New and Future Developments in Neurotoxins.

BACKGROUND: There are 7 known serotypes of botulinum neurotoxins (A through G). Currently, commercially available toxins are those in serotypes A and B. This paper will discuss new toxins on the horizon, developments in prolonging and shortening the duration of outcomes, and novel therapeutic indications on the horizon. OBJECTIVE: To provide insight into new toxins and new therapeutic modalities surrounding toxins on the horizon. METHODS: The authors have reviewed the relevant literature and shared their insights and opinions as to future developments in toxin research and potential clinical applications. CONCLUSION: Botulinum neurotoxin type E's faster onset and shorter duration of effect represent true clinical differentiators. Future development of botulinum neurotoxin type E for aesthetic and therapeutic uses will be in areas where fast onset and short duration of effect are desirable. Current challenges with neuromodulators include the need for frequent treatments and lack of reversal agents. Agents to address both challenges and novel indications, including inhibition of melanogenesis, are being developed.

Neurotoxins and Combination Therapies.

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

Embracing the Versatility of Botulinum Neurotoxins in Conventional and New Therapeutic Applications.

Botulinum neurotoxins (BoNTs) have been used for almost half a century in the treatment of excessive muscle contractility. BoNTs are routinely used to treat movement disorders such as cervical dystonia, spastic conditions, blepharospasm, and hyperhidrosis, as well as for cosmetic purposes. In addition to the conventional indications, the use of BoNTs to reduce pain has gained increased recognition, giving rise to an increasing number of indications in disorders associated with chronic pain. Furthermore, BoNT-derived formulations are benefiting a much wider range of patients suffering from overactive bladder, erectile dysfunction, arthropathy, neuropathic pain, and cancer. BoNTs are categorised into seven toxinotypes, two of which are in clinical use, and each toxinotype is divided into multiple subtypes. With the development of bioinformatic tools, new BoNT-like toxins have been identified in non-Clostridial organisms. In addition to the expanding indications of existing formulations, the rich variety of toxinotypes or subtypes in the wild-type BoNTs associated with new BoNT-like toxins expand the BoNT superfamily, forming the basis on which to develop new BoNT-based therapeutics as well as research tools. An overview of the diversity of the BoNT family along with their conventional therapeutic uses is presented in this review followed by the engineering and formulation opportunities opening avenues in therapy.

Beyond Wrinkles: A Comprehensive Review of the Uses of Botulinum Toxin.

BACKGROUND: Botulinum neurotoxin (BoNT) exhibits inhibitory effects on the neuromuscular junction, and its use is well established in cosmetic dermatology. Our review aims to analyze the evidence for its use in the treatment of various dermatological, neurological, gastroenterological, ophthalmological, otorhinolaryngological, dental, urological, gynecological, and cardiovascular disorders. METHODS: A systematic review of the literature was performed for studies published between 2012 and 2022 that discussed the therapeutic use of BoNT in human participants. A total of 58 studies were selected for inclusion in this review.  Results: We discovered a large range of therapeutic applications of BoNT toxin beyond aesthetic and US Food and Drug Administration (FDA)-approved non-aesthetic uses.  Conclusions: BoNT is a powerful neurotoxin that has varied FDA-approved indications and has been studied in a wide range of therapeutic applications. Further investigation through higher power studies is needed to assess the potential of BoNT and expand its versatility across other medical specialties.  J Drugs Dermatol. 2024;23(3):173-186. doi:10.36849/JDD.7243e.

Neuromodulators for Skin.

Neurotoxins are the most popular nonsurgical aesthetic procedure for men and women of all ages. Five botulinum toxin A (BoNTA) products represent the current palette of available BoNTA for cosmetic use. Off-label uses of BoNTA continue to expand and are now used for skin rejuvenation, to treat various skin disorders, and in facial nerve paralysis. Dermal and subdermal injections of dilute BoNTA has grown in popularity and been shown to improve skin texture and quality. Common targets for chemodenervation in facial nerve synkinesis are ipsilateral orbicularis oculi, mentalis, depressor anguli oris, buccinator, corrugator muscles, and the ipsilateral and/or contralateral frontalis.

