A study of the microbiological profile of filler-induced skin necrosis.

Skin necrosis is one of the most severe complications following filler injections, and can result in permanent aesthetic defects. Although an increasing number of studies have addressed the management of dermal filler complications, no study has described the spectrum of microbial pathogens. The aim of this study was to delineate the bacterial profile and prognostic factors of filler-related skin necrosis by reviewing the clinical and microbiological features of these patients. A retrospective medical record review of patients undergoing treatment for skin necrosis induced by fillers was conducted. In total, 10 cases were identified, with injection sites being the nasolabial fold (70%; n = 7), nasal dorsum (20%; n = 2) and nasal tip (10%; n = 1). Reviewing the culture results, the true culture-positive rate was found to be 50% after cases of contamination were excluded. To avoid permanent sequelae, all physicians should be aware of possible secondary infections when treating filler-induced skin necrosis.

Randomized, double-blind, active-controlled, multicentre, phase III clinical trial with two stages to assess the safety and efficacy of letibotulinum toxin a vs. onabotulinum toxin a for subjects with moderate to severe crow's feet.

BACKGROUND: Letibotulinum toxin A (LeBA) was approved by the Ministry of Food and Drug Safety (known as the Korea Food & Drug Administration) for cosmetic indications in 2012. However, the efficacy and safety of this newly introduced LeBA have not been investigated in crow's feet lines (CFL) treatment and standardization before its universal use. OBJECTIVE: The aim of this multicentre, double-blind, randomized, parallel, active-controlled Phase III clinical trial with two stages (ClinicalTrials.gov identifier: NCT03408236) was to investigate the non-inferiority of LeBA vs. the existing onabotulinum toxin A (OnBA) for the treatment of CFL. METHODS: A total of 240 subjects were randomized to either the test (LeBA) or control (OnBA) group. At the baseline and at weeks 4 while maximum smiling (primary efficacy assessment), 8, 12 and 16, investigator's on-site evaluation, independent evaluator, evaluation by the subjects, subjects' satisfaction assessment and safety assessment were performed. RESULTS: At week 4, the response rate of primary efficacy assessment was 69.75% and 68.33% in the test (LeBA) and control (OnBA) groups, respectively, without a significant difference. Other minor secondary evaluation results showed significant differences suggesting that LeBA offered better improvement than OnBA, but the overall results did not show significant differences between the two groups. CONCLUSION: This study showed that LeBA was as effective and safe as OnBA for the treatment of CFL at the same doses.

Systemic contact dermatitis induced by Rhus allergens in Korea: exercising caution in the consumption of this nutritious food.

Systemic contact dermatitis (SCD) develops when a person who was previously sensitized to an allergen is exposed to the same allergen via the systemic route. In East Asia, the use of lacquer for polishing furniture is common and a part of the traditional culture. Contact exposure to tableware polished with Rhus lacquer may lead to sensitization. In Korea, SCD is commonly observed after systemic exposure to Rhus, a nutritious food item consumed because of the common belief of it improving the immune system. In this study, we reviewed the medical records of 21 Korean patients with SCD caused by Rhus ingestion. We found that the most significant epidemiological factor for SCD was the season of the year. Furthermore, 66.67% of the patients presented with leucocytosis and 23.81% showed increased liver enzyme levels. It is important to educate people on the risks associated with the systemic ingestion of Rhus.

Registered Nurses (RNs)' knowledge sharing and decision-making: the mediating role of organizational trust.

AIM: This study study aimed to investigate the effects of explicit and tacit knowledge sharing on clinical decision-making abilities and the mediating role of trust among registered nurses at Korean hospitals. BACKGROUND: Decision-making abilities comprise a key area of nursing practice and link nurses' perceptions with behaviours. INTRODUCTION: Tacit knowledge is embedded within an individual and cannot be expressed or transmitted to other people in a specific form. Over time, new nurses gradually gain experience and tacit knowledge and become experts. Trust, an organizational characteristic, may serve as a potential mediator in the association between knowledge sharing and decision-making abilities among nurses. However, few studies have investigated the mediatory role of trust in this association. METHOD: The data were collected from 210 nurses selected via random sampling. The research instrument in the model included Knowledge-Sharing Behavior, Trust, and Clinical Decision-Making in Nursing Scale. Structural equation modelling was used to analyse the collected data. FINDINGS: The study findings showed that explicit knowledge sharing directly affects decision-making abilities, whereas tacit knowledge sharing is only associated with decision-making abilities when trust plays a mediating role. DISCUSSION: A higher level of organizational trust can improve clinical decision-making abilities via tacit knowledge sharing. CONCLUSION: This study demonstrated that unlike explicit knowledge, which is shared more easily, tacit knowledge sharing does not directly lead to clinical decision-making abilities. A higher level of organizational trust leads to a stronger beneficial effect of tacit knowledge sharing on clinical decision-making abilities. IMPLICATIONS FOR NURSING AND HEALTH POLICY: These findings concerning the mediatory role of trust on the association between knowledge sharing and clinical decision-making abilities provide new knowledge that will allow nurses, managers, and researchers to support the clinical decision-making abilities of nurses.

