double‐blind, placebo‐controlled phase and a 32‐week open‐label phase. Data were pooled to determine proportions of individuals with <15 headache days/month while on treatment during several time periods in the double‐blind phase (Weeks 21–24; any 12 consecutive weeks; Weeks 13–24) and the entire study (Weeks 53–56; any 12 consecutive weeks; any 4‐week period). We assessed the long‐term impact on mean monthly headache days and changes from baseline on the six‐item Headache Impact Test (HIT‐6) and Migraine‐Specific Quality of Life questionnaire version 2.1 (MSQv2.1). Results: We analyzed 1384 participants with chronic migraine (double‐blind: onabotulinumtoxinA, n = 688; placebo, n = 696; open‐label: n = 688 [onabotulinumtoxinA]). The discontinuation rates prior to the completion of the full 56‐week treatment period for onabotulinumtoxinA and placebo were 25.4% (n = 175) and 29.3% (n = 204), respectively. During Weeks 13–24 of the double‐blind phase, significantly more onabotulinumtoxinA‐treated (386/688 [56.1%]) than placebo‐treated (342/696 [49.1%]) individuals had <15 headache days/month (p = 0.010), with fewer monthly headache days for onabotulinumtoxinA versus placebo responders. The proportions of participants achieving <15 monthly headache days with onabotulinumtoxinA were 60.9% (419/688) at Weeks 25–56, 81.1% (558/688) at Weeks 53–56, and 79.4% (546/688) during any consecutive 12‐week period. Mean changes from baseline on the HIT‐6 and MSQv2.1 questionnaire surpassed within‐group minimal important difference thresholds in all periods. At Week 24, onabotulinumtoxinA‐treated participants who achieved <15 monthly headache days during Weeks 21–24 had a greater mean HIT‐6 score reduction (−6.5 vs. −1.4) and greater mean MSQv2.1 Role‐Function Restrictive score improvements (21.3 vs. 6.4) than those who did not achieve <15 monthly headache days during the same period. Conclusions: Participants who achieved <15 monthly headache days with onabotulinumtoxinA treatment achieved meaningful benefits in headache‐related disability and migraine‐specific quality of life compared with those who remained at or above the 15–monthly headache days threshold. Sustained benefits observed over 56 weeks support long‐term onabotulinumtoxinA use for the prevention of CM. Plain Language Summary: It is not always clear how we should define if a preventive treatment for chronic migraine (CM) is successful. People with CM have ≥15 headache days/month, so we looked at data from two groups of patients who received long‐term treatment with onabotulinumtoxinA: the first group decreased to <15 headache days/month, and the second group continued to have ≥15 headache days/month. We found that the patients whose headaches decreased to <15 headache days/month, which we called the response threshold, said that their headaches impacted their lives much less and that they had better quality of life compared to the group who still met CM diagnostic criteria at the end of treatment. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Botulinum toxin (BTX) injection can be an effective treatment for persistent pain and functional impairment associated with hypertrophy of the first dorsal interosseous muscle. It offers a non‐surgical and minimally invasive alternative for those who have failed conservative treatment, showcasing the therapeutic promise of BTX for addressing similar musculoskeletal conditions. [ABSTRACT FROM AUTHOR]

Background: The signs of aging seem to be more visible on the neck compared to other locations, especially if a patient has already gone through facial rejuvenation procedures. Treatment of the aging neck imposes a challenge to the clinician, since one single approach is usually not enough to achieve the desired result, requiring multiple injections and sessions, which apart from being painful for the patients, is time‐consuming for the clinician. Aim: To describe the use of calcium hydroxyapatite, incobotulinum toxin type A and Cohesive poly‐densified matrix hyaluronic acid diluted in the same syringe and injected in the same session for neck rejuvenation. Patients and Methods: Fifteen women, older than 18 years, with cervical skin flaccidity grade 1–4 in a previously validated 5‐point rating scale (Dermatologic Surg, 2016; 42, S94), who sought neck rejuvenation were injected in this pilot study with a single session with a combined hybrid mixture of calcium hydroxyapatite, incobotulinum toxin type A, and Cohesive poly‐densified matrix hyaluronic acid and followed up for 90–180 days. Results: At the 4‐month post injection evaluation, 93.3% of the patients presented at least 1‐grade improvement in the 5‐point scale as evaluated by the investigator. No serious adverse events were reported, being most mild and transient in nature. Conclusion: CaHA, incoBonTA, and CPM‐HA have complementary mechanisms of action and may be injected from the same syringe in the same session, boosting the final outcome, with high patient satisfaction, and ease of process for both patients and clinicians. [ABSTRACT FROM AUTHOR]

Background: Botulinum toxin type A injections are widely used for facial rejuvenation; however, research on people's satisfaction based on age is limited. This study assessed patient satisfaction with botulinum toxin injections for forehead, glabella, and periorbital wrinkles in Birjand, Iran. Patients and Methods: The current study examined 150 people aged 18 to 70 who requested botulinum toxin type A injection in the forehead, glabellar, and periorbital area in 2022, who visited the plastic surgery clinic and the authors' offices in Birjand City. To check patients' satisfaction, Facial Lines Treatment Satisfaction (FTS) Questionnaire was used. One month after botulinum toxin type A injection, this questionnaire was completed by the clients. Also, the brand type of botulinum toxin, age, gender of the clients, frequency of visits, and complications were collected in the relevant checklist. Results: The average age of participants was 38.8 ± 8.29 years with 73.3% being female. Masport botulinum toxin (MasoonDarou Pharmaceutical Company, I.R. Iran) was the most frequently used botulinum toxin brand at 66.7%. The average satisfaction score with the result of botulinum toxin injection in the forehead/glabella and periorbital area, in the age group under 30 years and 30–40 years, was significantly higher than in the age group over 50 years. The same indicators in the age group under 30 years old were significantly higher than in the 30–40 age group (p < 0.05). Furthermore, brand selection and the number of visits (first‐time vs. second‐time clients) demonstrated varied outcomes in satisfaction. There was a total of 62.7% side effects postinjection, with varying degrees of severity. [ABSTRACT FROM AUTHOR]

Objective: Intraglandular injection of botulinum toxin type A (BoNT/A) effectively treats sialorrhea. Myoepithelial cells (MECs) are essential for salivary secretion. The role of MECs in BoNT/A‐inhibited salivary secretion, and its underlying mechanisms remain unknown. Materials and Methods: BoNT/A was injected into rat submandibular glands (SMGs). At 1, 2, 4, 8, and 12 weeks postinjection, salivary flow rate of SMGs was measured. Electron microscopy, immunohistochemistry, immunofluorescence, and Western blot analysis were used to detect morphological and functional changes in MECs and chemical denervation in SMGs. Results: BoNT/A temporarily decreased salivary secretion in rat SMGs and this inhibitory effect lasted 4 weeks. During the inhibitory period, MECs atrophied and expressed reduced α‐smooth muscle actin (α‐SMA), vimentin, and phosphorylated myosin light chain 2 (p‐MLC2), suggesting that BoNT/A attenuated MEC contractility. Furthermore, BoNT/A cleaved synaptosome‐associated protein 25 (SNAP‐25) and decreased the expression and activity of acetylcholinesterase (AChE), indicating that BoNT/A‐induced chemical parasympathetic denervation of SMGs by cleaving SNAP‐25. Conclusions: BoNT/A temporarily caused MEC atrophy and decreased MEC contractility in rat SMGs, which contributed to reversible inhibition of salivary secretion. The underlying mechanisms involved temporary parasympathetic denervation caused by SNAP‐25 cleavage. These findings provide new insights into the mechanisms of BoNT/A‐inhibited salivary secretion. [ABSTRACT FROM AUTHOR]

Objectives: This review aimed to compare the effectiveness of three treatments: BTX A, CBZ, and OXB, in managing trigeminal neuralgia (TN). Material and Methods: We conducted a thorough search for research articles related to our issue using specific keywords on several databases, including Cochrane Central Register of Controlled Trials, Science Direct, Scopus, PubMed, Elsevier, Springer Journals, Ovid Medline, EBSCO, and Web of Science. Our focus was on publications from 1965 to 2023. Results: We retrieved 46 articles from the search and reviewed them carefully. Out of these, we selected 29 articles that met the inclusion criteria. Among the selected articles, 11 investigated the effects of CBZ and OXB, while 18 explored the impact of BTX A on the improvement of TN symptoms. The response rate ranged between 56% and 90.5% for CBZ and between 90.9% and 94% for OXB. The response rate for BTX A ranged between 51.4% and 100%. All these three treatments had a remarkable effect on the improvement of TN. Importantly, findings highlighted that side effects of CBZ and OXB could lead to treatment discontinuation in some cases, whereas BTX A's side effects have been minimal and less frequent. Conclusions: Consequently, BTX A emerges as a promising alternative for TN treatment. However, additional clinical trials are necessary to validate this finding, and further research is required to establish a standardized protocol for administering BTX A in TN. [ABSTRACT FROM AUTHOR]

