Histological Assessment of the Effectiveness of Microneedling Device-Assisted Filler Delivery.

BACKGROUND: Microneedling is used to enhance transcutaneous drug delivery. However, the extent to which microneedling devices impact filler delivery and whether this varies by filler type, microneedling device type, and treatment sequence is not known. OBJECTIVE: To histologically assess and quantify the delivery of commonly used fillers through microneedling, using both a microneedling pen and a microneedling roller. In addition, the authors investigated whether there is a variation in filler delivery based on the sequence of microneedling in relation to topical filler application. METHODS: Ex vivo human abdominal skin samples were subjected to microneedling pen or microneedling roller treatment. Black tissue marking ink, hyaluronic acid, poly-l-lactic acid, or undiluted calcium hydroxyapatite was topically applied before or immediately after microneedling treatment. RESULTS: Histological evaluation revealed a notable presence of black ink within channels formed by both microneedling treatments (15.5%-98.1%), whereas there was limited presence of the various filler types tested (0%-6.6%) in all settings. Topical application before microneedling treatment led to relatively higher filler/ink deposition within the channels formed by the microneedling treatments compared with topical application after microneedling. CONCLUSION: Transcutaneous delivery of fillers was not significantly helped by microneedling treatment, whereas the microneedling devices demonstrated effective delivery of an aqueous solution.

Efficacy and Safety of Low Fluence Nd:YAG Laser Treatment in Melasma: A Meta-Analysis and Systematic Review.

BACKGROUND: Low-fluence, multisession therapy of Nd:YAG laser has been widely used for treating melasma. OBJECTIVE: To evaluate the efficacy and safety of low-fluence Nd:YAG laser toning for melasma using a systematic review and meta-analysis. METHODS: The PubMed, Web of Science, Embase, and Cochrane Library databases were searched till December 2020. A total of 50 studies (1,772 patients) and 66 studies were selected for the evaluation of the efficacy and complications, retrospectively. RESULTS: The mean Melasma Area and Severity Index/modified Melasma Area and Severity Index scores for laser toning as monotherapy at <4, 4 to <8, 8 to <12, 12 to <24, and ≥24 weeks after treatment compared with that at pretreatment were -0.51, -0.91, -0.97, -0.92, 0.01 SD, whereas those as combination therapy were -1.64, -1.26, -0.94, not available, -1.45 SD, respectively. An increase in light value and a decrease in relative lightness index have remained up to 8 weeks after laser toning. Complications including hypopigmentation/leukoderma, postinflammatory hyperpigmentation, and recurrence were noted. The incidence of hypopigmentation/leukoderma correlated with the number of laser sessions (p = .036). CONCLUSION: Low-fluence Nd:YAG laser toning as combination therapy has shown better efficacy than monotherapy and the efficacy seems to diminish with time. This study suggests the positive correlation of hypopigmentation/leukoderma with the number of laser sessions.

Laser-Assisted and Device-Assisted Filler Delivery: A Histologic Evaluation.

BACKGROUND: Lasers and devices are used to enhance transcutaneous delivery of fillers. However, little has been published on the histologic findings of this form of laser/device-assisted delivery to determine the optimal devices and fillers. OBJECTIVE: To objectively evaluate the histological effects of laser-assisted and device-assisted filler delivery. METHODS: Ex vivo human abdominoplasty skin samples were treated with fractional CO 2 laser (ECO 2 , 120 µm tip, 120 mJ), fractional radiofrequency microneedling (FRMN, Genius, 1.5 mm, 20 mJ/pin), and microneedling (2.0 mm). Immediately after poly- l -lactic acid (PLLA), hyaluronic acid gel, calcium hydroxylapatite, and black tissue marking dye were topically applied. After treatment, biopsies were collected for histologic evaluation. RESULTS: Histology revealed that PLLA and black dye were found in greatest abundance, hyaluronic acid was found to a lesser extent, and calcium hydroxylapatite was least found within channels created by fractional CO 2 laser. Microneedling was effective only at delivering black dye, whereas FRMN failed to show significant channel formation or delivery of the studied products. CONCLUSION: Among the devices and fillers studied, fractional CO 2 laser and PLLA proved to be the most effective combination for laser/device-assisted filler delivery. Neither microneedling nor FRMN was effective as devices to enhance filler delivery.

