Gastric peroral endoscopic myotomy versus botulinum toxin injection for the treatment of refractory gastroparesis: results of a double-blind randomized controlled study.

INTRODUCTION: Gastric peroral endoscopic myotomy (G-POEM) is a promising technique for treating refractory gastroparesis. We present the first double-blind randomized study comparing the clinical efficacy of G-POEM versus pyloric botulinum toxin injection (BTI). METHODS: This randomized study, conducted in two expert centers, enrolled patients with refractory gastroparesis, medically managed for >6 months and confirmed by gastric emptying scintigraphy (GES), into two groups, G-POEM versus BTI, with follow-up of 1 year. The primary end point was the 3-month clinical efficacy, defined as a >1-point decrease in the mean Gastroparesis Cardinal Symptom Index (GCSI) score. Secondary end points were: 1-year efficacy, GES evolution, adverse events, and quality of life. RESULTS: 40 patients (22 women; mean age 48.1 [SD 17.4]), with mean symptom duration of 5.8 (SD 5.7) years, were randomized. Etiologies included idiopathic (n=18), diabetes (n=11), postoperative (n=6), and mixed (n=4). G-POEM showed a higher 3-month clinical success than BTI (65% vs. 40%, respectively; P=0.10), along with non-significantly higher 1-year clinical success (60% vs. 40%, respectively) on intention-to-treat analysis. The GCSI decreased in both groups at 3 months and 1 year. Only three minor adverse events occurred in the G-POEM group. The GES improvement rate was 72% in the G-POEM group versus 50% in the BTI group (non-significant). CONCLUSION: G-POEM seems to have a higher clinically relevant success rate than BTI, but this was not statistically demonstrated. This study confirms the interest in treatments targeting the pylorus, either mechanically or chemically, for managing refractory gastroparesis.

Effectiveness and safety of botulinum neurotoxin for treating dyssynergic defecation: A systematic review and meta-analysis.

Dyssynergic defecation (DD) is a common cause of chronic constipation. Owing to the lack of a comprehensive synthesis of available data on the effectiveness of botulinum neurotoxin (BoNT) for treating DD, we performed a systematic review and meta-analysis. We searched the PubMed, Embase, and Cochrane databases from inception to May 9, 2023. The outcomes comprise short-term and long-term symptom improvement, various anorectal function measurements, complications of fecal incontinence, and symptom improvement after repeated BoNT injections. A meta-analysis comparing BoNT injection with either surgery or biofeedback (BFB) therapy in treating DD was also conducted. Subgroup analysis and meta-regression were performed to identify possible moderator effects. We included five randomized controlled trials, seven prospective studies, and two retrospective observational studies. Short-term potential improvement in symptoms (event rate [ER], 66.4%; 95% CI, 0.513 to 0.783) was identified, but in the long-term (>12 months), this effect was decreased (ER, 38.2%; 95% CI, 0.267 to 0.511). Short-term improvements in objective anorectal physiologic parameters were also observed. Repeated BoNT injection was effective for patients with symptom recurrence. Subgroup analysis revealed enhanced long-term symptom improvement with high-dose BoNT, but this treatment also increased the risk of complications and recurrence compared with low doses. The effectiveness, complications, and recurrence of symptoms associated with BoNT injection and surgery did not differ significantly. BoNT injection significantly provided short-term symptom improvement but also heightened the risk of incontinence compared with BFB therapy. Our systematic review and meta-analysis indicated that BoNT could be beneficial for short-term symptom improvement in patients with DD, but this effect tended to decline 12 months after injection. Standardized BoNT intervention protocols remain warranted. Among the several treatments for DD, we concluded that BoNT injection is not inferior to other options considering its effectiveness in relieving symptoms, the associated complication development, and the risk of symptom recurrence.

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.

Systematic Review on Botulinum Toxin Injections as Diagnostic or Therapeutic Tool in Thoracic Outlet Syndrome.

