Comparison of lymphatic contrast-enhanced ultrasound and intravenous contrast-enhanced ultrasound in the preoperative diagnosis of axillary sentinel lymph node metastasis in patients with breast cancer.

OBJECTIVES: This study aimed to compare diagnostic efficiency for axillary sentinel lymph node (SLN) metastasis between lymphatic contrast-enhanced ultrasound (LCEUS) and intravenous contrast-enhanced ultrasound (ICEUS) in patients with breast cancer. We also examined whether adding ICEUS to LCEUS could improve the diagnostic accuracy of LCEUS. METHODS: Sixty-nine patients with breast cancer were recruited preoperatively. All patients underwent LCEUS followed by ICEUS, and the enhancement pattern of one SLN was analysed for each patient. The targeted SLN was marked with wire and excised during surgery. The imaging diagnosis was compared with the histopathological result. Diagnostic efficiency was compared among LCEUS, ICEUS, and the combination of LCEUS and ICEUS. RESULTS: The sensitivity values for LCEUS, ICEUS, and the combination of LCEUS and ICEUS were 86.2%, 82.6% and 93.1%, respectively. Specificity values for the three methods were 95.0%, 92.5% and 87.5%, respectively. Accuracy values for the three methods were 91.3%, 88.4% and 89.9%, respectively. The area under the receiver operating characteristic (ROC) curve for LCEUS was 0.906, and there was no significant difference among LCEUS, ICEUS, and the combination of LCEUS and ICEUS (p = 0.752). CONCLUSIONS: LCEUS may represent an accurate method for predicting SLN metastasis preoperatively. Our findings suggest that adding ICEUS to LCEUS for SLN evaluation in patients with breast cancer is unnecessary. ADVANCES IN KNOWLEDGE: This is the first study in which both LCEUS and ICEUS were performed for the same lymph node and the first to compare the diagnostic efficiency of LCEUS, ICEUS, and the combination of LCEUS + ICEUS.

Bleomycin administered by laser-assisted drug delivery or intradermal needle-injection results in distinct biodistribution patterns in skin: in vivo investigations with mass spectrometry imaging.

Bleomycin (BLM) is being repositioned in dermato-oncology for intralesional and intra-tumoural use. Although conventionally administered by local needle injections (NIs), ablative fractional lasers (AFLs) can facilitate topical BLM delivery. Adding local electroporation (EP) can augment intracellular uptake in the target tissue. Here, we characterize and compare BLM biodistribution patterns, cutaneous pharmacokinetic profiles, and tolerability in an in vivo pig model following fractional laser-assisted topical drug delivery and intradermal NI, with and without subsequent EP. In vivo pig skin was treated with AFL and topical BLM or NI with BLM, alone or with additional EP, and followed for 1, 2 and 4 h and eventually up to 9 d. BLM biodistribution was assessed by spatiotemporal mass spectrometry imaging. Cutaneous pharmacokinetics were assessed by mass spectrometry quantification and temporal imaging. Tolerability was evaluated by local skin reactions (LSRs) and skin integrity measurements. AFL and NI resulted in distinct BLM biodistributions: AFL resulted in a horizontal belt-shaped BLM distribution along the skin surface, and NI resulted in BLM radiating from the injection site. Cutaneous pharmacokinetic analyses and temporal imaging showed a substantial reduction in BLM concentration within the first few hours following administration. LSRs were tolerable overall, and all interventions permitted almost complete recovery of skin integrity within 9 d. In conclusion, AFL and NI result in distinct cutaneous biodistribution patterns and pharmacokinetic profiles for BLM applied to in vivo skin. Evaluation of LSRs showed that both methods were similarly tolerable, and each method has potential for individualized approaches in a clinical setting.

Granulomas and nongranulomatous nodules after filler injection: Different complications require different treatments.