Merkel Cell Hyperplasia Versus Intraepidermal Merkel Cell Carcinoma: A Comparative Study of 2 Cases.

ABSTRACT: Intraepidermal Merkel cell hyperplasia and Merkel cell carcinoma represent 2 histologically similar-appearing diagnoses with significant differences regarding prognosis and management. We present 1 case of each diagnosis to highlight characteristic histopathologic and immunohistochemical features. Our case of Merkel cell hyperplasia was identified by its small intraepidermal nest of monomorphic cells without atypia or mitoses, which demonstrated cytoplasmic, rather than perinuclear dot, patterning on CK20 staining. This can be contrasted with our case of intraepidermal Merkel cell carcinoma, which, despite a lack of dermal extension, demonstrated large nests of pleomorphic cells with frequent mitoses and apoptoses. The diagnosis was further confirmed by immunohistochemistry because CK20 staining showed classic perinuclear dot patterning. By presenting both diagnoses in parallel, this comparison aims to underscore crucial histopathologic and immunohistochemical similarities and differences.

Review of Lasers and Energy-Based Devices for Skin Rejuvenation and Scar Treatment With Histologic Correlations.

BACKGROUND: Lasers and energy-based devices (EBD) are popular treatments for skin rejuvenation and resurfacing. Achieving desired outcomes and avoiding complications require understanding the effects of these devices at a histologic level. Currently, no comprehensive review summarizing the histologic effects of laser and energy-based treatments exists. OBJECTIVE: To describe how lasers and EBD alter skin histology and improve the overall understanding of these devices. MATERIALS AND METHODS: A PubMed search was conducted for studies with histologic analysis of fractional picosecond laser, fractional radiofrequency microneedling, nonablative lasers, and ablative lasers. RESULTS: Fractional picosecond lasers induce intraepidermal and/or dermal vacuoles from laser-induced optical breakdown. Fractional radiofrequency microneedling delivers thermal energy to the dermis while sparing the epidermis, making it safer for patients with darker skin phototypes. Fractional nonablative lasers induce conical zones of coagulation of the epidermis and upper dermis. Ablative lasers vaporize the stratum corneum down to the dermis. Traditional ablative lasers cause diffuse vaporization while fractional ablative lasers generate columns of tissue ablation. CONCLUSION: Lasers and EBD are effective for skin resurfacing and rejuvenation and have different mechanisms with disparate targets in the skin. Safe and effective use of devices requires understanding the histologic laser-tissue interaction.

Acutely increased ß-hydroxybutyrate plays a role in the prefrontal cortex to escape stressful conditions during the acute stress response.

Ketone bodies can be increased in the blood under certain physiological conditions, but their role under such conditions remains to be clarified. In the present study, we found the increment and usage of ß-hydroxybutyrate (BHB) in the prefrontal cortex (PFC) during acute stress. BHB levels increased in the blood and PFC after 30-min acute immobilization stress, and BHB dehydrogenase 1 increased in the PFC simultaneously, but not in the hippocampus. Moreover, increased levels of acetyl-CoA, pyruvate carboxylase, and glutamate dehydrogenase 1 were found in the PFC, implicating the metabolism of increased BHB in the brain. Thus, we checked the levels of glutamate, glutamine, and GABA and found increased levels of glutamate and glutamine in the stressed group compared with that in the control group in the PFC. Exogenous administration of BHB enhanced struggling behaviors under stressful conditions. Our results suggest that the metabolism of BHB from peripheral blood in the PFC may contribute to acute stress responses to escape stressful conditions.

Wound Healing Profile After 1064- and 532-nm Picosecond Lasers With Microlens Array of In Vivo Human Skin.

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.

Comparative analysis of the association between various serum vitamin D biomarkers and sarcopenia.

