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Hee Kyung Kim,1,* Hyun-Jo Kim,2,* Jae Yun Kim,3 Myung Jin Ban,4 Jiwon Son,5 Yongsung Hwang,5,6 Sung Bin Cho7 1Department of Pathology, Soonchunhyang University Bucheon Hospital, Bucheon, Korea; 2CNP Skin Clinic, Cheonan, Korea; 3Department of Dermatology, Soonchunhyang University Hospital, Cheonan, Korea; 4Department of Otorhinolaryngology-Head and Neck Surgery, Soonchunhyang University Hospital, Cheonan, Korea; 5Soonchunhyang Institute of Medi-Bio Science (SIMS), Soonchunhyang University, Cheonan, Korea; 6Department of Integrated Biomedical Science, Soonchunhyang University, Cheonan, Korea; 7Yonsei Seran Dermatology and Laser Clinic, Seoul, Korea*These authors contributed equally to this workCorrespondence: Sung Bin Cho, Yonsei Seran Dermatology and Laser Clinic, Geumcheon REMAIN CITY 6F, 224 Siheung-daero, Geumcheon-gu, Seoul, 08628, Korea, Tel +82 2-2135-1375, Fax +82 70-8250-1375, Email drsbcho@gmail.comBackground: Single to multiple pulse packs of bipolar, alternating current radiofrequency (RF) oscillations have been used for various medical purposes using invasive microneedle electrodes. This study was designed to evaluate the effects of pulse widths and cycles of RF pulse packs on immediate and delayed thermal tissue reactions in in vivo rat skin.Methods: RF energy at the frequency of 1 MHz and power of 70 W was delivered at each experimental setting into in vivo rat skin at 1.5-mm microneedle penetration, and then, tissue samples were obtained after 1 h and 3, 7, 14, and 21 days and histologically analyzed.Results: A single-pulse-pack RF treatment generated coagulative necrosis zones in the dermal peri-electrode area and zones of non-necrotic thermal reactions in the dermal inter-electrode area. Multiple pulse-pack, RF-treated rat skin specimens revealed that the number and size of peri-electrode coagulative necrosis were markedly decreased by increasing the number of pulse packs and accordingly decreasing the conduction time of each pulse pack. The microscopic changes in RF-induced non-necrotic thermal reaction in the inter-electrode area were more remarkable in specimens treated with RF of 7 or 10 pulse packs than in specimens treated with RF of 1– 4 pulse packs.Conclusion: The gated delivery of multiple RF pulse packs using a bipolar, alternating current, 1-MHz RF system using insulated microneedle electrodes efficiently generates non-necrotic thermal tissue reactions over the upper, mid, and deep dermis and subcutaneous fat in the inter-electrode areas.Keywords: radiofrequency, bipolar, alternating current, gated pulse, tissue reaction, rat

Min Choi,1 Hye Sun Lee,2 Sung Bin Cho3 1R&D Center, Shenb Co., Ltd, Seoul, Korea; 2Department of Biostatistics, Yonsei University College of Medicine, Seoul, Korea; 3Yonsei Seran Dermatology and Laser Clinic, Seoul, KoreaCorrespondence: Sung Bin Cho, Yonsei Seran Dermatology and Laser Clinic, Geumcheon REMAIN CITY 6F, 224 Siheung-daero, Geumcheon-gu, Seoul, 08628, Korea, Tel +82.2-2135-1375, Fax +82.70-8250-1375, Email drsbcho@gmail.comBackground: Radiofrequency (RF) oscillations generate thermal tissue reactions, the patterns of which vary depending on the mode and efficiency of energy delivery. The aim of our study was to analyze patterns of RF-induced thermal tissue reactions according to the modes of RF delivery, including continuous and gated modes, using an alternating current, invasive bipolar RF device.Methods: RF energies at frequencies of 1 and 2 MHz were delivered at respective experimental settings into ex vivo bovine liver tissue at a 0.5-mm microneedle penetration depth. The tissue samples were then evaluated thermometrically. A histologic study was performed to evaluate RF-induced thermal tissue reactions at a 3.0-mm microneedle penetration depth.Results: Thermal imaging study revealed homogenous, well-demarcated, square-shaped zones of RF-induced thermal reactivity on the treated area. Multivariate linear regression analysis revealed that higher temperature elevations immediately after RF treatment (∆T1) were positively associated with RF frequency, power, conduction time/pulse pack, and off-time between pulse packs and negatively associated with total off time. In the 1-MHz experimental setting, higher ∆T1 showed a positive association with power, conduction time/pulse pack, and off-time between pulse packs and a negative association with the number of pulse packs. In the 2-MHz setting, however, higher ∆T1 was positively associated with only total treatment time.Conclusion: Thermometric effects during bipolar and gated RF treatments are significantly associated with the frequency, power, and pulse widths and cycles of pulse packs.Keywords: radiofrequency, bipolar, alternating current, gated pulse, tissue reaction, bovine liver