Dermal fillers are widely used for facial rejuvenation and reconstruction and present fewer risks than surgical approaches. Nevertheless, several complications may occur, including nodule formation. A nodule is a clinical sign corresponding to different etiologies, such as overcorrection, infection, allergic reaction, or granuloma. However, their treatment represents a diagnostic challenge. We present a retrospective review of 26 consecutive patients who underwent a biopsy for facial nodule formation more than 3 months after filler injections, to determine the diagnosis of the nodule and type of filler used. All patients were women (mean age, 57.8 years). Some patients suffered from different localizations: lip, 14 cases; nasolabial folds, 6; cheeks, 5; infraorbital region, 5; the glabella, 2; the temporal region, 1; and chin, 1 case. Only 5 (19.2%) patients knew the type of filler used, and in another 4 cases, the injector was able to provide some information. In 65.4% of cases, the filler type was unknown. Histopathological analysis revealed a "granulomatous" nodule in 30 sites and a "non-granulomatous" nodule in 4 cases. Concerning the type of filler, 5 different histopathological patterns were found. Our results demonstrate that a clinical history and histopathological analysis whether to confirm or not to confirm the diagnosis of granuloma and to identify the type of filler are essential tools to achieve an accurate diagnosis of the problem-oriented treatment of nodules after dermal filler injections. We propose an algorithm for the management of nodules after filler injection.

Randomized trial of electrodynamic microneedle combined with 5% minoxidil topical solution for the treatment of Chinese male Androgenetic alopecia.

Background: In treating androgenetic alopecia, 5% minoxidil is a commonly used topical drug. By using electrodynamic microneedle at the same time may increase absorption of minoxidil and further stimulate hair growth.Objective: A 24-week, randomized, evaluator blinded, comparative study was performed to evaluate the efficacy of treating Chinese male androgenetic alopecia using microneedle combined with 5% minoxidil topical solution. Methods: Randomized subjects received topical 5% minoxidil (group 1, n = 20), local electrodynamic microneedle treatments (group 2, n = 20), or local electrodynamic microneedle treatments plus topical 5% minoxidil (group 3, n = 20). A total of 12 microneedle treatments were performed every 2 weeks with 2ml 5% minoxidil delivery in group three during each microneedle treatment. Patient receiving topical 5% minoxidil applied 1 ml of the solution twice daily over the course of the study. A total of 60 Chinese male subjects with Norwood-Hamilton type III-VI androgenetic alopecia were treated.Results: The mean improvement in total hair density from baseline to 24 weeks was 18.8/cm2 in group 1, 23.4/cm2 in group 2, and 38.3/cm2 in group 3. The hair growth in the three groups was significantly different (P = 0.002), but there were no significant differences in toxicity found between the three groups.Conclusions: Treatment with microneedle plus topical 5% minoxidil was associated with the best hair growth.

Recent advances in microneedle composites for biomedical applications: Advanced drug delivery technologies.

In the twenty-first century, microneedles based drug delivery is drawing attention worldwide in the research due to current signs of progress in the controlled release drug delivery through microneedles. The microneedles represent a promising technology to deliver therapeutic compounds into the skin for chronic complications like osteoporosis, diabetes, cancer and induction of immune responses from protein and DNA vaccines. However, the delivery of hydrophilic drugs and macromolecular agents are challenging. In this write up authors included the meticulous illustration of the chronological development of fabrication of microneedles with respect to an assortment of techniques, their modifications, clinical trials and regulatory perspectives period of 2000-2019. This review summarizes characterization, fabrications, biological applications and challenges. Additionally, relevant patents based on microneedle from USPTO) database are also highlighted.

Effective Rejuvenation with Hyaluronic Acid Fillers: Current Advanced Concepts.

LEARNING OBJECTIVES: After studying this article, the participant should be able to: 1. Process several patient-specific factors before reaching an optimal treatment strategy with appreciation for facial balance. 2. Define the advantages and disadvantages of various hyaluronic acid preparations and delivery techniques, to achieve a specific goal. 3. Perform advanced facial rejuvenation techniques adapted to each facial zone, combining safety considerations. 4. Prevent and treat complications caused by inadvertent intraarterial injections of hyaluronic acid. SUMMARY: The growing sophistication and diversity of modern hyaluronic acid fillers combined with an increased understanding of various delivery techniques has allowed injectable filler rejuvenation to become a customizable instrument offering a variety of different ways to improve the face: volume restoration, contouring, balancing, and feature positioning/shaping-beyond simply fading skin creases. As more advanced applications for hyaluronic acid facial rejuvenation are incorporated into practice, an increased understanding of injection anatomy is important to optimize patient safety.

