Publications by authors named "Jeremy B Green"

125 Publications

Multicenter Pivotal Study Demonstrates Safety and Efficacy of a New Cellulite Procedure: 3-Month Results.

Aesthet Surg J 2022 Jul 5. Epub 2022 Jul 5.

Griffith University, School of Medicine, Southport, Queensland, Australia.

Background: Cellulite is an aesthetic condition affecting the appearance of skin in certain body regions and is associated with body dissatisfaction, psychosocial stress, and decreased quality of life. Previous studies have established the safety and feasibility of a novel, minimally-invasive device utilized for precisely identifying and verifiably releasing septa responsible for cellulite depressions. The single procedure is known as Targeted Verifiable Subcision (TVS).

Objectives: The objective of this single-arm, open-label, multicenter study was to evaluate the safety and efficacy of TVS for reducing the appearance of moderate to severe cellulite in the buttock and thighs of adult women.

Methods: Adult women 21-55 years of age and a BMI <30 kg/m2 with moderate or severe cellulite on the buttocks and/or thighs were eligible to be enrolled at 9 sites. Endpoint data includes results from 4 of the postprocedural follow-up visits at 24 hours, 7 days, 30 days, and 90 days (3 months). The primary endpoints were a mean ≥ 1 point reduction in the Cellulite Severity Scale (CSS) at 90 days and no related serious adverse events (SAEs) at 30 days.

Results: Seventy-four female participants with a mean BMI of 24.8 ± 2.7 and age of 41.4 ± 7.4 years received this single procedure. The mean improvement in CSS (N=68) was 1.5 ± 0.9 (p < 0.0001). There were no device-related SAEs at 30 days.

Conclusions: Targeted Verifiable Subcision for selectively identifying and verifiably releasing septa responsible for cellulite depressions is an effective and safe means for improving the appearance of moderate to severe cellulite in adult women.
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http://dx.doi.org/10.1093/asj/sjac179DOI Listing
July 2022

Aging of the Neck Decoded: New Insights for Minimally Invasive Treatments.

Aesthetic Plast Surg 2022 Jun 14. Epub 2022 Jun 14.

Department of Clinical Anatomy, Mayo Clinic College of Medicine and Science, Mayo Clinic, Stabile Building 9-38, 200 First Street, Rochester, MN, 55905, USA.

Background: Many signs of aging manifest in the neck region, including platysmal bands, excess skin, horizontal neck lines and decreasing contour of the neck. While the clinical signs of an aged neck are well-known, data determining the underlying aging process are limited.

Objective: To decode aging of the neck.

Materials And Methods: This prospective study investigated elasticity and firmness of skin, muscle activity and skin displacement upon muscular contraction in the neck in 77 young-, middle- and old-age individuals. Objective outcome measures, including 3-dimensional imaging, cutometry and surface electromyography, were utilized for all assessments.

Results: Mean firmness of skin decreased significantly from young to old individuals (0.37 ± 0.13 mm, 0.30 ± 0.12 mm and 0.26 ± 0.12 mm in young, middle and old subjects, respectively; p < 0.001). Gross elasticity decreased significantly from 75.1 ± 13.0% in young subjects, to 64.53 ± 15.7% in middle-aged subjects and 55.79 ± 13.0% in old subjects (p < 0.001). The mean y-axis skin displacement increased from 2.48 ± 4.33 mm in young subjects, to 3.11 ± 4.49 mm in middle-aged subjects and 3.61 ± 5.38 mm in old subjects (p = 0.006). The mean signal-to-noise ratio decreased significantly from 16.74 ± 5.77 µV in young subjects, to 14.41 ± 4.86 µV in middle-aged subjects and to 12.23 ± 5.99 µV in old subjects (p < 0.001).

Conclusion: This study provides insights into the interplay between skin elasticity, muscular activity and the reflected movement of the skin of the neck. Appreciation of these age-related changes lays the fundament for aesthetic treatments in this delicate region.

Level Of Evidence Iv: 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 .
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http://dx.doi.org/10.1007/s00266-022-02961-0DOI Listing
June 2022

In Search of the Most Attractive Lip Proportions and Lip Volume: An Eye Tracking- and Survey-Based Investigation.

Plast Reconstr Surg 2022 08 6;150(2):301-308. Epub 2022 Jun 6.

From the Department for Hand, Plastic, and Aesthetic Surgery, Ludwig-Maximilian University; Westmount Institute of Plastic Surgery; Skin Associates of South Florida and Skin Research Institute; private practice; CH Dermatologia; private practice; and Department of Clinical Anatomy, Mayo Clinic College of Medicine and Science.

Background: Despite various aesthetic trends, the ideal lip proportion and lip volume remains elusive. Thus, the aim of this study was to investigate the aesthetic perception of various lip shapes to identify the most attractive lips.

Methods: Fifty-nine White study participants with a mean age of 32.73 ± 9.4 years were asked to assess lips of various proportions and of various volumes. Gaze assessment and aesthetic rating of the same set of modified lip images were performed.

Results: The results revealed that the lip proportion that was rated to be most attractive was the 1:1.6 ratio (upper-to-lower lip, 4.21 of a possible 5). This lip proportion, however, was not the first one to be viewed on initial image display (1.20 sec) and had the shortest duration of a stable eye fixation within the 6-second image display interval (2.18 of 6 seconds). The lip volume that received the highest aesthetic rating was the 100 percent volume (original lip size), with 4.56 of a possible 5. This lip volume, however, had the third longest interval between initial image exposure and the first stable eye fixation (0.81 second) and had the shortest duration of stable eye fixations during the 6 seconds of image display (2.22 of 6 seconds).

Conclusion: The results presented could be potentially reflective of the internal cognitive processes during the involuntary and voluntary assessment of lip attractiveness.
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http://dx.doi.org/10.1097/PRS.0000000000009361DOI Listing
August 2022

The Fascias of the Forehead and Temple Aligned-An Anatomic Narrative Review.