Song Yi Lee,1,* Do Yeon Kim,1,* Sang Bum Suh,1 Ji Youn Suh,1 Sung Bin Cho2 1BNV Biolab, Seoul, Korea; 2Yonsei Seran Dermatology and Laser Clinic, Seoul, Korea*These authors contributed equally to this workCorrespondence: Sung Bin Cho, Yonsei Seran Dermatology and Laser Clinic, 224 Siheung-daero, Seoul, 08628, Korea, Tel +82 2-2135-1375, Fax +82 70-8250-1375, Email drsbcho@gmail.comBackground: Human fibroblast-derived multi-peptide factors (MPFs) promote wound repair by playing crucial roles in cell recruitment, adhesion, attachment, migration, and proliferation.Methods: Cultured human dermal fibroblasts (HDFs) were directly treated with non-contact low- and high-energy nitrogen plasma and further cultured in various conditioned media. Cell proliferation and wound-healing properties were evaluated.Results: In Opti-modified Eagle’s medium + GlutaMAX culture, reduced HDF viability was observed 24 h after 2-J/pulse plasma treatment and 12 and 24 h after 3-J/pulse treatment. Meanwhile, in dermal fibroblast-conditioned medium (DFCM) containing MPF culture, reduced HDF viability was observed only 24 h after 3-J/pulse treatment. Under DFCM-MPF culture, the wound area percentage was significantly decreased after 12 and 24 h in untreated HDFs; at 9, 12, and 24 h after 1-J/pulse plasma treatment; at 3, 6, 9, 12, and 24 h after 2-J/pulse plasma treatment; and at 9, 12, and 24 h after 3-J/pulse plasma treatment. Greater migration of HDFs with or without plasma treatment was found in DFCM-MPFs than in other conditioned media.Conclusion: Low-energy nitrogen plasma treatment promotes HDF proliferation and wound repair. DFCM-MPFs enhanced cell proliferation and improved the wound healing properties of HDFs treated with low- and high-energy plasma.Keywords: human dermal fibroblasts, multi-peptide factors, dermal fibroblast-conditioned media, plasma, nitrogen, cell proliferation, wound healing, cell migration

Sang Bum Suh,1,* Keun Jae Ahn,2,* Eun Jeong Kim,1 Ji Youn Suh,1 Sung Bin Cho3 1BNV Biolab, Seoul, Korea; 2Department of Science Education, Jeju National University, Jeju, Korea; 3Yonsei Seran Dermatology and Laser Clinic, Seoul, Korea*These authors contributed equally to this workCorrespondence: Sung Bin Cho, Yonsei Seran Dermatology and Laser Clinic, 224 Siheung-daero, Seoul, 08628, Korea, Tel +82 2-2135-1375, Fax +82 70-8250-1375, Email drsbcho@gmail.comBackground: Human dermal fibroblasts secrete numerous growth factors and proteins that have been suggested to promote wound repair and hair regeneration.Methods: Human dermal fibroblast-conditioned medium (DFCM) was prepared, and proteomic analysis was performed. Secretory proteins in DFCM were identified using 1-dimensional sodium dodecyl sulphate-polyacrylamide gel electrophoresis, in-gel trypsin protein digestion, and quantitative liquid chromatography tandem mass spectrometry (LC-MS/MS). Identified proteins were analyzed using bioinformatic methods for the classification and evaluation of protein–protein interactions.Results: Using LC-MS/MS, 337 proteins were identified in DFCM. Among them, 160 proteins were associated with wound repair, and 57 proteins were associated with hair regeneration. Protein–protein interaction network analysis of 160 DFCM proteins for wound repair at the highest confidence score (0.9) revealed that 110 proteins were grouped into seven distinctive interaction networks. Additionally, protein–protein interaction network analysis of 57 proteins for hair regeneration at the highest confidence score revealed that 29 proteins were grouped into five distinctive interaction networks. The identified DFCM proteins were associated with several pathways for wound repair and hair regeneration, including epidermal growth factor receptor, fibroblast growth factor, integrin, Wnt, cadherin, and transforming growth factor-β signaling pathways.Conclusion: DFCM contains numerous secretory proteins that comprise groups of protein–protein interaction networks that regulate wound repair and hair regeneration.Keywords: human dermal fibroblast, dermal fibroblast-conditioned media, proteomic analysis, secretory protein, wound repair, hair regeneration