A meta‐analysis was conducted to comprehensively evaluate the prophylactic and therapeutic efficacy of botulinum toxin type A (BTX‐A) in the treatment of facial hypertrophic scars. Computerised searches were performed in databases, from their inception to November 2023, including Embase, Google Scholar, Cochrane Library, Wanfang, PubMed and China National Knowledge Infrastructure databases, focusing on randomised controlled trials (RCTs) that investigated the use of BTX‐A for treating facial hypertrophic scars. Two researchers independently screened the literature, extracted data and conducted quality assessments. Stata 17.0 software was employed for data analysis. Seventeen RCTs were ultimately included, involving 1605 patients who underwent facial cosmetic surgery. The analysis revealed that compared with conventional treatments, BTX‐A significantly reduced visual analogue scale (VAS) scores (standardized mean difference [SMD]: −3.50, 95% confidence interval [CI]: −5.16 to −1.84, p < 0.001) and Vancouver scar scale (VSS) scores (SMD: −2.86, 95% CI: −4.03 to −1.68, p < 0.001), and narrowed scar width (SMD: −1.80, 95% CI: −2.48 to −1.13, p < 0.001), while also enhancing the overall effectiveness of the treatment. This study indicates that BTX‐A is an effective modality in the prophylaxis and treatment of facial hypertrophic scars, significantly alleviating scar‐related pain and preventing scar widening, and is thus worthy of broader clinical application. [ABSTRACT FROM AUTHOR]

Botulinum toxin type A (BoNT/A) has exhibited efficacy in postherpetic neuralgia (PHN) treatment, and this study aims to uncover its underlying mechanisms. Resiniferatoxin (RTX)‐induced PHN rats were given BoNT/A. Rat postoperative pain behaviors were assessed by Von Frey test. Cleaved‐synaptosomal protein 25 kDa (cl‐SNAP‐25) or cathelicidin antimicrobial peptide (CAMP) expression in rat dorsal root ganglia (DRG) was detected by immunofluorescence or immunohistochemistry. Healthy rat‐derived DRG neurons were transfected, incubated with lipopolysaccharides (LPS)/adenosine 5′‐triphosphate (ATP) to stimulate pyroptosis and treated with BoNT/A. The CCK‐8, Western blot, ELISA, and qRT‐PCR were used to assess the viability, levels of pyroptosis‐related proteins proinflammatory cytokine levels, as well as CAMP and ELANE mRNA levels. BoNT/A (30 U/kg) promoted cl‐SNAP‐25 expression in rat DRG and reversed RTX‐induced decrease of rat paw withdrawal thresholds and CAMP expression and increase of pyroptosis‐associated protein and inflammatory factor expression in rat DRG. CAMP interacted with ELANE in rat DRG neurons. BoNT/A attenuated LPS/ATP‐stimulated inhibition of viability and CAMP expression and upregulation of inflammatory mediators, pyroptosis‐related proteins, and ELANE expression in rat DRG neurons, which was counteracted by CAMP silencing. However, ELANE knockdown offset the effect of CAMP silencing in LPS/ATP/BoNT/A‐treated rat DRG neurons. On the whole, BoNT/A alleviates rat DRG neuron pyroptosis during PHN by upregulating CAMP to inhibit ELANE. [ABSTRACT FROM AUTHOR]

Background: Rosacea is a chronic inflammatory disease usually associated with persistent erythema and periodic flushing. This disease is difficult to treat, and the outcomes are often unsatisfactory and prone to recurrence. In recent years, botulinum toxin has been used as a new treatment for rosacea; however, its efficacy and safety remain under discussion. Although a systematic review of the effectiveness and safety of botulinum toxin has been previously conducted by other researchers, our systematic review and meta‐analysis evaluate the efficacy of botulinum toxin from a more comprehensive and detailed perspective to provide evidence for clinicians. Methods: Any study using botulinum toxin for the treatment of rosacea was considered for the analysis. Results: A total of 22 studies were included, 9 of which were randomized controlled trials involving 720 subjects. After treatment, all studies showed varying degrees of improvement in patient signs and symptoms along with reduced Clinician's Erythema Assessment (CEA) scores. The improvement was maintained for several months, and the adverse effects were mild and self‐limiting. Conclusion: Botulinum toxin may be an effective treatment for patients with rosacea; however, further clinical evidence is needed to confirm its long‐term efficacy and side effects. The study was preregistered with Prospero (CRD42022358911). [ABSTRACT FROM AUTHOR]

Aims: In studies utilizing a 20‐injection‐site paradigm of onabotulinumtoxinA treatment for overactive bladder (OAB), some patients performed clean intermittent catheterization (CIC). An alternative injection paradigm of fewer injections targeting the lower bladder may reduce the need for CIC by maintaining upper bladder function. This study evaluated the efficacy and safety of an unapproved alternative 10‐injection‐site paradigm targeting the lower bladder. Methods: In this phase 4, double‐blind, parallel‐group study, patients with OAB and urinary incontinence (UI) for ≥6 months with ≥3 episodes of urinary urgency incontinence (no more than 1 UI‐free day) and ≥8 micturitions per day over 3 days during screening were randomized 2:1 to onabotulinumtoxinA 100 U or placebo injected at 10 sites in the lower bladder. Results: Of 120 patients, 78 in the onabotulinumtoxinA group and 39 in the placebo group had efficacy assessments. In the double‐blind phase, mean change from baseline at week 12 in daily frequency of UI episodes was greater with onabotulinumtoxinA (−2.9) versus placebo (−0.3) (least squares mean difference [LSMD]: −2.99, p < 0.0001). Achievement of 100% (odds ratio [OR]: 6.15 [95% confidence interval, CI: 0.75–50.37]), ≥75% (OR: 7.25 [2.00–26.29]), and ≥50% improvement (OR: 4.79 [1.87–12.28]) from baseline in UI episodes was greater with onabotulinumtoxinA versus placebo. Reductions from baseline in the daily average number of micturitions (LSMD: −2.24, p < 0.0001), nocturia (LSMD: −0.71, p = 0.0004), and urgency (LSMD: −2.56, p < 0.0001) were greater with onabotulinumtoxinA than with placebo. Treatment benefit was improved or greatly improved in the onabotulinumtoxinA group (74.0% of patients) versus placebo (17.6%) (OR: 13.03 [95% CI: 3.23–52.57]). Mean change from baseline in Incontinence Quality of Life score was greater with onabotulinumtoxinA versus placebo (LSMD: 24.2, p = 0.0012). Two of 78 (2.6%) patients in the onabotulinumtoxinA group used CIC during the double‐blind period; no females used CIC during the double‐blind period. Commonly reported adverse events (≥5%) were urinary tract infection (UTI), dysuria, and productive cough for both groups; rate of UTI was higher with onabotulinumtoxinA versus placebo. Conclusion: In patients treated with onabotulinumtoxinA for OAB with UI, an unapproved alternative injection paradigm targeting the lower bladder demonstrated efficacy over placebo, with a low incidence of CIC. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effectiveness of ultrasound‐guided injection of botulinum toxin type A (BTX‐A) in treating sialorrhea. Methods: We recruited 32 sialorrhea subjects and they received an ultrasound‐guided injection of BTX‐A. The extent of salivation was evaluated according to the Visual Analog Scale (VAS), Drooling Severity and Frequency Scale (DSFS), and Saliva Flow Rate (SFR). Laryngeal secretions were evaluated based on Fiberoptic Endoscopic Evaluation of Swallowing (FEES) rated according to the Murray Secretion Scale (MSS). We assessed the extent of salivation and laryngeal secretions before injection and at 1, 2, and 4 weeks after injection. Results: The scores for the VAS, DSFS‐S, DSFS‐F, and DSFS‐T decreased significantly at 1, 2, and 4 weeks after injection compared with before injection (p <.05). Based on VAS, the efficacy was substantially higher at 2 and 4 weeks after injection than at 1 week after injection (p <.05). According to DSFS‐S and DSFS‐T, the efficacy was significantly higher at 4 weeks than at 1 week after injection (p <.05). The SFR and MSS scores at 1 and 2 weeks after injection were superior to those before injection (p <.05). Meanwhile, the SFR score 2 weeks after injection was superior to that 1 week after injection (p <.05). Conclusion: The ultrasound‐guided injection of BTX‐A can effectively reduce saliva secretion in patients with neurogenic dysphagia. Furthermore, it has the advantages of early onset time and lasting curative effects, which indicates that clinical promotion and application of this technique are justified. Level of Evidence: Level 3. [ABSTRACT FROM AUTHOR]