Facial Plast Surg Clin North Am 2022 May;30(2):215-224

Department of Clinical Anatomy, Mayo Clinic College of Medicine and Science, Mayo Clinic, Stabile Building 9-38, 200 First Street, Rochester, MN 55905, USA. Electronic address:

A thorough understanding of 3-dimensional facial anatomy and its fascial concepts is essential to allow for further development of novel surgical and nonsurgical treatment strategies to increase patient safety and effectiveness. The layered anatomy and its interconnections of the forehead, scalp, and temple is complex and is thus summarized and aligned in a unified nomenclature in this review. The scalp consists of 5 layers, which transition into 8 layers in the forehead and into a total of 13 layers in the temple.
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http://dx.doi.org/10.1016/j.fsc.2022.01.006DOI Listing
May 2022

Ultrasound Anatomy of the Dorsal Nasal Artery as it Relates to Liquid Rhinoplasty Procedures.

Facial Plast Surg Clin North Am 2022 May;30(2):135-141

Department of Clinical Anatomy, Mayo Clinic College of Medicine and Science, Rochester, MN, USA. Electronic address:

Nonsurgical rhinoplasty procedures using soft tissue fillers have gained popularity. With the increasing frequency of such procedures, the incidence of intra-arterial injection of soft tissue filler material and subsequent ischemia has also risen. This article analyzes the topographic anatomy of the dorsal nasal artery in the nasal soft tissue to potentially enhance patient safety in nonsurgical rhinoplasty procedures. The dorsal nasal artery shows a variable topographic course, especially in relationship to the procerus muscle. By understanding the topographic courses of the dorsal nasal artery, aesthetic practitioners may be able to perform nonsurgical rhinoplasty procedures with increased safety and efficacy.
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http://dx.doi.org/10.1016/j.fsc.2022.01.002DOI Listing
May 2022

Understanding Facial Aging Through Facial Biomechanics: A Clinically Applicable Guide for Improved Outcomes.

Facial Plast Surg Clin North Am 2022 May;30(2):125-133

Department of Clinical Anatomy, Mayo Clinic College of Medicine and Science, Mayo Clinic, Stabile Building 9-38, 200 First Street, Rochester, MN 55905, USA. Electronic address:

Understanding the relevance of anatomic and biomechanical principles is crucial when treating the face with soft tissue fillers to achieve a symmetric, soft, and natural-looking result while mitigating the risk of adverse events. The objective of this study is to summarize facial age-related effects, to relate them to facial biomechanics, and to establish guidelines for safe, effective, and esthetically pleasing full-face treatment following 3 basic principles while incorporating the latest scientific developments. This narrative review summarizes the current understanding of facial aging and its implications for facial biomechanics deduced from the authors' experience and research.
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http://dx.doi.org/10.1016/j.fsc.2022.01.001DOI Listing
May 2022

Facial Soft Tissue Repositioning With Neuromodulators: Lessons Learned From Facial Biomechanics.

Aesthet Surg J 2022 Apr 13. Epub 2022 Apr 13.

Department of Clinical Anatomy, Mayo Clinic College of Medicine and Science, Rochester, MN, USA.

Background: Neuromodulators have proven efficacy in reducing facial rhytides and have also been reported to improve jawline contour and the appearance of platysmal bands. Lifting effects of the tail of the eyebrow are expected outcomes when targeting the lateral peri-orbital region underscoring the versatility of neuromodulator treatments.

Objective: To analyze the clinical effectiveness of a novel neuromodulator-based injection algorithm with regards to its ability to reposition the middle and lower facial soft tissues.

Methods: Seventy-five study participants (8 males, 67 females) with a mean age of 37.5 (8.5) years were injected with neuromodulators in the subdermal plane of the mandibular soft tissues following a standardized algorithm. Live rating of clinical appearance was performed, as well as volume change and skin vector displacement using 3-dimensional imaging at baseline, day 14 and day 30.

Results: 3-dimensional volume analysis revealed an increase in midfacial volume by 0.46 cc, and a decrease of the lower facial volume by 0.30 cc compared to baseline. Additionally, an improvement of midfacial fullness (change of 0.13) and jawline contour (change of 0.44) was reported on clinical rating scales at day 30 compared to baseline.

Conclusions: Facial soft tissues can be repositioned during the 30 days follow-up period following a neuromodulator treatment; this was reflected through an increase in middle facial volume as well as through a decrease in lower facial volume. The novel injection algorithm presented can provide a safe and effective option for patients desiring improvement of midfacial fullness and jawline contour with neuromodulator treatment alone.
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http://dx.doi.org/10.1093/asj/sjac090DOI Listing
April 2022

Limited dilute lidocaine anesthesia: A useful technique with many practical applications.

J Cosmet Dermatol 2022 Apr 21;21(4):1445-1447. Epub 2022 Feb 21.

The Layt Clinic, Southport, Qld, Australia.

Background: Limited dilute lidocaine infiltration facilitates a comfortable procedure and a rapid recovery process following a novel intervention for reduction of cellulite. Infiltration of dilute lidocaine has many other practical applications in dermatologic surgery.

Objectives: This article describes a safe, effective technique for local infiltration of limited volume dilute lidocaine anesthesia in a cellulite reduction procedure.

Methods: The limited dilute lidocaine technique was utilized in studies of a novel device designed to reduce the appearance of cellulite by focal release of fibrous septa in a minimally invasive procedure. No sedation was used. A small (27- to 30-gauge) needle was used to deliver anesthesia to the entry sites. Then, a 20-gauge spinal needle was tunneled under the skin in the superficial plane to manually deliver anesthetic along the advancement pathway of the device and marked cellulite targets.

Results: During the initial studies, the mean delivered anesthesia volume was 357.2 ml (range, 250-525 ml) or 18.7 mg/kg (range, 11.1-28.4 mg/kg). The mean anesthesia time was 16 min (range, 8-32 min). The mean number of cellulite depressions treated was 19.8 (range, 11-34). Adverse events were closely monitored, and there were no signs of toxicity in any study patients. There were very low levels of discomfort; all patients reported the procedure was tolerable. This technique facilitates a time-efficient procedure and minimizes weeping of excess fluid during recovery.

Conclusions: When administered with care and skill, the limited dilute anesthesia technique is a safe, effective approach for local anesthesia with many practical applications in dermatologic surgery.
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http://dx.doi.org/10.1111/jocd.14825DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9305289PMC
April 2022

Tips and Tricks for Facial Toxin Injections with Illustrated Anatomy.