Dermal fibroblasts play a pivotal role in hair follicle regeneration during wound repair. Recently, dermal fibroblast-conditioned medium (DFCM), which contains multi-peptide factors (MPFs), has been used to promote wound repair.This study aimed to investigate the stimulatory effects of MPF-containing DFCM on hair growth.MPF-containing DFCM was prepared using human neonatal dermal fibroblasts. Outer root sheath (ORS) and dermal papilla (DP) cells were cultured in MPF-containing DFCM. We examined the expression and secretion of growth factors and cytokines using quantitative polymerase chain reaction and a growth factor array. In addition, the effect of MPFs on β-catenin activity was determined using the TOPflash assay. All experiments were repeated at least three times with separate batches of cells.MPF-containing DFCM increased keratinocyte growth factor (KGF), vascular endothelial growth factor (VEGF), and epidermal growth factor (EGF) mRNA expression in ORS cells and KGF and VEGF mRNA expression in DP cells. When ORS cells were treated with MPF-containing DFCM, the secretion of several growth factors, including EGF, VEGF, insulin-like growth factor-binding protein (IGFBP)-4, IGFBP-6, and fibroblast growth factor-7, was increased in the cell-cultured medium compared with that in control. Additionally, MPF-containing DFCM increased the transcriptional activation of β-catenin in DP cells.These results suggest that MPF-containing DFCM might stimulate hair growth by inducing growth factors in ORS and DP cells and regulating β-catenin in DP cells.

BACKGROUND Quantum molecular resonance (QMR) technology employs nonionizing high-frequency waves ranging from 4 to 64 MHz to generate low-intensity quanta of energy that interacts with cellular components. AIMS To evaluate the efficacy and safety of QMR treatment on postoperative perilesional edema and ecchymosis in patients with rhinoseptoplasty or revision rhinoseptoplasty. PATIENTS/METHODS In total, 30 patients were treated with QMR stimulation therapy (QMR group) once daily for 5 days, while another 30 patients were treated with conventional icepack application (control group). The duration of perilesional edema and ecchymosis were comparatively evaluated according to anatomic regions. RESULTS In both groups, the longest duration of postoperative edema and ecchymosis was found on the left anterior cheek, followed by the right anterior cheek, left lower eyelid, right lower eyelid, and right and left upper eyelids. The mean duration of overall postoperative perilesional edema was significantly shorter in the QMR group (2.0 ± 0.8 days) than the control group (4.6 ± 2.0 days); the mean duration of overall ecchymosis was also markedly shorter in the QMR group (2.9 ± 1.5 days) than control group (7.5 ± 2.9 days). Patient satisfaction after postoperative QMR treatment was rated as 2.2 ± 0.8, whereas patient satisfaction in control group was rated as 1.6 ± 0.9. CONCLUSION Our clinical study demonstrated that postrhinoseptoplasty QMR treatment effectively reduces the duration of postoperative perilesional edema and ecchymosis without remarkable side effects. We suggest that QMR treatment can be considered as an alternative option for noninvasively managing postrhinoseptoplasty perilesional edema and ecchymosis.

Background. Although several energy devices targeting sebaceous glands have been developed, an effective and safe therapeutic tool for hyperseborrhea is still needed. Nonthermal atmospheric-pressure plasma (NTAPP) induces microscopic tissue reactions in sebaceous glands of rat skin. Objective. The aim of the study is to investigate the effects of NTAPP on sebum production in human skin in vivo followed by an experimental study of human sebocytes. Methods. Fourteen healthy volunteers with oily facial skin underwent three sessions of argon- and nitrogen-NTAPP treatment at a 1-week interval and were followed up for 8 weeks. The casual sebum level, sebum excretion rate, and porphyrin index were evaluated. Histological analysis was performed using skin biopsy specimens taken from two subjects at the baseline and week 2. SZ95 sebocytes were stimulated with testosterone and linoleic acid (T/LA) with or without treatment with NTAPP. BODIPY and Nile red staining were used for qualitative lipids analysis. Proliferation and differentiation markers were also assessed. Results. Casual sebum levels and sebum excretion rates in facial skin decreased by 26 and 24%, respectively, at week 4 compared to those of the baseline. Porphyrin index also decreased by 38% at week 2. Histologically, NTAPP-treated human skin showed no obvious thermal injury, but the number of Ki67+ cells in the sebaceous glands decreased at week 2. Argon- and nitrogen-NTAPP attenuated T/LA-induced increases in neutral lipid accumulation, Ki67+ cells, and peroxisome proliferator-activated receptor-ɣ transcription in human sebocytes at energy settings that did not induce apoptosis. Conclusion. Argon- and nitrogen-NTAPP can be a safe and effective therapeutic tool for hyperseborrhea-associated diseases such as acne. This trial is registered with NCT04917835.