Nanofat Needling: A Novel Method for Uniform Delivery of Adipose-Derived Stromal Vascular Fraction into the Skin.

A novel method for delivering nanofat into the skin is presented. The principle is based on documented experience with introduction of agents into the skin by means of microneedling.

Rapid Production of Human VEGF-A following Intradermal Injection of Modified VEGF-A mRNA Demonstrated by Cutaneous Microdialysis in the Rabbit and Pig In Vivo.

Chemically modified mRNA is a novel, highly efficient, biocompatible modality for therapeutic protein expression that may overcome the challenges and safety concerns with current gene therapy strategies. We explored the efficiency of intradermally injected modified VEGF-A165 mRNA (VEGF-A mRNA) formulated in a biocompatible citrate/saline buffer to locally produce human VEGF-A165 protein. Rabbits (n=4) and minipigs (n=3) were implanted with subcutaneous microdialysis probes close to the injection sites and interstitial-fluid samples and skin biopsies were analysed for production of VEGF-A protein over time for up to 8 hours. Three to 4 hours after the intradermal injection of VEGF-A mRNA, detectable levels of human VEGF-A protein were seen in the microdialysis eluates in both species. In the pig, the VEGF-A concentrations increased dose-dependently reaching a maximum 6 hours after dosing (62.7±28.4, 357.6±240.6, and 746.3±210.2 pg/mL following injection of 24, 120, and 600 µg VEGF-A mRNA, respectively). Likewise, in tissue biopsies harvested at study end (8 hours after VEGF-A mRNA injection), the content of VEGF-A protein increased dose-dependently. In contrast, VEGF-A protein was not detected in eluates originating from sites injected with citrate/saline vehicle. It is concluded that intradermal injection of VEGF-A mRNA is associated with a rapid and local production of VEGF-A protein. Considering the pro-angiogenic effect of VEGF-A, VEGF-A mRNA may hold promise for regenerative treatment of patients with diabetic wounds and ischemic cardiovascular disease.

Needle-free delivery of DNA: Targeting of hemagglutinin to MHC class II molecules protects rhesus macaques against H1N1 influenza.

Conventional influenza vaccines are hampered by slow and limited production capabilities, whereas DNA vaccines can be rapidly produced for global coverage in the event of an emerging pandemic. However, a drawback of DNA vaccines is their generally low immunogenicity in non-human primates and humans. We have previously demonstrated that targeting of influenza hemagglutinin to human HLA class II molecules can increase antibody responses in larger animals such as ferrets and pigs. Here, we extend these observations by immunizing non-human primates (rhesus macaques) with a DNA vaccine encoding a bivalent fusion protein that targets influenza virus hemagglutinin (HA) to Mamu class II molecules. Such immunization induced neutralizing antibodies and antigen-specific T cells. The DNA was delivered by pain- and needle-free jet injections intradermally. No adverse effects were observed. Most importantly, the immunized rhesus macaques were protected against a challenge with influenza virus.

Full-face augmentation using Tissuefill mixed with platelet-rich plasma: "Q.O.Fill".

BACKGROUND: Hyaluronic acid fillers have become popular soft tissue filler augmentation agents over the past several years. Q.O.Fill (JW Pharmaceutical Co., Ltd., Seoul, Korea) is a newly developed soft tissue augmentation agent using Tissuefill (hyaluronic acid derivatives) mixed with platelet-rich plasma (PRP). The purposes of this study were to describe the Q.O.Fill method and evaluate the outcome of face augmentation. METHODS: A retrospective chart review was performed over a 2-year period. Seventy-five Asian participants with a mean age of 43.5 years were enrolled in the study. Mean total injection volume (baseline and touch-up) per participant was 8.9 mL. All participants underwent injection of Tissuefill mixed with PRP, Q.O.Fill. The results were evaluated using photographs and according to patients' satisfaction. RESULTS: Six months after the last injection, 100% of participants had improvement. At month 6, 97.3% of participants remained least improved over the baseline, and 90.7% felt much better or a little better until 2 years after the injection. The incidence of complications was low. CONCLUSIONS: The study showed that Q.O.Fill injection resulted in a very good aesthetic outcome and few adverse events. We believe that a facial augmentation with Tissuefill mixed with PRP is a safe and effective treatment method.