Beyond Wrinkles: A Comprehensive Review of the Uses of Botulinum Toxin.

BACKGROUND: Botulinum neurotoxin (BoNT) exhibits inhibitory effects on the neuromuscular junction, and its use is well established in cosmetic dermatology. Our review aims to analyze the evidence for its use in the treatment of various dermatological, neurological, gastroenterological, ophthalmological, otorhinolaryngological, dental, urological, gynecological, and cardiovascular disorders. METHODS: A systematic review of the literature was performed for studies published between 2012 and 2022 that discussed the therapeutic use of BoNT in human participants. A total of 58 studies were selected for inclusion in this review. RESULTS: We discovered a large range of therapeutic applications of BoNT toxin beyond aesthetic and US Food and Drug Administration (FDA)-approved non-aesthetic uses. CONCLUSIONS: BoNT is a powerful neurotoxin that has varied FDA-approved indications and has been studied in a wide range of therapeutic applications. Further investigation through higher power studies is needed to assess the potential of BoNT and expand its versatility across other medical specialties. J Drugs Dermatol. 2023;22(9): doi:10.36849/JDD.7243e.

Placement of High Dose Neurotoxins for Treatment-Resistant Rosacea.

Rosacea is a chronic inflammatory skin condition characterized by facial flushing, erythema, telangiectasias, and papulopustular lesions. Treatment for rosacea includes limiting inciting factors and reducing inflammation with topical and oral therapies. Traditional therapies primarily focus on the papulopustular or background erythematotelangiectatic component of rosacea, leaving symptoms of flushing poorly controlled and profoundly impacting the quality of life of patients. Neuromodulators have been speculated to improve the flushing component of rosacea by reducing mast cell degranulation and the release of neuropeptides. However, its use for symptomatic relief in refractory flushing rosacea has been limited by side effects such as facial muscle weakness or paralysis. We present the use of strategic placement of high-dose neuromodulators for treatment-resistant rosacea. This approach has resulted in the gradual stabilization of symptoms, improved quality of life, and superior side effect profile. Silence C, Kourosh AS, Gilbert E. Placement of high-dose neurotoxins for treatment-resistant rosacea. J Drugs Dermatol. 2023;22(6):605-606. doi:10.36849/JDD.7237.

Botulinum Neurotoxin Injections in Children with Self-Injurious Behaviors.

Self-injurious behaviors are repetitive, persistent actions directed toward one's body that threaten or cause physical harm. These behaviors are seen within a broad spectrum of neurodevelopmental and neuropsychiatric conditions, often associated with intellectual disability. Injuries can be severe and distressing to patients and caregivers. Furthermore, injuries can be life-threatening. Often, these behaviors are challenging to treat and require a tiered, multimodal approach which may include mechanical/physical restraints, behavioral therapy, pharmacotherapy, or in some cases, surgical management, such as tooth extraction or deep brain stimulation. Here, we describe a series of 17 children who presented to our institution with self-injurious behaviors in whom botulinum neurotoxin injections were found helpful in preventing or lessening self-injury.

[Research progress of botulinum toxin type A in the treatment of chronic rhinitis].

Botulinum toxin（BoNT）, a superfamily of neurotoxins produced by the bacterium Clostridium botulinum, disturbs the signal transmission at the neuromuscular and neuroglandular junctions by inhibiting the neurotransmitter release from the presynaptic nerve terminal. BoNT has been widely used in neuromuscular, hypersecretory, and autonomic nerve system disorders. In recent years, botulinum toxin type A（BoNT-A） has been used to treat chronic rhinitis. Studies have shown that intranasal administration of BoNT-A is safe and effective, and can reduce nasal symptoms in rhinitis patients with long-lasting effects. This article reviews the research progress of BoNT-A in the treatment of chronic rhinitis.