Split-axilla comparison study of 0.5-MHz, invasive, bipolar radiofrequency treatment using insulated microneedle electrodes for primary axillary hyperhidrosis.

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 < .001; and group × time, P = .048) between treatment group and time. CONCLUSION: PAH can be effectively and safely treated with invasive, multilayered, multiple-pass, 0.5-MHz, bipolar RF treatment, particularly with LC/LP.

Facultative CTCF sites moderate mammary super-enhancer activity and regulate juxtaposed gene in non-mammary cells.

Precise spatiotemporal gene regulation is paramount for the establishment and maintenance of cell-specific programmes. Although there is evidence that chromatin neighbourhoods, formed by the zinc-finger protein CTCF, can sequester enhancers and their target genes, there is limited in vivo evidence for CTCF demarcating super-enhancers and preventing cross talk between distinct regulatory elements. Here, we address these questions in the Wap locus with its mammary-specific super-enhancer separated by CTCF sites from widely expressed genes. Mutational analysis demonstrates that the Wap super-enhancer controls Ramp3, despite three separating CTCF sites. Their deletion in mice results in elevated expression of Ramp3 in mammary tissue through augmented promoter-enhancer interactions. Deletion of the distal CTCF-binding site results in loss of Ramp3 expression in non-mammary tissues. This suggests that CTCF sites are porous borders, allowing a super-enhancer to activate a secondary target. Likewise, CTCF sites shield a widely expressed gene from suppressive influences of a silent locus.

Efficacy and safety of non-invasive body tightening with high-intensity focused ultrasound (HIFU).

BACKGROUND: Noninvasive skin-tightening devices have become increasingly popular in response to increasing demand for improvements in skin laxity and tightening with minimal risk and recovery time. OBJECTIVE: We evaluated the efficacy and safety of HIFU for skin tightening in the face and body. METHODS: A total of 32 Korean subjects enrolled in this prospective clinical trial. The subjects were treated with HIFU to both cheeks, lower abdomen, and thigh. Skin elasticity was measured before and after treatment using a Cutometer (CT575, Courage and Khazaka® , Cologne, Germany). Three blinded, experienced dermatologists evaluated paired pre- and post-treatment (week 4 and 12) photographs according to the Global Aesthetic Improvement Scale (GAIS). Participants also completed self-assessments using GAIS. Subjects rated their pain on a numeric rating scale (NRS) immediately, 7 days, 4 weeks, and 12 weeks after treatment. RESULTS: Skin elasticity measured via a Cutometer was significantly improved 12 weeks after treatment at all treated sites (P<.05). Both IGAIS and SGAIS showed significant improvements 12 weeks after treatment. Immediately after treatment the mean NRS score was 3.00±1.586, but no pain was reported at 4 and 12 weeks post-treatment. No serious adverse effects were observed during the follow-up period. CONCLUSION: HIFU safely and effectively improves skin elasticity and clinical contouring of the face and body.

Immunosuppressive therapy versus alternative donor hematopoietic stem cell transplantation for children with severe aplastic anemia who lack an HLA-matched familial donor.

We compared the outcomes of immunosuppressive treatment (IST) with those of alternative donor hematopoietic stem cell transplantation (HSCT) in children and adolescents with severe aplastic anemia (SAA). The medical records of 42 patients with SAA who received frontline IST (N=19) or frontline HSCT with an alternative donor (N=23) between 1998 and 2012 were analyzed retrospectively. Six patients responded in the frontline IST group, whereas 11 underwent salvage HSCT after IST failure. Twenty-one of 23 patients who underwent frontline HSCT survived without treatment failure. The estimated failure-free survival rate of the frontline HSCT group was higher than that of the frontline IST group (91.3% vs 30.7% respectively, P<0.001). Six of 11 patients who underwent salvage HSCT experienced event-free survival (EFS). The estimated EFS of the frontline HSCT group was higher than that of the salvage HSCT group (91.3% vs 50.9% respectively, P=0.015). The outcome of alternative donor HSCT was better than commonly reported rates, especially in patients who underwent frontline HSCT. These results suggest that frontline alternative donor HSCT may be a better treatment option than IST for children and adolescents with SAA who lack a human leukocyte Ag-matched familial donor.