Background Picosecond-domain laser treatment using a microlens array (MLA) or a diffractive optical element (DOE) generates micro-injury zones in the epidermis and upper dermis. Objective To investigate interactive tissue reactions between MLA-type picosecond laser pulses and cohesive polydensified matrix hyaluronic acid (CPMHA) filler in the dermis. Methods In vivo rats with or without CPMHA pretreatment were treated with a 1064-nm picosecond-domain neodymium:yttrium-aluminum-garnet (Nd:YAG) laser using an MLA or DOE. Skin samples were obtained at post-treatment days 1, 10, and 21 and histologically and immunohistochemically analyzed. Results Picosecond-domain Nd:YAG laser treatment with an MLA-type or a DOE-type handpiece generated fractionated zones of pseudo-cystic cavitation along the lower epidermis and/or upper papillary dermis at Day 1. At Day 21, epidermal thickness, dermal fibroblasts, and collagen fibers had increased. Compared to CPMHA-untreated rats, rats pretreated with CPMHA showed marked increases in fibroblasts and collagen fibers in the papillary dermis. Immunohistochemical staining for the hyaluronic acid receptor CD44 revealed that MLA-type picosecond laser treatment upregulated CD44 expression in the basilar epidermis and dermal fibroblasts. Conclusions We suggest that the hyaluronic acid-rich environment associated with CPMHA treatment may enhance MLA-type picosecond-domain laser-induced tissue reactions in the epidermis and upper dermis.

Atmospheric-pressure, non-thermal plasma destroys microorganisms by directly reacting with hydrocarbon molecules in the cell wall and/or by damaging the cytoplasmic membrane, proteins, and DNA with charged particles and reactive species. The aim of our study was to evaluate the antibacterial and anticandidal effects of atmospheric-pressure, non-thermal, nitrogen- and argon-plasma pulses on various pathogen preparations. The resultant antibacterial and anticandidal effects were assessed by evaluating percent and log reduction values for pathogen colonies. Nitrogen-plasma pulses emitted at an energy of 1.5 J and argon-plasma pulses generated at 0.5 J elicited remarkable antibacterial effects on Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus (MRSA) and anticandidal effects on Candida albicans. Nitrogen-plasma pulses at a pulse count of five elicited remarkable antibacterial effects on Cutibacterium acnes at the energy settings of 1.75, 2.5, and 3 J, but not at 1 J. Meanwhile, argon-plasma pulses showed antibacterial effects on C. acnes at an energy of 0.5 and 0.65 J. Nitrogen- or argon-plasma pulses exert antibacterial and anticandidal effects on bacterial and fungal pathogens.

Although several energy devices targeting sebaceous glands have been developed, an effective and safe therapeutic tool for hyperseborrhea is needed. Non-thermal atmospheric-pressure plasma (NTAPP) induces microscopic tissue reactions in sebaceous glands of rat skin in vivo. Fifteen healthy volunteers with oily facial skin underwent three sessions of argon- and nitrogen-NTAPP treatment. The casual sebum level, sebum excretion rate, porphyrin index, and histological analysis were evaluated. Argon- and nitrogen-NTAPP pulses were applied to testosterone and linoleic acid (T/LA)-treated human SZ95 sebocytes. Lipids were assessed using BODIPY and quantitative Nile red staining. Proliferation and differentiation markers were assessed. Argon- and nitrogen-NTAPP pulses suppressed casual sebum levels and sebum excretion rates in the skin, at week 4. The porphyrin index revealed a 38% reduction at week 2. Skin biopsy samples showed no obvious thermal coagulation, but the number of Ki67+ cells in the sebaceous glands decreased at week 2. Argon- and nitrogen-NTAPP inhibited T/LA-induced increases in lipid synthesis, Ki67+ cells, and peroxisome proliferator-activated receptor-ɣ transcription in human sebocytes without apoptosis. Argon- and nitrogen-NTAPP therapy is a safe and effective method for reducing sebum excretion in oily human skin and inhibits lipogenesis and cell proliferation in human sebocytes.

Background For medical purposes, plasma can be generated from inert gaseous sources in a device by ultra-high-frequency generators and emitted to target tissue at a pulse duration in the milliseconds. Objective To evaluate argon and nitrogen plasma pulse-induced tissue reactions in the skin and skin appendages of an in vivo animal model. Methods Argon and nitrogen plasma pulses were non-invasively delivered to in vivo rat skin at various experimental settings. Specimens were histologically evaluated following hematoxylin and eosin and Masson's trichrome staining. Results At low-energy settings of 1.0, 1.5, and 2.0 J, nitrogen plasma treatments generated noticeable tissue coagulation at the depths of 31.5 ± 8.3, 94.9 ± 16.9, and 171.6 ± 19.7 µm, respectively, at Day 0. At high-energy settings of 2.5 and 3.0 J, nitrogen plasma treatments generated marked tissue coagulation at the depths of 381.7 ± 33.6 µm and 456.3 ± 75.7 µm, respectively, at Day 0. Conclusions Treatment with argon plasma induces microscopic changes in the epidermis, dermis, and sebaceous glands without generating excessive thermal injury, whereas that with nitrogen plasma elicits energy-dependent thermal coagulation in the epidermis and dermis with remarkable neocollagenesis.