Botulinum Toxin-A Injection in Chronic Pelvic Pain Syndrome Treatment: A Systematic Review and Pooled Meta-Analysis.

INTRODUCTION: Pain management of patients with chronic pelvic pain syndrome (CPPS) is challenging, because pain is often refractory to conventional treatments. Botulinum toxin A (BTX-A) may represent a promising therapeutic strategy for these patients. The aim of this systematic review was to investigate the role of BTX-A in CPPS treatment. METHODS: We reviewed the literature for prospective studies evaluating the use of BTX-A in the treatment of CPPS. A comprehensive search in the PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials databases was performed from English language articles published between January 2000 and October 2021. The primary outcome was to evaluate pain improvement in CPPS after BTX-A treatment. Pooled meta-analysis of the included studies, considering the effect of BTX-A on pain evaluated at last available follow-up compared to baseline values, was performed together with meta-regression analysis. RESULTS: After screening 1001 records, 18 full-text manuscripts were selected, comprising 13 randomized clinical trials and five comparative studies. They covered overall 896 patients of both sexes and several subtype of CPPS (interstitial cystitis/bladder pain syndrome, chronic prostatitis/prostate pain syndrome, chronic scrotal pain, gynecological pelvic pain, myofascial pelvic pain). The clinical and methodological heterogeneity of studies included makes it difficult to do an overall estimation of the real effect of BTX-A on pain and other functional outcomes of various CPPS subtypes. However, considering pooled meta-analysis results, a benefit in pain relief was showed for BTX-A-treated patients both in the overall studies populations and in the overall cohorts of patients with CPP due to bladder, prostate, and gynecological origin. CONCLUSIONS: BTX-A could be an efficacious treatment for some specific CPPS subtypes. Higher level studies are needed to assess the efficacy and safety of BTX-A and provide objective indications for its use in CPPS management.

Prediction Model for Identifying Computational Phenotypes of Children with Cerebral Palsy Needing Neurotoxin Treatments.

Factors associated with neurotoxin treatments in children with cerebral palsy (CP) are poorly studied. We developed and externally validated a prediction model to identify the prognostic phenotype of children with CP who require neurotoxin injections. We conducted a longitudinal, international, multicenter, double-blind descriptive study of 165 children with CP (mean age 16.5 ± 1.2 years, range 12−18 years) with and without neurotoxin treatments. We collected functional and clinical data from 2005 to 2020, entered them into the BTX-PredictMed machine-learning model, and followed the guidelines, "Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis". In the univariate analysis, neuromuscular scoliosis (p = 0.0014), equines foot (p < 0.001) and type of etiology (prenatal > peri/postnatal causes, p = 0.05) were linked with neurotoxin treatments. In the multivariate analysis, upper limbs (p < 0.001) and trunk muscle tone disorders (p = 0.02), the presence of spasticity (p = 0.01), dystonia (p = 0.004), and hip dysplasia (p = 0.005) were strongly associated with neurotoxin injections; and the average accuracy, sensitivity, and specificity was 75%. These results have helped us identify, with good accuracy, the clinical features of prognostic phenotypes of subjects likely to require neurotoxin injections.

Design and Rationale of a Phase 2 Study of NeurOtoxin (Botulinum Toxin Type A) for the PreVention of Post-Operative Atrial Fibrillation - The NOVA Study.