Background: Hypertrophic scar (HS) is a common disease in plastic and cosmetic surgery, with limited treatment options, and is a challenge for clinicians. Objectives: This study aimed to evaluate the efficacy of fractional carbon dioxide (CO2) laser combined with botulinum toxin type A (BTXA) in treating HSs in rabbit ears and to provide new strategies for treating HS. Methods: Twenty‐four New Zealand white rabbits with induced HSs were randomly divided into one control and three treatment groups. After 4 weeks of modeling, BTXA (2.0 U) was injected into the HS of the BTXA and combination groups, whereas a fractional CO2 laser (combo mode, deep energy: 12.5 mJ; super energy: 90 mJ) was used in the fractional CO2 laser and combination groups. The laser treatments were repeated after 2 weeks. The HSs in the rabbit ears were observed and photographed 5 weeks after the first treatment. The scar thickness in each group was measured and compared, and the scar elevation index (SEI) was determined using hematoxylin and eosin staining. Collagen content and alignment were observed using Masson's trichrome staining. Western blotting and immunohistochemistry were performed to analyze scar‐related protein levels. Results: Hypertrophic scars were reduced in all treatment groups compared with the control group. The combination group had lower scar thickness, SEI, and expression of scar‐related proteins in HSs, with an appearance similar to that of normal rabbit ear skin. Furthermore, the fibroblast content and collagen deposition decreased significantly in the combination group (p < 0.001). Conclusions: Fractional CO2 laser combined with BTXA more effectively reduced HSs by inhibiting fibroblast proliferation, decreasing transforming growth factor‐β1 and α‐ smooth muscle actin expression, and causing collagen remodeling. [ABSTRACT FROM AUTHOR]

Objectives: Tight junctions (TJs) are involved in the regulation of salivary secretion via paracellular pathway. Botulinum toxin type A (BTXA) is widely used for the treatment of hypersecretion diseases such as sialorrhea. This study aimed to investigate the role of TJs in BTXA‐inhibited secretion of the submandibular gland (SMG). Materials and Methods: BTXA was injected into the SMGs of rats, and the same amount of saline was injected as a control. Western blot, real‐time PCR, and immunofluorescence staining were used to detect the expression and distribution of TJ proteins. Paracellular permeability was evaluated using the transepithelial electrical resistance (TER) measurements and fluorescent tracer detection in BTXA‐stimulated SMG‐C6 cells. Results: BTXA injection into the SMGs of rats led to increased expression of claudin (Cldn) −1 and Cldn3. Immunofluorescence staining showed no significant changes in the distribution of TJ proteins. In vitro, BTXA increased the TER values and significantly reduced the permeability of fluorescent tracer, suggesting that BTXA decreased the paracellular permeability. The expression levels of Cldn1, Cldn3, and Cldn4 were upregulated after BTXA treatment. Conclusion: The expression of TJ proteins changed in both animal models and SMG‐C6 cells after BTXA treatment, which may contribute to the inhibition of salivary secretion. [ABSTRACT FROM AUTHOR]

Background: The objective is to review the technique of onabotulinumtoxinA injection treatment in the glabellar and frontal regions using the PREEMPT (Phase III REsearch Evaluating Migraine Prophylaxis Therapy) paradigm, with review of the aesthetic issues related to the procedure. OnabotulinumtoxinA is an effective medication for the prevention of chronic migraine. The PREEMPT injection paradigm has been validated in randomized clinical trials and real‐world settings. This treatment includes injections in the forehead and glabella area. In addition, for aesthetic uses, glabella onabotulinumtoxinA injections are done in similar muscles specifically the procerus, corrugator supercilii, and frontalis muscles. Often patients who have been injected with onabotulinumtoxinA for chronic migraine have concerns about their appearance and will ask if they can see an aesthetic injector to improve this. This is a difficult issue as onabotulinumtoxinA should be injected with an interval of 10–12 weeks to avoid development of antibodies against onabotulinumtoxinA, so all injections (migraine and aesthetic) should ideally be done close together; however, if an aesthetic injection is done on the same day as a PREEMPT injection, the effect of the PREEMPT injection will not yet be visible as it takes time for onabotulinumtoxinA effects to be seen. Thus, there is a risk of a potential overdose in a particular area if aesthetic injections are done without input from the PREEMPT injector. Methods: This is a narrative review supported by photographic documentation showing the technique of onabotulinumtoxinA injection of the upper face, considering anatomical differences between patients, and combining the needs in neurology and aesthetic medicine fields. Results: Practitioners treating chronic migraine often modify some of the principles of the PREEMPT paradigm. Many practitioners are unsure about injections in the glabellar and frontal areas. The authors present a technique for using the PREEMPT protocol and adapting this to the individual patient's anatomy to prevent an unsightly appearance or ptosis. In addition, sites are provided where an aesthetic injector could inject to improve the patient's appearance without overlapping with the PREEMPT injection sites. Conclusion: Adherence to the PREEMPT injection protocol provides an evidence‐based approach to achieving clinical benefit for patients with chronic migraine. Aesthetic elements of the treatment of the glabella and forehead require additional attention. The authors provide practical considerations and recommendations regarding this. [ABSTRACT FROM AUTHOR]

Background: The combination of botulinum toxin type A (BoNT/A) and energy equipment have been widely used in the clinic. Aims: To determine whether the energy of microneedle fractional radiofrequency (MFR) affects the efficacy of BoNT/A and to provide an optimal strategy for the energy device in combination with BoNT/A in the clinic. Methods: First, a total of 45 females with moderate‐to‐severe periorbital crow's feet wrinkles were enrolled and divided into three groups according to different treatment methods and intervals, including BoNT/A injection alone, BoNT/A injected immediately after MFR treatment and BoNT/A injected 7 days after MFR treatment. The photographs were compared before treatment and 4 weeks after treatment. Then, the mouse models were established by combining MFR with BoNT/A at different intervals, to evaluate muscle strength, muscle mass, muscle nutritional markers, and important cytokines levels. Results: All patients in each group had high satisfaction. The MFR + BoNT/A (immediately) group could improve dynamic wrinkles, but the others had more significant efficacy (p < 0.05). The results of mouse models showed that all BoNT/A groups induced different degrees of muscle paralysis in vivo, but the paralytic effect induced by the BoNT/A group, MFR + BoNT/A (interval of 3‐day) group, and MFR + BoNT/A (interval of 7‐day) group were higher than others and the expression levels of muscle nutritional markers in NMJ tissues were significantly upregulated. Conclusion: MFR has a certain reduction effect on the activity of BoNT/A, and this reduction effect would last for 3 days after MFR treatment. [ABSTRACT FROM AUTHOR]

Background: Despite the absence of Phase III clinical trial data to support their use, 3.4% of all neurotoxin treatments performed internationally for esthetic purposes in 2020 were performed in patients 65 years of age and older. Objectives: To investigate the efficacy and safety of prabotulinumtoxinA for the treatment of moderate to severe glabellar lines in the subset of Phase III clinical trial participants who were 65 years of age and older. Methods: Post hoc analyses were performed on all patients who had been treated with a single dose of 20 U prabotulinumtoxinA in the three 150‐day, placebo‐controlled Phase III glabellar line clinical studies. Patients were grouped by age: ≥65 years (n = 70) versus <65 years (n = 667). The endpoints of primary interest were the proportion of responders with a ≥1‐point improvement from baseline at maximum frown on the 4‐point Glabellar Line Scale and treatment‐related adverse events. Results: For the efficacy endpoint of primary interest, responder rates among patients 65 years of age and older were numerically less than those of patients less than 65 years by an absolute mean difference of just −2.7% across all visits; none of the differences at any visit were statistically significant. The most common treatment‐related adverse event was headache, occurring in 5.7% of those 65 years of age and older and in 9.7% of those less than 65 years. Conclusions: 20 U prabotulinumtoxinA administered for the treatment of glabellar lines was efficacious in patients 65 years of age and older; it was also well tolerated by this cohort. [ABSTRACT FROM AUTHOR]

