Efficacy and safety of a novel 785 nm picosecond neodymium-doped yttrium aluminum garnet laser for the treatment of facial benign pigmented lesions in Asian skin: a pilot study.

BACKGROUND AND OBJECTIVES: Benign pigmented lesions and a general uneven tone in people with skin of color are growing issues that have been presented to dermatologists. To the best of our knowledge, this is the first controlled study to examine the efficacy and safety of using the newly introduced 785 nm neodymium-doped yttrium aluminum garnet (Nd:YAG) picosecond laser to treat facial benign pigmented lesions in Asian patients with diffractive lens array. MATERIALS AND METHODS: A 785 nm Nd:YAG picosecond laser was used to treat 15 healthy female volunteers older than 18 years who had Fitzpatrick skin types II-IV and facial benign pigmented lesions. Each volunteer received five weekly treatments in dual modes. The clinical improvement was assessed by independent investigators and by objectively measuring the melanin index. RESULTS: After the treatment, the melanin and erythema indices decreased, and the pigmented lesions showed clinical improvements. No serious adverse effects were observed during the study period. CONCLUSIONS: A 785 nm Nd:YAG picosecond laser may be safe and effective in treating facial benign pigmented lesions in Asian skin.

Facial Cutaneous Rosai-Dorfman Disease: Dermoscopic Findings with Successful Surgical Treatment.

Rosai-Dorfman disease (RDD) is a rare non-Langerhans cell histiocytosis characterized by an accumulation of activated histiocytes within the affected tissues. It is a heterogeneous disease that includes the classical (nodal) and extra-nodal variants. The cutaneous form of the disease without the characteristic lymphadenopathy is rare and is often misdiagnosed as other dermatologic diseases. Misdiagnosis as lymphoproliferative and infectious diseases such as lymphoma and tuberculosis have been reported in the literature. Herein, we report a case of facial cutaneous RDD with successful surgical treatment. In addition, we provide dermoscopic findings and literature review as dermoscopy can be a useful adjuvant tool in the diagnosis of cutaneous RDD.

Tumor microenvironment-responsive histidine modified-hyaluronic acid-based MnO2 as in vivo MRI contrast agent.

Tumor microenvironment (TME)-responsive manganese dioxide (MnO2) nanoparticles as a good T1 contrast agent could reduce unwanted toxicity and improve the accuracy of cancer detection. Despite these distinct advantages of MnO2-based nanoparticles, their synthesis involves multi-step processes with relatively long synthesis times. In this study, we synthesized histidine-modified hyaluronic acid (HA-His), and the prepared HA-His conjugates quickly reduce permanganate to MnO2, leading to facile production of HA-His/MnO2 nanoparticles with good water-dispersibility and stability under biological conditions. The synthesized HA-His/MnO2 nanoparticles readily responded to the TME (low pH, high H2O2, and high glutathione), and they were internalized into SCC7 cells with high CD44 expression. Moreover, the systemically administered HA-His/MnO2 nanoparticles with biocompatibility were specifically accumulated in tumor tissues, thereby efficiently enhancing T1 contrast in MRI. Therefore, the HA-His/MnO2 nanoparticles synthesized herein can be used as a promising T1 contrast agent for tumor MR imaging.

Efficacy and Safety of Cold-Induced Noninvasive Targeted Fat Reduction in Pseudogynecomastia.

BACKGROUND: Treatment options for pseudogynecomastia are limited, and the demand for noninvasive breast fat reduction is increasing. OBJECTIVE: We evaluated the efficacy and safety of a cold-induced lipolysis device for treating pseudogynecomastia. METHODS: In this 16-week prospective trial, a total of 15 male patients with pseudogynecomastia were treated twice with cryolipolysis. The primary endpoint was a change in the chest circumference from baseline at posttreatment week 8. Secondary endpoints were changes in body weight, fat thickness assessed using ultrasonography, independent evaluator- and patient-rated improvement, and Simon's gynecomastia class (SGC) grading. RESULTS: The primary assessment, a reduction of 3.05 cm in the mean chest circumference at 8 weeks post-treatment compared to baseline, was statistically significant. The treatment effect was cumulative, with a steady decrease in chest circumference and fat thickness over the 16-week study period. The mean pain score immediately after the first session of treatment was 2.0±1.36, based on a scale of 0~10, with a score of 10 being the worst pain ever experienced. The pain decreased substantially after the end of the procedure. CONCLUSION: Cryolipolysis was demonstrated to be an effective and safe option for reducing breast fat in pseudogynecomastia. Male with mild to moderate breast enlargement without skin excess can be ideal candidates.