BACKGROUND: The optimal diagnostic and treatment algorithm for patients with suspected thoracic outlet syndrome (TOS) remains challenging. Botulinum toxin (BTX) muscle injections have been suggested to shrink muscles in the thoracic outlet reducing neurovascular compression. This systematic review evaluates the diagnostic and therapeutic value of BTX injections in TOS. METHODS: A systematic review of studies reporting BTX as a diagnostic or therapeutic tool in TOS (or pectoralis minor syndrome as TOS subtype) was conducted in PubMed, Embase, and CENTRAL databases on May 26, 2022. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement was followed. Primary end point was symptom reduction after primary procedure. Secondary end points were symptom reduction after repeated procedures, the degree of symptom reduction, complications, and duration of clinical effect. RESULTS: Eight studies (1 randomized controlled trial [RCT], 1 prospective cohort study, and 6 retrospective cohort studies) were included reporting 716 procedures in at least 497 patients (at minimum 350 primary and 25 repeated procedures, residual unclear) diagnosed with presumably only neurogenic TOS. Except for the RCT, the methodological quality was fair to poor. All studies were designed on an intention to treat basis, one also investigated BTX as a diagnostic tool to differentiate pectoralis minor syndrome from costoclavicular compression. Reduction of symptoms was reported in 46-63% of primary procedures; no significant difference was found in the RCT. The effect of repeated procedures could not be determined. Degree of symptom reduction was reported by up to 30-42% on the Short-form McGill Pain scale and up to 40 mm on a visual analog scale. Complication rates varied among studies, no major complications were reported. Symptom relief ranged from 1 to 6 months. CONCLUSIONS: Based on limited quality evidence, BTX may provide short-lasting symptom relief in some neurogenic TOS patients but remains overall undecided. The role of BTX for treatment of vascular TOS and as a diagnostic tool in TOS is currently unexploited.

A Retrospective and Anatomical Study Describing the Injection of Botulinum Neurotoxins in the Depressor Anguli Oris.

SUMMARY: The depressor anguli oris acts to lower the lateral corners of the mouth and can cause an individual to appear sad or angry and contribute to the development of the labiomental folds. Many patients can benefit from the injection of small amounts of botulinum neurotoxin into the depressor anguli oris to enable the lip elevators to reposition the corners of the mouth. Although effective, the procedure is off-label, and the proximity of the depressor anguli oris to the depressor labii inferioris, particularly inferiorly, can lead to inadvertent treatment of the latter, resulting in lip asymmetry. The authors have taken a threefold approach to establish a depressor anguli oris injection technique that provides optimal aesthetic outcomes with a low incidence of adverse events. This involved, first, reviewing the limited existing literature for studies discussing depressor anguli oris anatomy and botulinum neurotoxin treatment technique; second, supplementing information from the published literature with information from cadaver dissections to demonstrate the relationship between the depressor anguli oris and surrounding anatomical structures; and third, performing a retrospective chart review of 275 patients treated with the authors' three-point injection technique. Combining data from published studies, cadaver dissections, and clinical experience, the authors demonstrate that a three-point technique performed in the upper half of the depressor anguli oris is associated with good clinical outcome and avoids common side effects related to injection or spread of neurotoxin to adjacent muscles. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Forehead Movement Discrepancies After Botulinum Toxin Injections: A Review of Etiology, Correction, and Prevention.

BACKGROUND: Forehead rhytides are a popular target for botulinum toxin injections, but neuromodulation of the frontalis can be fraught with complications because of its anatomic complexity and integral role in brow position and expressivity. OBJECTIVE: This article explores common forehead movement discrepancies that can occur after neuromodulation of the frontalis, as well as how to correct and prevent them. METHODS: A review of the literature was conducted and combined with clinical experience to examine underlying forehead anatomy, etiology and correction of forehead movement discrepancies, and important factors to consider before injecting the frontalis with botulinum toxin. RESULTS AND CONCLUSION: Variable anatomy from person to person necessitates an individualized treatment approach to achieve the best cosmetic results and prevent the occurrence of forehead movement discrepancies.

