Clinical Perspectives on the Injectability of Cross-Linked Hyaluronic Acid Dermal Fillers: A Standardized Methodology for Commercial Product Benchmarking with Inter-Injector Assessments.

The injectability of cross-linked hyaluronic acid (HA) dermal fillers is influenced by polymer concentration, polymer cross-linking type and degree, the presence of lidocaine or other functional excipients, types of syringes, and injection techniques. Finished product injectability constitutes a critical quality attribute for clinical injectors, as it strongly influences product applicability and ease of use in aesthetic medicine. While injectable product extrusion force specifications are provided by the respective device manufacturers, the qualitative informative value of such datasets is low for injectors wishing to compare product brands and technologies from an injectability standpoint. Therefore, the present study comparatively assessed 28 cross-linked HA dermal fillers (JUVÉDERM®, Restylane®, BELOTERO®, TEOSYAL RHA®, and STYLAGE® brands) using various injectability benchmarking setups for enhanced clinical-oriented relevance. Manual product injections were performed by three specialized and experienced clinicians, whereas automatic product extrusion was performed using a Texture Analyzer instrument. The various hydrogel products were injected into ex vivo human skin and into SimSkin® cutaneous equivalents to appropriately account for injection-related counterpressure. The injectability results revealed important variability between and within product brands, with a strong influence of the local anesthetic lidocaine, HA contents, and needle gauge size. Critical appraisals of the investigated products were performed, notably from manufacturing process-based and clinical ease of application-based standpoints, centered on respective experimental injectability quality levels. Generally, it was confirmed that each HA-based dermal filler product requires specific expertise for optimal injection, mainly due to differing viscoelastic characteristics and injectability attributes. Overall, the present study set forth evidence-based and clinical-oriented rationale elements confirming the importance for injectors to work with injectable products with which they are experienced and comfortable to optimize clinical results.

[Training in reconstructive surgery in sub-Saharan Africa : the « 2nd Chance ¼ model]. / Formation en chirurgie réparatrice en Afrique subsaharienne : le modèle « 2nd Chance ¼.

Based in Geneva since 2010, 2nd Chance's mission is the development of reconstructive surgery care in resource-limited countries with a focus on sub-Saharan Africa, through teaching and advocacy activities. We develop the surgical management of patients on the one hand, providing training for African surgical teams. On the other hand, we support surgical procedures for patients, in the areas of reconstructive surgery, giant goiters, obstetric fistulas and anesthesia so that quality care is guaranteed for the long term. Despite the hurdles caused by the COVID crisis, training programs resumed at the end of 2020, with the implementation of the 2021-2025 strategy focusing on patient care and follow-up in the surgical setting through improved peri-operative safety and prevention of complications.

Basée à Genève depuis 2010, « 2nd Chance ¼ a pour mission le développement des soins en chirurgie réparatrice dans les pays à ressources limitées avec un focus sur l'Afrique subsaharienne, au moyen d'activités d'enseignement et de plaidoyer. Nous développons la prise en charge chirurgicale des patients tout en assurant la formation des équipes chirurgicales africaines dans les domaines de la chirurgie reconstructive, des goitres géants, des fistules obstétricales et de l'anesthésie afin que des soins de qualité soient garantis à long terme. Malgré les obstacles induits par la crise du Covid-19, les programmes de formation ont repris fin 2020, avec une stratégie 2021-2025 mettant l'accent sur les soins et le suivi du patient dans son contexte chirurgical.

Hyaluronic Acid After Subcutaneous Injection-An Objective Assessment.

BACKGROUND: Hyaluronic acid (HA) fillers are the preferred injectable products for aesthetic correction of skin depressions and restoration of facial volume. OBJECTIVE: To investigate the subcutaneous distribution of 3, biophysically distinct, CE-marked and FDA-approved HA fillers. MATERIALS AND METHODS: BELB, JUVV, and RESL were injected ex vivo in porcine and human skin. Immediately after injection, the skin samples were snap-frozen, cross-sectioned, and visualized using stereomicroscopy and full-field optical coherence tomography. Images were compared with histological sections after hematoxylin and eosin staining. RESULTS: Hyaluronic acid fillers were distributed as homogeneous bolus in the ex vivo skin. The injection bulks were found to preserve the fibrous trabecular network, shift the fat lobules, and displace the adjacent adipocyte layers independently of the formulation injected. CONCLUSION: For the first time, the subcutaneous injection of 3 HA fillers with markedly different biophysical properties was systematically investigated by complementary visualization techniques. Despite their different properties, no difference in distribution was found after subcutaneous injection. The global preservation of the hypodermis structure observed was consistent with the good tolerability seen in clinical practice after implantation of the HA fillers in the subcutaneous skin layer.

Ultrasound and Histologic Examination after Subcutaneous Injection of Two Volumizing Hyaluronic Acid Fillers: A Preliminary Study.