PRE-OPerative ECHOcardiograhy for prevention of cardiovascular events after non-cardiac surgery in intermediate- and high-risk patients: protocol for a low-interventional, mixed-cohort prospective study design (PREOP-ECHO).

BACKGROUND: Cardiac evaluation using transthoracic echocardiography before noncardiac surgery is common in real-world practice. However, evidence supporting preoperative echocardiography is lacking. This study aims to evaluate the additional benefit of preoperative echocardiography in predicting postoperative cardiovascular events (CVE) in noncardiac surgery. METHODS: This study is designed as a multicenter, prospective study to assess the utility of preoperative echocardiography in patients undergoing intermediate- or high-risk noncardiac surgery. This trial comprises two studies: (1) a randomized controlled trial (RCT) for patients undergoing intermediate-risk surgery with fewer than three clinical risk factors from the revised cardiac risk index (intermediate-risk group) and (2) a prospective cohort study for patients undergoing intermediate-risk surgery with three or more clinical risk factors, or who undergo high-risk surgery regardless of the number of clinical risk factors (high-risk group). We hypothesize that the use of preoperative echocardiography will reduce postoperative CVEs in patients undergoing intermediate- to high-risk surgery through discovery of and further intervention for unexpected cardiac abnormalities before elective surgery. A total of 2330 and 2184 patients will be enrolled in the two studies. The primary endpoint is a composite of all-cause death; aborted sudden cardiac arrest; type I acute myocardial infarction; clinically diagnosed unstable angina; stress-induced cardiomyopathy; lethal arrhythmia, such as sustained ventricular tachycardia or ventricular fibrillation; and/or newly diagnosed or acutely decompensated heart failure within 30 days after surgery. DISCUSSION: This study will be the first large-scale prospective study examining the benefit of preoperative echocardiography in predicting postoperative CVE. The PREOP-ECHO trial will help doctors identify patients at risk of postoperative CVE using echocardiography and thereby reduce postoperative CVEs. TRIAL REGISTRATION: The Clinical Research Information Service KCT0006279 for RCT and KCT0006280 for prospective cohort study. Registered on June 21, 2021.

Utilization of Ultrasonography in Dermatology: Two Case Reports of Calcinosis Cutis.

Development of newer generation of cost-effective ultrasonic devices in recent years has increased the use of ultrasonography in dermatology. Several lesions can be diagnosed and managed using ultrasonography. Calcinosis cutis involves the deposition of insoluble calcium salts in the cutaneous and subcutaneous tissues. On ultrasonography, it specifically presents as hyperechoic deposits with a posterior acoustic shadowing artifact due to the acoustic properties of calcium. A 62-year-old female patient presented with a solitary, skin-colored, palpable nodule on the inner side of the right lower leg. The lesion was beneath the intact skin and detectable only on palpation. However, ultrasonography demonstrated a clear delineation of the lesion, showing hyperechoic deposits with a posterior acoustic shadow (15 MHz, linear probe). Skin biopsy and curettage were performed, revealing histological features consistent with calcinosis cutis. Four weeks after the procedure, ultrasonography performed to evaluate the outcome of treatment, showed recurrence. Another 18-year-old female patient presented with a skin-colored deep-seated nodule on the left temple. On ultrasonography, linear hyperechoic deposits with a posterior acoustic shadow were visible. Skin biopsy was performed, and histopathologic features showed calcified material in the subcutaneous tissue. These two cases of calcinosis cutis highlight the diagnostic value of ultrasonography in dermatology.