Lipoma removal using a high-frequency ultrasound-guided injection of a Class III CE-marked device-Empirical findings.

BACKGROUND: Lipomas are very common benign neoplasms, which constitute 99% of all adipose-derived tumors. Main treatment option includes surgical excision, which is unacceptable for a number of patients seeking ways to improve esthetic appearance of their skin. Therefore, alternative treatment options are being sought. OBJECTIVE: The aim of the present study was to assess the efficacy of lipoma removal using a Class III CE-marked device (Aqualyx™) administered as a high-frequency ultrasound-guided injection (intralipotherapy). METHODS: A total of 17 lipomas were treated. The procedure involved a high-frequency ultrasound-guided injection. A maximum of 3 injections per a lipoma were performed. High-frequency ultrasound was used for assessing the size of lipomas and monitoring treatment-induced changes to the lipomas and adjacent tissue. RESULTS: Response to treatment was achieved in all cases. A complete removal was achieved in 70.59% of lipomas. The remaining 29.41% of lipomas were not completely removed, yet significantly reduced in size. CONCLUSION: An injection of Aqualyx™, a CE-marked drug, is a good noninvasive treatment of lipomas. Ultrasound guided procedure is recommended, as it ensures appropriate technique and enables monitoring treatment-induced changes. Considering a low number of published reports of such treatment, it is crucial to continue this research.

Background and Update for S1602 "A Phase III Randomized Trial to Evaluate the Influence of BCG Strain Differences and T Cell Priming with Intradermal BCG Before Intravesical Therapy for BCG-naïve High-grade Non-muscle-invasive Bladder Cancer.

The S1602 Intergroup trial is a randomized phase III clinical trial that aims to test two important hypotheses: (1) priming with intradermal bacillus Calmette-Guérin (BCG) vaccine prior to standard intravesical BCG improves response to BCG in terms of recurrence-free survival and (2) Tokyo-172 BCG strain is non-inferior to TICE BCG in terms of time to high-grade recurrence. The study was approved by the Cancer Therapy Evaluation Program of the National Cancer Institute and activated in spring 2017. Here, we provide a synopsis of the study background, design, and update of the clinical trial.

Introducing Platelet-Rich Stroma: Platelet-Rich Plasma (PRP) and Stromal Vascular Fraction (SVF) Combined for the Treatment of Androgenetic Alopecia.

BACKGROUND: Androgenetic alopecia (AGA) is characterized by miniaturization of the hair follicles gradually causing conversion of terminal hairs into vellus hairs, leading to progressive reduction of the density of hair on the scalp. Approved therapeutic options are limited and show side effects. OBJECTIVES: To evaluate injections of stromal vascular fraction (SVF), which is rich in adipose-derived stromal cells (ASCs) in combination with platelet-rich plasma (PRP) in the upper scalp as a new autologous treatment option for AGA. METHODS: Ten male patients (age range, 25-72 years), suffering from AGA at stage II to III according to the Norwood-Hamilton scale, have been treated with a single injection of autologous PRS (ACPSVF: combination of PRP and SVF) in the upper scalp. Preinjection and 6 and 12 weeks postinjection changes in hair density were assessed using ultra high-resolution photography (Fotofinder). RESULTS: Hair density was significantly increased after 6 weeks and 12 weeks postinjection (P = 0.013 and P < 0.001). In hair-to-hair matching analyses, new hair grew from active follicles. Furhtermore nonfunctioning hair follicles filled with hyperkeartotic plugs, up to today assumed incapable of forming new hair, proved to grow new hair. No side effects were noted after treatment. CONCLUSIONS: A single treatment of platelet-rich stroma injected in the scalp of patients with AGA significantly increased hair density within 6 to 12 weeks. Further research is required to determine the optimal treatment regimen. Preferred options to our opinion include the repetition of PRS or additional treatments with PRP.

Injection Depth in Intradermal Therapy: Update and Correction of Published Data.