Background: Previous studies concerning the effect of botulinum toxin in masseter muscle have mainly reported effects observed through inspection of facial features or differences in pain levels. One systematic review of studies utilizing objective measurements reported that long‐term muscular effect of botulinum neurotoxin injections into masseter muscle was inconclusive. Objective: To evaluate the duration of reduced maximal voluntary bite force (MVBF) after botulinum toxin intervention. Methods: The intervention group was comprised of individuals seeking aesthetic treatment for masseter reduction (n = 20), the reference group (n = 12) comprised of individuals with no intervention. Intervention through 25 units of Xeomin® (Merz Pharma GmbH & Co KGaA, Frankfurt am Main, Germany) botulinum neurotoxin type A injected into the masseter muscles bilaterally (totalling 50 units). A reference group did not receive any intervention. MVBF was measured in Newtons using a strain gauge meter at the incisors and first molars. MVBF was measured at baseline, at 4 weeks, 3 months, 6 months, and after 1 year. Results: Both groups were similar in terms of bite force, sex and age at baseline. MVBF remained similar compared to baseline in the reference group. At 3 months, a significant reduction at all measurement points was observed in the intervention group; at 6 months, this reduction was no longer significant. Conclusion: A single intervention of 50 units of botulinum neurotoxin results in a reversible MVBF reduction of at least 3 months, although a visually discernable reduction may be more long‐lasting. [ABSTRACT FROM AUTHOR]

Background: Botulinum toxin type A (BoNT‐A) can not only reduce the dynamic wrinkles but also improve the skin quality. This study aims to quantitaively and comprehensively assess the improvement of dynamic wrinkles and skin quality following BoNT‐A treatment on the upper face. Methods: Patients were recruited to receive BoNT‐A treatment of the glabellar, frontal, and lateral periorbital wrinkles. Antera 3D camera was used to evaluate the skin quality and dynamic wrinkle severity. Follow‐up visits were at 1 week, 1 month, 3 months, and 6 months after treatment. Different filters were utilized to quantitatively detect the severity of fine wrinkles (FWS), the volume of pores (PV), the roughness of skin texture (STR), and the severity of dynamic wrinkles (DWS). Results: Twenty‐four participants (average 30.5 ± 7.2 years) were recruited. The significant improvement of PV, FWS, and STR in different areas usually maintained from 1 to 6 months after injections but of DWS only existed within 3 months. For each area, the improvement rates of FWS, PV, and STR peaked at 3 months or 6 months after treatment while the maximal improvement of DWS was observed at 1 month posttreatment. Conclusion: After BoNT‐A treatment for dynamic wrinkles on the upper face, the skin quality of target regions can also be ameliorated. The improvement of skin quality and dynamic wrinkles presented unparallel patterns. The former is with a slower onset but longer duration while the latter exhibits a more rapid onset but shorter duration. [ABSTRACT FROM AUTHOR]

Background: Treatment of horizontal forehead lines with botulium toxin type A is a common procedure that helps achieve a youthful and rejuvenated look. Adequate knowledge of the anatomy and an individualized treatment approach is the key to successful treatment outcome. Aim: To evaluate the cosmetic outcome following treatment of dynamic forehead wrinkles by locking the line of convergence using botulinum toxin type A. Patients and Methods: Fifty female patients with dynamic forehead wrinkles were included. The line of convergence was identified, and injection points were determined. Patients received injections of botulinum toxin type A in the upper part of the frontalis along the line of convergence. Patients were evaluated before injection and the response was evaluated after 2 weeks and after 3 months of injection. Results: Post‐treatment significant decrease in dynamic wrinkle scale was detected. The distance between the medial and lateral canthi and their corresponding lower brow margins on maximum brow elevation was also significantly decreased after treatment. Meanwhile, the validated brow positioning score revealed no significant change in the resting brow position when pre‐and post‐treatment scores were compared. Conclusions: Treating forehead wrinkles by injecting botulinum toxin along the line of convergence is an effective technique that requires less overall amount of toxin, improves the appearance of the wrinkles and minimizes the risk of development of side effects. [ABSTRACT FROM AUTHOR]

Background: For the treatment of sternal keloids, corticosteroid therapy has side effects including abnormal sebum secretion and acne. Relapse of keloids is common after corticosteroid injection in patients with oily skin. To reduce side effects and keloid recurrence, we used a combination of botulinum toxin type A (BTX‐A) and hyaluronic acid (HA) as synergetic management for multiple sternal keloids in patients with oily skin. Methods: In total, 58 patients with multiple sternal keloids who received monthly steroid injections were retrospectively included. Thirty‐two patients in the intervention group received an additional injection of BTX‐A/HA on the same day as the first injection of the steroid, while the remaining 26 patients were treated as the control group. At baseline and follow‐up visits, sebum production and transepidermal water loss (TEWL) were assessed as primary outcomes, and the Vancouver Scar Scale (VSS) score, keloid recurrence, visual analog scale (VAS) score, and patient satisfaction were assessed as secondary outcomes. Results: In the control group, average sebum production and TEWL were increased to 132% and 104% of baseline, respectively, at the 24‐week follow‐up. In the intervention group, average sebum production and TEWL reached nadir at the 8‐week follow‐up and then increased to 96% and 91% of baseline, respectively, at the 24‐week follow‐up. Sternal keloid relapse was observed in 88.5% of the patients in the control group and none of the patients in the intervention group. The total VSS score at 24 weeks was 11.04 ± 0.14 and 8.93 ± 0.26 (p < 0.001) in the control group and intervention group, respectively, and the VAS score was 75 ± 5.10 and 19.14 ± 3.80 (p < 0.001) in the control group and intervention group, respectively. Higher patient satisfaction was reported in the intervention group. Conclusions: Microneedle delivery of BTX‐A/HA decreases sebum production while improving skin barrier function. Thus, this combined therapy can relieve the side effects of corticosteroid therapy and reduce keloid recurrence. [ABSTRACT FROM AUTHOR]

Background: Botulinum toxin type A (BoNT‐A) injection is a popular cosmetic procedure in East Asian countries, and there are multiple types of toxins on the market. Whether different toxin types induce different changes in the masseter has not been studied. Objective: We aimed to investigate and compare the changes induced by injection of different types of BoNT‐A in the masseter. Methods: Upon retrospective review of clinical records and routine ultrasound examination results of patients who underwent BoNT‐A injection, four groups were set for comparison: unapproved toxin, OnabotulinumtoxinA, LanbotulinumtoxinA, and non‐injected. Clinical records and ultrasound images were collected. Ultrasound images were taken in both horizontal and coronal planes. Elasticity of the masseter muscle was also investigated by measuring the surface wave speed. Results: A total of 24 patients were included (six patients per group). All patients were young females. For the non‐injected group, the deep inferior tendon was clear and the muscle bundles were arranged, with little fibrous content. Patients who received unapproved toxin injection showed highly disarranged muscle and fiber bundles, with much fiber content present. The changes in OnabotulinumtoxinA and LanbotulinumtoxinA groups were in between those in the non‐injected and unapproved toxin groups. Muscle rigidity was the highest in the unapproved toxin group, and generally higher in injected groups compared with the non‐injected group. Conclusion: Different types of BoNT‐A may induce different changes in the masseter. [ABSTRACT FROM AUTHOR]

Background: Large calves are considered unattractive. Botulinum toxin type A (BoNT‐A), acting as a neurotoxin that reduces muscle contraction, is widely used in calf contouring. However, there lacks detailed anatomical data to guide clinical injection. Objectives: This study aims to use ultrasonography to provide depth information of the calf muscles and determine the morphological types of the gastrocnemius muscle. Methods: Ultrasound scanning was performed at six sites on 40 Chinese adults. A real‐time ultrasound scannerwas used to detect the depth of the gastrocnemius muscle and the soleus muscle. Results: The thickness of the gastrocnemius muscle and the soleus muscle was measured. The depth from the skin to the surface, the middle, and the bottom of the gastrocnemius muscle was measured. The morphology of gastrocnemius muscle was classified into four different types under ultrasound according to the muscle bulge pattern. Conclusion: This study took ultrasonic measurements of Asian calves to guide accurate and effective BoNT‐A injection in real clinical practice. [ABSTRACT FROM AUTHOR]