BACKGROUND: Vitamin D status is associated with muscle strength and maintenance of muscle fibers. However, which serum vitamin D biomarker better reflects sarcopenia remains unclear. The aim of this study was to investigate associations between various serum vitamin D biomarkers (total 25-hydroxy vitamin D [25(OH)D], bioavailable 25(OH)D, 24,25-dihydroxyvitamin D [24,25(OH)2 D], and vitamin D metabolite ratio [VMR]) and sarcopenia. METHODS: The data for 83 hip fracture patients were finally included in the analysis. Sarcopenia was defined according to the Asia Working Group for Sarcopenia (AWGS) criteria. Measurements of 24,25(OH)2 D and 25(OH)D were made using solid-phase extraction (SPE) and subsequent liquid chromatography-tandem mass spectrometry (LC-MS/MS). Vitamin D binding protein (VDBP) concentration was measured using an enzyme-linked immunosorbent assay. The VMR was calculated by dividing serum 24,25(OH)2 D by serum 25(OH)D and then multiplying by 100. Based on total 25(OH)D, VDBP, and albumin concentrations, bioavailable 25(OH)D concentrations were calculated using the equations from the other previous studies. RESULTS: Bioavailable 25(OH)D levels were significantly (p = 0.030) decreased in the sarcopenia group compared with the non-sarcopenia group. Results of ROC analysis for the diagnosis of sarcopenia using serum level of bioavailable of 25(OH)D revealed that the cutoff point for bioavailable 25(OH)D was 1.70 ng/ml (AUC = 0.649, p < 0.001). In the group with a bioavailable 25(OH)D less than 1.70 ng/ml, the incidence of sarcopenia increased by 3.3 times (odds ratio: 3.33, p = 0.013). CONCLUSION: We demonstrated that bioavailable 25(OH)D was associated with sarcopenia among the various serum vitamin D biomarkers. Bioavailable vitamin D might be helpful for assessing the risk of sarcopenia.

Cutaneous spindle cell adenolipoma with eccrine and apocrine differentiation.

Cutaneous spindle cell adenolipoma (SCAL) is a recently described rare variant of lipoma with 11 cases reported to date. Here we report a consultation case of a 77-year-old male who presented with a nodule on the right nasolabial fold, diagnosed as apocrine fibroadenoma or sebaceous hyperplasia by an outside pathologist. The specimen revealed an ill-defined dermal tumor composed of mature adipocytes, bland spindle cells, ropey collagen, and dilated eccrine and apocrine glands and ducts in a fibromyxoid stroma. The spindle cells were positive for CD34 and negative for S100 protein and SOX10. These findings are consistent with those of cutaneous SCAL. The pathogenesis of this entity is controversial and includes a hamartomatous process, derivation from adipose tissue surrounding eccrine glands, or preexisting glands entrapment within a growing lipoma. In the present case, the glandular component is extensive and includes both eccrine and apocrine differentiation, which has not been previously described and further supports the hamartomatous nature. Awareness of this rare entity is helpful to prevent confusion with other look-alike primary and metastatic cutaneous lesions.

Eccrine duct dilatation in neutrophilic scarring alopecias.

BACKGROUND: Eccrine duct dilatation (EDD) has been noted to occur significantly more often in primary lymphocytic scarring alopecias compared with non-scarring alopecias, thus serving as a possible histopathologic marker for primary scarring alopecias with a lymphocytic infiltrate. This study aims to determine the presence and role of EDD in primary neutrophilic scarring alopecias. METHODS: We performed a retrospective review comparing primary scarring alopecia (neutrophilic, n = 90; lymphocytic, n = 100) and non-scarring alopecia (n = 123) for presence of EDD, seen in Boston University School of Medicine between 2013 and 2017. RESULTS: EDD was more commonly seen in primary neutrophilic scarring (62.2%, 56/90) and primary lymphocytic scarring alopecias (54.0%, 54/100) than in non-scarring alopecias (25.2%, 31/123) (P < 0.001). Albeit uncommon, non-scarring alopecias exhibited the biggest ratio of dilated eccrine duct lumen to background duct lumen (14.33), followed by lymphocytic (10.99) and neutrophilic scarring alopecias (6.66). CONCLUSION: EDD is seen more frequently in primary scarring alopecias compared with non-scarring alopecias and usually found in sections containing inflammation and dermal fibrosis, serving as a possible histopathologic clue for a scarring process. Non-scarring alopecias have significantly fewer but considerably larger EDD which, may imply a different pathologic cause.