Plast Reconstr Surg 2022 Feb;149(2):303e-312e

From the Westmount Institute of Plastic Surgery; Skin Associates of South Florida and Skin Research Institute; CH Dermatologia; Shino Bay Cosmetic Dermatology & Laser Institute; Department of Dermatology, Nova Southeastern University College of Osteopathic Medicine; private practice; Gold Skin Care Center, Tennessee Clinical Research Center; Ocean Clinic; Department for Hand, Plastic, and Aesthetic Surgery, Ludwig Maximilian University of Munich; Clinical Research Unit, Erevna Innovations, Inc.; Division of Plastic Surgery, McGill University; and Department of Clinical Anatomy, Mayo Clinic College of Medicine and Science.

Learning Objectives: After studying this article, the participant should be able to: 1. Recognize facial muscle contraction direction and muscle morphology based on skin surface movements and facial rhytides. 2. Classify different muscle contraction patterns and target respectively with the recommended dosage and injection technique. 3. Apply the presented injection techniques to the patients' individual anatomy with greater precision and without affecting adjacent muscles or causing other adverse events.

Summary: Facial muscular anatomy has recently gained increased attention, with new investigative methodologies and new injection techniques arising on the market. These recent advancements have increased our understanding about the functional anatomy of facial muscles and have changed the way health care professionals see and understand their interplay during various facial expressions and in determining facial shape. This new anatomical understanding of facial muscles and their interaction has resulted in superior neuromodulator treatment outcomes with fewer side effects and with increased precision. The latter is of greatest importance, as all facial muscles act as a unit and connect with each other. It is therefore paramount to target during neuromodulator treatments only the muscle responsible for the aesthetic effect desired and not other adjacent muscles, which can have different or even antagonistic effects. Conventional anatomy was previously limited to two-dimensional explanations of muscle locations without incorporating their detailed action or their three-dimensional location of extent. The "new" anatomy incorporates those novel concepts and, once understood, will help health care providers to understand better and to "read" the underlying muscular anatomy based on the wrinkle status and based on the change in skin surface landmarks based on the actions of the underlying musculature. The following article summarizes tips and tricks, pearls and pitfalls, and dos and don'ts during facial neuromodulator injections along with a guide toward adverse event management and patient outcome assessment with special focus on the underlying anatomy.
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http://dx.doi.org/10.1097/PRS.0000000000008708DOI Listing
February 2022

Validated 5 - Point photonumeric scales for the assessment of hand atrophy.

J Cosmet Dermatol 2022 Mar 28;21(3):933-939. Epub 2022 Jan 28.

Private Practice, New York, USA.

Objective: Quantifying the degree of dorsal hand atrophy is a challenging endeavor, but often necessary, in both the clinical and the research setting. The aim of this investigation was to create and consecutively validate a 5-point photonumeric scale for assessment of dorsal hand atrophy.

Material And Methods: A medical team created a novel 5-point photonumeric scale. Twelve international raters were involved in the digital validation, while five raters performed a live validation.

Results: For the digital validation of the Croma Hand Atrophy Assessment Scale, a total of 72 subjects (58 females, 14 males) with a mean age of 43.0 ± 14.4 years [18-73 years] were assessed. For the live validation, 88 subjects (73 females, 15 males) with a mean age of 45.0 ± 14.1 years [20-73 years] were rated. The results revealed almost perfect intra-rater (ICC: 0.90 [95% CI: 0.88-0.92]) and inter-rater agreements (ICC: 0.85 [95% CI: 0.81-0.89] and 0.86 [95% CI:0.82-0.89]) in the digital validation and substantial intra-rater (ICC: 0.79 [95% CI: 0.75-0.82]) and inter-rater agreements (ICC: 0.75 [95% CI: 0.68-0.81] and ICC: 0.67 [95% CI: 0.54-0.77]) in the live validation.

Conclusion: The created scale to assess dorsal hand atrophy has been shown to provide substantial-to-almost perfect agreement in the digital and live validation cycles and reached comparable intra-rater and inter-rater agreement to already published and validated scales. It is expected that the created scale will help physicians and researchers in the assessment of hand atrophy in the clinical and research setting in the future.
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http://dx.doi.org/10.1111/jocd.14776DOI Listing
March 2022

Mutations in Hcfc1 and Ronin result in an inborn error of cobalamin metabolism and ribosomopathy.

Nat Commun 2022 01 10;13(1):134. Epub 2022 Jan 10.

Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX, 77030, USA.

Combined methylmalonic acidemia and homocystinuria (cblC) is the most common inborn error of intracellular cobalamin metabolism and due to mutations in Methylmalonic Aciduria type C and Homocystinuria (MMACHC). Recently, mutations in the transcriptional regulators HCFC1 and RONIN (THAP11) were shown to result in cellular phenocopies of cblC. Since HCFC1/RONIN jointly regulate MMACHC, patients with mutations in these factors suffer from reduced MMACHC expression and exhibit a cblC-like disease. However, additional de-regulated genes and the resulting pathophysiology is unknown. Therefore, we have generated mouse models of this disease. In addition to exhibiting loss of Mmachc, metabolic perturbations, and developmental defects previously observed in cblC, we uncovered reduced expression of target genes that encode ribosome protein subunits. We also identified specific phenotypes that we ascribe to deregulation of ribosome biogenesis impacting normal translation during development. These findings identify HCFC1/RONIN as transcriptional regulators of ribosome biogenesis during development and their mutation results in complex syndromes exhibiting aspects of both cblC and ribosomopathies.
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http://dx.doi.org/10.1038/s41467-021-27759-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8748873PMC
January 2022

Methods of Palate Culture in Later Palatogenesis: Elevation, Horizontal Outgrowth, and Fusion.

Methods Mol Biol 2022 ;2403:63-80

Centre for Craniofacial and Regenerative Biology, King's College London, London, SE1 9RT, UK.

The ex vivo culture of the palate has provided a versatile model in which to study palatogenesis. Dysmorphias of the palate remain one of the most common birth defects globally, with great scope for future research in both normal and dysmorphic palatogenesis. This process can be studied in the mouse model using both the hyperoxic rolling culture of maxillary explants and Trowell-type static cultures, which are optimal for the study of different stages of palate development respectively. Here, we describe both methods: the former for the study of palatal shelf elevation and horizontal growth, and the latter for palatal shelf fusion . Both are applicable in murine embryos cultured at embryonic day 13.5 using nonspecialist equipment.
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http://dx.doi.org/10.1007/978-1-0716-1847-9_6DOI Listing
January 2022

Validated 5-point photonumeric scales for the assessment of the jowls and chin.