BACKGROUND: This study examined the influence of hyaluronic acid (HA) crosslinking technology on the ultrasound and histologic behavior of HA fillers designed for subcutaneous injection. METHODS: One subject received subcutaneous injections of 0.25 ml Cohesive Polydensified Matrix (CPM) and Vycross volumizing HA in tissue scheduled for abdominoplasty by bolus and retrograde fanning techniques. Ultrasound analyses were performed on days 0 and 8 and histologic analyses on days 0 and 21 after injection. A series of simple rheologic tests was also performed. RESULTS: Day 0 ultrasound images after bolus injection showed CPM and Vycross as hypoechogenic papules in the hypodermis. CPM appeared little changed after gentle massage, whereas Vycross appeared more hyperechogenic and diminished in size. Ultrasound images at day 8 were similar. On day 0, both gels appeared less hypoechogenic after retrograde fanning than after bolus injection. Vycross was interspersed with hyperechogenic areas (fibrous septa from the fat network structure) and unlike CPM became almost completely invisible after gentle massage. On day 8, CPM appeared as a hypoechogenic pool and Vycross as a long, thin rod. Day 0 histologic findings confirmed ultrasound results. Day 21 CPM histologic findings showed a discrete inflammatory reaction along the injection row after retrograde fanning. Vycross had a more pronounced inflammatory reaction, particularly after retrograde fanning, with macrophages and giant cells surrounding the implant. Rheologic tests showed CPM to have greater cohesivity and resistance to traction forces than Vycross. CONCLUSIONS: CPM HA volumizer appears to maintain greater tissue integrity than Vycross after subcutaneous injection with less inflammatory activity.

A one carbon staple for orthogonal copper-catalyzed azide-alkyne cycloadditions.

We describe herein the use of α-hydroxy-ß-azidotetrazoles, easily prepared in one step from α,ß-epoxynitriles, as new scaffolds for orthogonal CuAAC reactions performed on the same carbon atom. After a first ligation involving an alkyne with the ß-azido moiety, treatment with EDC smoothly releases an alkyne from the remaining α-hydroxytetrazole, ready for a second CuAAC reaction. This "double click" process can be performed iteratively, leading to triazolamers.

N-Arylazetidines: Preparation through Anionic Ring Closure.

We report herein an efficient synthesis of diversely substituted N-aryl-2-cyanoazetidines based on an anionic ring-closure reaction. These compounds can be prepared from ß-amino alcohols in enantiomerically pure form through a three-step sequence involving (i) copper-catalyzed N-arylation, (ii) N-cyanomethylation of the secondary aniline, and (iii) one-pot mesylation followed by ring closure induced by a base. This high-yielding sequence gives access to azetidines with a predictable and adjustable substitution pattern and also with predictable diastereoselectivity. These compounds are susceptible to multiple further derivatizations through Suzuki coupling or nitrile transformation, thus appearing as valuable new scaffolds for medicinal chemistry. Their rigid shape, featuring an almost planar N-arylamine and a planar four-membered ring, was revealed by both AM1 calculations and X-ray crystallography.

Optimizing the arterialized venous flap.

BACKGROUND: Outcome of arterialized venous flaps is quite varied. The authors' initial experiments showed that a good vascular bed contributes significantly to survival of the flap. In continuation of these experiments, this study aimed to understand the influence of architectural variations on flap outcome. METHODS: Fasciocutaneous flaps were designed on the ears of New Zealand rabbits, and the animals were randomized into four groups having flaps that used the larger anterior marginal vein (1.3 mm) or the smaller central vein (0.6 mm) for arterial inflow, with or without isolation of the flap from its bed with a silicone sheet. Flaps were observed for area of flap survival and vasculature was assessed by microangiography. RESULTS: Using the smaller central vein for arterial inflow (n = 15), arterialized venous flaps had an excellent outcome, with good flap survival in 100 percent of the animals (survival of >85 percent of flap area), and a mean flap survival area of 99.4 +/- 1.6 percent. Even when neovascularization was prevented by isolation of the flaps (n = 14), 92 percent of central vein flaps showed good survival, with a mean flap survival area of 93.3 +/- 7.3 percent, which was significantly better than that of anterior marginal vein flaps (n = 22), which showed good flap survival in only 27 percent of the animals (mean flap survival area, 76.4 +/- 12.1 percent). CONCLUSIONS: Survival of arterialized venous flaps is optimized by using smaller-caliber veins for inflow and reserving larger-caliber veins for outflow. This regulates inflow and avoids high blood pressure, and arterialized venous flaps behave as physiologic flaps do, by not relying on neovascularization for survival.

Regulatory effects of interleukin (IL)-1, interferon-beta, and IL-4 on the production of IL-1 receptor antagonist by human adipose tissue.

Adipose tissue is the source of production and site of action of several pro- and antiinflammatory cytokines. We have recently shown that white adipose tissue (WAT) is a major producer of the antiinflammatory IL-1 receptor antagonist (IL-1Ra). Because IL-1Ra serum levels are elevated 7-fold in human obesity and an excess of this protein has been implicated in the acquired resistance to leptin and insulin, we investigated the regulation of IL-1Ra in human WAT. We demonstrate that IL-1Ra is mainly produced by adipocytes, rather than the stromal fraction of WAT, and that IL-1alpha and beta, as well as interferon-beta (IFN-beta), strongly up-regulate the expression and secretion of IL-1Ra in WAT. Moreover, human WAT expresses the receptors and proteins known to be required for the action of IL-1 (IL-1 receptor type I, IL-1 receptor accessory protein) and IFN-beta (IFN-alpha/beta receptor subunits 1 and 2). Finally, human WAT actively secretes these regulatory cytokines, suggesting that they up-regulate IL-1Ra through a local autocrine/paracrine action, which is hypothesized to play a regulatory role in adipogenesis and metabolism.