Extreme stiff knee recurvatum following manipulation under anesthesia and botulinum neurotoxin injection.

In this article we report a case of stiff, neglected extreme recurvatum knee deformity in a 17-year-old female. This is the first reported case in the literature of an acquired ligamentous stiff extreme knee recurvatum following manipulation under anesthesia and botulinum neurotoxin injection. Μodified Judet quadricepsplasty combined with Ilizarov external hinged frame fixation was implemented. This dual technique can be considered as a rational approach for such an extreme deformity as it stabilizes, progressively corrects, and prevents recurrence. A patellar tendon rupture caused by the increasing tension of the extensor mechanism following the correction was treated successfully using a cadaveric Achilles tendon allograft.

Transverse facial artery: Its role in blindness after cosmetic filler and botulinum toxin injections.

Masseter injections for cosmetic or pathological reasons are increasingly common, as are filler injections using dual or multiplane techniques in the lateral facial regions or for jawline contouring. The occurrence of blindness following these procedures often remains unexplained. This study aimed to determine the anatomical explanation for this debilitating complication by investigating the transverse facial artery and its relation to the masseter. For this purpose, we dissected 35 cheek specimens with latex injections and 10 specimens without latex. The external carotid artery was dissected up to its bifurcation into the maxillary and superficial temporal arteries. Results showed that the transverse facial artery arose from the superficial temporal or external carotid artery that runs between the zygomatic arch and the parotid duct. Three types of transverse facial arteries were observed: type I: a short artery that did not extend beyond the masseter muscle; type II: a transverse artery that ran to the nasolabial fold and anastomosed to the facial artery; and type III: a sizable transverse artery that substituted the hypoplastic facial artery, continued as the angular artery, and then anastomosed to the dorsal nasal artery. Knowledge of these three types of transverse facial arteries is a prerequisite to study the vascular territory. Type III provides an explanation for the occurrence of blindness after lateral face injections. We consequently define a line that runs from the tragus to the outer quarter of the upper lip as the risk area, while the safe zone is located on either side of this line.

The Bidirectional Movement of the Frontalis Muscle: Introducing the Line of Convergence and Its Potential Clinical Relevance.

BACKGROUND: Cosmetic treatment of the forehead using neuromodulators is challenging. To avoid adverse events, the underlying anatomy has to be understood and thoughtfully targeted. Clinical observations indicate that eyebrow ptosis can be avoided if neuromodulators are injected in the upper forehead, despite the frontalis muscle being the primary elevator. METHODS: Twenty-seven healthy volunteers (11 men and 16 women) with a mean age of 37.5 ± 13.7 years (range, 22 to 73 years) and of diverse ethnicity (14 Caucasians, four African Americans, three Asians, and six of Middle Eastern descent) were enrolled. Skin displacement vector analyses were conducted on maximal frontalis muscle contraction to calculate magnitude and direction of forehead skin movement. RESULTS: In 100 percent of investigated volunteers, a bidirectional movement of the forehead skin was observed: the skin of the lower forehead moved cranially, whereas the skin of the upper forehead moved caudally. Both movements converged at a horizontal forehead line termed the line of convergence, or C-line. The position of the C-line relative to the total height of the forehead was 60.9 ± 10.2 percent in men and 60.6 ± 9.6 percent in women (p = 0.941). Independent of sex, the C-line was located at the second horizontal forehead line when counting from superior to inferior (men, n = 2; women, n = 2). No difference across ethnicities was detected. CONCLUSIONS: The identification of the C-line may potentially guide practitioners toward more predictable outcomes for forehead neuromodulator injections. Injections above the C-line could mitigate the risk of neuromodulator-induced brow ptosis.

Oily sensitive skin: A review of management options.