BACKGROUND: This paper sought to compare calculated injection depth data with published report claims concerning intradermal therapy and skin rejuvenation of the face, hands, neck, and décolleté. OBJECTIVE: A mathematical formula was employed to assess the injection depth, and data from literature were retrieved and compared with the calculated figures to determine whether the claims about the injection depth proved correct. METHODS: Based on a study by Della Volpe et al., involving 140 skin residues adapted for plastic surgery, we have calculated injection depths from published reports on intradermal therapy and skin rejuvenation while comparing these figures with the published injection depth claims. RESULTS: Most injections were not performed at the claimed depth, with over 70% of them carried out in the fat layer, thus, the hypodermis. This is not the recommended depth for a refined injection technique in the intradermal therapy field. CONCLUSION: Whilst examining our study results, two different possibilities come to mind. We must either: 1) review and correct the existing histological classification; and/or 2) better learn to correctly inject in the superficial-dermis, mid-dermis, and deep-dermis. In other words, a perfect control over the needle penetration angle and implanted part appears urgently required.

J Drugs Dermatol. 2018;17(1):89-96.

[Treatment of wrinkles of the upper lip by emulsified fat or "Nanofat": Biological and clinical study about 4 cases]. / Traitement des ridules de la lèvre supérieure par graisse émulsifiée ou « Nanofat ¼ : étude biologique et clinique à propos de 4 cas.

OBJECTIVE: Emulsified fat injection showed its interest in aesthetic facial surgery. The adipose tissue harvested is mechanically emulsified and filtered. The suspension obtained is injected into the dermis through small diameter needles (27 to 30 gauges). The objective of our study was to evaluate the biological composition of emulsified fat and its clinical effectiveness in the treatment of peri-oral wrinkles in 4 patients aged 50 to 59 years. MATERIAL AND METHOD: Each patient received an intradermal injection of emulsified fat in the peri-oral wrinkles prepared from abdominal fat under local anesthesia. The cell viability, stromal vascular fraction (FVS) composition in emulsified fat and the adipocyte differentiation capacity of mesenchymal stem cells (MSC) were studied. The clinical results were evaluated by standardized photographs, 3D microphotography, confocal microscopy, and self-evaluation of patient satisfaction over a period of 4 months. RESULTS: The biological study of the emulsified fat found a lysis of all the adipocytes. The mean number of FVS cells was 126,330±2758 cells by cc of emulsified fat with preserved cell viability (85.1±6.84 %) and a good proportion of regeneratives cells (18.77±6.2 %). The clinical study found a tendency to decrease the volume of wrinkles on standardized photography and 3D microphotography no significative. Patients were satisfied with treatment with an average score of 7±1.15/10 to 4 months. CONCLUSION: Intradermal injection of emulsified fat seems to be an interesting treatment of face wrinkles. Our study has shown its safety, but additional studies seems necessary to confirm its clinical efficacy.

Prevention of Fat Embolism in Fat Injection for Gluteal Augmentation, Anatomic Study in Fresh Cadavers.

INTRODUCTION: Liposuction is a popular surgical procedure. As in any surgery, there are risks and complications, especially when combined with fat injection. Case reports of fat embolism have described a possible explanation as the puncture and tear of gluteal vessels during the procedure, especially when a deep injection is planned. METHODS: A total of 10 dissections were performed in five fresh cadavers. Each buttocks was divided into four quadrants. We focused on the location where the gluteal vessels enter the muscle and the diameter of the vessels. Colorant at two different angles was injected (30° and 45°). We evaluated the relation of the colorant with the main vessels. RESULTS: We found two perforators per quadrant. The thickness of the gluteal muscle was 2.84 ± 1.54 cm. The area under the muscle where the superior gluteal vessels traverse the muscle was located 6.4 ± 1.54 cm from the intergluteal crease and 5.8 ± 1.13 cm from the superior border of the muscle. The inferior gluteal vessels were located 8.3 ± 1.39 cm from the intergluteal crease and 10 ± 2.24 cm from the superior border of the muscle. When we compared the fat injected at a 30° angle, the colorant stayed in the muscle. Using a 45° angle, the colorant was in contact with the superior gluteal artery and the sciatic nerve. No puncture or tear was observed in the vessels or the nerve. CONCLUSIONS: The location where the vessels come in contact with the muscle, which can be considered for fat injection, were located in quadrants 1 and 3. A 30° angle allows for an injection into the muscle without passing into deeper structures, unlike a 45° injection angle.