Head and forehead hyperhidrosis (HFH) is a disease that causes a large amount of sweating from the head region, and it significantly reduces patients' quality of life. Only a few reports have shown the effectiveness of botulinum toxin type A (BTX‐A) local injection therapy (BTX‐A therapy) for HFH. To clarify the benefits of BTX‐A for HFH, BTX‐A therapy was performed in 15 patients, and its efficacy was evaluated. The amount of sweating was measured by the ventilation capsule method and Minor's iodine‐starch test. Evaluation was also performed using the Hyperhidrosis Disease Severity Scale (HDSS) and the Dermatology Life Quality Index (DLQI). In most cases, a remarkable antiperspirant effect was observed from 2 weeks after the injection, and the effect lasted for approximately 30 weeks. HDSS and DLQI improved along with the decrease in sweating. Two patients (13.3%) complained of transient mild ptosis. There were no serious side‐effects. This study showed that BTX‐A therapy is a safe and effective treatment for HFH. [ABSTRACT FROM AUTHOR]

Background: Previous studies indicate that the efficacy and durability of a single AbobotulinumtoxinA (ABO) treatment for moderate to severe glabellar lines may be enhanced with increasing dose, while safety outcomes remain consistent with those of the licensed dose (50 U). Aims: Evaluation of subject‐reported indicators of treatment efficacy, satisfaction, and psychological well‐being with ABO dose escalation. Methods: A Phase 2, 36‐week, multicenter, randomized, dose‐ranging, double‐blind, placebo‐controlled study was conducted in adults with moderate to severe glabellar lines. Subjects received a single ABO treatment, dosed at 50, 75, 100, or 125 U, or placebo. Efficacy endpoints comprised subject‐assessed improvement in line severity of ≥1‐grade from baseline at maximum frown, global aesthetic improvement scale (GAIS) grade, FACE‐Q™ appraisal of lines, psychological well‐being and age, and subject satisfaction. Results: The study included 399 subjects (88.2% were female). Respective responder rates (≥1‐grade improvement) with ABO 50–125 U doses ranged between 96.3%–100% at Week 4, 65.0%–67.9% at Week 24, and 33.8%–44.4% at Week 36. GAIS responder rate and FACE‐Q appraisal of lines showed a similar pattern of change. Satisfaction was high and psychological well‐being was improved from Week 4 through Week 36, with natural, youthful, and refreshed appearance reported for all ABO doses. Conclusions: A single ABO treatment (dosed at 50–125 U) provided significant and sustained improvements in glabellar line severity over durations up to 36 weeks, versus placebo. Treatment satisfaction was high with all doses. Participants reported natural and youthful appearance, alongside improvements in psychological well‐being. [ABSTRACT FROM AUTHOR]

Background: Masseter muscle hypertrophy (MMH) usually presents with cosmetic concerns as it may lead to widening of the lower face. Apart from the traditional surgical approaches, botulinum toxin type A (BTA) injection is a non‐invasive treatment option available. There are no standard guidelines for this procedure. Objectives: To study the efficacy of botulinumtoxin A in MMH for lower face contouring. Methodology: The Cochrane Library, PubMed/MEDLINE, Google‐scholar, Science‐Direct database, and ResearchGate from inception until September 2021 were searched using the keywords "botulinumtoxin type A," "masseter muscle hypertrophy," "lower face contouring," and "masseter botox." All available retrospective and prospective studies, case‐series, case‐reports, and expert reviews were included with an emphasis on efficacy of BTA in MMH and units injected into the muscle, points of placement, adverse events, and the duration of its effect. Reference lists of the resultant articles, as well as relevant reviews, were also searched. Result: 40 articles were shortlisted for the review, of which 14 studies with sample‐size ≥10 in accordance with the study requirements were summarized in a tabular form for analysis and easy comparison and reference. Conclusion: BTA injection is a non‐invasive, safe, and effective treatment for MMH. The optimum number of BTA units could not be ascertained due to wide variability in the studies as well as ethnicity of patients and extent or some measurement of MMH. The points of placement of injection should be well within the boundaries of the masseter muscle. The maximum effect of BTA after a single injection session is usually seen in ~3 months, and the duration may last for 6–12 months. Multiple injection sessions may be required to maintain a long‐term effect. Injection technique and total number of injection units of neuromodulator must be individualized for each patient. [ABSTRACT FROM AUTHOR]

Previous studies have used botulinum toxin type A (BTXA) to improve postoperative and hypertrophic scars; however, there is lack of detailed verification on the safety and effectiveness of this approach. This study aimed to evaluate the therapeutic effect of BTXA on postoperative hypertrophic scars and its influence on cytokine expression in animal models. A computerised search of different databases was performed, including PubMed, Web of Science, Scopus, Cochrane, Embase, CNKI, and Wanfang, up to 10 March 2021. A meta‐analysis was performed using R 4.0.0 based on hypertrophic index, epithelialisation time, wound area, and vascular endothelial growth factor (VEGF) expression. Eleven studies were included. The meta‐analysis showed a significant difference in hypertrophic index (standardised mean difference [SMD] = −2.63, 95% confidence interval [CI]: −3.50 to −1.76, P <.01), wound area (SMD = −0.54, 95% CI: −1.24 to 0.16, P <.01), and VEGF expression (SMD = −2.56, 95% CI: −3.50 to −1.62, P <.01). This study shows that BTXA is safe and effective in preventing and treating scar hypertrophy in animal models, but excessive doses of BTXA and BTXA to treat large areas should be avoided. [ABSTRACT FROM AUTHOR]

Introduction: When applying botulinum toxin in the upper third of the face, it is important to consider the balance between the elevator and depressor muscles of the eyebrows. Depressor supercilii muscle block leads to elevation of the medial portion of the eyebrow and correction of the oblique lines in the frown. Objectives: The intention is to highlight the importance of the depressor supercilii muscle block as a useful tool to reposition the medial portion of the eyebrow. Patients and methods: Three cases are presented, in whom botulinum toxin is applied conventionally and subsequently on the depressor supercilii muscle after the subjective sensation of flattening of the glabella and increasing distance between the eyebrows referred by the patients. Results: The application of botulinum toxin type A on the depressor supercilii muscle is an effective measure to facilitate the elevation of the medial portion of the eyebrow, after the conventional application in between the eyebrows treating the orbicularis, corrugator, and procerus muscles. Conclusions: Depressor supercilii muscle block can be considered when applying botulinum toxin type A in the upper third of the face, in cases where there is loss of facial aesthetic harmony. This is given by the subjective perspective of the patient due to a change in the natural expression of their face with a sensation of flattening of the glabella and distancing of the medial portion of the eyebrows, occurring after the use of a conventional technique at that anatomical level, where patients may report a "feline" or "avatar" appearance. [ABSTRACT FROM AUTHOR]

Background: The human face significantly affects the individuals' quality of life, attitude, and mental state. The study of anatomy would always be on the spotlight, as the beauty of the face is desired by humans worldwide. However, age, stress, and negative emotions could lead to stimulation of the corrugator supercilii and procerus muscles in the glabellar region and, subsequently, to alterations in face's characteristics, which could be associated with isolation and avoidance of engaging in social contacts. Aims: Here, we aimed to examine the degree to which treatment with botulinum toxin type A (BoNT A) can affect patients' quality of life and mental state. Patients/Methods: The data collection was performed using 11 questionnaires, which were filled by 83 individuals who underwent BoNT A treatment (sex, 95% female and 5% male; mean age, 48 years). Results: The results showed that the treatment with BoNT A improved the patients' social and psychological behavior, and their opinion regarding their appearance. This effect developed within 1 month following completion of the treatment. Moreover, the effect was higher in patients' social behavior and was better in patients aged 40–49 years compared to those aged <40 and ≥49 years. Conclusions: Thus, BoNT A treatment could be considered as an important way to improve the social behavior and socialization of individuals by raising their psychology and self‐esteem. [ABSTRACT FROM AUTHOR]