BACKGROUND: Post-operative AF (POAF) is the most common complication following cardiac surgery, occurring in 30% to 60% of patients undergoing bypass and/or valve surgery. POAF is associated with longer intensive care unit/hospital stays, increased healthcare utilization, and increased morbidity and mortality. Injection of botulinum toxin type A into the epicardial fat pads resulted in reduction of AF in animal models, and in two clinical studies of cardiac surgery patients, without new safety observations. METHODS: The objective of NOVA is to assess the use of AGN-151607 (botulinum toxin type A) for prevention of POAF in cardiac surgery patients. This randomized, multi-site, placebo-controlled trial will study one-time injections of AGN-151607 125 U (25 U / fat pad) and 250 U (50 U / fat pad) or placebo during cardiac surgery in ∼330 participants. Primary endpoint: % of patients with continuous AF ≥ 30 s. Secondary endpoints include several measures of AF frequency, duration, and burden. Additional endpoints include clinically important tachycardia during AF, time to AF termination, and healthcare utilization. Primary and secondary efficacy endpoints will be assessed using continuous ECG monitoring for 30 days following surgery. All patients will be followed for up to 1 year for safety. CONCLUSIONS: The NOVA Study will test the hypothesis that injections of AGN-151607 will reduce the incidence of POAF and associated resource utilization. If demonstrated to be safe and effective, the availability of a one-time therapy for the prevention of POAF would represent an important treatment option for patients undergoing cardiac surgery.

Botulinum Toxin Injection Plus Topical Diltiazem for Chronic Anal Fissure: A Randomized Double-Blind Clinical Trial and Long-term Outcome.

BACKGROUND: Chemical sphincterotomy avoids the risk of permanent incontinence in the treatment of chronic anal fissure, but it does not reach the efficacy of surgery and recurrence is high. Drug combination has been proposed to overcome these drawbacks. OBJECTIVE: This study aimed to compare the clinical, morphological, and functional effects of combined therapy with botulinum toxin injection and topical diltiazem in chronic anal fissure and to assess the long-term outcome after healing. DESIGN: This is a randomized, controlled, double-blind, 2-arm, parallel-group trial with a long-term follow-up. SETTINGS: This study was conducted at a tertiary care center. PATIENTS: A total of 70 consecutive patients were referred to the gastroenterology department of a hospital in Valencia, Spain. INTERVENTION: After botulinum toxin injection (20 IU), patients were randomly assigned to local diltiazem (diltiazem group) or placebo gel (placebo group) for 12 weeks. MAIN OUTCOME MEASURES: The primary outcome was fissure healing (evaluated by video register by 3 independent physicians). Secondary outcomes included symptomatic relief (30-day diary), effect on anal sphincters (manometry), safety, and long-term recurrence (24 months and 10 years). RESULTS: Healing was achieved per protocol in 13 of 25 (52%) patients of the diltiazem group and 11 of 30 (36.7%) patients of the placebo group (p = 0.25); on an intention-to-treat basis in 37.1% and 31.4% (p = 0.61). Both groups displayed significant reduction of anal pressures. Thirty percent reported minor and transitory incontinence, without differences between groups. Nine (69.2%) of the diltiazem group and 6 (54.5%) of the placebo group experienced a relapse at 24 months (p = 0.67). The overall recurrence rate at 10 years was 83.3% (20/24 patients). LIMITATIONS: This study was limited by the loss of patients during the trial. The low healing rate led to a small cohort to assess recurrence. CONCLUSIONS: Combined botulinum toxin injection and topical diltiazem is not superior to botulinum toxin injection in the treatment of chronic anal fissure. Both options offer suboptimal healing rates. Long-term recurrence is high (>80% at 10 years) and might appear at any time after healing. See Video Abstract at http://links.lww.com/DCR/B527. INYECCIN DE TOXINA BOTULNICA MS DILTIAZEM TPICO EN FISURA ANAL CRNICA UN ENSAYO CLNICO ALEATORIZADO DOBLE CIEGO Y RESULTADOS A LARGO PLAZO: ANTECEDENTES:La esfinterotomía química evita el riesgo de incontinencia permanente en el tratamiento de la fisura anal crónica, pero no alcanza la eficacia de la cirugía y la recurrencia es alta. Se ha propuesto la combinación de fármacos para superar estos inconvenientes.OBJETIVO:Comparar los efectos clínicos, morfológicos y funcionales de la terapia combinada con inyección de toxina botulínica y diltiazem tópico en fisura anal crónica y evaluar el resultado a largo plazo después de la cicatrización.DISEÑO:Ensayo aleatorizado, controlado, doble ciego, de dos brazos, de grupos paralelos con un seguimiento a largo plazo.ESCENARIO:Estudio realizado en un centro de atención terciaria.PACIENTES:Un total de 70 pacientes consecutivos referidos al servicio de gastroenterología de un hospital de Valencia, España.INTERVENCIÓN:Después de la inyección de toxina botulínica (20UI), los pacientes fueron asignados al azar a diltiazem local (grupo de diltiazem) o gel de placebo (grupo de placebo) durante 12 semanas.PRINCIPALES MEDIDAS DE RESULTADO:El resultado primario fue la cicatrización de la fisura (evaluado por registro de video por tres médicos independientes). Los resultados secundarios incluyeron alivio sintomático (diario de 30 días), efecto sobre los esfínteres anales (manometría), seguridad y recurrencia a largo plazo (24 meses y 10 años).RESULTADOS:La curación se logró por protocolo en 13/25 (52%) en el grupo de Diltiazem y 11/30 (36,7%) en el grupo de Placebo (p = 0.25); por intención de tratar en el 37.1% y el 31.4%, respectivamente (p = 0.61). Ambos grupos mostraron una reducción significativa de las presiones anales. El 30% refirió incontinencia leve y transitoria, sin diferencias entre grupos. 9 (69.2%) del grupo de Diltiazem y 6 (54.5%) del grupo de placebo recurrieron a los 24 meses (p = 0.67). La tasa global de recurrencia a los 10 años fue del 83.3% (20/24 pacientes).LIMITACIONES:La pérdida de pacientes a lo largo del ensayo. La baja tasa de curación llevó a una pequeña cohorte para evaluar la recurrencia.CONCLUSIONES:La inyección combinada de toxina botulínica y diltiazem tópico no es superior a la inyección de TB en el tratamiento de la fisura anal crónica. Ambas opciones ofrecen tasas de curación subóptimas. La recurrencia a largo plazo es alta (> 80% a los 10 años) y puede aparecer en cualquier momento después de la curación. Consulte Video Resumen en http://links.lww.com/DCR/B527.

