Background: Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined. Methods: This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months. Conclusion This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.

Langerhans cell histiocytosis (LCH) is a rare inflammatory neoplasia of the dendritic cells that can affect the whole body and commonly affect the pediatric age. Adult onset LCH is relatively rare, and the cutaneous form without any other organ involvement is much more uncommon. A 62-year-old woman visited the clinic presenting pruritic erythematous papule and nodules on the whole body, from which she suffered for several years. Skin biopsy showed hyperkeratosis, mild acanthosis, intra-epidermal tumor cell infiltration, and band-like tumor cell infiltration. Cells infiltrating the epidermis and dermis showed characteristics consistent with Langerhans cells. Immunohistochemical analysis revealed tumor cells highlighted with CD1a and S-100, but not with CD68, and therefore, diagnosed as LCH. The patient showed no evidence of any other organ manifestation, which led the final diagnosis of single-system LCH. This case highlights a rare adult-onset cutaneous form of single-system LCH with skin manifestations very similar to prurigo nodularis.

Background: In the current situation, where severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is rapidly spreading, vaccines for coronavirus are thought to be the most effective approach to containing the situation.However, limited comparative data are available on cutaneous adverse reactions to coronavirus vaccination in Korea. Objective: We retrospectively reviewed the clinical and histopathological characteristics of adverse cutaneous reactions following coronavirus vaccination. Methods: We retrospectively reviewed the clinical and histopathological characteristics of 95 patients who were vaccinated with Pfizer, Moderna, AstraZeneca, and Janssen vaccines and visited the Dermatology Departments of Dankook University Hospital and Chungnam National University Hospital. Results: The mean age was 49.3±17.5 years. Patients who received the AstraZeneca vaccine had an average age of 61.7±10.8 years, significantly higher than those in the Pfizer (44.1±18.7 years) and Moderna (42.5±15.0 years) groups (p＜0.001). Of the 95 patients, 36 (37.9%) were diagnosed with urticaria, 24 (25.3%) with morbilliform eruption, 18 (18.9%) with petechiae and purpura, and eight (8.4%) with erythema multiforme. Additionally, there were diagnoses of erythema nodosum, alopecia areata, eczema, generalized pustular psoriasis, acute generalized exanthematous pustulosis, pityriasis rosea, and bullous pemphigoid. In the AstraZeneca-vaccinated group, the proportion of morbilliform eruptions was significantly higher than that in the Pfizer- and Moderna-vaccinated groups (p=0.008). The Pfizer- and Moderna-vaccinated groups had higher rates of urticaria than did the AstraZeneca-vaccinated group. However, this difference was not statistically significant (p=0.083). Conclusion This study described the clinical characteristics of cutaneous adverse reactions after coronavirus vaccination.

A 62-year-old man with multiple myeloma visited our clinic with multiple painful erythematous to purpuric nodules on his whole body. He received a skin biopsy which showed septal and lobular inflammation with vasculitis, and multiple amoebic organisms were found.Polymerase chain reaction and culture were performed and an Acanthamoeba triangularis infection was diagnosed. This is the first report on cutaneous acanthamoebiasis caused by A. triangularis, suggesting that A. triangularis should be regarded as a clinical pathogen that can cause ocular as well as disseminated infection.

Background: Tacrolimus is the most commonly used immunosuppressive drug in solid organ transplantation. After administering a conventional twice-daily dose of tacrolimus, peak levels were achieved within the first 1.5 to 2 hours. A group of patients showed different early absorption phase of tacrolimus after kidney transplantation. Methods: Trough(C0 ) and 1.5-hour blood levels (C1.5 ) of tacrolimus were measured in 95 kidney transplantation recipients. Patients with a C1.5 /C0 < 1.5 and > 1.5 were defined as those having flat pattern peaks and as controls, respectively. Transplantation outcomes were compared between the groups. Whole exome sequencing was performed to investigate the genetic susceptibility to flat pattern peaks. Results: Twenty-eight patients showed flat pattern peaks. The mean C1.5 /C0 values were 1.13 ± 0.22 and 3.78 ± 1.25 in the flat pattern peak and control groups, respectively. In multivariate analysis, flat pattern peak was an independent risk factor for biopsy-proven acute rejection (BPAR) and/or borderline change (P = 0.014). Patients having flat pattern peaks showed significantly lower post-transplant 36-month estimated glomerular filtration rate (P = 0.001). Two single nucleotide variants in ABCB1 genes, rs1922242 and rs2235035, were associated with flat pattern peaks (P = 0.019 and P = 0.027, respectively). Conclusion Both of C1.5 and C0should be measured to distinguish the patients showing unique initial absorption. A C1.5 /C0 ratio lower than 1.5 was associated with an increased risk of BPAR and/or borderline change. Single nucleotide variants s in ABCB1 gene might influence the flat pattern peaks of tacrolimus absorption.

