Turn Your AART into a HIT Using a Complete Range of Aesthetic Injectables: Methodology for Combining Products to Maximise Patient Outcomes.

Purpose: Optimizing outcomes of aesthetic treatments with injectable products usually requires a consideration of the entire face to ensure balance, along with combination treatments that align with the patient's goals. To help injectors, a method of assessing the patient and developing an individualized, holistic treatment plan was developed. This methodology is termed Assessment, Anatomy, Range, and Treatment (AART™) and Holistic Individualized Treatments (HITs™). This article aims to describe and evaluate the novel and systematic AART-HIT™ methodology. Methods: The AART-HIT™ methodology, including its associated diagnostic tool the Facial Assessment Scale (FAS™), were developed to aid injectors in completing a patient assessment in which the entire face is evaluated, the relevant anatomy is considered, the science behind the available range of products is understood, and the treatment plan is individualised for the patient. Specifically, the HITs™ are methodologic tools for practitioners to perform a standardized, full facial assessment and to create an individualized treatment approach to holistically address a patient's aesthetic concerns. The use of this methodology in clinical practice was assessed via a survey, deployed to twenty-eight clinicians. Results: Over 85% of participants agreed that the AART-HIT™ methodology was adequate for their needs. Additionally, 100% of participants agreed that the temporal sequencing of HITs™ and the FAS™ diagnostic tool was useful in clinical practice. Furthermore, over 70% of participants agreed that the anatomical locations identified in each HIT™ were sufficient, while over 80% responded that the HITs™ adequately represented the range of products. Finally, over 85% of participants agreed that the HITs™ covered different ethnic skin types and various patient ages and, over 80% of participants responded that they would not add additional elements to any of the 5 HITs™. Conclusion: The AART-HIT™ methodology, including the FAS™ were comprehensive enough for clinical use in providing a personalised treatment plan for individual patients.

The Role of Clinical Examination in Midface Volume Correction Using Hyaluronic Acid Fillers: Should Patients Be Stratified by Skin Thickness?

BACKGROUND: Aesthetic physicians have several hundred injectable products to select from. Due to differences in their manufacturing technology, these products display varying biophysical qualities, such as their cohesivity and lift capacity. Currently, there is no guidance to objectively selecting the best product for a particular patient. Therefore, an algorithmic approach is required to take specific skin characteristics into consideration. OBJECTIVES: To evaluate (1) whether subjects seeking injectable treatments for midfacial volume loss and/or contour deficiency can be stratified based on specific skin characteristics (eg, thickness, fat quantity, bony structure) and (2) whether particular hyaluronic acid fillers perform best when used in such particular strata. METHODS: This was a prospective, Phase IV, open-label, single-center clinical trial. Thirty female patients with midface/cheek volume loss and/or contour deficiency were recruited (mean age, 53.5 years; SD, 12.57; range, 35-75 years). Subjects were treated with either Restylane Lyft (HAL) or Restylane Volyme (HAV) and followed for 4 months post-injection. Treatment allocation was based on the treating physician's clinical evaluation and compared with ultrasound evaluation. Ultrasound images were used to confirm stratification. Safety and efficacy assessments were performed at each study visit: baseline, week 2, week 4, week 8, and week 16. Subgroup analyses evaluated whether particular strata performed best when treated with specific products. RESULTS: The 2 investigative products varied in their efficacy, depending on the characteristics of the subject. CONCLUSIONS: The use of a treatment algorithm may improve outcomes for patients seeking injectable treatments for midfacial volume loss and contour deficiencies.

Docosahexaenoic Acid Sensitizes Leukemia Lymphocytes to Barasertib and Everolimus by ROS-dependent Mechanism Without Affecting the Level of ROS and Viability of Normal Lymphocytes.

