Dermoscopic features of an unusual case of targetoid hemosiderotic nevus / 고신대학교의과대학학술지

Targetoid hemosiderotic nevus (THN) is a rare variant of melanocytic nevus, characterized by a sudden development of a targetoid ecchymotic halo around a pre-existing nevus. THN clinically raises concern for malignant transformation due to its abrupt change in color and size. THN should be distinguished from other diseases showing a peripheral halo, including targetoid hemosiderotic hemangioma, halo nevus, and Meyerson nevus. Dermoscopy can help clinicians to differentiate THN from these diseases. The typical dermoscopic features of THN are known to be divided into two distinctive areas: the central melanocytic area and the peripheral ecchymotic area. In our case, dermoscopy revealed a novel bull’s eye pattern composed of a central area with characteristic features of benign melanocytic nevus, an intermediated white circular ring, and a peripheral milky red area. When a sudden change occurs in a pre-existing nodule showing targetoid features, dermoscopy should be considered before conducting a biopsy or surgical intervention.

Laboratory information management system for COVID-19 non-clinical efficacy trial data / 한국실험동물학회지

Background@#As the number of large-scale studies involving multiple organizations producing data has steadily increased, an integrated system for a common interoperable format is needed. In response to the coronavirus disease 2019 (COVID-19) pandemic, a number of global efforts are underway to develop vaccines and therapeutics. We are therefore observing an explosion in the proliferation of COVID-19 data, and interoperability is highly requested in multiple institutions participating simultaneously in COVID-19 pandemic research. @*Results@#In this study, a laboratory information management system (LIMS) approach has been adopted to systemically manage various COVID-19 non-clinical trial data, including mortality, clinical signs, body weight, body temperature, organ weights, viral titer (viral replication and viral RNA), and multiorgan histopathology, from multiple institutions based on a web interface. The main aim of the implemented system is to integrate, standardize, and organize data collected from laboratories in multiple institutes for COVID-19 non-clinical efficacy testings. Six animal biosafety level 3 institutions proved the feasibility of our system. Substantial benefits were shown by maximizing collaborative high-quality non-clinical research. @*Conclusions@#This LIMS platform can be used for future outbreaks, leading to accelerated medical product development through the systematic management of extensive data from non-clinical animal studies.

PRR16/Largen Induces Epithelial-Mesenchymal Transition through the Interaction with ABI2 Leading to the Activation of ABL1 Kinase

Advanced or metastatic breast cancer affects multiple organs and is a leading cause of cancer-related death. Cancer metastasis is associated with epithelial-mesenchymal metastasis (EMT). However, the specific signals that induce and regulate EMT in carcinoma cells remain unclear. PRR16/Largen is a cell size regulator that is independent of mTOR and Hippo signalling pathways. However, little is known about the role PRR16 plays in the EMT process. We found that the expression of PRR16 was increased in mesenchymal breast cancer cell lines. PRR16 overexpression induced EMT in MCF7 breast cancer cells and enhances migration and invasion. To determine how PRR16 induces EMT, the binding proteins for PRR16 were screened, revealing that PRR16 binds to Abl interactor 2 (ABI2). We then investigated whether ABI2 is involved in EMT. Gene silencing of ABI2 induces EMT, leading to enhanced migration and invasion. ABI2 is a gene that codes for a protein that interacts with ABL proto-oncogene 1 (ABL1) kinase. Therefore, we investigated whether the change in ABI2 expression affected the activation of ABL1 kinase. The knockdown of ABI2 and PRR16 overexpression increased the phosphorylation of Y412 in ABL1 kinase. Our results suggest that PRR16 may be involved in EMT by binding to ABI2 and interfering with its inhibition of ABL1 kinase. This indicates that ABL1 kinase inhibitors may be potential therapeutic agents for the treatment of PRR16-related breast cancer.

Loss of EMP2 Inhibits Melanogenesis of MNT1 Melanoma Cells via Regulation of TRP-2

Melanogenesis is the production of melanin from tyrosine by a series of enzyme-catalyzed reactions, in which tyrosinase and DOPA oxidase play key roles. The melanin content in the skin determines skin pigmentation. Abnormalities in skin pigmentation lead to various skin pigmentation disorders. Recent research has shown that the expression of EMP2 is much lower in melanoma than in normal melanocytes, but its role in melanogenesis has not yet been elucidated. Therefore, we investigated the role of EMP2 in the melanogenesis of MNT1 human melanoma cells. We examined TRP-1, TRP-2, and TYR expression levels during melanogenesis in MNT1 melanoma cells by gene silencing of EMP2. Western blot and RT-PCR results confirmed that the expression levels of TYR and TRP-2 were decreased when EMP2 expression was knocked down by EMP2 siRNA in MNT1 cells, and these changes were reversed when EMP2 was overexpressed. We verified the EMP2 gene was knocked out of the cell line (EMP2 CRISPR/Cas9) by using a CRISPR/Cas9 system and found that the expression levels of TRP-2 and TYR were significantly lower in the EMP2 CRISPR/Cas9 cell lines. Loss of EMP2 also reduced migration and invasion of MNT1 melanoma cells. In addition, the melanosome transfer from the melanocytes to keratinocytes in the EMP2 KO cells cocultured with keratinocytes was reduced compared to the cells in the control coculture group. In conclusion, these results suggest that EMP2 is involved in melanogenesis via the regulation of TRP-2 expression.