J Cosmet Dermatol 2022 Feb 12;21(2):600-607. Epub 2021 Dec 12.

Department for Hand, Plastic and Aesthetic Surgery, Ludwig - Maximilian University Munich, Munich, Germany.

Objective: The objective of this investigation was to create and to examine the reproducibility and validity of 5-point photonumeric assessment scales that allow objective assessment of chin retrusion and jawline sagging using a digital and a live validation.

Material And Methods: Two new 5-point photonumeric scales created to assess chin projection and jawline sagging were validated by 12 experts in a digital validation and by 5 experts in a live validation setting. Intra-rater agreement and inter-rater agreement were assessed.

Results: For the digital validation, an almost perfect intra-rater (Kappa: 0.89 [95% CI: 0.86-0.91]) and almost perfect inter-rater agreement in both sessions (Kappa: 0.80 [95% CI: 0.74-0.86] and 0.80 [95% CI: 0.74-0.86]) was achieved for the Croma Chin Projection Assessment Scale, while intra-rater agreement (Kappa: 0.88 [95% CI: 0.85-0.91]) was almost perfect for the Croma Jawline Sagging Assessment Scale and inter-rater agreement being substantial in the first session (Kappa: 0.76 [95% CI: 0.71-0.81]) and almost perfect in the second session (Kappa: 0.81 [95%CI: 0.76-0.85]). For the live validation, intra-rater agreement was almost perfect for the Croma Chin Projection Assessment Scale (Kappa: 0.82 [95%CI: 0.74-0.90]) and the Croma Jawline Sagging Assessment Scale (Kappa: 0.83 [95%CI: 0.77-0.89]), while inter-rater agreement was substantial in both sessions for both scales.

Conclusion: The created chin and jawline photonumeric grading scales are valid and reliable tools for assessing chin projection and jawline sagging. The scales will be of value for standardized chin evaluation and quantifying outcomes in clinical research and daily practice.
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http://dx.doi.org/10.1111/jocd.14661DOI Listing
February 2022

Validated 5-point photonumeric scales for the assessment of the periorbital region.

J Cosmet Dermatol 2022 Jan 5;21(1):158-166. Epub 2021 Dec 5.

Cosmetic Laser Dermatology, San Diego, California, USA.

Objective: The objective of this investigation was to create and validate 5-point photonumeric scales for the assessment of dynamic crow's feet, static crow's feet, and infraorbital hollows.

Material And Methods: Three novel 5-point photonumeric scales were created by a medical team. A total of 12 raters from all over the world performed a digital validation, and a total of 5 raters a live validation of the created scale.

Results: The statistical analysis revealed almost perfect intra-rater and inter-rater reliability in the digital validation of the scales for the assessment of static and dynamic crow's feet as well as infraorbital hollows. In the live validation, both crow's feet scales showed almost perfect intra-rater reliability, while the Croma Infraorbital Hollow Assessment Scale showed substantial intra-rater reliability. Inter-rater reliability was substantial for all three scales in the live validation. All three scales, the Croma Dynamic Crow's Feet Assessment Scale, Croma Static Crow's Feet Assessment Scale, and Croma Infraorbital Hollow Assessment Scale, were validated digitally and in a live setting.

Conclusion: The created scales to assess infraorbital hollowing, dynamic and static crow's feet have been shown to provide substantial to almost perfect agreement in the digital and live validation and can thus be considered as helpful tools in the clinical and research setting. While technical methods and appliances to assess the degrees of severity of age-dependent features are advancing, validated scales are of great importance due to their ease of use and, as shown by the validations, reliability, and reproducibility.
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http://dx.doi.org/10.1111/jocd.14643DOI Listing
January 2022

Real-Time Ultrasound Imaging of the Tear Trough: Lessons Learned From Functional Anatomy.

Aesthet Surg J 2022 04;42(5):518-526

Department of Clinical Anatomy, Mayo Clinic Rochester, MN, USA.

Background: The tear trough is one of the most challenging facial regions for soft-tissue filler injections. A thorough understanding of the underlying facial, muscular, and vascular anatomy is crucial to perform safe and effective tear trough injectable treatments.

Objectives: The authors sought to evaluate the location and function of the angular vein in the tear trough in 3 different facial expressions: repose, smiling, and max. orbicularis oculi contraction.

Methods: Twenty study participants with a mean age of 48.3 years and mean BMI of 24.5 kg/m2 were investigated via functional ultrasound imaging. The diameter of the angular vein and the velocity and direction of venous blood flow were analyzed in repose, smiling, and during max. orbicularis oculi contraction.

Results: The angular vein was identified in 100% of the cases to travel inside the orbicularis oculi muscle (intra-muscular course) within the tear trough, whereas the angular artery was not identified in this location. The distance between the angular vein and the inferior orbital rim was (lateral to medial): 4.6 mm, 4.5 mm, 3.9 mm, and 3.8 mm. The caudally directed blood flow was in repose 10.2 cm/s and was 7.3 cm/s at max. orbicularis oculi muscle contraction; however, no blood flow was detectable during smiling.

Conclusions: The diameter and the venous blood flow of the angular vein varied between the 3 tested facial expressions. Based on these anatomical findings, the deep injection approach to the tear trough is recommended due to the intramuscular course of the angular vein.
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http://dx.doi.org/10.1093/asj/sjab351DOI Listing
April 2022

Safety and efficacy of microneedling technology in the treatment of acne scars.

J Cosmet Dermatol 2021 Nov 1;20(11):3482-3491. Epub 2021 Oct 1.

Department of Clinical Anatomy, Mayo Clinic College of Medicine and Science, Rochester, Minnesota, USA.

Background: Current options for the reduction of acne scarring (eg, ablative laser resurfacing) are associated with considerable side effects and limitations in terms of patient population. Percutaneous collagen induction via microneedling poses an alternative treatment method due to its low rates of reported adverse events and side effects.

Objective: To assess the safety and effectiveness of microneedling treatments in reducing acne scars.