BACKGROUND: Due to the ever-increasing demands for the personalized care, people seek for the tailored management according to the accurate identification of their skin type. The Baumann Skin Type Indicator, which was proposed by Leslie Baumann, is composed of four parameters: oily or dry, resistant or sensitive, pigmented or nonpigmented, and wrinkled or tight. Among these, oily sensitive skin experiences significant discomfort and resists ordinary treatment. AIMS: In this article, we will review the clinical manifestations, underlying pathogenesis and recommendations on treatment options that may be utilized to help patients with oily sensitive skin. PATIENTS/METHODS: Literature search was conducted using PubMed. The literature concerning Baumann Skin Type Indicator and oily sensitive skin type were considered. RESULTS: Oily sensitive (OS)-type skin is a complex of oily and sensitive skin that causes significant discomfort and undergoes stubborn resistance to treatments. Sebum dysfunction and hypersensitivity may play a key role in the development of sensitive skin. Considering the pathogenesis of OS-type skin, treatment should focus on both seborrhea and hypersensitivity. CONCLUSION: Clinicians can effectively treat the oily sensitive skin by understanding underlying pathogenesis of it. Further investigations are necessary to reach a consensus on the basic pathophysiology and optimal management guidelines for oily sensitive skin.

Report: A case report of Meige syndrome-like blepharospasm caused by ingestion of allopurinol.

One case of allopurinol-caused rare adverse reactions was reported. One male 51-year-old patient presented blurred vision, streaming eyes, photophobia and blepharospasm sequentially 1 week after oral administration of allopurinol. Complete remission was obtained after Botulinum toxin was locally injected. Allopurinol may cause Meige syndrome-like blepharospasm, the mechanism of which may be related to the inhibition of dopamine activity by affecting adenosine level in the brain.

Mycobacterium abscessus infections following injection of botulinum toxin.

BACKGROUND: The incidence of Mycobacterium abscessus infections has increased in recent years. Some of these infections are caused by invasive cosmetic procedures. AIMS: Raising the awareness of cosmetic procedure related Mycobacterium abscessus infection for clinicians. PATIENTS/METHODS: We presented a 28-year-old woman who developed multiple erythema and painful nodules in her lower extremities after injections of botulinum toxin. RESULTS: Mycobacterium culture and strain identification of the tissue confirmed Mycobacterium abscessus. Combination antibiotics therapy was given and the lesion healed with scar and pigmentation. CONCLUSION: Mycobacterium abscessus infections following injection of botulinum toxin are rare and easily misdiagnosed as common suppurative infections. Early microbiologic tests are necessary for diagnose. Standardized operation should be performed to avoid this particular infection.

Reanimação estática do lábio inferior na paralisia facial como complicação de preenchimento / Static lower lip reanimation as a filler complication of facial paralysis

Procedimentos de rejuvenescimento facial substitutos da cirurgia tradicional tornaram-se cada vez mais populares para promover uma aparência jovial com procedimentos minimamente invasivos, como toxina botulínica injetável, preenchimento de tecidos moles e peelings químicos. No entanto, complicações podem ocorrer mesmo na presença de um injetor habilidoso e experiente. Apresentamos o caso de uma paciente submetida a reanimação labial estática usando retalho dermoadiposo para lesão do nervo facial direito após remoção de nódulos como complicação de preenchimento. A "abordagem modificada de bull horn" foi realizada para elevação do lábio superior em torno das asas nasais e columela e ao longo do sulco nasolabial direito. O retalho foi desepitelizado e obtido. Usando a ponta aberta de uma pequena cânula de lipoaspiração, a porção distal do retalho foi encapsulada e fixada diretamente em C-loop e foram utilizados pontos U, transfixando o retalho para o periósteo do arco zigomático. Nos três anos de seguimento não foram observadas complicações significativas e a paciente não relatou nenhuma limitação funcional ou insatisfação com o aspecto das cicatrizes no sulco nasolabial e ao redor das asas nasais e da columela.

