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BACKGROUND Botulinum toxin A (BoNT-A) is widely used in treating dystonia and spasticity to managing chronic migraine and cosmetic applications. However, its immunogenic potential presents challenges, such as the development of neutralizing antibodies that lead to diminished therapeutic efficacy over time, known as secondary nonresponse. OBJECTIVE This review aims to bridge the knowledge gap regarding the immunogenic mechanisms of BoNT-A and to explore effective management strategies to mitigate these immune responses. MATERIALS AND METHODS The authors conducted a systematic search in databases including PubMed, Embase, and Web of Science, using keywords related to BoNT-A's immunogenicity. The selection process refined 157 initial articles down to 23 relevant studies, which underwent analysis to investigate the underlying mechanisms of immunogenicity and the factors influencing it. RESULTS The analysis revealed that both the neurotoxin component and the neurotoxin-associated proteins could elicit an immune response. However, only antibodies against the core toxin influence therapeutic outcomes. Various patientspecific factors such as genetic predispositions and prior immune experiences, along with treatment-related factors such as dosage and frequency, play crucial roles in shaping these responses. CONCLUSION Understanding the specific immunogenic triggers and responses to BoNT-A is critical for optimizing treatment protocols and improving patient outcomes. [ABSTRACT FROM AUTHOR]

Background: Platelet-rich plasma (PRP) is widely used in various medical and surgical specialties for its regenerative properties, including aesthetics (facial rejuvenation, hair restoration, and skin tightening) and orthopedics (treatment of tendinitis and osteoarthritis). However, the inconsistent literature on PRP's efficacy and safety leads to critical knowledge gaps. This systematic review evaluates quality control measures in PRP preparation and application and explores the regulatory environment governing its clinical use. Methods: Following PRISMA guidelines, a comprehensive search was conducted across multiple databases, including PubMed, EMBASE, and Web of Science, for studies published from January 2020 to April 2024. The review included randomized controlled trials (RCTs) involving human participants undergoing PRP treatment for aesthetic or regenerative purposes. Key parameters such as the PRP preparation methods, platelet concentration, and quality control measures were analyzed. The study protocol was registered with PROSPERO (ID: CRD42024557669). Results: Out of 75 RCTs involving 5726 patients, the review identified significant variability in PRP preparation methods and application techniques, including differences in centrifugation protocols and platelet concentration levels. A new evidence-based scoring system, the William–Eqram Scoring System for PRP Quality Reporting (WESS-PQR), was proposed to address these inconsistencies. Correlation analysis revealed a strong positive correlation (r = 0.79) between proper temperature control during preparation and PRP efficacy. Initial platelet count assessment showed a moderate positive correlation (r = 0.57) with efficacy. Conclusions: Standardized PRP preparation protocols and robust regulatory frameworks are urgently needed to ensure the safety and efficacy of PRP treatments. The proposed WESS-PQR scoring system can serve as a valuable tool for clinicians and researchers, promoting consistency and reliability in PRP applications. [ABSTRACT FROM AUTHOR]