Methods: A total of 22 patients (18 females and 4 males) with a mean age of 38 ± 7.6 years were assessed regarding the appearance of facial acne scarring. Acne scars were assessed via the Acne Scar Assessment Scale (ASAS) and the Goodman and Baron acne scar grading scale before and after two/three treatments. Additionally, the post-interventional development of side reactions, adverse events, and patient-reported outcomes (eg, pain/discomfort, skin redness) was reported.

Results: Compared to baseline, the mean ASAS value was improved statistically significantly on average by 1.41 and 1.46 after the second treatment as assessed by the independent raters and the patients, respectively. In patients who received a total of three treatments, a statistically significant mean improvement in ASAS value of 1.35 and 1.66 compared to baseline was assessed by the independent raters and patients, respectively. No unexpected adverse events were reported. The severity and rate of side reactions decreased over the course of this study.

Conclusion: Microneedling treatments can pose a safe and effective option in the reduction of acne scarring. In this study, microneedling helped achieving a significant reduction of acne scars while showing high patient safety.
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http://dx.doi.org/10.1111/jocd.14502DOI Listing
November 2021

Computational biology: Turing's lessons in simplicity.

Authors:
Jeremy B A Green

Biophys J 2021 10 2;120(19):4139-4141. Epub 2021 Sep 2.

Centre for Craniofacial Regeneration and Biology, King's College London, London, United Kingdom. Electronic address:

Biophysical modeling of development started with Alan Turing. His two-morphogen reaction-diffusion model was a radical but powerful simplification. Despite its apparent limitations, the model captured real developmental processes that only recently have been validated at the molecular level in many systems. The precision and robustness of reaction-diffusion patterning, despite boundary condition-dependence, remain active areas of investigation in developmental biology.
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http://dx.doi.org/10.1016/j.bpj.2021.08.041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8516674PMC
October 2021

Change in Rheologic Properties of Facial Soft-Tissue Fillers across the Physiologic Angular Frequency Spectrum.

Plast Reconstr Surg 2021 Aug;148(2):320-331

From the Department of Clinical Anatomy, Mayo Clinic College of Medicine and Science; Division of Anatomy, Department of Medical Education, Albany Medical College; Division of Dermatology, University of Toronto; private practice; Skin Associates of South Florida, Skin Research Institute; the Erevna Innovations, Inc., Clinical Research Unit; Division of Plastic Surgery, McGill University; and the Department for Hand, Plastic and Aesthetic Surgery, Ludwig-Maximilian University.

Background: The number of soft-tissue filler injections performed in the United States is constantly increasing and reflects the high demand for enhanced facial and body attractiveness. The objective of the present study was to measure the viscoelastic properties of soft-tissue fillers when subjected to different testing frequencies. The range of tested frequencies represents clinically different facial areas with more [lips (high frequency)] or less [zygomatic arch (low frequency)] soft-tissue movement.

Methods: A total of 35 randomly selected hyaluronic acid-based dermal filler products were tested in an independent laboratory for their values of G', G″, tan δ, and G* at angular frequencies between 0.1 and 100 radian/second.

Results: The results of the objective analyses revealed that the viscoelastic properties of all tested products changed between 0.1 and 100 radian/second angular frequency. Changes in G' ranged from 48.5 to 3116 percent, representing an increase in their initial elastic modulus, whereas changes in G″ ranged from -53.3 percent (i.e., decrease in G″) to 7741 percent (i.e., increase in G″), indicating both an increase and a decrease in their fluidity, respectively.

Conclusions: The increase in G' would indicate the transition from a "softer" to a "harder" filler, and the observed decrease in G″ would indicate an increase in the filler's "fluidity." Changes in the frequency of applied shear forces such as those occurring in the medial versus the lateral face will influence the aesthetic outcome of soft-tissue filler injections.
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http://dx.doi.org/10.1097/PRS.0000000000008188DOI Listing
August 2021

Early perturbation of Wnt signaling reveals patterning and invagination-evagination control points in molar tooth development.

Development 2021 07 22;148(14). Epub 2021 Jul 22.

Program in Craniofacial Biology and Department of Orofacial Sciences, University of California, San Francisco, CA 94143, USA.

Tooth formation requires complex signaling interactions both within the oral epithelium and between the epithelium and the underlying mesenchyme. Previous studies of the Wnt/β-catenin pathway have shown that tooth formation is partly inhibited in loss-of-function mutants, and gain-of-function mutants have perturbed tooth morphology. However, the stage at which Wnt signaling is first important in tooth formation remains unclear. Here, using an Fgf8-promoter-driven, and therefore early, deletion of β-catenin in mouse molar epithelium, we found that loss of Wnt/β-catenin signaling completely deletes the molar tooth, demonstrating that this pathway is central to the earliest stages of tooth formation. Early expression of a dominant-active β-catenin protein also perturbs tooth formation, producing a large domed evagination at early stages and supernumerary teeth later on. The early evaginations are associated with premature mesenchymal condensation marker, and are reduced by inhibition of condensation-associated collagen synthesis. We propose that invagination versus evagination morphogenesis is regulated by the relative timing of epithelial versus mesenchymal cell convergence regulated by canonical Wnt signaling. Together, these studies reveal new aspects of Wnt/β-catenin signaling in tooth formation and in epithelial morphogenesis more broadly.
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http://dx.doi.org/10.1242/dev.199685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8326921PMC
July 2021

Skin Tightening With Hyperdilute CaHA: Dilution Practices and Practical Guidance for Clinical Practice.

Aesthet Surg J 2022 01;42(1):NP29-NP37

Department of Medicine/Dermatology, University of Washington, Seattle, WA, USA.

Background: Over the past several years, hyperdilute calcium hydroxylapatite (CaHA) has emerged as an effective modality for improving skin quality and managing laxity in the face, arms, hands, neck, décolletage, upper arms, abdomen, buttocks, and upper legs, as well as for treating cellulite and striae. Whereas undiluted CaHA is used to provide volume, hyperdilute CaHA is distributed across a much larger surface area in a more superficial plane to stimulate neocollagenesis and elastin formation over time. The absence of lymphocytic infiltrates and predominance of type 1 collagen in the tissue response to CaHA make hyperdilute CaHA a valuable tool for nonsurgical skin tightening.