Factors Affecting Depth of Penetration in Microneedling- and Laser-Assisted Drug Delivery: The Importance of Timing of Topical Application.

BACKGROUND: Microneedling- and laser-assisted drug delivery are emerging techniques used to treat various conditions. However, key parameters affecting drug penetration remain unknown. OBJECTIVE: This study aims to investigate the importance of timing of topical application, needle length, and device type for drug delivery. MATERIALS AND METHODS: Skin harvested from cosmetic surgeries was treated with black ink applied before or after treatment with a microneedling pen (MP), roller, or fractional ablative CO2 laser, and incubated for different time intervals. Ink penetration was additionally tested using different needle lengths. Sandwich estimator was used for statistical analysis. RESULTS: Ink applied before MP penetrated deeper compared to ink applied afterward at 1 and 3 hours, and roller microneedling in both the ink-before and -after scenarios at 1, 3, and 6 hours (p < .05). Microneedling demonstrated lateral extension of ink beyond microchannels with increased ink penetration over time. CO2 laser demonstrated ink localization within microthermal zones without time-dependent increases in depth after 30 minutes. Ink penetration increases by 0.06 mm per 1 mm increase in needle length. CONCLUSION: Ink applied before MP results in the deepest penetration of ink. Microneedling offers unique advantages in transdermal delivery as its channels exhibit increasing penetration over time and lateral extension of product.

Botulinum Toxin Injections for Leg Contouring in East Asians.

BACKGROUND: A common aesthetic concern among East Asian women is enlarged calves. Although surgical resection has been a traditional treatment option, botulinum toxin injections into the gastrocnemius muscle are an emerging, noninvasive alternative. OBJECTIVE: To perform a literature review on botulinum toxin injections for leg contouring. MATERIALS AND METHODS: A literature review was conducted using PubMed, Web of Science, Embase, and Cochrane's CENTRAL database to identify articles relating to combinations of the terms botulinum toxin, gastrocnemius, calves, and leg contouring. RESULTS: Based on the limited publications to date, the authors prepared a review on how to treat an enlarged calf with botulinum toxin including injection techniques, anticipated efficacy, outcome monitoring, and potential side effects. CONCLUSION: Botulinum toxin injections for calf reduction are an emerging, noninvasive treatment option. Studies to date suggest that it is an efficacious method with few immediate side effects. Future areas for investigation include defining the criteria for calf hypertrophy, minimum effective dosage of botulinum toxin, and the potential long-term effects of injections.

Histologic Effects of Fractional Laser and Radiofrequency Devices on Hyaluronic Acid Filler.

BACKGROUND: Hyaluronic acid fillers (HAFs) and energy-based devices are frequently used sequentially. However, the effect of using fractional devices directly over HAF is unclear. OBJECTIVE: To evaluate histologic changes after fractional laser and radiofrequency (RF) therapies applied over preinjected HAF. MATERIALS AND METHODS: Abdominoplasty skin samples were divided into 8 zones. Intradermal injections of HAF were performed to 7 zones with 1 zone as untreated control. Six of 7 HAF injected zones were then treated with the following devices: 1,540-, 1,550-, 1927-, and 10,600-nm fractional lasers, and fractional bipolar RF delivered through insulated and noninsulated microneedles. After treatment, biopsies were collected for H&E staining. RESULTS: Histology revealed HAF in the mid to deep dermis. Treatment with 1,540-, 1,550-, 1927-, and 10,600-nm lasers did not result in any morphologic changes of HAF, although thermal changes from 1,540- and 1,550-nm lasers were in very close proximity to the filler. The RF devices demonstrated thermal damage of HAF along the microneedle tracks. CONCLUSION: Hyaluronic acid filler is unaffected by fractional lasers in this model. Fractional RF devices, which produce deeper dermal penetrations, will cause thermal damage of HAF. Caution is advised in using microneedle RF over recently injected filler. Study limitations include use of nonfacial skin and lack of inflammatory response in an ex-vivo model.

Extensive CD34-to-CD90 Fibroblast Transition Defines Regions of Cutaneous Reparative, Hypertrophic, and Keloidal Scarring.