Phase I Trial of Intra-arterial Administration of Autologous Bone Marrow-Derived Mesenchymal Stem Cells in Patients with Multiple System Atrophy.

BACKGROUND: This study is aimed at investigating the safety and tolerability of the intra-arterial administration of autologous bone marrow-derived mesenchymal stem cells (BM-MSCs) in patients with multiple system atrophy- (MSA-) cerebellar type (MSA-C). METHODS: This was a single-center, open-label phase I clinical trial in patients with MSA-C. A three-stage dose escalation scheme (low-dose, 3.0 × 105 cells/kg; medium-dose, 6.0 × 105 cells/kg; high-dose, 9.0 × 105 cells/kg) was applied to determine the maximum tolerated dose of intra-arterial administration of BM-MSCs based on the no-observed-adverse-effect level derived from the toxicity study. The occurrence of adverse events was evaluated 1 day before and 1, 14, and 28 days after BM-MSC therapy. Additionally, we assessed changes in the Unified MSA Rating Scale (UMSARS) score 3 months after BM-MSC treatment. RESULTS: One serious adverse drug reaction (ADR) of leptomeningeal enhancement following the intra-arterial BM-MSC administration occurred in one patient in the low-dose group. The safety review of the Internal Monitoring Committee interpreted this as radiological evidence of the blood-brain barrier permeability for MSCs. No other ADRs were observed in the medium- or high-dose groups. In particular, no ischemic lesions on diffusion-weighted images were observed in any of the study participants. Additionally, the medium- and high-dose groups tended to show a slower increase in UMSARS scores than the low-dose group during the 3-month follow-up. CONCLUSION: The present study confirmed that a single intra-arterial administration of autologous BM-MSCs is a safe and promising neuroprotective strategy in patients with MSA-C.

A catenin of the plakophilin-subfamily, Pkp3, responds to canonical-Wnt pathway components and signals.

Vertebrate beta-catenin plays a key role as a transducer of canonical-Wnt signals. We earlier reported that, similar to beta-catenin, the cytoplasmic signaling pool of p120-catenin-isoform1 is stabilized in response to canonical-Wnt signals. To obtain a yet broader view of the Wnt-pathway's impact upon catenin proteins, we focused upon plakophilin3 (plakophilin-3; Pkp3) as a representative of the plakophilin-catenin subfamily. Promoting tissue integrity, the plakophilins assist in linking desmosomal cadherins to intermediate filaments at desmosome junctions, and in common with other catenins they perform additional functions including in the nucleus. In this report, we test whether canonical-Wnt pathway components modulate Pkp3 protein levels. We find that in common with beta-catenin and p120-catenin-isoform1, Pkp3 is stabilized in the presence of a Wnt-ligand or a dominant-active form of the LRP6 receptor. Pkp3's levels are conversely lowered upon expressing destruction-complex components such as GSK3ß and Axin, and in further likeness to beta-catenin and p120-isoform1, Pkp3 associates with GSK3beta and Axin. Finally, we note that Pkp3-catenin trans-localizes into the nucleus in response to Wnt-ligand and its exogenous expression stimulates an accepted Wnt reporter. These findings fit an expanded model where context-dependent Wnt-signals or pathway components modulate Pkp3-catenin levels. Future studies will be needed to assess potential gene regulatory, cell adhesive, or cytoskeletal effects.

Sildenafil-triggered multi-culprit ST-segment elevation myocardial infarction: a case report.

Sildenafil citrate and its generic forms are widely used to treat erectile dysfunction worldwide. Sildenafil citrate associated myocardial infarction is rarely reported in patients with no previous coronary artery disease. Herein, we present a case of a 40-year-old man with no cardiovascular risk factors other than heavy smoking and heavy drinking with no known previous ischemic symptoms, who had an ST-segment elevation myocardial infarction after receiving sildenafil citrate. From this case report, we emphasize that as sildenafil is increasingly being used as a recreational drug as it is widely available without a physician's prescription, physicians should be aware that it may reveal the underlying cardiovascular problem. Thus, physicians must also consider the underlying medical conditions when prescribing sildenafil.