Objectives: The aim of this study was to provide practical step-by-step guidance on patient selection, dilution practices, and optimal injection technique to facilitate incorporation of the technique into clinical practice.

Methods: Over the course of 3 regional meetings in the United States, 12 expert physician injectors participated in live webinars as part of a continuing medical education program.

Results: The practical guidance in this manuscript is based upon the most frequently requested information by audience members and the information considered critical for success by the authors.

Conclusions: The minimally invasive nature of filler injection results in little downtime, making this treatment particularly appealing. The recommendations presented are consistent with previously published consensus guidelines on hyperdilute CaHA but are intended to serve as "how-to" guidance based on the experience of expert injectors who have successfully treated the face and body.

Level Of Evidence: 4:
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http://dx.doi.org/10.1093/asj/sjab269DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8849118PMC
January 2022

After the Temporal Lifting Technique-What comes next?

J Cosmet Dermatol 2021 Dec 21;20(12):3857-3862. Epub 2021 Jul 21.

Department of Clinical Anatomy, Mayo Clinic College of Medicine and Science, Rochester, MN, USA.

Background: The temporal lifting technique can provide lateral facial lifting when administering hyaluronic acid (HA)-based soft tissue fillers into the subdermal plane of the temple. However, the central facial oval is not influenced by this technique.

Objectives: To identify the safety and esthetic effectiveness of additional midfacial injection points (in addition to the temporal lifting technique) that can volumize the medial midface, lift the lateral face, and increase jawline contouring when included into a full-face injection algorithm.

Methods: The patient records of nine consecutive patients (all females) with a mean age of 35.0 (8.4) years and a mean body mass index of 21.7 (2.4) kg/m were retrospectively analyzed after a full-face injection algorithm was performed using HA-based fillers. The additional injection points target the supraperiosteal plane of the medial zygomatic arch, the lateral infraorbital region, and the pyriform fossa using both needles and cannula.

Results: No adverse events were observed during the 6-month retrospective observational period. The volume of the medial midface increased, the volume of the lateral midface decreased, and the contour of the jawline improved; all effects reached a highly statistically significant level with p < 0.001.

Conclusion: Despite each individual injection is currently performed on a daily clinical basis the evaluated injection algorithm following the temporal lifting technique shows some evidence that it is safe and esthetically effective. Future studies will need to confirm the results presented herein in a larger sample and with objective outcome measures to guide safe and effective esthetic outcomes.
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http://dx.doi.org/10.1111/jocd.14247DOI Listing
December 2021

The Influence of Different Light Angles During Standardized Patient Photographic Assessment on the Aesthetic Perception of the Face.

Aesthetic Plast Surg 2021 12 13;45(6):2751-2759. Epub 2021 May 13.

Department of Clinical Anatomy, Mayo Clinic College of Medicine and Science, Mayo Clinic, Stabile Building 9-38, 200 First Street, Rochester, MN, 55905, USA.

Background: 2D baseline and follow-up clinical images are potentially subject to inconsistency due to alteration of imaging parameters. However, no study to date has attempted to quantify the magnitude by which such images can be influenced.

Objective: The objective of the present study is to identify the magnitude by which images can be influenced by changing the imaging light angle.

Methods: This study is based on the evaluation of 2D frontal images of the face and included a total of 51 subjects of which n = 14 were males and n = 37 were females. Faces were photographed at 0°, 30°, and 60° light angle under identical and standardized conditions. Images were randomized and rated by 27 blinded raters for age, facial attractiveness, body mass index (BMI), temporal hollowing, lower cheek fullness, nasolabial sulcus severity, and jawline contour.

Results: Facial attractiveness decreased, facial unattractiveness increased and the evaluated BMI (based on facial assessment) increased statistically significantly at 60°. The assessment of regional facial scores, i.e., temporal hollowing, lower cheek fullness, and jawline contour, showed no statistically meaningful changes both at 30° and at 60° light angle.

Conclusion: The results indicate that there might be an observed blind range in light angle (0°-30°) which does not influence facial assessment. Increasing the light angle past the threshold value to 60° might result in a statistically significant impact on facial perception which should be accounted for when documenting and/or presenting facial 2D images.

Level Of Evidence V: 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 .
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http://dx.doi.org/10.1007/s00266-021-02314-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8677634PMC
December 2021

Deformation of Needle Tips During Facial Soft Tissue Filler Injections: An Electron-Microscopic Study.

Aesthet Surg J 2021 11;41(12):NP2011-NP2019

Department of Clinical Anatomy, Mayo Clinic College of Medicine and Science, Rochester, MN, USA.

Background: Injectable soft tissue fillers are used on a global scale for a variety of aesthetic indications. Despite their widespread use, there is a dearth of information regarding needle deformation following injection procedures. Repeated injections with the same needle could lead to progressive needle tip deformation, potentially resulting in decreased precision and increased patient discomfort.

Objectives: The objective of this study was to quantify the magnitude of needle tip deformation utilizing scanning electron microscopy (SEM) image analysis.

Methods: An observational study was performed evaluating 4 differently sized needles following soft tissue filler injections for 5 different aesthetic indications (zygomatic arch, infraorbital, midcheek, nasolabial sulcus, and perioral) in patients aged 36 to 64 years. Following treatment, each needle was visualized and imaged through SEM, and the percentage of deformation in relation to the total amount of needle tip surface was calculated.

Results: The factor most influencing needle tip damage was revealed to be the number of injection passes, ie, dermal transitions. Per injection procedure, an increase in needle tip damage of 4.7% occurred. Touching the bone deformed the needle tip by 9.6% and an increase in needle size resulted in 0.13% more damage.

Conclusions: To the authors' knowledge, this is the first SEM investigation to provide objective evidence for the deformation of needle tips after repeated facial soft tissue filler injections. These data may help improve patient safety and comfort during these minimally invasive procedures.

Level Of Evidence: 3:
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http://dx.doi.org/10.1093/asj/sjab211DOI Listing
November 2021

Influence of Rheological Properties and Needle Size on Extrusion Forces of Hyaluronic Acid Based Soft Tissue Fillers.