BACKGROUND: CD90 fibroblasts have been described arising from and replacing the homeostatic CD34 network in scleroderma, but have not been specifically examined in other forms of cutaneous fibrosis. OBJECTIVES: To address expression, timelines, and spatial relationships of CD90, CD34, and smooth muscle actin (SMA) expressing fibroblasts in scars and to examine for the presence of a CD34-to-CD90 transition. METHODS: One hundred and seventeen scars (reparative/hypertrophic/keloidal) were evaluated for CD90, CD34, and SMA expression. Double-staining immunohistochemistry for CD90/CD34 was performed to identify CD90/CD34 transitioning cells, confirmed by double-color immunofluorescence. In addition, some scars were double-stained with CD90/SMA, CD90/procollagen-1, or SMA/procollagen-1 to evaluate spatial relationships and active collagen synthesis. Expression was graded as diffuse, minority, and negative. RESULTS: Most scars demonstrate a CD90/CD34 pattern, and dual CD90/CD34 fibroblasts were observed in 91% of scars. In reparative scars, CD90 expression reverses to a CD34/CD90 state with maturation. Pathologic scars exhibit prolonged CD90 expression. Both CD90 and SMA fibroblasts collagenize scars, although CD90 fibroblasts are more prevalent. CONCLUSIONS: CD90 fibroblasts likely arise from the resting CD34 fibroblastic network. Actively collagenizing scar fibroblasts exhibit a CD90/CD34 phenotype, which is prolonged in pathologic scars. CD90 fibroblasts are likely important players in cutaneous scarring.

Design and Synthesis of Anti-Cancer Chimera Molecules Based on Marine Natural Products.

In this paper, the chemical conjugation of marine natural products with other bioactive molecules for developing an advanced anti-cancer agent is described. Structural complexity and the extraordinary biological features of marine natural products have led to tremendous research in isolation, structural elucidation, synthesis, and pharmacological evaluation. In addition, this basic scientific achievement has made it possible to hybridize two or more biologically important skeletons into a single compound. The hybridization strategy has been used to identify further opportunities to overcome certain limitations, such as structural complexity, scarcity problems, poor solubility, severe toxicity, and weak potency of marine natural products for advanced development in drug discovery. Further, well-designed marine chimera molecules can function as a platform for target discovery or degradation. In this review, the design, synthesis, and biological evaluation of recent marine chimera molecules are presented.

Pattern analysis of 532- and 1064-nm microlens array-type, picosecond-domain laser-induced tissue reactions in ex vivo human skin.

Optical pulses from picosecond lasers can be delivered to the skin using microlens array (MLA) optics or a diffractive beam splitter to generate multiple, focused, high-intensity, micro-injury zones in the epidermis and dermis. The aim of our study was to histopathologically and immunohistochemically evaluate the patterns of 532- and 1064-nm MLA-type, picosecond laser-induced tissue reactions in human skin immediately after treatment. Picosecond neodymium:yttrium-aluminum-garnet (Nd:YAG) laser treatment using an MLA-type beam at the wavelengths of 532 nm and 1064 nm was delivered ex vivo to human skin. Irradiated skin specimens were then microscopically analyzed after hematoxylin and eosin staining and CD31 and Melan-A immunostaining. A single pulse of 532-nm MLA-type, picosecond laser treatment elicited cystic cavitation lesions at sizes of 83.4 ± 16.5 µm × 70.2 ± 17.3 µm (31-mm distance step) and 91.0 ± 44.7 µm × 81.2 ± 36.3 µm (48-mm distance step) in the epidermis and papillary dermis. Meanwhile, a single pulse of 1064-nm laser treatment generated cystic cavitation lesions at sizes of 107.0 ± 18.1 µm × 83.3 ± 37.4 µm (single-pulse mode) and 100.8 ± 40.4 µm × 83.1 ± 29.4 µm (dual-pulse mode) throughout the lower epidermis and upper papillary dermis. Lining epithelial cells in cystic cavitation lesions in the epidermis showed Melan-A-positive immunoreactivity, while cystic cavitation lesions in the dermis exhibited CD31-positive or CD31-negative/Melan-A-negative immunoreactivity. The present data can be used to predict 532- and 1064-nm MLA-type, picosecond-domain laser-induced tissue reactions in human skin.