Objective: To assess the efficacy and safety of botulinum toxin treatment (onabotulinumtoxinA 200 units) for Japanese patients with neurogenic detrusor overactivity caused by spinal cord injury or multiple sclerosis. Methods: Patients with urinary incontinence refractory to pharmacological treatment were enrolled and randomized in a phase III trial. A single dose of onabotulinumtoxinA (n = 11) or placebo (n = 10) was given in the double‐blind phase, and repeat injections of onabotulinumtoxinA were given in the subsequent open‐label phase. Outcomes included urinary incontinence episodes, urodynamics, patient‐reported outcomes and adverse events. Results: The onabotulinumtoxinA group showed a numerically greater reduction in the number of urinary incontinence episodes per day than the placebo group, with the difference between the groups at week 6 of −3.02 (95% confidence interval −5.85 to −0.19). The onabotulinumtoxinA group also showed greater improvements in urodynamic assessments. Adverse events related to onabotulinumtoxinA injections were hematuria, urinary retention, urinary bladder hemorrhage, autonomic dysreflexia and epididymitis. Most events were deemed mild or moderate. Conclusions: Intradetrusor injections of onabotulinumtoxinA are efficacious and tolerable for Japanese patients with neurogenic detrusor overactivity‐related symptoms that are difficult to manage with anticholinergics and/or β3‐adrenergic receptor agonists. [ABSTRACT FROM AUTHOR]

Objective: In this study, we sought to determine the expression profiles of long non‐coding RNAs (lncRNAs) and messenger RNAs (mRNAs) and construct functional networks to analyze their potential roles following botulinum toxin type A (BTXA)‐mediated inhibition of salivary secretion. Methods: The submandibular gland of rats in the BTXA and control groups was injected with BTXA and saline, respectively. Microarray analysis was used to identify the differentially expressed lncRNAs and mRNAs. Gene ontology and pathway analysis were performed to examine the biological functions. Functional networks, including lncRNA‐mRNA co‐expression and competing endogenous RNA (ceRNA) networks, were constructed to reveal the interaction between the coding and non‐coding genes. Results: Microarray analysis revealed that 254 lncRNAs and 631 mRNAs were differentially expressed between the BTXA and control groups. Bioinformatic analysis revealed that most of the mRNAs were closely related to transmembrane transporter activity. lncRNA‐mRNA co‐expression and ceRNA networks were constructed, and several critical mRNA‐lncRNA axes and key microRNAs related to salivary secretion were identified. Conclusions: Our study identified differentially expressed lncRNAs and mRNAs through microarray analysis and explored the interactions between the coding and non‐coding genes through bioinformatic analysis. These findings provide new insights into the mechanism of BTXA‐mediated inhibition of salivary secretion. [ABSTRACT FROM AUTHOR]

Background: Botulinum toxin type A (BoNT- A) injection remains the leading medical cosmetic procedure worldwide, with a high rate of patient satisfaction. However, it still suffers from patients' fear of being unable to transmit their emotions and of looking frozen from unnatural results. Aim: This study aimed to determine whether BoNT- A can decrease the intensity of emotions in facial expressions. Patients/Methods: In this single- center prospective study, 42 patient investigators assessed four patients' facial expressions for six emotions and neutral faces, before and after injection of 36 IU or 48 IU of onabotulinumtoxinA, using photographs. Photographs were presented on a tablet to the investigators. Results: There were no statistical differences between the before and after photographs for the intensity of emotions for all expressions (P > .05) except for the expression of surprise in the group of patients that received 48 IU of the injection (protocol with injection of the frontalis muscle). All patient investigators answered negatively to the question "Do you think that this patient has a 'frozen face'?". Conclusion: This study shows that esthetic injection of BoNT- A in the upper face has no negative effects on facial expressions and does not lead to the feared "frozen face" when it is injected with respect for best practice guidelines. This study can be used as an example for patients who have some reticences against BoNT- A injection. [ABSTRACT FROM AUTHOR]

Background: Hypertrophic scar is a common complication in would healing process, and how to effectively prevent and treat it has been a hot and difficult research issue. Previous studies have showed that botulinum toxin type A (BTA) has effects on the prevention and treatment of hypertrophic scar, but little is known about the specific mechanisms. Objective: This study aimed to explore the potential mechanisms of BTA on the inhibition of hypertrophic scar formation. Methods: Hypertrophic scar-derived human fibroblasts were cultured and then treated with transforming growth factor-β1 (TGF-β1) and various concentrations of BTA. Cell proliferation and viability were measured by CellTiter 96® AQueous One Solution Cell Proliferation Assay and trypan blue staining, respectively. The total amount of collagen was examined using Sirius red staining. Collagen I and Collagen III in the culture supernatant were evaluated by enzyme-linked immunosorbent assay. Reverse transcription-quantitative polymerase chain reaction and Western blot analysis were performed to detect the transcription and translation levels. Results: Our results revealed that BTA decreased the proliferation of hypertrophic scar-derived human fibroblasts. The mRNA and protein expression levels of alphasmooth muscle actin, collagen I, and collagen III induced by TGF-β1 were inhibited by BTA in a dose-dependent manner. BTA also inhibited the phosphorylation of Smad2/3 and ERK. Conclusion: BTA decreased the proliferation of fibroblasts and prevented overdeposition of ECM through the inhibition of the TGF-β1/Smad and ERK pathways. The findings of this study provide new scientific reference for the prevention and treatment of hypertrophic scar. [ABSTRACT FROM AUTHOR]

Background: Both age‐related and congenital volume deficiencies may be addressed through the injection of hyaluronic acid (HA) fillers. Deep injection provides structural support, more superficial fat‐tissue injection mediates contouring, and superficial intradermal use of HA filler and/or onabotulinumtoxinA may be used for refinement. Aims: To evaluate the clinical efficacy, patient satisfaction, and safety of the MD Codes approach as a proposed standardized methodology for full‐face rejuvenation. Methods: This was a retrospective, single‐center study of 250 consecutive adult patients undergoing full‐face rejuvenation with HA fillers (Vycross) and onabotulinumtoxinA based on the MD Codes approach. Results: The mean age was 39.4 ± 11.6 years, and 80.4% were female. All patients were treated with HA filler in the midface; 89.6% were also treated in the upper face, and 63.2% in the lower face. The mean number of syringes used was 14 ± 4 (range 4‐25), with more syringes typically required in older versus younger patients. All patients received onabotulinumtoxinA treatment. Mean FACE‐Q Appearance‐Related Psychosocial Distress score decreased from 54.3 ± 9.3 pretreatment to 36.1 ± 8.9 at 3 months post‐treatment (P <.05). The most common complications were bruising (35.2%), transient soft‐tissue edema (14.0%), and prolonged periorbital edema (3.6%). Conclusions: Full‐face rejuvenation based on the MD Codes approach provides significant esthetic improvements, with no major safety issues observed. [ABSTRACT FROM AUTHOR]

Background: Botulinum toxin type A (BTA) injection is a widely‐used procedure to correct cosmetic problems caused by muscular hyperactivity. "Cobblestone chin" refers to the appearance of remarkable chin creases caused by mentalis contraction. Aims: The aim of this case report is to raise the awareness of paradoxical bulging after BTA injection in mentalis. Patient/Methods: A 26‐year‐old female asked for cosmetic correction of the "cobblestone chin". BTA injection was performed routinely to the mentalis muscle. However, on the second day after injection, an unusual paradoxical bulging at chin was presented. Results: We speculated that the imbalanced relaxation of mentalis caused by improper injection and uneven diffusion of BTA is responsible for the bulging. After a supplementary injection of BTA in the remaining hyperactive muscle fibers based on the ultrasound examination, the bulging was relieved and chin contour improved significantly. Conclusion: Injection of BTA in mentalis should cover the whole thickness of the muscle to prevent imbalanced paralysis and paradoxical chin bulging, especially in severe mentalis hyperactivity cases. [ABSTRACT FROM AUTHOR]