Transcutaneous pneumatic injection of glucose solution: a morphometric evaluation of in vivo micropig skin and tissue-mimicking phantom.

BACKGROUND: Needle-free, transcutaneous pneumatic injection systems can be used to deliver therapeutic solutions to targeted layers of skin in a minimally invasive manner. METHODS: To evaluate jet infiltration patterns and tissue reactions, 5% isotonic and 20% hypertonic glucose solutions were pneumatically injected into in vivo micropig skin. Gelatin TM phantom was additionally prepared to analyze penetration and dispersion patterns for different experimental settings. RESULTS: As immediate tissue reactions in the in vivo micropig skin, distinct pneumatic injection injury zones (PIIZs) in the dermis, extending from the papillary dermis deep into the dermo-subcutaneous junction, were generated with the 5% and 20% glucose solutions and with pneumatic pressures of 4.64 and 5.7 bars, respectively. PIIZs markedly decreased in appearance at 1 day after treatment, accompanied by inflammatory cell infiltration, and disappeared at 7 days post-treatment with increased collagen and elastin production. In TM phantom study, the PIIZs created by 20% glucose mainly comprised a single, homogenous, round to oval zone, whereas those created by 5% glucose were irregular and multi-lobular. CONCLUSION: The present study suggests that transcutaneous pneumatic injection therapy may exert mechanical stimulatory effects, immediate tissue shrinkage via hypertonic solutions, and late tissue regeneration effects during wound healing.

Prognostic relevance of pretransplant Deauville score on PET-CT and presence of EBV DNA in patients who underwent autologous stem cell transplantation for ENKTL.

High-dose chemotherapy and autologous stem cell transplantation (ASCT) for extranodal natural killer/T-cell lymphoma (ENKTL) is a reasonable option for a subset of patients. The impact of response status, according to positron emission tomography/computed tomography (PET/CT) results and/or presence of circulating EBV DNA prior to ASCT, has not yet been established. We analyzed 27 ENKTL patients with pre-ASCT circulating EBV DNA who had undergone pre-ASCT PET/CT between 2009 and 2014. We classified patients into two groups based on the result of pretransplantation assessment: a favorable risk group (pretransplant five-point Deauville score (DS) of 1-2 based on PET/CT and no detectable EBV DNA) and an unfavorable risk group (DS 1-2 with detectable EBV DNA, DS 3-5 with or without detectable EBV DNA). After a median follow-up of 37 months, overall survival and PFS were significantly different between the two groups (median OS: not reached for favorable risk group vs 7.0 months for unfavorable risk group, P=0.017; median PFS: 16.0 vs 5.0 months, P=0.019). Multivariate analysis revealed that pre-ASCT DS and EBV DNA was the only independent prognostic factor considering stage, IPI and NKPI. Precise assessment of the status of disease before transplantation may provide more benefit from ASCT to ENKTL patients.

ROS1 Kinase Inhibitors for Molecular-Targeted Therapies.

ROS1 is a pivotal transmembrane receptor protein tyrosine kinase which regulates several cellular processes like apoptosis, survival, differentiation, proliferation, cell migration, and transformation. There is increasing evidence supporting that ROS1 plays an important role in different malignancies including glioblastoma, colorectal cancer, gastric adenocarcinoma, inflammatory myofibroblastic tumor, ovarian cancer, angiosarcoma, and non small cell lung cancer; thus, ROS1 has become a potential drug discovery target. ROS1 shares about 49% sequence homology with ALK primary structure; therefore, wide range of ALK kinase inhibitors have shown in vitro inhibitory activity against ROS1 kinase. After Crizotinib approval by FDA for the management of ALK-rearranged lung cancer, ROS1-positive tumors have been focused. Although significant advancements have been achieved in understanding ROS1 function and its signaling pathways plus recent discovery of small molecules modulating ROS1 protein, a vital need of medicinal chemistry efforts is still required to produce selective and potent ROS1 inhibitors as an important therapeutic strategy for different human malignancies. This review focuses on the current knowledge about different scaffolds targeting ROS1 rearrangements, methods to synthesis, and some biological data about the most potent compounds that have delivered various scaffold structures.