'Tough love': The experiences of midwives giving women sterile water injections for the relief of back pain in labour.

OBJECTIVE: To explore midwives' experiences of administering sterile water injections (SWI) to labouring women as analgesia for back pain in labour. DESIGN: A qualitative study, which generated data through semi-structured focus group interviews with midwives. Data were analysed thematically. SETTING: Two metropolitan maternity units in Queensland, Australia. PARTICIPANTS: Eleven midwives who had administered SWI for back pain in labour in a randomised controlled trial. FINDINGS: Three major themes were identified including: i. SWI, is it an intervention?; ii. Tough love, causing pain to relieve pain; iii. The analgesic effect of SWI and impact on midwifery practice. KEY CONCLUSIONS: Whilst acknowledging the potential benefits of SWI as an analgesic the midwives in this study described a dilemma between inflicting pain to relieve pain and the challenges encountered in their discussions with women when offering SWI. Midwives also faced conflict when women requested SWI in the face of institutional resistance to its use. IMPLICATIONS FOR PRACTICE: The procedural pain associated with SWI may discourage some midwives from offering women the procedure, providing women with accurate information regarding the intensity and the brevity of the injection pain and the expected degree of analgesic would assist in discussion about SWI with women.

The effect of intradermal administration of inactive platelet-rich plasma on flap viability in rats.

PURPOSE:: To evaluate the effect of inactive form of platelet rich plasma (PRP) on the flap viability. METHODS:: Thirty six rats were used. Rats were divided into six groups then 9x3 cm random pattern skin flaps were elevated from dorsum of all rats. For precluding vascularization from the base, a silicone layer was placed under the flap in groups 2(only flap+silicone), 4(saline+silicone) and 6(PRP+silicone). In groups 1(only flap), 2(only flap+silicone) nothing was done except flap surgery. In groups 3(saline) and 4(saline+silicone), saline was applied intradermally , in groups 5(PRP) and 6(PRP+silicone), inactive form of PRP which obtained from different 16 rats was applied intradermally, into certain points of flaps immediately after surgery. After 7 days flap necrosis ratio was measured in all groups. RESULTS:: Mean necrosis rate in group 5(PRP) (16.05%) was statistically significantly lower than group 1(only flap) (31,93%) and group 3(saline) (30,43%) (p<0.001). Mean necrosis rate in group 6(PRP+silicone) (36.37%) was statistically significantly lower than group 2(only flap+silicone) (47.93%) and group 4(saline+silicone) (45.65%) (p<0.001). CONCLUSION:: Intradermal inactive platelet rich plasma administration decreases flap necrosis so for skin application.

The effect of intradermal administration of inactive platelet-rich plasma on flap viability in rats

Abstract Purpose: To evaluate the effect of inactive form of platelet rich plasma (PRP) on the flap viability. Methods: Thirty six rats were used. Rats were divided into six groups then 9x3 cm random pattern skin flaps were elevated from dorsum of all rats. For precluding vascularization from the base, a silicone layer was placed under the flap in groups 2(only flap+silicone), 4(saline+silicone) and 6(PRP+silicone). In groups 1(only flap), 2(only flap+silicone) nothing was done except flap surgery. In groups 3(saline) and 4(saline+silicone), saline was applied intradermally , in groups 5(PRP) and 6(PRP+silicone), inactive form of PRP which obtained from different 16 rats was applied intradermally, into certain points of flaps immediately after surgery. After 7 days flap necrosis ratio was measured in all groups. Results: Mean necrosis rate in group 5(PRP) (16.05%) was statistically significantly lower than group 1(only flap) (31,93%) and group 3(saline) (30,43%) (p<0.001). Mean necrosis rate in group 6(PRP+silicone) (36.37%) was statistically significantly lower than group 2(only flap+silicone) (47.93%) and group 4(saline+silicone) (45.65%) (p<0.001). Conclusion: Intradermal inactive platelet rich plasma administration decreases flap necrosis so for skin application.