A Randomized, Evaluator-Blinded, Multi-Centered Study to Compare Injectable Poly-D, L-Lactic Acid Versus Hyaluronic Acid for Nasolabial Fold Augmentation.

BACKGROUND: Injectable poly-D, L-lactic acid (PDLLA), under the brand name of AestheFill (Chaeum Pharma GmbH, Berlin, Germany), is a biocompatible, biodegradable, and biostimulatory product used to correct soft tissue volume loss. Its efficacy and safety have not been fully studied in a large cohort. OBJECTIVES: To evaluate the efficacy and safety of a novel dermal filler injectable poly-D, L-lactic acid. METHODS: This is an evaluator-blinded, multi-centered, randomized controlled trial to compare the efficacy and safety of PDLLA versus hyaluronic acid in the correction of nasolabial fold. Two hundred and sixty patients with moderate to severe nasolabial fold were enrolled and randomized to treatment group (PDLLA) or control group (hyaluronic acid). Each patient received PDLLA or hyaluronic acid injection for nasolabial fold augmentation and followed up for 52 weeks. Wrinkle Severity Rating Scale (WSRS) and Global Aesthetic Improvement Scale (GAIS) were used to evaluate topical nasolabial fold augmentation and overall improvement, respectively. RESULTS: At 24 weeks, 67.6% of patients in the PDLLA group had at least 1-grade improvement in WSRS, compared to 60.9% of patients in the control group with at least 1-grade improvement in WSRS (p<0.05). At each visit, PDLLA group showed more improvement from the baseline in WSRS than the control group. PDLLA was safe and well-tolerated with no severe adverse events. CONCLUSIONS: PDLLA shows non-inferior efficacy in correcting nasolabial fold compared to hyaluronic acid.

The AestheCode System: A Safe and Efficient Guide for AestheFill Injection.

AestheFill is a biostimulator based on poly-D,L-lactic acid. It is supplied as lyophilized powders and is referred to as a versatile biostimulator. According to the amount of water added, the suspensions can be vary in thickness which can be divided into four groups for different indications: the thickest suspension (D1.5-3) for nose or chin augmentation, thick suspension (D3-6) for deep wrinkle correction, thin suspension (D6-12) for shallow wrinkle correction, and super-thin suspension (D12-24) for skin rejuvenation. However, practitioners may be confused about which filler thickness, injection layer, method, and amount should be chosen for their patients. Biostimulators tend to form non-inflammatory nodules if technical mishaps occur during injection. Based on 10 years of AestheFill injection experience, the authors proposed the AestheCode system for the safe and effective injection of AestheFill.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 .

Retrograde flow phenomenon of poly-D,L-lactic acid filler injection over lower eyelids.

The occurrence of 'retrograde flow along the cannula/needle tract' during filler injections has not been extensively addressed in the existing literature, possibly because it is often imperceptible unless the injection is conducted at a superficial layer. In our experience with poly-D,L-lactic acid filler for lower eyelid injections, we have observed and documented this phenomenon through the skin. This article aims to elucidate and illustrate the retrograde flow phenomenon and discuss the factors influencing it.

miR-328-3p Affects Axial Length Via Multiple Routes and Anti-miR-328-3p Possesses a Potential to Control Myopia Progression.

Purpose: We previously reported miR-328-3p as a novel risk factor for myopia through a genetic association study of the PAX6 gene. In the present study, we first explored the effects of miR-328-3p on other myopia-related genes, and then tested whether anti-miR-328-3p may be used for myopia control. Methods: The luciferase report assay and transient transfection were used to confirm miR-328-3p target genes. The chromatin immunoprecipitation (ChIP) assay was used to investigate retinoic acid receptor on the miR-328-3p promoter. Mice and pigmented rabbits were induced to have myopia by the form deprivation method, and then anti-miR-328-3p oligonucleotide was topically instilled to the myopic eyes. The axial length was measured to assess the therapeutic effect of anti-miR-328-3p. A toxicity study using much higher doses was conducted to assess the safety and ocular irritation of anti-miR-328-3p. Results: The report assay and transfection of miR-328-3p mimic confirmed that miR-328-3p dose-dependently decreased both mRNA and protein expression of fibromodulin (FMOD) and collagen1A1 (COL1A1). We subsequently showed that FMOD promoted TGF-ß1 expression, and overexpression of FMOD increased the phosphorylation levels of p38-MAPK and JNK. The ChIP study showed that retinoic acid binds to miR-328-3p promoter and up-regulates miR-328-3p expression. In myopic animal studies, anti-miR-328-3p was as effective as 1% atropine and had a dose-dependent effect on suppressing axial elongation. In the toxicity study, anti-miR-328-3p did not cause any unwanted effects in the eyes or other organs. Conclusions: Micro (mi)R-328-3p affects myopia development via multiple routes. anti-miR-328-3p possesses a potential as a novel therapy for myopia control.

Nonsurgical lower eyelid rejuvenation using injectable poly-d,l-lactic acid in Asian patients.