Physician Compliance with Nutrition Support Team Recommendations: Effects on the Outcome of Treatment for Critically Ill Patients

Purpose@#Attending physicians in Korea are aware of the existence of the Nutrition Support Team (NST), but even when the NST are consulted, compliance with their recommendations may be low. This study was performed to identify physicians’ compliance with the NST advice and how this affected the outcome of treatment for critically ill patients. @*Methods@#This study was a retrospective observational study. Critically ill patients who were older than 18 years, younger than 90 years, and had been admitted and managed in the intensive care unit were selected for this study. Patients were assigned to either the compliance group or the non-compliance group according to physician compliance with the NST advice. Each group were compared using variables such as calorie supply, protein supply, laboratory findings, hospital stay, 30-day mortality, and survival rate. @*Results@#The compliance group (81% of cases) was supplied with a significantly higher energy (1,146.36 ± 473.45 kcal vs. 832.45 ± 364.28 kcal, p < 0.01) and a significantly higher protein (55.00 ± 22.30 g/day vs. 42.98 ± 24.46 g/day, p = 0.04) compared with the non-compliance group. There was no significant difference in the basic demographics between groups, although the compliance group had a better outcome in the 30-day mortality rate (8% vs. 26%, p = 0.02), and in survival beyond 1 year (Crude model, hazard ratio: 2.42, CI: 1.11-5.29). @*Conclusion@#Critically ill patients whose attending physician complied with the NST advice, received an increased energy intake and supply of protein which was positively associated with survival.

A Case Report on the Dermoscopic Features of Spark’s Nevus

Spark’s nevus is a compound word composed of Spitz nevus and Clark’s nevus. It is one of the combined melanocytic nevi which is more common in female and usually presents as a sharp circumscribed hyperpigmented macule on the lower extremities. On histopathologic findings, both cytologic features of Spitz nevus characterized as large spindle or epithelioid melanocytes containing large nuclei with abundant cytoplasm, and architecture of Clark’s nevus characterized as elongation of rete ridges, bridging of the nests, concentric and lamellar fibrosis can be seen. A 24-year-old female presented with an asymptomatic, solitary, dark-brown-colored papule surrounded by brownish patch that looked similar to dysplastic nevus or malignant melanoma on the buttock. On dermoscopic examination, it showed brown-to-black globules, diffuse homogenous pigmentation with blue-white structures, and a surrounding brownish reticular pattern that faded away. On histopathologic findings, overall asymmetrical structure, epithelioid large melanocytes containing large nuclei with abundant cytoplasm, and Kamino body were seen in the central portion. Also, lentiginous hyperplasia, bridging of the nests composed of melanocytes containing foamy cytoplasm, concentric and lamellar fibrosis along with the elongation of rete ridge, and perivascular lymphocytic infiltration were seen in the peripheral portion. The diagnosis of Spark’s nevus was made. Following its definition, this combined nevus is diagnosed histopathologically, but the clinicodermoscopic features have not been well described. Herein, we report a case of Spark’s nevus in which dermoscopy was helpful for differentiating it from malignant melanoma.

Erratum: Folliculotropic Mycosis Fungoides in 20 Korean Cases: Clinical and Histopathologic Features and Response to Ultraviolet A-1 and/or Photodynamic Therapy

In the originally published version of this article, complete anonymity was not achieved.

Folliculotropic Mycosis Fungoides in 20 Korean Cases: Clinical and Histopathologic Features and Response to Ultraviolet A-1 and/or Photodynamic Therapy

BACKGROUND: Folliculotropic mycosis fungoides (FMF) is a variant of mycosis fungoides (MF) that is characterized clinically by variable types of skin eruptions, including plaques, acneiform lesions, and alopecic patches. Histopathologically, FMF is characterized by folliculotropic infiltrates. OBJECTIVE: This study was conducted to scrutinize the clinical and histopathologic features of FMF in Koreans and the responses to phototherapy. METHODS: Twenty Koreans diagnosed with MF who had histopathologic evidence of folliculotropism were enrolled. RESULTS: Eighteen patients had head-and-neck-region infiltration, while five had solitary lesion. In all patients, the atypical lymphocytic infiltrate had a perifollicular distribution. Twelve patients were treated with ultraviolet A (UVA)-1. Eleven of these 12 patients with early-stage FMF experienced >80% improvement (8: complete remission; 3: partial remission). Four patients, including 2 who relapsed after UVA-1, were treated with photodynamic therapy (PDT), reaching complete remission after PDT. CONCLUSION: As FMF has variable clinical presentations, skin biopsy is required to confirm the diagnosis. And both UVA-1 and methyl aminolevulinate-PDT are clinically effective in treatment of early-stage FMF.

Degos-Like Lesions Associated with Systemic Lupus Erythematosus

Degos disease, also referred to as malignant atrophic papulosis, was first described in 1941 by Köhlmeier and was independently described by Degos in 1942. Degos disease is characterized by diffuse, papular skin eruptions with porcelain-white centers and slightly raised erythematous telangiectatic rims associated with bowel infarction. Although the etiology of Degos disease is unknown, autoimmune diseases, coagulation disorders, and vasculitis have all been considered as underlying pathogenic mechanisms. Approximately 15% of Degos disease have a benign course limited to the skin and no history of gastrointestinal or central nervous system (CNS) involvement. A 29-year-old female with history of systemic lupus erythematosus (SLE) presented with a 2-year history of asymptomatic lesions on the dorsum of all fingers and both knees. The patient had only skin lesions and no gastrointestinal or CNS vasculitis symptoms. Her skin lesions were umbilicated, atrophic porcelain-white lesions with a rim of erythema. On the basis of clinical, histologic, and laboratory findings, a diagnosis of Degos-like lesions associated with SLE was made. The patient had been treated for SLE for 7 years. Her treatment regimen was maintained over a 2 month follow-up period, and the skin lesions improved slightly with no development of new lesions.