J Drugs Dermatol 2021 May;20(5):498-502

Background: To date no precise data are available for extrusion forces related to the G-prime and G-double-prime of fillers in combination with different 27G and 30G needles. Therefore, the objective of this study was to analyze extrusion forces of various product-needle-combinations containing two different 27G and two different 30G needles in combination with fillers of a wide range of elastic moduli starting from 2.0 – 166.0 Pa.

Material And Methods: Four different fillers with the following elastic moduli 1.87, 11.65, 61.80, 165.50 Pa were combined with four different needles: 27G ½”, internal diameter: 0.300 μm; 27G ½”, internal diameter: 0.241 μm; 30G ½”, internal diameter: 0.241 μm and 30G ½“, internal diameter: 0.240 μm. Product-needle-combination were subjected to uni-axial mechanical testing and the respective extrusion force was measured.

Results: The results of this study revealed that the G-prime and the G-double-prime of a product are statistically significantly related to their extrusion force, with higher G-prime/G-double-prime products requiring higher extrusion forces. The results additionally revealed that whether the size of the needle was described as 27G or 30G by the respective manufacturer statistically significant differences between the measured extrusion forces were detected.

Conclusion: Injectors need to be aware that not every 27G/30G needle has the same extrusion force even though the external diameter is similar (27G or 30G); this might additionally influence the ability to withdraw blood during a pre-injection aspiration manoeuvre. J Drugs Dermatol. 20(5): doi:10.36849/JDD.5237.
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http://dx.doi.org/10.36849/JDD.5237DOI Listing
May 2021

Quantitative Analysis of the Lifting Effect of Facial Soft-Tissue Filler Injections.

Plast Reconstr Surg 2021 May;147(5):765e-776e

From private practice; the Department for Hand, Plastic, and Aesthetic Surgery, Ludwig Maximilian University; the Division of Anatomy, Department of Medical Education, Albany Medical College; Skin Associates of South Florida; and the Department of Clinical Anatomy, Mayo Clinic College of Medicine and Science, Mayo Clinic.

Background: Although injectable soft-tissue fillers are frequently used for facial rejuvenation, there is a dearth of objective data evaluating the tissue-lifting effects. Current practices for efficacy evaluation include some subjectivity. This study seeks to evaluate the lifting effects of facial soft-tissue fillers in a quantifiable, objective setting.

Methods: Twenty fresh hemifaces obtained from 10 Caucasian body donors (seven women and three men) with a mean age of 83.5 ± 6.8 years and a mean body mass index of 25.3 ± 4.3 kg/m2 were injected with soft-tissue fillers following a predefined treatment algorithm. Three-dimensional surface scanning procedures were performed to assess postinjection effects.

Results: Injections in the medial face [i.e., forehead, medial midface, and perioral (chin and labiomandibular sulcus)] increased the local surface volume by 0.67, 0.56, and 0.87 cc and created local (but not regional) lifting effects of 1.11, 0.11, and 0.74 mm. Injections in the lateral face (temple, lateral midface, and jawline) changed the local surface volume by 0.45, 0.02, and -0.38 cc, and created local lifting effects of 0.57, 0.81, and 0.29 mm, respectively. Lateral face injections, however, created additional regional lifting effects by co-influencing neighboring lateral facial regions, which was not observed for medial face injections.

Conclusions: This cadaveric study provides evidence that soft-tissue fillers, although typically classified as volumizers, can induce lifting effects of the face. Whereas temporal deep supraperiosteal injections have limited lifting effects, the combined effects of subdermal injections of the temple, lateral midface, and mandibular angle can induce lifting effects of the total lateral face.

Clinical Question/level Of Evidence: Therapeutic, V.
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http://dx.doi.org/10.1097/PRS.0000000000007857DOI Listing
May 2021

A landmark-free morphometrics pipeline for high-resolution phenotyping: application to a mouse model of Down syndrome.

Development 2021 03 12;148(18). Epub 2021 Mar 12.

Centre for Craniofacial Biology & Regeneration, King's College London, UK

Characterising phenotypes often requires quantification of anatomical shape. Quantitative shape comparison (morphometrics) traditionally uses manually located landmarks and is limited by landmark number and operator accuracy. Here, we apply a landmark-free method to characterise the craniofacial skeletal phenotype of the Dp1Tyb mouse model of Down syndrome and a population of the Diversity Outbred (DO) mouse model, comparing it with a landmark-based approach. We identified cranial dysmorphologies in Dp1Tyb mice, especially smaller size and brachycephaly (front-back shortening), homologous to the human phenotype. Shape variation in the DO mice was partly attributable to allometry (size-dependent shape variation) and sexual dimorphism. The landmark-free method performed as well as, or better than, the landmark-based method but was less labour-intensive, required less user training and, uniquely, enabled fine mapping of local differences as planar expansion or shrinkage. Its higher resolution pinpointed reductions in interior mid-snout structures and occipital bones in both the models that were not otherwise apparent. We propose that this landmark-free pipeline could make morphometrics widely accessible beyond its traditional niches in zoology and palaeontology, especially in characterising developmental mutant phenotypes.
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http://dx.doi.org/10.1242/dev.188631DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969589PMC
March 2021

Improvements in Submental Contour up to 3 Years After ATX-101: Efficacy and Safety Follow-Up of the Phase 3 REFINE Trials.

Aesthet Surg J 2021 10;41(11):NP1532-NP1539

the executive director of global development, Allergan Aesthetics, an AbbVie Company, Irvine, CA, USA.

Background: ATX-101 (deoxycholic acid) significantly reduced submental fat (SMF) severity in two 24-week Phase 3 studies (REFINE-1 and REFINE-2).

Objectives: The aim of this study was to evaluate the durability of effect and long-term safety of ATX-101.

Methods: REFINE study patients who maintained ≥1-grade improvement on the Clinician-Reported SMF Rating Scale (CR-1 responders) 12 weeks after their last REFINE treatment were eligible for enrollment in this multicenter, double-blind, nontreatment, long-term, follow-up study (NCT02163902). The primary endpoint was CR-1 response at Years 1, 2, and 3. Patient-reported satisfaction, psychological impact, and adverse events were monitored.