Purpose: To assess conventional MRI features associated with residual soft-tissue sarcomas following unplanned excision (UPE), and to compare the diagnostic performance of conventional MRI only with that of MRI including diffusion-weighted imaging (DWI) for residual tumors after UPE. Materials and Methods: We included 103 consecutive patients who had received UPE of a soft-tissue sarcoma with wide excision of the tumor bed between December 2013 and December 2019 and who also underwent conventional MRI and DWI in this retrospective study. The presence of focal enhancement, soft-tissue edema, fascial enhancement, fluid collections, and hematoma on MRI including DWI was reviewed by two musculoskeletal radiologists. We used classification and regression tree (CART) analysis to identify the most significant MRI features. We compared the diagnostic performances of conventional MRI and added DWI using the McNemar test. Results: Residual tumors were present in 69 (66.9%) of 103 patients, whereas no tumors were found in 34 (33.1%) patients. CART showed focal enhancement to be the most significant predictor of residual tumors and correctly predicted residual tumors in 81.6% (84/103) and 78.6% (81/103) of patients for Reader 1 and Reader 2, respectively. Compared with conventional MRI only, the addition of DWI for Reader 1 improved specificity (32.8% vs. 56%, 33.3% vs. 63.0%, P < 0.05), decreased sensitivity (96.8% vs. 84.1%, 98.7% vs. 76.7%, P < 0.05), without a difference in diagnostic accuracy (76.7% vs. 74.8%, 72.9% vs. 71.4%) in total and in subgroups. For Reader 2, diagnostic performance was not significantly different between the sets of MRI (P > 0.05). Conclusion After UPE of a soft-tissue sarcoma, the presence or absence of a focal enhancement was the most significant MRI finding predicting residual tumors. MRI provided good diagnostic accuracy for detecting residual tumors, and the addition of DWI to conventional MRI may increase specificity.

Purpose: This retrospective chart review study was conducted to examine the frequency of delirium and to identify the risk factors of delirium in elderly surgical patients. Methods: The subjects of this study were 394 patients aged 65 years or older who underwent surgery. The diagnosis of delirium was based on the nursing assessment records with scores from the day of surgery to the 4th day after surgery. The collected data were analyzed by binary logistic regression analysis. Results: The incidence of delirium was 4.3%, and delirium occurred most frequently on the first day of surgery and lasted for 2.16 days on average. Of delirium patients, 76.5% underwent gastrointestinal surgery, and the most common delirium pattern was disorientation. In terms of the characteristics of the subjects, the occurrence of delirium was statistically different by age (x 2=10.79, p=.005), systemic-specific disease (x 2 =9.63, p=.047), use of delirium-inducing drug(benzodiazepine) before surgery (x 2 =15.90, p<.001), walking ability before surgery (x 2 =7.65, p=.006), history of delirium (x 2 =35.92, p<.001), and emergency surgery (x 2 =16.40, p<.001). As risk factors of delirium, gastrointestinal surgery was found to increase the risk of delirium by 12.57 times (95% CI=2.45~64.46, p=.002), and the use of benzodiazepines before surgery was shown to increase delirium by 10.07 times (95% CI=2.21~45.87, p=.003). Conclusion It is necessary for nurses to actively evaluate delirium using screening tools for early detection and prevention of delirium in elderly surgical patients with delirium risk factors.