BACKGROUND Long-pulsed (LP) lasers at pulse durations of 1-300 ms have been used to destroy nests of nevi cells by selectively targeting pigment chromophores. OBJECTIVE To evaluate dual-wavelength LP laser-induced tissue reactions. METHODS The patterns of LP 755-nm alexandrite (Alex) and/or 1064-nm neodymium (Nd):yttrium-aluminum-garnet (YAG) laser-induced tissue reactions were macroscopically evaluated using a tattoo-embedded phantom. Additionally, a pilot in vivo human study was performed for common acquired melanocytic nevus, of which dermoscopic images and high-speed cinematographs were obtained. RESULTS Combinations of Nd:YAG and Alex laser treatments at interpulse intervals of 10 or 20 ms generated round to oval zones of photothermal and photoacoustic injury in two distinctive areas containing disintegrated tattoo particles. Treatment at interpulse intervals of 10 or 20 ms between Alex and Nd:YAG pulses elicited lesser degrees of thermal damage to surrounding tissues, compared to treatment at 100 or 200 ms. Immediately after combined LP laser treatment of human nevus lesions in vivo, Nd:YAG-Alex treatment at a 20-ms interpulse interval exhibited more remarkable crusting and erosive appearances than Alex-Nd:YAG treatment. CONCLUSION For treating pigmented disorders, sequential delivery of LP Nd:YAG and Alex pulses at short interpulse intervals of 10-20 ms can effectively destroy nests of pigment chromophores.

Background Autologous adipose-derived stromal vascular fraction treatments have been shown to elicit antiinflammatory, antifibrotic, immunomodulatory, angiogenic, and regenerative effects. Injections of adipose-derived stromal vascular fraction have been used to treat severely scarred tissues. Methods Revision septorhinoplasty was performed in 40 patients with severely contracted noses. Clinical outcomes and adverse events were compared between one group of patients treated with adjuvant adipose-derived stromal vascular fraction injections and a control group of patients treated with adjuvant 0.9% preservative-free saline injections. Results In the adipose-derived stromal vascular fraction group, nasal lengths were estimated at 4.2 ± 0.2 cm at baseline to 5.1 ± 0.2 cm at 18 months after revision septorhinoplasty. The lengths of nasal tip projection improved from 2.2 ± 0.2 cm at baseline to 2.9 ± 0.1 cm 18 months after surgery. In addition, nasofrontal angles improved from 125.6 ± 5.1 degrees at baseline to 128.1 ± 4.8 degrees 18 months after surgery. Nasolabial angles in the adipose-derived stromal vascular fraction group were estimated at 105.8 ± 6.5 degrees at baseline and 94.9 ± 5.6 degrees 18 months after surgery. Of these, nasal length, nasal tip projection, and nasolabial angle, but not nasofrontal angle, values improved more in the adipose-derived stromal vascular fraction group than in the control group. Conclusion Preoperative and postoperative adjuvant adipose-derived stromal vascular fraction treatment markedly improved the therapeutic outcomes of revision rhinoseptoplasty of severely contracted noses without major side effects. Clinical question/level of evidence Therapeutic, III.

Background and objectives The aim of this study is to histologically characterize the wound healing process of in vivo human skin treated with 1064- and 532-nm microlens array (MLA)-type picosecond lasers. Study design/materials and methods Three patients (Fitzpatrick skin types II-IV), who were undergoing future cosmetic abdominoplasties, were treated with 1064- and 532-nm MLA-type lasers under different fluence settings. Treatments were performed 2 weeks, 1 week, and immediately prior to surgery. Skin samples were harvested from the resected tissue with 8 mm punch biopsies immediately after the abdominoplasties were performed. Results The study demonstrates that intraepidermal vacuoles, created from tissue damage induced by the laser, are histologically resolved within 1 week without persistent damage to the dermoepidermal junction or vasculature. After 2 weeks, all foci of microscopic epidermal necrotic debris had either resolved or migrated to more superficial levels in the stratum corneum. There was no evidence of persistent vascular damage, increased melanophages, or accumulation of melanin in the dermis at 2 weeks. Furthermore, the 1064-nm picosecond laser with the high fluence setting demonstrated the capacity to fractionally ablate the epidermis and induce multifocal fibrosis in the papillary dermis in lighter skin types. Conclusion This is the first study to demonstrate the wound healing profile of in vivo human skin after treatment with the picosecond 1064- and 532-nm MLA-type lasers. It shows that laser-induced tissue damage is histologically resolved within 2 weeks, clinically reflecting a favorable safety profile and short downtime. The study also shows that the picosecond laser can be used to induce either fractional ablative or non-ablative effects, depending on the fluence settings used. Lasers Surg. Med. © 2021 Wiley Periodicals LLC.