Tetrodotoxin, a Potential Drug for Neuropathic and Cancer Pain Relief?

Tetrodotoxin (TTX) is a potent neurotoxin found mainly in puffer fish and other marine and terrestrial animals. TTX blocks voltage-gated sodium channels (VGSCs) which are typically classified as TTX-sensitive or TTX-resistant channels. VGSCs play a key role in pain signaling and some TTX-sensitive VGSCs are highly expressed by adult primary sensory neurons. During pathological pain conditions, such as neuropathic pain, upregulation of some TTX-sensitive VGSCs, including the massive re-expression of the embryonic VGSC subtype NaV1.3 in adult primary sensory neurons, contribute to painful hypersensitization. In addition, people with loss-of-function mutations in the VGSC subtype NaV1.7 present congenital insensitive to pain. TTX displays a prominent analgesic effect in several models of neuropathic pain in rodents. According to this promising preclinical evidence, TTX is currently under clinical development for chemo-therapy-induced neuropathic pain and cancer-related pain. This review focuses primarily on the preclinical and clinical evidence that support a potential analgesic role for TTX in these pain states. In addition, we also analyze the main toxic effects that this neurotoxin produces when it is administered at therapeutic doses, and the therapeutic potential to alleviate neuropathic pain of other natural toxins that selectively block TTX-sensitive VGSCs.

From Poison to Promise: The Evolution of Tetrodotoxin and Its Potential as a Therapeutic.