In vivo evaluation of novel particle-free polycaprolactone fillers for safety, degradation, and neocollagenesis in a rat model.

Dermal fillers have become popular due to the increased demand for skin rejuvenation products. Polycaprolactone (PCL), a newly developed bioresorbable medical polymer, has emerged as a durable and safe dermal filler. However, available PCL fillers cause irritation; carrier gels can coagulate PCL particles, block the injection needle, and cause nonhomogeneity of particle suspensions that could be responsible for the observed side effects. To relieve pain, premixing PCL filler with lidocaine. However, this formulation changes the property of the CMC portion of the PCL filler, and possibly results in an uneven suspension of the PCL particles. Hence, a particle-free PCL homogeneously solubilized in water was developed to overcome these limitations. This study aimed to assess the in vivo safety, biodegradability, and neocollagenesis ability of a novel PCL filler, DLMR01 using a rat model. Fillers were characterized after injecting a vehicle control or DLMR01 using a digital camera, folliscope, and a three-dimensional profiling system. Biopsy was performed to evaluate biocompatibility and neocollagenesis. Skin elasticity was measured using a Cutometer. DLMR01 caused no needle occlusion by particle aggregation or laborious injectability. Filler nodules dispersed to surrounding tissues within 6 hours without further granuloma formation. Histological inspection revealed no tissue residual material or foreign body reaction during the 12-week test period. DLMR01 increased dermal thickness, collagen regeneration, and skin elasticity. In conclusion, this study demonstrates the potential of DLMR01 for dermal rejuvenation in a rat model.

Intralesional Electrocoagulation With Insulated Microneedle for the Treatment of Periorbital Syringomas: A Retrospective Analysis.

BACKGROUND: Conventional treatment options for periorbital syringomas are often unsatisfactory because of inevitable surface damage from the procedure and frequent recurrence rate of the tumors. OBJECTIVES: The authors sought to ascertain the efficacy and safety of intralesional electrosurgery utilizing a monopolar radiofrequency device with a single insulated microneedle for the treatment of periorbital syringomas. METHODS: A retrospective analysis was performed employing data from medical records, routine questionnaires, and clinical photographs of 55 patients with periorbital syringoma who underwent intralesional electrosurgery. RESULTS: Approximately one-half of the patients (50.9%) experienced marked resolution after 1 treatment. The lesion clearance rate increased and lesion severity decreased each time the treatment was repeated. No persistent therapy-related adverse event was found except transient erythema or crusting. CONCLUSIONS: Intralesional electrosurgery with insulated microneedle is an effective and safe treatment option for periorbital syringomas.

Efficacy and Safety of a Novel Botulinum Toxin A for Masseter Reduction: A Randomized, Double-Blind, Placebo-Controlled, Optimal Dose-Finding Study.

BACKGROUND: A wide lower face and a square jaw are considered esthetic problems, particularly in Asia. OBJECTIVE: To investigate the optimal dose of a novel botulinum toxin (prabotulinum toxin A) for treating masseteric hypertrophy. METHODS: Ninety subjects with masseteric hypertrophy were randomly divided into 5 groups and treated with placebo (A, normal saline) or prabotulinum toxin A (B: 24, C: 48, D: 72, and E: 96 units). Photography, ultrasonography, and 3-dimensional imaging were performed before and after injection at baseline and at 4, 8, 12, and 16 weeks after treatment. The participants also rated their satisfaction. RESULTS: Masseter thickness significantly reduced in all groups at 12 weeks, compared with that in the placebo group. A dose-dependent reduction in masseter thickness was observed at the resting and maximal clenching positions. Sonography and 3-dimensional imaging revealed a gradual reduction in masseter thickness and volume, respectively, during the first 12 weeks. Despite being slightly effective, a dose of 24 units might be insufficient for resolving square face problems. Patients in Group E reported discomfort during jaw movement. CONCLUSION: Prabotulinum toxin A could effectively improve lower face contour without major complications, with an optimal dose of 48 to 72 units, followed by reinjection after 12 weeks.