Results: In total, 224 patients (ATX-101, n = 113; placebo, n = 111) were enrolled. Maintenance of CR-1 response was significantly better in the ATX-101 group than in the placebo group at Year 1 (86.4% vs 56.8%; P < 0.001), Year 2 (90.6% vs 73.8%; P = 0.014), and Year 3 (82.4% vs 65.0%; P = 0.03). Most (74%) ATX-101‒treated patients satisfied at 12 weeks remained satisfied at Year 3. Significant reductions from baseline in psychological impact scores were sustained through Year 3 (P < 0.001). No new treatment-related adverse events were reported.

Conclusions: Improvements in submental contour achieved with ATX-101 are maintained for 3 years in most patients. No new safety signals emerged.

Level Of Evidence: 2:
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http://dx.doi.org/10.1093/asj/sjab100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8520020PMC
October 2021

Intraarterial Degradation of Calcium Hydroxylapatite Using Sodium Thiosulfate - An In Vitro and Cadaveric Study.

Aesthet Surg J 2021 04;41(5):NP226-NP236

Department of Clinical Anatomy, Mayo Clinic College of Medicine and Science, Rochester, MN, USA.

Background: The most severe complications following soft tissue filler injections result from the intraarterial administration of the filler product. Although hyaluronic acid-based filler can be trans-arterially dissolved with hyaluronidase, no information is available on calcium hydroxylapatite (CaHA)-based fillers.

Objective: The authors sought to test whether CaHA-based fillers can be trans-arterially dissolved by sodium thiosulfate (STS) when evaluated in cadaveric and in vitro models.

Methods: Human cadaveric facial arterial segments were each filled with 0.2 cc of commercially available CaHA product and submerged for 24 hours in 4 different STS-containing solutions: 10 cc STS (300 mg/cc) (pure, 1:1 dilution, 1:2 dilution), 0.9% saline and 10 cc STS (300 mg/cc), and 300 IU (bovine) hyaluronidase in a 1:1 ratio.

Results: Intraarterial CaHA was detected in human facial artery segments after 24 hours independent of the STS concentration employed. Submerging the arterial segments in STS (300 mg/cc) and 300 IU (bovine) hyaluronidase (1:1 ratio) also did not dissolve the intraarterial CaHA product. Gray scale analyses did show, however, that increasing concentrations of STS resulted in increased disintegration of CaHA in an in vitro experimental setting.

Conclusions: The results of this study indicate that STS is limited in its potential to dissolve intraarterial CaHA of cadaveric human facial arteries, despite the fact that it appears effective when in direct contact with the CaHA. Adverse events caused by intraarterial administration of CaHA-based fillers still lack a suitable antidote.
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http://dx.doi.org/10.1093/asj/sjaa350DOI Listing
April 2021

To click or not to click - The importance of understanding the layers of the forehead when injecting neuromodulators - A clinical, prospective, interventional, split-face study.

J Cosmet Dermatol 2021 May 8;20(5):1385-1392. Epub 2020 Dec 8.

Department of Clinical Anatomy, Mayo Clinic College of Medicine and Science, Rochester, MN, USA.

Background: Differences in the effectiveness of neuromodulator treatments for horizontal forehead lines dependent on depth of product administration have been described. However, knowledge in respect to the fascial anatomy of the forehead still remains elusive.

Aims: To relate the fascial anatomy of the forehead to the effectiveness of neuromodulator treatments by conducting a clinical, prospective, interventional split-face study in which injections for the treatment of horizontal forehead lines are performed differently between facial sides.

Methods: This study included a total of n = 14 patients with a mean age of 35.71 (7.8) years and mean body mass index of 21.9 (3.0) kg/m . One side of the forehead was injected superficially by positioning the product in the superficial fatty layer, whereas the contralateral side was injected deep targeting the supraperiosteal plane (random selection). The treatment outcome was rated by the physician and by two independent observers according to a forehead line severity scale (0-4) at 14 and at 30 days.

Results: All three observers agreed in their ratings (ICC: 0.942) that the deep injection technique resulted in a superior outcome: D14 (superficial vs deep) 0.17 (0.4) vs 0.14 (0.4; P = .583) at rest and 1.26 (0.6) vs 0.43 (0.5; P < .001) for frontalis contraction; D30 0.17 (0.4) vs 0.14 (0.3) at rest (P = .583) and 1.21 (0.6) vs 0.43 (0.5; P < .001) for frontalis contraction.

Conclusion: The results of this study underscore how detailed anatomic knowledge can enhance results of aesthetic interventions, in this case horizontal forehead line treatment with neuromodulators.
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http://dx.doi.org/10.1111/jocd.13875DOI Listing
May 2021

The Influence of Different Treatment Combinations on Skin Laxity and Dimpling.

J Drugs Dermatol 2020 Nov;19(11):1030-1038

Objective: The aim of the study was to identify the effectiveness of the combination of tissue stabilized guided subcision, microfocused ultrasound, and minimally invasive calcium hydroxylapatite injections in various sequences for treating skin surface irregularities of the buttocks and thighs.

Material And Methods: 61 females (body mass index: 22.6 ± 2.4 kg/m², age: 37.2 ± 6.8 years) were enrolled in this randomized interventional prospective study. Treatment arms included a variable combination and sequence of three treatment modalities: (1) Tissue-stabilized guided subcision, (2) microfocused ultrasound, and (3) calcium hydroxylapatite injections. Six months after the final intervention skin laxity and skin dimpling severity scores were assessed by the study participants, the treating physicians and by eleven blinded independent board-certified experts.

Results: No adverse events were observed during the study that required intervention outside the standard of care treatment protocol. The combination of three treatment modalities was shown to provide greater improvement in skin laxity 1.88 (95% CI, 0.66–5.37) and skin dimpling 1.31 (95% CI, 0.61–2.81) scores as compared to any combination of two modalities. The combination of concomitant microfocused ultrasound and calcium hydroxylapatite injections followed three months later by tissue stabilized guided subcision yielded the greatest improvement in skin laxity 2.23 (95% CI, 0.51–9.82) and skin dimpling 1.79 (95% CI, 0.67–4.78) at 9-month follow-up.

Conclusion: This study provides evidence for the effectiveness of combination therapies for the improvement of skin surface irregularities on the buttocks and thighs. J Drugs Dermatol. 2020;19(11): 1030-1038. doi:10.36849/JDD.2020.5117.
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November 2020
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