Background: Onabotulinumtoxin A (Onabot A) has already marked its name in history as the first to be approved for aesthetic indications, namely glabellar (GL), crow's feet (CFL) and forehead lines (FHL), with 64 units of cumulative dose.Objective: As more real-world evidence and robust randomised clinical studies exist, the authors sought to conduct a meta-analysis with trial sequential analysis to combine the available data with approved doses for GL, CFL and FHL to explore the effect and duration of simultaneous treatment with Onabot A.Methods: PubMed/MEDLINE, EMBASE and other national clinical trial registries were searched for randomized controlled trials (RCTs) from January 2010 to July 2022. The meta-analysis, trial sequential analysis and the investigator-assessed time to return to the non-responder status in GL, CFL and FHL following Onabot A were plotted to elicit a cumulative dose-adjusted response curve using the Kaplan-Meier analysis with the log-rank test.Results: Fourteen RCTs were eligible for quantitative analysis. A total of 8369 subjects were recruited across the trials. The meta-analysis results show that Onabotulinum toxin a is very effective in reducing moderate to severe GL, CFL and FHL. The cumulative Z-curve for GL, CFL and FHL t also exceeds the information size. Kaplan-Meier analysis with the log-rank test demonstrated that simultaneous treatment of GL, CFL and FHL requires 182 days (95% CI 179, 215) (p < 0.00002) to return to the non-responder status.Conclusions: Treatment of the upper facial expression lines with Onabot A has proven effective with a longer duration of effects with the approved doses of 64 units. Until future trials explore the dose titration in males, neuromuscular junction mapping, and pharmaco-epigenetic profiling to explore the role and effect of messenger ribonucleic acid (mRNA) on sprouting, clinicians should adhere to the most substantial scientific evidence available. [ABSTRACT FROM AUTHOR]

Background Botulinum toxin A (BTX-A) is commonly employed as a neuromodulator in several neurological diseases and aesthetic indications. Formation of neutralizing antibodies (NAbs) after BTX-A injections may be responsible for treatment failure. Objectives The authors sought to quantify the prevalence of NAbs following treatment with Abobotulinumtoxin A, Incobotulinumtoxin A, and Onabotulinumtoxin A for therapeutic indications. Methods An electronic systematic search (2000-2020) of PubMed, Scopus, Web of Science, and Embase was conducted. Original studies reporting prevalence of NAbs were included. Data analysis was carried out through open meta-analysis softwares. Results Forty-three studies involving 8833 patients were included in this meta-analysis. The incidence of NAbs was 1.8% (summary estimate = 0.018, 95% CI [0.012, 0.023]); a meta-regression analysis revealed that BTX-A duration was significantly associated with increased incidence of NAbs (P  = 0.007). Patients with dystonia had the highest incidence (7.4%) of NAbs against BTX-A (summary estimate = 0.074, 95% CI = [0.045, 0.103], I2 = 93.%, P  < 0.00) followed by patients with spasticity (6.7%) and urological indications (6.2%). Abobotulinumtoxin A was associated with the highest incidence of NAbs (7.4%) (summary estimate = 0.074, 95% CI = [0.053, 0.096], I2 = 97.24%, P  < 0.00) by the Incobotulinumtoxin A and Onabotulinumtoxin A 0.3% (summary estimate <0.003%, 95% CI = [−0.001, 0.007], P  < 0.003). Conclusions Although the overall incidence of NAbs following BTX-A injections is relatively low, patients with secondary nonresponse to BTX-A with no apparent causes should be investigated for NAbs. A consensus needs to be developed for the optimal management of such patients. Level of Evidence: 2 [ABSTRACT FROM AUTHOR]

Background Aesthetic physicians rely on certain anecdotal beliefs regarding the safe practice of filler injections. These include a presumed safety advantage of bolus injection after a negative aspiration. Objectives The authors sought to review and summarize the published literature on inadvertent intravascular injection of hyaluronic acid and to investigate whether the technique of aspiration confers any safety to the practitioner and the patient. Methods Pertinent literature was analyzed and the current understanding of the safety of negative and positive aspiration outlined. Results The available studies demonstrate that aspiration cannot be relied on and should not be employed as a safety measure. It is safer to adopt injection techniques that avoid injecting an intravascular volume with embolic potential than utilize an unreliable test to permit a risky injection. Conclusions To prevent intravascular injection, understanding "injection anatomy" and injection plane and techniques such as slow, low-pressure injection are important safety measures. Assurance of safety when delivering a bolus after negative aspiration does not appear to be borne out by the available literature. If there is any doubt about the sensitivity or reliability of a negative aspiration, there is no role for its utilization. Achieving a positive aspiration would just defer the risk to the next injection location where a negative aspiration would then be relied on. Level of Evidence: 4 [ABSTRACT FROM AUTHOR]