Background/Aims: Prokinetics such as mosapride citrate CR (conventional-release; Gasmotin) are commonly used in functional dyspepsia (FD). This study aims to evaluate the efficacy and safety of once-a-day mosapride citrate SR (DWJ1252), a sustained-release formulation of mosapride citrate, compared with mosapride citrate CR 3 times a day, in patients with FD. Methods: In this multicenter, randomized, double-blind, active-controlled, non-inferiority study, 119 patients with FD (by the Rome III criteria, 60 for mosapride citrate SR and 59 for mosapride citrate CR) were randomly allocated to mosapride citrate SR once daily or mosapride citrate CR thrice daily for 4 weeks in 16 medical institutions. Primary end point was the change in gastrointestinal symptom (GIS) score from baseline, assessed by GIS questionnaires on 5-point Likert scale after 4-week treatment. Secondary end points and safety profiles were also analyzed. Results: The study included 51 and 49 subjects in the mosapride citrate SR and mosapride citrate CR groups, respectively. GIS scores at week 4 were significantly reduced in both groups (mean ± SD: − 10.04 ± 4.45 and − 10.86 ± 5.53 in the mosapride citrate SR and mosapride citrate CR groups, respectively; P < 0.001), and the GIS changes from baseline did not differ between the 2 groups (difference, 0.82 point; 95% CI, − 1.17, 2.81; P = 0.643). Changes in GIS at weeks 2 and 4 and quality of life at week 4, and the improvement rates of global assessments at weeks 2 and 4, did not differ between the groups. Adverse events were similar in the 2 groups, and there were no serious adverse events. Conclusion In patients with FD, mosapride citrate SR once daily is as effective as mosapride citrate CR thrice daily, with a similar safety profile.

The therapeutic effects of mesenchymal stem cells (MSCs) in musculoskeletal diseases (MSDs) have been verified in many human and animal studies. Although some tissues contain MSCs, the number of cells harvested from those tissues and rate of proliferation in vitro are not enough for continuous transplantation. In order to produce and maintain stable MSCs, many attempts are made to induce differentiation from pluripotent stem cells (iPSCs) into MSCs. In particular, it is also known that the paracrine action of stem cell-secreted factors could promote the regeneration and differentiation of target cells in damaged tissue. MicroRNAs (miRNAs), one of the secreted factors, are small non-coding RNAs that regulate the translation of a gene. It is known that miRNAs help communication between stem cells and their surrounding niches through exosomes to regulate the proliferation and differentiation of stem cells. While studies have so far been underway targeting therapeutic miRNAs of MSDs, studies on specific miRNAs secreted from MSCs are still minimal. Hence, our ultimate goal is to obtain sufficient amounts of exosomes from iPSC-MSCs and develop them into therapeutic agents, furthermore to select specific miRNAs and provide safe cell-free clinical setting as a cell-free status with purpose of delivering them to target cells. This review article focuses on stem cell therapy on MSDs, specific microRNAs regulating MSDs and updates on novel approaches.

Purpose: In this trial, we investigated the efficacy and safety of adjuvant letrozole for hormone receptor (HR)-positive breast cancer. Here, we report the clinical outcome in postmenopausal women with HR-positive breast cancer treated with adjuvant letrozole according to estrogen receptor (ER) expression levels. Methods: In this multi-institutional, open-label, observational study, postmenopausal patients with HR-positive breast cancer received adjuvant letrozole (2.5 mg/daily) for 5 years unless they experienced disease progression or unacceptable toxicity or withdrew their consent. The patients were stratified into the following 3 groups according to ER expression levels using a modified Allred score (AS): low, intermediate, and high (AS 3–4, 5–6, and 7–8, respectively). ER expression was centrally reviewed. The primary objective was the 5-year disease-free survival (DFS) rate. Results: Between April 25, 2010, and February 5, 2014, 440 patients were enrolled. With a median follow-up of 62.0 months, the 5-year DFS rate in all patients was 94.2% (95% confidence interval [CI], 91.8–96.6). The 5-year DFS and recurrence-free survival (RFS) rates did not differ according to ER expression; the 5-year DFS rates were 94.3% and 94.1%in the low-to-intermediate and high expression groups, respectively (p = 0.6), and the corresponding 5-year RFS rates were 95.7% and 95.4%, respectively (p = 0.7). Furthermore, 25 patients discontinued letrozole because of drug toxicity. Conclusion Treatment with adjuvant letrozole showed very favorable treatment outcomes and good tolerability among Korean postmenopausal women with ER-positive breast cancer, independent of ER expression.