BACKGROUND: Filler injection for lower eyelid rejuvenation remains a difficult subject due to many complicated anatomic changes as the face ages. OBJECTIVES: To propose an alternative, simple, and effective filler injection method in lower eyelids for Asian patients. METHODS: Any patient who has tear trough deformities, infra-orbital hollows, nasojugal grooves, dark eye circles, as well as mild eyebags is a potential candidate for this method. Our filler choice is injectable poly-d,l-lactic acid (PDLLA; AestheFill; REGEN). PDLLA must be reconstituted with sterile water for injection (SWFI) before administration. When the patient's troughs, grooves, or volume deficit are classes II and III, 3-4 ml of SWFI and 1 ml of lidocaine are used. When the deficits are class I, 5-7 ml of SWFI and 1 ml of lidocaine are used. With the fanning injection technique, a wide region that covers all the deficits is evenly injected. The depth is under the dermis layer. The total amount of filler injection is not more than 2 ml on each side. RESULTS: Since 2019, we have injected more than 100 patients by following these steps in Taiwan. The level of patient satisfaction is high. Only some mild and transient post-injection complications such as edema, erythema, and ecchymosis were found. CONCLUSIONS: We propose an alternative, simple and effective method for non-surgical lower eyelid rejuvenation for Asian patients. However, anyone who wants to perform this procedure should be well-trained and knowledgeable about the anatomy, product, and procedure to prevent adverse events.

Reconstitution of Injectable Poly-d,l-lactic Acid: Efficacy of Different Diluents and a New Accelerating Method.

Injectable poly-d,l-lactic acid (PDLLA) is a new collagen-stimulating filler containing PDLLA microspheres and carboxymethyl cellulose. It is available as a lyophilized powder that must be reconstituted with a diluent before administration. The aims of this study were to investigate the efficacy of different diluents and a new accelerating "back-and-forth" method. METHODS: Six different diluents, sodium bicarbonate, sterile water for injection (SWFI), normal saline, lidocaine, lidocaine with epinephrine (lidocaine + E), and mannitol, were tested. The recommended "vortex" method for preparation of thin suspensions and a new back-and-forth method suitable for both thin and thick suspensions were compared. Gross and microscopic views of the prepared suspensions were examined. RESULTS: Using the vortex method, only mannitol and SWFI are found to be effective reconstitution diluents for injectable PDLLA. Using the back-and-forth method, all six diluents can be used for reconstitution of injectable PDLLA. Moreover, the time needed for reconstitution of injectable PDLLA by this back-and-forth method is very short, regardless of the thickness of the suspension. CONCLUSIONS: Clinically, only SWFI can be used for reconstitution of injectable PDLLA by "hand-shaking" or vortex method. To accelerate the reconstitution time especially when using small amount of SWFI, back-and-forth is the method of choice. Besides, when SWFI is not available, other diluents such as normal saline, lidocaine, or lidocaine + E can be used by this novel back-and-forth reconstitution method.

Pelvic retroperitoneal cyst during pregnancy.

OBJECTIVE: The diagnosis and treatment of adnexal mass during pregnancy is a major challenge for obstetricians. A rare case is reported of retroperitoneal cystic lesion during pregnancy. CASE REPORT: A 31-year-old woman was diagnosed with an adnexal cystic lesion at 8 weeks of gestation and underwent laparoscopic surgery at 14 weeks of gestation. During laparoscopic surgery, the bilateral ovaries and tubes were normal, but the lesion was located on the right-side retroperitoneal area. Aspiration and enucleation were performed successfully by laparoscopy. The pathology report revealed mucinous cystadenoma. The patient had a smooth pregnancy course and delivered a healthy baby at 39 weeks of gestation. CONCLUSION: Laparoscopic surgery is a safe procedure in the management of pregnant women with suspicious adnexal cystic lesions.

Downregulation of the integrin α(v) signaling pathway in uterine leiomyomas.

OBJECTIVE: To investigate alterations of integrin α(v), survival and apoptosis signaling pathways in uterine leiomyomas. MATERIALS AND METHODS: In a prospective study of 50 women with uterine leiomyomas that had been pathologically confirmed, specimens were obtained laparoscopically from 2007 to 2009. The expressions of integrin α(v) signaling pathways (Ras/Raf/ERK1/2, Akt and cleaved caspase-3), surface microstructures by surface electron microscopy and immunohistochemical findings were assessed. RESULTS: The study yielded novel results: (1) the integrin α(v) expression approached a low level (mRNA 0.39 ± 0.06, protein 0.47 ± 0.08) with coherent alterations of its downstream signaling molecules (Ras, p-c-Raf, p-ERK1/2) (p < 0.001); (2) smoother surface microstructures of uterine leiomyomas were correlated with low integrin α(v) expressions, and (3) survival signaling and apoptosis signaling were significantly down- and upregulated respectively (p < 0.001). CONCLUSION: Integrin α(v) and related survival signaling pathways were downregulated, but the apoptosis was upregulated in uterine leiomyomas. Benign smooth-contoured tumors may have low integrin expressions and cancer invasion potentials.