Background: Chemical reconstruction of skin scars (CROSS) applies a high strength acid focally to treat atrophic scars. Although this method has gained popularity over the past two decades, no standardized treatment guideline exists for CROSS method in the treatment of atrophic scars. Aims: The purpose of this comprehensive review is to evaluate the indications, detailed techniques, efficacy and safety of CROSS method. Materials and methods: An extensive literature review was conducted to identify articles relating to CROSS method for atrophic scars from 2002 to 2018. Results: The literature search yielded 19 articles meeting criteria. CROSS method has been used for the treatment of acne scars, varicella scars, enlarged pores and depressed surgical scars. In studies using the quantile grading scale for acne scars, 60-100% of patients showed >25% improvement. In two studies for varicella scars, 83-100% of patients showed >25% improvement. CROSS method seems to be effective specifically for ice-pick scars. It is well tolerated and safe in Fitzpatrick skin phototypes I-V. Most reported complications are temporary and include post-inflammatory dyspigmentation, erythema, pain, pruritus, infection and widening of scars. Conclusion: This literature review suggests that CROSS method is a safe and effective treatment for atrophic scars, especially ice-pick scars, in skin types I-V. However, current published works have several limitations, including small sample sizes, lack of control group, different concentrations of acid, different frequency of treatments and follow-up periods. Larger, randomized, controlled studies are needed to elucidate the optimal treatment protocol of CROSS method.

Background Intense focused ultrasound (IFU) and radiofrequency (RF) systems generate thermal tissue reactions in multiple zones in the skin, with the microscopic features thereof varying according to energy sources and treatment parameters. Objective To evaluate interactive thermal tissue reactions of IFU and RF in cadaveric skin. Methods Thermal reaction patterns generated by IFU, invasive bipolar RF, and non-invasive monopolar RF treatments were analyzed in cadaveric skin of the inner thigh. Additionally, combination treatment, including IFU and invasive bipolar RF, IFU and non-invasive monopolar RF, invasive bipolar RF and IFU, and non-invasive monopolar RF and IFU, was delivered to cadaveric skin and microscopically evaluated. Results Combination treatment with 1.5-mm IFU followed by 1.5-mm invasive RF elicited multiple thermal injury zones of coagulation and ablation in the mid to lower dermis. Therein, IFU-induced thermal reactions were indistinguishable from RF-induced thermal reactions. Non-invasive RF treatment on IFU-pretreated cadaveric tissue specimens exhibited greater degrees of thermal injury, with wider and deeper penetration, compared to non-invasive RF treatment alone. Furthermore, RF-pretreated tissues showed marked differences in the patterns of IFU-induced thermal tissue reactions. Conclusion Our data suggest that combination treatments with IFU and RF elicit various patterns of interactive thermal tissue reactions.

Background Transcutaneous pneumatic injection (TPI) is a minimally invasive, needle-free modality that can be used to forcefully deliver solution into soft tissues of the face and scalp. Objective To evaluate the effects of TPI of 5% isotonic and 20% hypertonic glucose solutions in in vivo human skin for face lifting. Methods and materials A prospective, split-face, evaluator-blinded comparison study was performed on 10 Korean participants who were treated with three sessions of TPI using 5% isotonic and 20% hypertonic glucose solutions. Results The following assessment parameters were improved after TPI therapy using 5% isotonic glucose solution in descending order of mean global aesthetic improvement scale (GAIS) score: perioral expression wrinkles, zygomatic wrinkles or mid-cheek furrows, eyebrow ptosis, jowl sagging, marionette line, horizontal forehead lines, nasolabial folds, and blepharochalasis. Meanwhile, TPI therapy using 20% hypertonic glucose solution improved the following assessment parameters: zygomatic wrinkles or mid-cheek furrows, perioral expression wrinkles, eyebrow ptosis, blepharochalasis, marionette line, jowl sagging, nasolabial folds, and horizontal forehead lines. Linear mixed models revealed a significant interaction between treatment groups and time. Conclusion Our data demonstrated that TPI treatment with 20% hypertonic glucose solution elicited earlier and more pronounced therapeutic responses, compared to 5% isotonic glucose solution.

BACKGROUND Energy-delivering devices can be used to induce thermal coagulation of the eccrine sweat glands for treating primary axillary hyperhidrosis (PAH). OBJECTIVE The objective of this study was to compare the efficacy and safety of invasive, bipolar radiofrequency (RF) treatment for PAH. METHODS A split-axilla study was performed to compare the clinical outcomes of 0.5 MHz, invasive, bipolar RF treatment with treatment settings of a longer conduction time and lower power (LC/LP) vs a shorter conduction time and higher power (SC/HP) for treating PAH. RESULTS The in vivo study revealed median hyperhidrosis disease severity scale scores of 1.5 (interquartile range [IQR], 1-2) at 1 month and 1 (IQR, 1-2) at 3 months after treatment with the LC/LP setting, compared to baseline. Meanwhile, the other side of the axillae treated with the SC/HP setting showed scores of 2 (IQR, 2-2) at 1 month and 2 (IQR, 1.25-2) at 3 months. Analysis via a linear mixed model revealed a significant interaction (group, P = .011; time, P