New indications are being reported for intradermal botulinum toxin type A (BTX‐A) owing to its anti‐inflammatory and antipruritic actions. Its successful use for dyshidrotic hand eczema and lichen simplex has been reported in a few cases, while its utility in dry palmar eczema not associated with hyperhidrosis has not yet been investigated. The aim of this study was the assessment of the additive efficacy and tolerability of BTX‐A in chronic dry palmar eczema. This prospective non‐randomized side‐by‐side comparative study included 30 cases of chronic bilateral dry palmar eczema with no associated hyperhidrosis. Combined emollients and topical mid‐potency steroid on one side were compared with an additive 100 units of intradermal BTX‐A on the other side for efficacy and tolerability using both patient‐ and physician‐oriented scores over a period of 6 months. Timing and extent of improvement and relapse were recorded on both sides, together with the frequency of development of side‐effects. Both lines were effective and well tolerated, with significantly greater reduction of symptom and sign scores and higher overall patient satisfaction on the side receiving BTX‐A, an effect which lasted for a significantly longer duration on this side (4 months) as compared with the other side (1 month). In conclusion, intradermal BTX‐A at a dose of 100 units/palm is beneficial and well tolerated in chronic dry palmar eczema. Compared with topical steroid and emollients alone, its addition yielded superior efficacy that was longer lasting and more satisfactory to the patients, while exerting a steroid‐sparing effect. [ABSTRACT FROM AUTHOR]

Background: Botulinum toxin type A injection is a common aesthetic treatment that can be used alone or in combination to rejuvenate the entire face and neck. Objectives: To assess the safety and efficacy of a full‐face approach with botulinum toxin type A. Methods: This was a single‐center, retrospective review of data from 189 patients receiving full‐face and neck treatment with onabotulinumtoxinA in the following areas: glabellar lines, crow's feet lines, forehead lines, bunny lines, sagging nasal tip, gummy smile, marionette lines, mentalis, masseter, and lateral/anterior platysma. Results: The mean age was 56.6 ± 9.2 years, and 94.7% were women (n = 179). Patients received a total of 394 full‐face treatments (mean: 2.1 per person; range 1‐7). The mean quantity of onabotulinumtoxinA injected was 113.8 ± 17.6 units per treatment (range: 50‐180 units). The most frequently injected areas were the glabella/crow's feet/forehead (n = 383; 97.2%), platysma (n = 378; 95.9%), bunny lines (n = 283; 71.8%), and chin (n = 120; 30.5%). Six patients (3.2%) experienced complications: five cases of unwanted diffusion from the mentalis into the depressor labii inferioris and one case of right eyelid ptosis after injection in the upper third. All were minor and none appeared to be related to overall dose. Conclusions: Full‐face and neck treatment with onabotulinumtoxinA can be performed without substantial safety concerns, often leading to excellent results. This approach may become increasingly prevalent in the coming years. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy and safety of onabotulinumtoxinA (botulinum toxin type A) 100 U in patients with overactive bladder and urinary incontinence. Methods: This was a phase III, randomized, double‐blind, placebo‐controlled trial in Japanese patients who were inadequately managed with overactive bladder medications (anticholinergics and/or β3‐adrenergic receptor agonists). Eligible patients were randomized 1:1 to receive a single dose of either onabotulinumtoxinA or placebo into the detrusor muscle (n = 124 each). The primary end‐point was the change in the number of daily urinary incontinence episodes at week 12 from baseline. Secondary end‐points included volume voided per micturition, other symptomatic measures (urinary urgency incontinence, micturition, urgency and nocturia) and patient‐reported outcomes. Results: In the onabotulinumtoxinA group, there was a significantly greater decrease from baseline in the mean number of daily urinary incontinence episodes compared with the placebo group (2.16; P < 0.001), and significantly greater improvement for all secondary end‐points (P < 0.05). Urinary tract infection, dysuria, urinary retention and post‐void residual urine volume increased represented adverse events occurring at a higher rate in the onabotulinumtoxinA group. The majority of these were mild or moderate in severity. Conclusions: Statistically significant and clinically relevant improvements in symptoms and patient‐reported outcomes, and tolerability were seen in patients with overactive bladder and urinary incontinence who had been inadequately managed with overactive bladder medications after using onabotulinumtoxinA. [ABSTRACT FROM AUTHOR]

Background: The intraglandular application of botulinum neurotoxin type A (BoNT-A) is used in patients with neuromotor disorders to control the escape of saliva. The aim of this study was to analyze the impact of repeated treatment with BoNT-A on the submandibular-sublingual complex of rats.Methods: A total of 35 Wistar rats were divided into three groups: control group (C), in which animals were not treated; group B, treated with 2.5 U intraglandular injections of BoNT-A (Prosigne® ) and group G, that received bovine gelatine (Prosigne stabilizer). Three applications were performed in intervals of 35 days. Twelve and 35 days after ending the treatment, submandibular-sublingual complex was collected for histological analysis. Immunohistochemical reactions for calponin and specific muscle actin were also performed, besides detection of apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay.Results: A decrease in mucosal and serous acini diameter was observed, with increased interstitial space after 12 days of treatment with BoNT-A, which was observed in a lesser degree on the 35th day. At 12 days, immunohistochemical analysis revealed a decrease in myoepithelial cells of serous acini in group B. TUNEL methods evidenced apoptosis in animals from group B.Conclusions: BoNT-A caused histological and cellular changes in submandibular-sublingual complex, followed by a tendency toward reversal after 35 days. The reversal characteristic of cellular changes in the submandibular-sublingual complex suggests that this BoNT-A formulation may be safely used for sialorrhea treatment. [ABSTRACT FROM AUTHOR]

Botulinum Toxin Type A is a potent neurotoxin that is produced by a gram‐positive bacteria clostridium botulinum. Its utilization in the treatment of various medical condition has expanded over the years in both medical and esthetic uses. It is being preferred by most physicians due to its efficacy and lack of side effects. It can be used as monotherapy or combined therapy. The aim of this review study was to show the role and mechanism of action of Botulinum toxin type A in the treatment and prevention of hypertrophic scars and keloids. The clear mechanisms underlying hypertrophic scars and keloids are still not clearly understood; however, the mechanism of action of Botulinum toxin type A has been shown to include action on wound tension, action on collagen, and action on fibroblasts. Different randomized controlled trials, double‐blind, and placebo‐controlled studies have been conducted to investigate its use in treatment and prevention of hypertrophic scars and keloids, and it still is one of the active areas of research in Dermatology and related fields. Method: In March 2018, we performed a literature search in PubMed for clinical studies, clinical trials, case reports, controlled trials, randomized controlled trials, and systemic reviews. The search terms we used were "BOTULINUM TOXIN" AND "HYPERTROPHIC SCARS" OR "KELOIDS" (from 1980). The search resulted in 1000 articles, out of these 35 articles met our inclusion exclusion criteria. Our inclusion criteria included relevant original articles relevant, critical systemic reviews, and crucial referenced articles, exclusion criteria included duplicates and articles not published in English language. We have reviewed these papers to show the role and mechanism of action of Botulinum toxin type A in the treatment and prevention of hypertrophic scars and keloids. [ABSTRACT FROM AUTHOR]

Summary: Background: Enlarged, hypertrophy calf muscles are common in Asian women and can cause psychological burden. Botulinum toxin A (BTA) has been widely used in treating masseteric muscle hypertrophy and it's efficacious as a noninvasive method for calf‐contouring has been reported. Food and Drug Administration has approved onabotulinumtoxin A (ONA, Botox; Allergan Inc, Irvine, CA, USA) for upper face rejuvenation and it has off‐label uses for calf‐contouring. A recently introduced Prabotulinumtoxin A (NABOTA®, PRA; Daewoong Pharmaceutical, Seoul, Korea) demonstrated a comparable efficacy and safety to ONA for masseter reduction. Objective: To compare the efficacy and safety of PRA and ONA gastrocnemius muscle reduction. Methods: This is an experimental, randomized, controlled double‐blind study. Twenty‐two patients were randomized to receive 100 units PRA and ONA on each calf and were asked to come for follow‐up visit for up to 6 months. Clinical photographic documentation, calf circumference measurement (upright position and tiptoe), isokinetic analysis, and ultrasonographic imaging were performed to evaluate the treatment result. In addition, patients' satisfaction and side effect were also recorded. Results: All patients completed the study without serious side effect occurred during the whole study period. The mean calf circumference of the ONA‐ and PRA‐treated patients in upright position at baseline was 35.42 ± 1.35 cm and 36.49 ± 2.98 cm, respectively (P = 0.137). The mean calf circumference in upright position decreased significantly as early as 2 weeks after treatment, both in ONA group and in PRA group (P = 0.004 and P = 0.003, respectively), and continued to decrease until 6 months after treatment (P = 0.002 and P < 0.001, respectively). There was no statistically significant difference in mean calf circumference when comparing between ONA and PRA group at any time of follow‐up period. For the tiptoe position, only in the PRA group that showed significant reduction as early as two weeks and lasted up to 6 months of follow‐up (P < 0.001). The isokinetic analysis showed no significant reduction on both maximum torque and average work value in two groups. The ultrasonographic imaging revealed that the mean thickness of the lateral head of the gastrocnemius showed significant only in PRA‐treated group at 2‐, 3‐, and 6‐months of follow‐up; meanwhile, the mean thickness of the medial head showed significant reduction at 2‐ and 6‐months, with a slight increase at 3‐months follow‐up in two groups. The patients' satisfaction rate and doctor's evaluation also showed no statistically significant difference between both groups. Conclusion: This study demonstrated that PRA and ONA provided comparable efficacy and safety in gastrocnemius muscle reduction. [ABSTRACT FROM AUTHOR]