The aim of the present study was: (i) to investigate the possibility of sensitizing leukemia lymphocytes to anticancer drugs using docosahexaenoic acid (DHA); (ii) to find combinations with synergistic cytotoxic effect on leukemia lymphocytes, without or with only very low cytotoxicity towards normal lymphocytes; (iii) and to clarify the role of reactive oxygen species (ROS) in the induction of apoptosis and cytotoxicity by such combinations. The study covered 15 anticancer drugs, conventional and new-generation. Well-expressed synergistic cytotoxic effects were observed after treatment of leukemia lymphocytes (Jurkat) with DHA in combination with: barasertib, lonafarnib, everolimus, and palbociclib. We selected two synergistic combinations, DHA with everolimus or barasertib, and investigated their effects on viability of normal lymphocytes, as well as on the production of ROS and induction of apoptosis in both cell lines (leukemia and normal). At the selected concentrations, DHA, everolimus and barasertib (applied separately) were cytotoxic towards leukemia lymphocytes, but not normal lymphocytes. In leukemia cells, the cytotoxicity of combinations was accompanied by strong induction of apoptosis and production of ROS. In normal lymphocytes, drugs alone and in combination with DHA did not affect the level of ROS and did not induce apoptosis. To our knowledge, the present study is the first to report synergistic ROS-dependent cytotoxicity between DHA and new-generation anticancer drugs, such as everolimus and barasertib, that is cancer cell-specific (particularly for acute lymphoblastic leukemia cells Jurkat). These combinations are harmless to normal lymphocytes and do not induce abnormal production of ROS in these cells. The data suggest that DHA could be used as a supplementary component in anticancer chemotherapy, allowing therapeutic doses of everolimus and barasertib to be reduced, minimizing their side-effects.

Lymph node mapping using quantum dot-labeled polymersomes.

The present study was designed to investigate whether poly-ion complex hollow vesicles (polymersomes), based on chemically-modified chitosan, are appropriate for lymph node mapping in the context of their application in the development of theranostic nanosized drug delivery systems (nano-DDS). The experiments were performed on Balb/c nude mice (colon cancer-grafted). The mice were subjected to anesthesia and quantum dot (QD(705))-labeled polymersomes (d-120 nm) were injected intravenously via the tail vein. The optical imaging was carried out on Maestro EX Imaging System (excitation filter: 435-480 nm; emission filter: 700 nm). A strong fluorescent signal, corresponding to QD(705) fluorescence, was detected in the lymph nodes, as well as in the tumor. A very weak fluorescent signal was found in the liver area. The half-life of QD(705)-labelled polymersomes was 6 ± 2 hours in the bloodstream and 11 ± 3 hours in the lymph nodes. The data suggest that polymersomes are very promising carriers for lymph node mapping using QD as a contrast agent. They are useful matrix for development of nano-formulations with theranostic capabilities.

Delivery of size-controlled long-circulating polymersomes in solid tumours, visualized by quantum dots and optical imaging in vivo.

The present study was designed to investigate whether poly-ion complex hollow vesicles (polymersomes), based on chemically modified chitosan, are appropriate for passive tumour targeting in the context of their application as drug carriers. The experiments were performed on colon cancer-grafted mice. The mice were subjected to anaesthesia and injected intravenously with water-soluble nanoparticles: (1) QD705-labelled polymersomes (average size ∼120 nm; size distribution ∼10%) or (2) native QD705. The optical imaging was carried out on Maestro EX 2.10 In Vivo Imaging System (excitation filter 435-480 nm; emission filter 700 nm, longpass). In the case of QD705, the fluorescence appeared in the tumour area within 1 min after injection and disappeared completely within 60 min. A strong fluorescent signal was detected in the liver on the 30th minute. The visualization of tumour using QD705 was based only on angiogenesis. In the case of QD705-labelled polymersomes, the fluorescence appeared in the tumour area immediately after injection with excellent visualization of blood vessels in the whole body. A strong fluorescent signal was detected in the tumour area within 16 hours. This indicated that QD705-labelled polymersomes were delivered predominantly into the tumour due to their long circulation in the bloodstream and enhanced permeability and retention effect. A very weak fluorescent signal was found in the liver area. The data suggest that size-controlled long-circulating polymersomes are very promising carriers for drug delivery in solid tumours, including delivery of small nanoparticles and contrast substances.