Background For the restoration of horizontal neck wrinkles, multimodal approaches using neuromodulators, intensity focused ultrasound (IFU), and fine line fillers are recommended. Objective To evaluate the efficacy and safety of a 1-day, multimodal approach for horizontal neck wrinkles. Methods Twelve female patients with horizontal neck wrinkles were treated with a combined treatment of IFU, cohesive polydensified matrix hyaluronic acid (CPMHA), and incobotulinumtoxinA. Therapeutic outcomes were assessed on Day 0 and 1, 2, 3, and 6 months thereafter. Results Horizontal neck wrinkles decreased significantly in length from a median at baseline of 269.75 mm (interquatile range [IQR], 235.35-302.94 mm) to 91.5 mm (IQR, 51.4-108.61 mm) at 1 month, 92.3 mm (IQR, 69.66-132.07 mm) at 2 months, 101.88 mm (IQR, 86-146.77 mm) at 3 months, and 109.48 mm (IQR, 85.06-148.17 mm) at 6 months after the combined treatment. The median global aesthetic improvement scale scores were 3.5 (IQR, 2-4) at 1 month, 3 (IQR, 3-3.5) at 2 months, 3 (IQR, 2-4) at 3 months, and 3 (IQR, 3-3) at 6 months. Post-treatment petechiae resolved completely within 7 days, and CPMHA-induced lumps disappeared within 1 month. Conclusion The present data demonstrated that the multimodal, combined treatment used in the present study provides satisfactory and long-lasting therapeutic outcomes by targeting different pathogenetic factors of horizontal neck wrinkles.

Laser- or light-assisted therapies have been used to improve the perifollicular environment by upregulating the expression of growth factors and signaling molecules for hair restoration. The aim of our study was to preclinically and clinically evaluate the therapeutic efficacy and safety of a 1927-nm fractionated thulium laser on pattern hair loss (PHL). An in vivo hairless mouse study and an in vivo human skin environmental scanning electron microscopy (ESEM) study were performed with different power and energy settings. Thereafter, an evaluator-blinded, split-scalp study was conducted to evaluate hair thickness and density in 10 PHL patients treated with 12 sessions of fractionated thulium laser treatment with or without post-laser treatment application of a growth factor-containing (GF) solution. In in vivo hairless mouse skin, inverted cone-shaped zones of thulium laser-induced tissue coagulation (LITC) were noted immediately after treatment in the epidermis and upper to mid-dermis without remarkable ablative tissue injury. The ESEM study revealed round to oval-shaped zones of non-ablative LITC on the surface of the stratum corneum of a human subject immediately after laser irradiation. In PHL patients, 12 sessions of thulium laser monotherapy at 1-week intervals resulted in significantly increased hair density and thickness. Post-laser treatment application of GF solution offered additional therapeutic efficacy by improving hair density and thickness on the split scalp. The use of a fractionated thulium laser with or without post-laser therapy application of GF solution to treat PHL elicited remarkable improvements in hair thickness and hair counts.

Needleless transcutaneous pneumatic injections (TPIs) are a minimally invasive way to deliver the solution into the skin for therapeutic purposes. The suggested action mechanisms of TPI therapy include mechanical stimulation, immediate tissue shrinkage and late wound healing.Thirteen Korean patients were treated with TPI for atrophic skin disorders, including acne scars, striae albae, post-furuncle, or carbuncle scars, and horizontal wrinkles with lipoatrophy. At each TPI treatment session, a single pass was made along with the atrophic skin lesions without overlapping. Thereafter, two dermatologists objectively evaluated the clinical improvement in the lesions in the photographs via the global aesthetic improvement scale (GAIS).One month after the final treatment, the overall mean GAIS score was 2.3 ± 0.8. Six of the 13 (46.2%) patients exhibited clinical improvement of grade 3, five (38.5%) patients grade 2 and two (15.4%) patients grade 1. The overall mean subjective satisfaction score with the TPI treatment was 2.3 ± 0.9. Six of the 13 (46.2%) patients achieved subjective satisfaction of grade 3, six (46.2%) patients grade 2 and one (7.7%) patient grade 0.The present study demonstrated that the TPI treatment is effective and safe for treating atrophic skin disorders of varying causes in Korean patients.

During laser treatment for tattoo removal, pigment chromophores absorb laser energy, resulting in fragmentation of the ink particles via selective photothermolysis. The present study aimed to outline macroscopic laser-tattoo interactions in tissue-mimicking (TM) phantoms treated with picosecond- and nanosecond-domain lasers. Additionally, high-speed cinematographs were captured to visualize time-dependent tattoo-tissue interactions, from laser irradiation to the formation of photothermal and photoacoustic injury zones (PIZs). In all experimental settings using the nanosecond or picosecond laser, tattoo pigments fragmented into coarse particles after a single laser pulse, and further disintegrated into smaller particles that dispersed toward the boundaries of PIZs after repetitive delivery of laser energy. Particles fractured by picosecond treatment were more evenly dispersed throughout PIZs than those fractured by nanosecond treatment. Additionally, picosecond-then-picosecond laser treatment (5-pass-picosecond treatment + 5-pass-picosecond treatment) induced greater disintegration of tattoo particles within PIZs than picosecond-then-nanosecond laser treatment (5-pass-picosecond treatment + 5-pass-nanosecond treatment). High-speed cinematography recorded the formation of PIZs after repeated reflection and propagation of acoustic waves over hundreds of microseconds to a few milliseconds. The present data may be of use in predicting three-dimensional laser-tattoo interactions and associated reactions in surrounding tissue.