Prevalence of type 5 familial hemophagocytic lymphohistiocytosis in Korea and novel mutations in STXBP2.

Familial hemophagocytic lymphohistiocytosis (F-HLH or FHL) is a potentially fatal immune dysregulation syndrome with a heterogeneous genetic background. Most recently, STXBP2 has been identified as the causative gene of type 5 FHL (FHL5) with a worldwide distribution. In this study, we investigated the prevalence of FHL5 in Korea. About 50 Korean pediatric patients with HLH who lacked pathogenic mutations in PRF1, UNC13D, or in STX11 from the previous series of 72 patients with HLH were analyzed for STXBP2 mutations by conventional sequencing analyses. As a result, we found one patient with two novel mutations of STXBP2: c.184A>G and c.577A>C. c.184A>G (p.Asn62Asp) was located within a highly conserved region of the STXBP2 protein and predicted to be deleterious. c.577A>C in exon 7 resulted in incomplete splicing mutation with exon 7 skipping concurrent with exon 7-retained transcript with p.Lys193Gln substitution. The frequency of FHL5 was ~1% (1/72) in Korean pediatric patients with HLH. This is the first study on FHL5 in Korea, and the data from a nationwide patient cohort provide another piece of genetic profiles of FHL.

High intensity focused ultrasound as a potential new modality for the treatment of pigmentary skin disorder.

BACKGROUND/PURPOSE: The clinical skin tightening benefits of high intensity focused ultrasound (HIFU) have been established, but its mechanism of action in pigmented skin disorders remains unknown. We macroscopically and histopathologically investigated dermatological changes after HIFU at different exposure doses in a UVB-induced guinea pig model of hyperpigmentation. METHODS: We applied HIFU irradiation at 0.1 and 0.2 J/cm(2) to UVB-induced spotty hyperpigmentation in guinea pig skin. The therapeutic effects of HIFU were judged based on gross appearance using photography, dermoscopy, and chromametry during a period of 3 weeks after HIFU irradiation. Histological assessments were performed using Fontana-Masson staining 1 day before and 3 weeks after HIFU irradiation. RESULTS: Macroscopically, UVB-induced hyperpigmentation was significantly reduced 2 weeks after HIFU with 0.2 J/cm(2) , and 3 weeks after HIFU with 0.1 J/cm(2) . Histopathologically, the heavy deposition of melanin in the epidermis induced by UVB exposure was reduced 3 weeks after HIFU irradiation. CONCLUSION: We confirmed that HIFU has a positive effect on UVB-induced hyperpigmentation as well as mechanical destructive activity. We suggest that HIFU may be useful as an alternative modality for human patients suffering from skin pigmentary conditions.

Improved methods for selective cryolipolysis results in subcutaneous fat layer reduction in a porcine model.

BACKGROUND/AIMS: Cryolipolysis is a noninvasive method for the selective reduction of localized fat tissues. It has demonstrated efficacy in both clinical and preclinical trials; however, despite its popularity, its mechanisms of action and evaluation methods are not yet fully defined. The purpose of this study was to improved methods for cryolipolysis using a porcine model. METHODS: The abdomens of female PWG micro-pigs were treated with a cooling device (CRYOLIPO II(™)), and we examined the treatment effects using photography, three-dimensional photography, ultrasound, gross, and microscopic pathology, and serum lipid level analyses in order to determine the mechanism of action, efficacy, and safety of CRYOLIPO II(™). RESULTS: CRYOLIPO II(™) successfully reduced abdominal fat in our porcine model. Gross and microscopic histological results confirmed the noninvasive cold-induced selective subcutaneous fat destruction, and showed increases in pre-adipocyte differentiation and in the activation of lipid catabolism. In particular, we found that CRYOLIPO II(™) may increase PPARδ (delta) levels in adipose tissue at 30-60 days post-treatment. CONCLUSION: Fat reduction by cryolipolysis was successfully achieved in our porcine model. Thus, our findings indicate that CRYOLIPO II(™) may be a promising fat reduction device for body contouring and fat reduction in humans, and that cryolipolysis exerts its effects, at least partly, by targeting the PPARδ signaling pathway. These results show that both investigative and diagnostic potentials capacity.