Exon skipping is an efficient technique to inhibit specific gene expression induced by a short-sequence peptide nucleic acid (PNA).To date, there has been no study on the effects of PNA on skin pigmentation. In melanocytes, the tripartite complex is responsible for the transport of mature melanosomes from the nucleus to the dendrites. The tripartite complex is composed of Rab27a, Mlph (Melanophilin), and Myosin Va. Defects in the protein Mlph, a melanosome transport-related protein, are known to cause hypopigmentation. Our study shows that Olipass peptide nucleic acid (OPNA), a cell membrane-permeable PNA, targets exon skipping in the Mlph SHD domain, which is involved in Rab27a binding. Our findings demonstrate that OPNA induced exon skipping in melan-a cells, resulting in shortened Mlph mRNA, reduced Mlph protein levels, and melanosome aggregation, as observed by microscopy. Therefore, OPNA inhibits the expression of Mlph by inducing exon skipping within the gene. These results suggest that OPNA, which targets Mlph, may be a potential new whitening agent to inhibit melanosome movement.

Background/Aims: Daratumumab has shown an encouraging antitumor effect in patients with multiple myeloma (MM), and was known to alter the immune properties by off-targeting immunosuppressive cells. Here, we aimed to evaluate the change in absolute lymphocyte count (ALC) as a surrogate marker for predicting survival outcomes of patients treated with daratumumab. Methods: Between 2018 and 2021, the medical records of patients with relapsed/refractory MM (RRMM) treated with daratumumab monotherapy at 10 centers in South Korea were reviewed. We collected the ALC data at pre-infusion (D0), day 2 after the first infusion (D2), and prior to the third cycle of daratumumab therapy (D56). Results: Fifty patients who were administered at least two cycles of daratumumab were included. Overall response rate was 54.0% after two cycles of daratumumab treatment. On D2, almost all patients experienced a marked reduction in ALC. However, an increase in ALC on D56 (ALCD56) was observed in patients with non-progressive disease, whereas failure of ALC recovery was noted in those with progressive disease. Patients with ALCD56 > 700/μL (n = 39, 78.0%) had prolonged progression- free survival (PFS) and overall survival (OS) than those with ALCD56 ≤ 700/μL (median PFS: 5.8 months vs. 2.6 months, p = 0.025; median OS: 24.1 months vs. 6.1 months, p = 0.004). In addition, ALCD56 >700/μL was a significant favorable prognostic factor for PFS (hazard ratio [HR], 0.22; p = 0.003) and OS (HR, 0.23; p = 0.012). Conclusions Increase in ALC during daratumumab treatment was significantly associated with prolonged survival outcomes in patients with RRMM. The ALC value can predict clinical outcomes in patients treated with daratumumab.

Recent several reports have demonstrated that periodontitis is prevalent and adversely affects the survival in patients with chronic kidney disease (CKD) or end-stage kidney disease. However, its impact on transplant outcomes remains uncertain. Methods: This retrospective cohort study included 136 and 167 patients, respectively, who underwent living donor kidney transplantation (KT) at Seoul National University Hospital from July 2012 to August 2016 and Korea University Hospital from April 2008 to October 2018. We divided patients into three groups according to stages of periodontitis based on a new classification system. Results: Patients with severe periodontitis were older, had a higher prevalence of diabetes, a higher body mass index and C-reactive protein level, a lower cardiac output, and were more likely to be smokers, indicating its association with chronic systemic inflammation. After KT, stage IV periodontitis was independently associated with a lower incidence of acute T cell-mediated rejection, suggesting the possible effect of periodontitis on immune function. However, 1-year and 3-year estimated glomerular filtration rates were not different. Among the KT recipients followed up more than 3 years, new-onset cardiovascular disease occurred in nine patients, and coronary artery disease occurred more frequently in patients with stage IV periodontitis. However, diabetes was the independent predictor of new-onset coronary artery disease in multivariate logistic regression analysis. Conclusion: Our findings showed that periodontitis might be an important player in determining posttransplant outcomes in recipients. Further interventional trials to test whether treating periodontitis could modify transplant outcome are needed.

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.

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.

BACKGROUND AND OBJECTIVES: Although complete revascularization is known superior to incomplete revascularization in ST elevation myocardial infarction (STEMI) patients with multi-vessel coronary artery disease (MVCD), there are no definite instructions on the optimal timing of non-culprit lesions percutaneous coronary intervention (PCI). We compared 1-year clinical outcomes between 2 different complete multi-vessel revascularization strategies.METHODS: From the Korea Acute Myocardial Infarction Registry-National Institute of Health, 606 patients with STEMI and MVCD who underwent complete revascularization were enrolled from November 2011 to December 2015. The patients were assigned to multi-vessel single-staged PCI (SS PCI) group (n=254) or multi-vessel multi-staged PCI (MS PCI) group (n=352). Propensity score matched 1-year clinical outcomes were compared between the groups.RESULTS: At one year, MS PCI showed a significantly lower rate of all-cause mortality (hazard ratio [HR], 0.42; 95% confidential interval [CI], 0.19–0.92; p=0.030) compared with SS PCI. In subgroup analysis, all-cause mortality increased in SS PCI with cardiogenic shock (HR, 4.60; 95% CI, 1.54–13.77; p=0.006), age ≥65 years (HR, 4.00; 95% CI, 1.67–9.58, p=0.002), Killip class III/IV (HR, 7.32; 95% CI, 1.68–31.87; p=0.008), and creatinine clearance ≤60 mL/min (HR, 2.81; 95% CI, 1.10–7.18; p=0.031). After propensity score-matching, MS PCI showed a significantly lower risk of major adverse cardiovascular event than SS PCI.CONCLUSIONS: SS PCI was associated with worse clinical outcomes compared with MS PCI. MS PCI for non-infarct-related artery could be a better option for patients with STEMI and MVCD, especially high-risk patients.
Arteries ; Coronary Artery Disease ; Coronary Vessels ; Creatinine ; Humans ; Korea ; Mortality ; Myocardial Infarction ; Myocardial Revascularization ; Percutaneous Coronary Intervention ; Propensity Score ; Shock, Cardiogenic