Tetrodotoxin (TTX) is a potent neurotoxin that was first identified in pufferfish but has since been isolated from an array of taxa that host TTX-producing bacteria. However, determining its origin, ecosystem roles, and biomedical applications has challenged researchers for decades. Recognized as a poison and for its lethal effects on humans when ingested, TTX is primarily a powerful sodium channel inhibitor that targets voltage-gated sodium channels, including six of the nine mammalian isoforms. Although lethal doses for humans range from 1.5-2.0 mg TTX (blood level 9 ng/mL), when it is administered at levels far below LD50, TTX exhibits therapeutic properties, especially to treat cancer-related pain, neuropathic pain, and visceral pain. Furthermore, TTX can potentially treat a variety of medical ailments, including heroin and cocaine withdrawal symptoms, spinal cord injuries, brain trauma, and some kinds of tumors. Here, we (i) describe the perplexing evolution and ecology of tetrodotoxin, (ii) review its mechanisms and modes of action, and (iii) offer an overview of the numerous ways it may be applied as a therapeutic. There is much to be explored in these three areas, and we offer ideas for future research that combine evolutionary biology with therapeutics. The TTX system holds great promise as a therapeutic and understanding the origin and chemical ecology of TTX as a poison will only improve its general benefit to humanity.

Moisture Response Films Versus the Starch Iodine Test for the Detection of Palmar Hyperhidrosis.

BACKGROUND: The starch iodine test (SIT) is the gold-standard diagnostic tool for primary palmar hyperhidrosis (PPH). OBJECTIVE: This study aimed to evaluate the clinical effectiveness and safety profile of a novel approach for the detection of PPH by moisture response films (MRF) in comparison to the SIT. METHODS: This prospective comparative study of the 2 tests was conducted on 17 patients with PPH. Disease severity was evaluated by the SIT and the MRF methods during 4 sessions (twice before and twice after botulinum toxin [BTX] injections) on different days and by different investigators. The physician's global assessment (PGA) scoring of the comparable visual results was evaluated by 2 blinded independent dermatologists. The Hyperhidrosis Disease Severity Scale (HDSS) scores of the patients at baseline and after the BTX injections were correlated with the SIT and MRF results. RESULTS: The objective PGA scoring of the SIT results demonstrated poor correlation, whereas the objective PGA scoring of the MRF results correlated highly with the patients' HDSS scores both at baseline and after the BTX injections. CONCLUSION: Analysis of palmar hyperhidrosis by means of MRF was superior to SIT and was demonstrated to be more efficient, convenient, and accurate.

The Efficacy and Safety of Botulinum Toxin Injections in Preventing Postoperative Scars and Improving Scar Quality: A Systematic Review and Meta-Analysis.

BACKGROUND: Scars exposed on the body surface lead to a large psychological burden on patients. However, no satisfactory scar treatments exist. Botulinum toxin type A is a neurotoxin that has been widely applied in the plastic and cosmetic surgery field. The purpose of this meta-analysis was to assess the efficacy and safety of botulinum toxin in scar management. METHODS: PubMed, the Cochrane Library, EMBASE, MEDLINE, and Web of Science were searched for randomized controlled trials that evaluated the efficacy of botulinum toxin injections in preventing postoperative scars and improving scars quality and were published prior to Dec. 29, 2020. The outcome indicators were the visual analog scale score, Vancouver scar scale score, Stony Brook scar evaluation scales score, scar width, patient self-assessment results, and complications. RESULTS: Seventeen randomized controlled trials with a total of 633 cases were identified in this meta-analysis. The quantitative synthesis results showed that compared with the control group, the botulinum toxin group had a significantly lower VSS score (MD = -0.97, 95%CI = -1.56 to -0.39, p = 0.001), higher VAS score (MD = 1.26, 95%CI = 1.04 to 1.47, p < 0.00001), thinner scar width (MD = -0.25, 95%CI = -0.37 to -0.12, p < 0.0001) and higher patient satisfaction (RR = 3.38 95%CI = 1.45 to 7.89, p = 0.005). There were no significant differences between the two groups in the number of adverse events. CONCLUSIONS: This meta-analysis demonstrated that botulinum toxin injections can significantly improve cosmetic appearance and postoperative scar quality. At the therapeutic dose, no significant complications were observed, indicating that botulinum toxin injections are safe. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Impact of Botulinum Toxin on Hirschsprung-Associated Enterocolitis After Primary Pull-Through.