Facial rejuvenation procedures to circumvent traditional surgery have become increasingly popular to promote a youthful appearance with minimally invasive procedures such as injectable botulinum toxin, soft-tissue fillers, and chemical peels. Nevertheless, complications can occur even with an astute and experienced injector. Here we present the case of a patient who underwent static lip reanimation using a dermoadiposal flap for right facial nerve damage following nodule removal as a filler complication. A "modified bulls horn approach" to the upper lip lift was performed around the nasal wings and columella and along the right nasolabial fold. The flap was de-epithelized and harvested. Using the open tip of a small liposuction cannula, the distal portion of the flap was tunneled and fixed directly in a C-loop fashion using U stitches, transfixing the flap to the periosteum of the zygomatic arch. At 3 years follow-up, no significant complications were observed, and the patient reported no functional limitations or dissatisfaction with the scars in the nasolabial fold or around the nasal wings and columella.

Comparative effects of various absorbable threads in a rat model.

BACKGROUND: Conventional procedures including botulinum toxin and filler injections have their limitations in improving deep wrinkles and decreasing tissue laxity, and possess the propensity for vascular accidents. Absorbable thread is a recently commercialized field, but there is little evidence on comparative superiority. OBJECTIVES: We observed the effects of polydiaxanone (PDO) threads with different number of strands in relation to collagen production and histopathology in a rat model. MATERIALS AND METHODS: Dorsal skin of rat was divided into five different compartments and four different PDO threads and monofilament poly-lactic acid (PLA) thread were inserted. Tissue samples were obtained at week 1, 2, and 12 after the procedure for histopathologic review and real-time PCR for quantification of collagen. RESULTS: Multiple PDO filaments produced more collagen at 2 weeks. Single-stranded PLA thread insertion resulted in more Col1α1 levels than the double PDO thread and also showed the most Col1α3 production at week 2. The amount of collagen showed a sharp decline at week 12. Histologic evaluation showed retained threads surrounded by fibrous capsule-like structure at week 12. CONCLUSION: We were able to observe more collagen production in multiple stranded PDO threads compared to a single strand and that increasing number of threads leads to more collagen synthesis.

Safety and Efficacy of EB-001, a Novel Type E Botulinum Toxin, in Subjects with Glabellar Frown Lines: Results of a Phase 2, Randomized, Placebo-Controlled, Ascending-Dose Study.

BACKGROUND: Botulinum neurotoxins, which are widely used commercially for therapeutic and cosmetic applications, have historically belonged to serotypes A and B. Serotype E has a distinct profile with a faster onset and shorter duration of effect. EB-001 is a proprietary formulation of serotype E in development for aesthetic (cosmetic) and therapeutic uses. METHODS: This first-in-human, randomized, double-blinded, placebo-controlled, ascending-dose cohort study enrolled 42 subjects who received EB-001 (n = 35) or placebo (n = 7). The efficacy primary outcome was the proportion of subjects with a two-grade investigator-rated improvement in glabellar frown line severity at maximum frown. Safety evaluations included adverse events, laboratory tests, and physical examinations. RESULTS: A two-grade investigator-rated response was observed starting in the third cohort (EB-001), with increased rates observed at higher doses. Onset of clinical effect was within 24 hours, with a duration ranging between 14 and 30 days for the highest doses. Adverse event incidence was low, with the most common being mild to moderate headache. There were no serious adverse events or ptosis, and there were no clinically significant changes in other safety assessments. CONCLUSIONS: In this clinical study in glabellar frown lines, EB-001 showed favorable safety, tolerability, and dose-dependent efficacy, with an 80 percent response rate at the highest dose. The maximum clinical effect of EB-001 was seen within 24 hours and lasted between 14 and 30 days. This differentiated EB-001 profile supports its development for aesthetic and therapeutic applications where fast onset and short duration of effect are desirable. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.