Background/Aims: For metastatic renal cell carcinoma (RCC), various prognostic scoring systems have been developed. However, owing to the low prevalence of nonclear cell RCC, the three most commonly used tools were mainly developed based on patients with clear cell histology. Accordingly, this study applied three prognostic models to Korean non-clear cell RCC patients treated with first-line temsirolimus. Methods: This study analyzed data for 74 patients with non-clear cell RCC who were treated with temsirolimus as the first-line therapy at eight medical centers between 2011 and 2016. The receiver-operating characteristic (ROC) curves for the different prognostic models were analyzed. Results: Twenty-seven (36.5%), 24 (32.4%), and 44 patients (59.5%) were assigned to the poor prognosis groups of the Memorial Sloan-Kettering Cancer Center (MSKCC), International Metastatic RCC Database Consortium (IMDC), and Advanced Renal Cell Carcinoma (ARCC) risk stratification models, respectively. All three prognostic models reliably discriminated the risk groups to predict progression-free survival and overall survival (p < 0.001). The area under the ROC curve (AUC) for progression and survival was highest for the ARCC model (0.777; 0.734), followed by the IMDC (0.756; 0.724) and the MSKCC (0.742; 0.712) models. Furthermore, the sensitivity and specificity for predicting progression were highest with the ARCC model (sensitivity 63.6%, specificity 85.7%), followed by the MSKCC (sensitivity 58.2%, specificity 86.5%) and the IMDC models (sensitivity 56.4%, specificity 85.7%). Conclusions All three prognostic models accurately predicted the survival of the non-clear cell RCC patients treated with temsirolimus as the first-line therapy. Furthermore, the ARCC risk model performed better than the other risk models in predicting survival.

BACKGROUND AND OBJECTIVES: Although complete revascularization is known superior to incomplete revascularization in ST elevation myocardial infarction (STEMI) patients with multi-vessel coronary artery disease (MVCD), there are no definite instructions on the optimal timing of non-culprit lesions percutaneous coronary intervention (PCI). We compared 1-year clinical outcomes between 2 different complete multi-vessel revascularization strategies. METHODS: From the Korea Acute Myocardial Infarction Registry-National Institute of Health, 606 patients with STEMI and MVCD who underwent complete revascularization were enrolled from November 2011 to December 2015. The patients were assigned to multi-vessel single-staged PCI (SS PCI) group (n=254) or multi-vessel multi-staged PCI (MS PCI) group (n=352). Propensity score matched 1-year clinical outcomes were compared between the groups. RESULTS: At one year, MS PCI showed a significantly lower rate of all-cause mortality (hazard ratio [HR], 0.42; 95% confidential interval [CI], 0.19–0.92; p=0.030) compared with SS PCI. In subgroup analysis, all-cause mortality increased in SS PCI with cardiogenic shock (HR, 4.60; 95% CI, 1.54–13.77; p=0.006), age ≥65 years (HR, 4.00; 95% CI, 1.67–9.58, p=0.002), Killip class III/IV (HR, 7.32; 95% CI, 1.68–31.87; p=0.008), and creatinine clearance ≤60 mL/min (HR, 2.81; 95% CI, 1.10–7.18; p=0.031). After propensity score-matching, MS PCI showed a significantly lower risk of major adverse cardiovascular event than SS PCI. CONCLUSIONS SS PCI was associated with worse clinical outcomes compared with MS PCI. MS PCI for non-infarct-related artery could be a better option for patients with STEMI and MVCD, especially high-risk patients.

Purpose: The Advanced Prostate Cancer Consensus Conference (APCCC) 2015 was based on topics withcontroversy in the field of advanced prostate cancer. To understand the Korean urologists perspective regardingthe issues, we have conducted a questionnaire named Prostate Cancer Summit (PCAS) 2016, with 9 importantsubtopics. Materials and Methods: Total 9 subtopics have been decided and questions were developed regarding eachsubtopic. The questions were based on that of APCCC 2015 and translated into Korean for better understanding.Total 51 panelists have voted online on 85 different questions. Results: The survey concluded that testosterone should be measured as a diagnostic criterion for castrationresistance prostate cancer (CRPC) and that consensus was reached on issues such as the use of androgenreceptor pathway inhibitors in the treatment of predocetaxel and postdocetaxel in CRPC patients. In addition,76% of the participants agreed that imaging tests were needed before new treatment in CRPC patients, anda majority of participants agreed that periodic imaging tests are necessary regardless of symptoms during treatmentfor CRPC. However, some issues, such as the use of prostate-specific antigen-based triggers for remediationin CRPC patients, the endocrine manipulation in nonmetastatic CRPC patients, and the onset of treatment inasymptomatic metastatic CRPC patients, were not agreed. Conclusions The results from PCAS 2016 has addressed some of the issues with controversy. Although thevoting results are subjective, it will help guide treatment decisions in topics with less evidence.