The demand for the use of mice as animal models for elucidating the pathophysiologies and pathogeneses of oral motor disorders has been increasing in recent years, as more and more kinds of genetically modified mice that express functional disorders of the stomatognathic system become available. However, the fundamental characteristics of mouse jaw movements during mastication have yet to be fully elucidated. The purpose of this study was to investigate the roles of the masseter and temporalis muscles, and the mechanisms of motor coordination of these muscles for increasing masticatory efficiency in the closing phase in mice. Twenty-two male Jcl: ICR mice were divided into control ( n = 8), masseter-hypofunction ( n = 7) and temporalis-hypofunction groups ( n = 7). Botulinum neurotoxin type A (Bo NT⁄A) was used to induce muscle hypofunction. The masticatory movement path in the horizontal direction during the occlusal phase became unstable after Bo NT⁄A injection into the masseter muscle. Bo NT⁄A injection into the temporalis muscle decreased antero-posterior excursion of the late-closing phase corresponding to the power phase of the chewing cycle. These results suggest that the masseter plays an important role in stabilizing the grinding path, where the food bolus is ground by sliding the posterior teeth from back to front during the occlusal phase. The temporalis plays a major role in retracting the mandible more posteriorly in the early phase of closing, extending the grinding path. Masticatory efficiency is thus increased based on the coordination of activities by the masseter and temporalis muscles. [ABSTRACT FROM AUTHOR]

Aims To determine if minimizing the number of onabotulinumtoxinA (BTX) injection sites to one to three locations provides similar clinical efficacy and duration of effect compared to the established technique in treating patients with neurogenic (NDO) or idiopathic detrusor overactivity (IDO). Methods Prospective data were collected on BTX naïve patients with NDO or IDO who were intolerant or refractory to oral medications. Patients were treated with 100-300 U of BTX via one to three injection sites. Patients completed the International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF) prior to and after treatment. The primary endpoint was defined as ICIQ-SF score improvement of >5 points. Secondary endpoints included subjective success, complete continence, quality of life score, post void residual (PVR), duration of effect and adverse events. Results Fourty-five patients (22 IDO, 23 NDO) were included. ICIQ-SF score improvement of >5 points was achieved in 73% (IDO 55%, NDO 91%) and the subjective success rate was 69% (50% IDO, 87% NDO). 52% of NDO patients attained complete continence. PVR increased by a mean of 32 and 156 ml in the IDO and NDO groups. Hematuria occurred in 6.7% and symptomatic urinary tract infection occurred in 11.1%. No systemic BTX adverse events occurred. Mean duration of effect was 31 weeks. Conclusions Our technique for administering BTX via one to three intradetrusor injection sites has similar clinical efficacy and rates of adverse events compared to the established technique for treating patients with IDO and NDO. Neurourol. Urodynam. 36:1104-1107, 2017. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Aims To study the expression of cleaved synaptosomal associated protein of 25 kDa (cSNAP-25) in the bladder wall injected with onabotulinumtoxinA (onabotA) or abobotulinumtoxinA (abobotA) and compare the relative potency of these two brands. Methods One injection of 0.5 U of onabotA or abobotA diluted in 2 µl of saline was carried out in the bladder dome of adult female mice, whose bladders were exposed by laparotomy. Three days later bladders were collected, divided in five segments (dome, upper, middle and lower body, and trigone) and each one was sectioned and immunoreacted against cSNAP-25, the end product of botulinum toxin type A (BoNT/A) activity. From each of the five segments one section was taken at random and the number of cSNAP-25 immunoreactive (IR) fibers was determined. Results Each injection resulted in the cleavage of SNAP-25 in all bladder sections, including those of the more distant segment from the injection point. The average number of cSNAP-25 positive fibers was higher in the onabotA, 341 ± 301, than in the abobotA-treated mice, 208 ± 152 ( P = 0.003). The number of cSNAP-25 IR fibers varied three to five-fold between animals of each experimental group. Conclusions These findings confirm that, when injected in the bladder wall, in the same unit amount and same volume, onabotA is 1.6 times more potent to cleave SNAP-25 than abobotA. The conversion ratio suggested by these experiments is 1:1.6 between onabotA and abobotA. Each injection, although preformed in the same way, may induce substantially different amounts of cSNAP-25. Neurourol. Urodynam. 36:86-90, 2017. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 72-year-old male patient diagnosed with multiple sclerosis (MS) since the age of 26, initially presenting with left-side hemiparesis. It notes the patient developed bouts of left periorbital intense pain, without dysautonomic signs at age 65; and also mentions treatment with Botulinum toxin type A (BTX-A).

The most international dosing guidelines on the use of botulinum toxin type A ( BTXA) drugs support a 1:1 dose relationship between Ona BTXA and Inco BTXA and 1:2.5 between OnaBTXA and AboBTXA. However, different facial zones demonstrate different doses conversion ratios. The comparative analysis of nine consensuses on the use of Abo-, Ona-, and Inco BTXA in the United States, Russia, and Europe has been performed. We conducted a review of publications adopting the key words 'botulinum toxin consensus,' 'botulinum toxin guideline.' Information search has been carried out primarily in specialized databases ( DB). To find the relevant RCTs and guidelines/consensuses, the following databases were used: PubMed and Medline that were screened up to May 2008. Results regarding dose ratios for Ona BTXA:Abo BTXA and Inco BTXA:Abo BTXA showed that in most cases it is characterized both by increase and by decrease compared to the ratio of 1:2.5. The mean value of dose ratios Ona BTXA:Abo BTXA adopted in the United States is 1:2.8. The ratio Inco BTXA:Abo BTXA according to international and Russian data is 1:1.9. There are some differences in clinical approach of BTXA use in certain countries. In Russia, low doses are recommended for 'crow's feet' and forehead. The US consensus recommends a higher dosage to correct perioral wrinkles. Despite many years of experience in using BTXA, there is no strict international uniformity of clinical guidelines. The recommended doses for the individual areas of the face may differ in different countries. Therefore, physicians in their practice should be guided not by international consensuses, but prefer a national guidelines. [ABSTRACT FROM AUTHOR]

Introduction Knee flexion contracture ( KFC) remains a common complication of haemoarthrosis in children and young adults with haemophilia. If the KFC is not treated properly it produces disability, postural and gait abnormalities. Objective Evaluate the effectiveness of conservative treatment of KFC with Botulinum toxin type A ( BTX-A) in PWH. Methods Seventeen patients were treated, with 21 affected knees. Mean age was 26 years. The mean follow up was 12 months. We evaluated flexion and KFC pretreatment BTX-A and up to 12 months posttreatment. BTX-A application was in hamstring and calf muscles. To evaluate the function, a questionnaire about different activities was made, and it was checked 3, 6 and 12 months after BTX-A. According to the degree of KFC, knees were divided into 3 groups: Group 1: −10° to −30° ( n = 10), Group 2: −31° to −45° ( n = 6) Group 3: −46° or more ( n = 5). Results The average KFC improved from −38° to −24°. The improvement was 14° ( P < 0.001). The average KFC improvement was 9° in group 1, 17° in group 2, and 23° in group 3. There was a high correlation between the improvement in KFC and the total score of the questionnaire R = 0.77. Conclusions Treatment of KFC with BTX-A improves knee-related functional activities, with the advantage of being a low-cost procedure and easy to apply. [ABSTRACT FROM AUTHOR]