BACKGROUND: Hirschsprung-associated enterocolitis (HAEC) is a serious potential complication after primary pull-through surgery for Hirschsprung's disease (HSCR). Administration of anal botulinum toxin (BT) injection may improve obstructive symptoms at the internal anal sphincter, leading to improved fecal passage. The timing of administration and effects on delay or prevention of HAEC are unknown. We hypothesized that BT administration increased the postoperative time to HAEC and aimed to investigate whether anal BT administration after primary pull-through surgery for HSCR is associated with increased time to inpatient HAEC admission development. METHODS: We performed a retrospective cohort study examining children with HSCR at US children's hospitals from 2008 to 2018 using the Pediatric Health Information System database with an associated primary pull-through operation performed before 60 d of age. The intervention assessed was the administration of BT concerning the timing of primary pull-through, and two groups were identified: PRO (received BT at or after primary pull-through, before HAEC) and NOT (never received BT, or received BT after HAEC). The primary outcome was time from pull-through to the first HAEC admission. The Cox proportional hazards model was developed to examine the BT administration effect on the primary outcome after controlling for patient-level covariates. RESULTS: We examined a total of 1439 children (67 in the PRO and 1372 in the NOT groups). A total of 308 (21.4%) developed at least one episode of HAEC, including 76 (5.3%) who had two or more episodes. Between 2008 and 2018, the frequency of BT administration has increased from three to 20 hospitals with a frequency of administration between 2.2% and 16.2%. Prophylactic BT (PRO) was not associated with increased time to HAEC event on adjusted analysis. CONCLUSIONS: Among children with HSCR undergoing primary pull-through surgery, prophylactic BT administration did not demonstrate increased time to first HAEC event. A better-powered study with prophylactic BT is required to determine the effect on HAEC occurrence and timing. LEVEL OF EVIDENCE: Level II (retrospective cohort study).

Improving the Appearance of Surgical Facial Scars With IncobotulinumtoxinA and Microneedling.

BACKGROUND: The appearance of post-surgical scars on the face is a major concern for surgeons and a source of anxiety for patients after Mohs surgery due to nonmelanoma skin cancer (NMSC). The objective of this retrospective study was to assess the effectiveness of combining incobotulinumtoxinA and microneedling to improve the appearance of post-operative facial scars. Enrolled subjects underwent surgical removal of facial NMSCs followed by flap reconstruction by the same surgeon during 2014 (n=35) and 2015 (n=35). Sutures were removed 7 days after the procedure. Subjects treated during 2014 received no additional treatment and served as a control group. Subjects treated during 2015 also received micro-doses of incobotulinumtoxinA along the scar border and microneedling of the surgical area. Microneedling was repeated after 15 days. Scar severity was determined by the surgeon and an independent dermatologist using the modified Vancouver Scar Scale (VSS) scores on day 7 and day 30 following suture removal. Patient Satisfaction Scale scores were also determined using a 5-point scale on day 30. Mean (SD) VSS scores were 10.4 (1.14) on day 7 among treated subjects vs. 9.5 (1.88) among control subjects (P<0.05). On day 30, mean VSS scores had decreased to 1.1 (0.89) for treated subjects vs. 7.6 (1.72) for control subjects (P<0.05). Patient Satisfaction Scores were significantly higher among treated patients vs control subjects (4.45 vs 3.14; P<0.001). The use of incobotulinumtoxinA is a promising therapeutic option for improving scar appearance. Combined with microneedling, it significantly reduced VSS scores and improved overall satisfaction of treated subjects following surgery for NMSCs. J Drugs Dermatol. 2020;19(6): doi:10.36849/JDD.2020.4772.