Oily sensitive skin: A review of management options.

BACKGROUND: Due to the ever-increasing demands for the personalized care, people seek for the tailored management according to the accurate identification of their skin type. The Baumann Skin Type Indicator, which was proposed by Leslie Baumann, is composed of four parameters: oily or dry, resistant or sensitive, pigmented or nonpigmented, and wrinkled or tight. Among these, oily sensitive skin experiences significant discomfort and resists ordinary treatment. AIMS: In this article, we will review the clinical manifestations, underlying pathogenesis and recommendations on treatment options that may be utilized to help patients with oily sensitive skin. PATIENTS/METHODS: Literature search was conducted using PubMed. The literature concerning Baumann Skin Type Indicator and oily sensitive skin type were considered. RESULTS: Oily sensitive (OS)-type skin is a complex of oily and sensitive skin that causes significant discomfort and undergoes stubborn resistance to treatments. Sebum dysfunction and hypersensitivity may play a key role in the development of sensitive skin. Considering the pathogenesis of OS-type skin, treatment should focus on both seborrhea and hypersensitivity. CONCLUSION: Clinicians can effectively treat the oily sensitive skin by understanding underlying pathogenesis of it. Further investigations are necessary to reach a consensus on the basic pathophysiology and optimal management guidelines for oily sensitive skin.

Efficacy and Safety of High-Intensity Focused Ultrasound for Noninvasive Abdominal Subcutaneous Fat Reduction.

BACKGROUND: Demand for noninvasive body contouring has increased. OBJECTIVE: We evaluated the efficacy and safety of a thermal high-intensity focused ultrasound (HIFU) device for abdominal body shaping. PATIENTS AND METHODS: Adults with a body mass index ≤30 kg/m and an abdominal subcutaneous fat tissue thickness ≥2.5 cm were enrolled for HIFU treatment at energy levels of 150 J/cm (first session) and 135 J/cm (second session). The primary end point was a change from baseline waist circumference at post-treatment Week 8. Secondary efficacy end points were: changes in body weight, waist/hip ratio, and fat thickness assessed by ultrasound, caliper, and a fat CT scan. The Global Aesthetic Improvement Scale was evaluated by both investigators and subjects. RESULTS: The primary assessment achieved statistical significance, showing a reduction of 3.43 cm in mean waist circumference. The treatment effect was cumulative, with a steady decrease in waist circumference and fat thickness. The mean pain scores immediately after treatment were 4.45 ± 2.74 on a scale of 1 to 10 with 10 being the most painful, which decreased to 1.10 ± 1.33 after 1 week. CONCLUSION: High-intensity focused ultrasound is an effective and safe treatment modality for reducing waist circumference in nonobese individuals with focal fat accumulation.

Prospective, preclinical comparison of the performance between radiofrequency microneedling and microneedling alone in reversing photoaged skin.

BACKGROUND: There is a tremendous demand for dermal rejuvenation with minimal invasiveness and patient downtime. AIMS: In this study, we evaluated the performance of nonfractional monopolar radiofrequency for the improvement of photoaged skin texture and wrinkles. METHODS: In total, 32 6-week-old female hairless mice were randomized into four groups of eight mice each: (a) healthy control, (b) UVB-exposed, (c) UVB + microneedling, and (d) UVB + microneedle RF. After applying each treatment modality, skin surface was globally investigated and histologically evaluated senile skin change. Immunohistochemistry was tested with the primary antibody to collagen type I and III. RESULTS: After UVB exposure, the Ra value was significantly increased, leading to clinical development of wrinkles with xerotic scales. Depth and number of wrinkles showed gradual improvement in RF-treated mice. The mean Ra value of the RF-treated group decreased significantly. The RF-treated group showed decreased epidermal thickness, suppression of dermal inflammatory cell infiltration, and increased density of collagen fibers and amount of elastic fibers. CONCLUSIONS: Microneedle RF treatment alleviates photoaged skin texture and wrinkles in this mouse model. To the best of our knowledge, our results provide the first evidence that a nonfractional monopolar microneedle radiofrequency device may contribute to the treatment of UV-damaged skin.