Non-focused ultrasound and high-intensity focused ultrasound (HIFU) devices induce lipolysis by generating acoustic cavitation and coagulation necrosis in targeted tissues. We aimed to investigate the morphometric characteristics of immediate tissue reactions induced by 2 MHz, 13-mm focused HIFU via two-dimensional ultrasound images and histologic evaluation of cadaveric skin from the abdomen and thigh. Acoustic fields of a 2 MHz, 38-mm HIFU transducer were characterized by reconstruction of the fields using acoustic intensity measurement. Additionally, abdominal and thigh tissues from a fresh cadaver were treated with a HIFU device for a single, two, and three pulses at the pulse energy of 130 J/cm2 and a penetration depth of 13 mm. Acoustic intensity measurement revealed characteristic focal zones of significant thermal injury at the depth of 38 mm. In both the abdomen and thigh tissue, round to oval ablative thermal injury zones (TIZs) were visualized in subcutaneous fat layers upon treatment with a single pulse of HIFU treatment. Two to three HIFU pulses generated larger and more remarkable ablative zones throughout subcutaneous fat layers. Finally, experimental treatment in a tumescent infiltration-like setting induced larger HIFU-induced TIZs of an oval or columnar shape, compared to non-tumescent settings. Although neither acoustic intensity measurement nor cadaveric tissue exactly reflects in vivo HIFU-induced reactions in human tissue, we believe that our data will help guide further in vivo studies in investigating the therapeutic efficacy and safety of HIFU-induced lipolysis.

Background Studies have shown melasma lesions to be distributed across the face in centrofacial, malar, and mandibular patterns. Meanwhile, however, melasma lesions of the periorbital area have yet to be thoroughly described. Methods We analyzed normal and ultraviolet light-exposed photographs of patients with melasma. The periorbital melasma lesions were measured according to anatomical reference points and a hierarchical cluster analysis was performed. Results The periorbital melasma lesions showed clinical features of fine and homogenous melasma pigmentation, involving both the upper and lower eyelids that extended to other anatomical sites with a darker and coarser appearance. The hierarchical cluster analysis indicated that patients with periorbital melasma can be categorized into two clusters according to the surface anatomy of the face. Significant differences between cluster 1 and cluster 2 were found in lateral distance and inferolateral distance, but not in medial distance and superior distance. Comparing the two clusters, patients in cluster 2 were found to be significantly older and more commonly accompanied by melasma lesions of the temple and medial cheek. Conclusion Our hierarchical cluster analysis of periorbital melasma lesions demonstrated that Asian patients with periorbital melasma can be categorized into two clusters according to the surface anatomy of the face.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Background Nonsurgical correction of drooping of the corners of the mouth requires a multimodal approach combining botulinum toxin and soft tissue filler injections. Objective To validate a nonsurgical therapeutic approach for correcting a "saddened" appearance characterized by drooping mouth corners, oral commissures, and/or marionette lines. Methods In this prospective, evaluator-blinded study, monophasic hyaluronic acid (MHA) was infiltrated to correct drooping mouth corners in four steps, deep oral commissures in two steps, and/or deep marionette lines in two steps, in that order. Then, incobotulinumtoxinA was injected along the depressor anguli oris and mentalis muscles. Results The total volumes of MHA used in steps 1-4 were 0.2 mL (interquartile range [IQR]: 0.19-0.3) for the right side of the face and 0.25 mL (IQR: 0.2-0.3) for the left side; total volumes in steps 5-8 were 0.18 mL (IQR: 0-0.4) for the right side and 0.15 mL (IQR: 0-0.33) for the left side. The total mean dose of incobotulinumtoxinA was 26.5 units (IQR: 24-28). The median degrees of drooping of the mouth corners were -4° (IQR: -7° to -2°) at baseline, -1° (IQR: -3° to 1°) at post-treatment 2 weeks, and -1° (IQR: -3° to 0°) at post-treatment 3 months. Median Global Aesthetic Improvement Scale scores were 3 (IQR: 2-3) at post-treatment 2 weeks and 3 (IQR: 2-3.75) at 3 months. Conclusion Our results demonstrated that nonsurgical treatment with MHA and incobotulinumtoxinA provides satisfactory therapeutic outcomes in patients with a saddened appearance by correcting drooping of the mouth corners, deep oral commissures, and/or deep marionette lines.