Spheroid-Induced Epithelial-Mesenchymal Transition Provokes Global Alterations of Breast Cancer Lipidome: A Multi-Layered Omics Analysis.

Metabolic rewiring has been recognized as an important feature to the progression of cancer. However, the essential components and functions of lipid metabolic networks in breast cancer progression are not fully understood. In this study, we investigated the roles of altered lipid metabolism in the malignant phenotype of breast cancer. Using a spheroid-induced epithelial-mesenchymal transition (EMT) model, we conducted multi-layered lipidomic and transcriptomic analysis to comprehensively describe the rewiring of the breast cancer lipidome during the malignant transformation. A tremendous homeostatic disturbance of various complex lipid species including ceramide, sphingomyelin, ether-linked phosphatidylcholines, and ether-linked phosphatidylethanolamine was found in the mesenchymal state of cancer cells. Noticeably, polyunsaturated fatty acids composition in spheroid cells was significantly decreased, accordingly with the gene expression patterns observed in the transcriptomic analysis of associated regulators. For instance, the up-regulation of SCD, ACOX3, and FADS1 and the down-regulation of PTPLB, PECR, and ELOVL2 were found among other lipid metabolic regulators. Significantly, the ratio of C22:6n3 (docosahexaenoic acid, DHA) to C22:5n3 was dramatically reduced in spheroid cells analogously to the down-regulation of ELOVL2. Following mechanistic study confirmed the up-regulation of SCD and down-regulation of PTPLB, PECR, ELOVL2, and ELOVL3 in the spheroid cells. Furthermore, the depletion of ELOVL2 induced metastatic characteristics in breast cancer cells via the SREBPs axis. A subsequent large-scale analysis using 51 breast cancer cell lines demonstrated the reduced expression of ELOVL2 in basal-like phenotypes. Breast cancer patients with low ELOVL2 expression exhibited poor prognoses (HR = 0.76, CI = 0.67-0.86). Collectively, ELOVL2 expression is associated with the malignant phenotypes and appear to be a novel prognostic biomarker in breast cancer. In conclusion, the present study demonstrates that there is a global alteration of the lipid composition during EMT and suggests the down-regulation of ELOVL2 induces lipid metabolism reprogramming in breast cancer and contributes to their malignant phenotypes.

Comparative Evaluation of the Biodegradability and Wrinkle Reduction Efficacy of Human-Derived Collagen Filler and Hyaluronic Acid Filler.

BACKGROUND: The development of fillers for wrinkle prevention is growing to meet rising demands to reduce the aging of skin. OBJECTIVE: In this experiment, we confirmed the effects of human collagen and hyaluronic acid filler biodegradation for wrinkle reduction using a photo-aging mouse model. MATERIALS AND METHODS: A total of 10 hairless mice (SKH1-Hrhr) were randomly divided into two groups and injected with hyaluronic acid and human-derived collagen filler. At 0, 2, 4, 8, and 12 weeks, PRIMOSlite®, folliscope, and MRI were used to evaluate the biodegradability of the fillers after the injections. We also studied the photo-aging mouse model for skin roughness and histological evaluation and confirmed that the filler injection had excellent anti-wrinkle effects. RESULTS: Human-derived collagen fillers had excellent biodegradability compared to that of hyaluronic acid fillers. The skin surface roughness in the photo-aging mouse models was significantly reduced after injections of human-derived collagen filler. CONCLUSION: Our results showed that the human-derived collagen filler had excellent biodegradability and effectively reduced wrinkle formation in a photo-aging mouse model. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .