Structural Insights for β-Lactam Antibiotics

Antibiotic resistance has emerged as a global threat to modern healthcare systems and has nullified many commonly used antibiotics. β-Lactam antibiotics are among the most successful and occupy approximately two-thirds of the prescription antibiotic market. They inhibit the synthesis of the peptidoglycan layer in the bacterial cell wall by mimicking the D-Ala-D-Ala in the pentapeptide crosslinking neighboring glycan chains. To date, various β-lactam antibiotics have been developed to increase the spectrum of activity and evade drug resistance. This review emphasizes the three-dimensional structural characteristics of β-lactam antibiotics regarding the overall scaffold, working mechanism, chemical diversity, and hydrolysis mechanism by β-lactamases. The structural insight into various β-lactams will provide an in-depth understanding of the antibacterial efficacy and susceptibility to drug resistance in multidrug-resistant bacteria and help to develop better β-lactam antibiotics and inhibitors.

Effect of Early Tracheostomy on Clinical Outcomes in Patients with Prolonged Acute Mechanical Ventilation: A Single-Center Study / 결핵

BACKGROUND: The purpose of this study was to investigate the effect of early tracheostomy on clinical outcomes in patients requiring prolonged acute mechanical ventilation (≥96 hours).METHODS: Data from 575 patients (69.4% male; median age, 68 years), hospitalized in the medical intensive care unit (ICU) of a university-affiliated tertiary care hospital March 2008–February 2017, were retrospectively evaluated. Early and late tracheostomy were designated as 2–10 days and >10 days after translaryngeal intubation, respectively.RESULTS: The 90-day cumulative mortality rate was 47.5% (n=273) and 258 patients (44.9%) underwent tracheostomy. In comparison with the late group (n=115), the early group (n=125) had lower 90-day mortality (31.2% vs. 47.8%, p=0.012), shorter stays in hospital and ICU, shorter ventilator length of stay (median, 43 vs. 54; 24 vs. 33; 23 vs. 28 days; all p<0.001), and a higher rate of transfer to secondary care hospitals with post-intensive care settings (67.2% vs. 43.5% p<0.001). Also, the total medical costs of the early group were lower during hospital stays than those of the late group (26,609 vs. 36,973 USD, p<0.001).CONCLUSION: Early tracheostomy was associated with lower 90-day mortality, shorter ventilator length of stay and shorter lengths of stays in hospital and ICU, as well as lower hospital costs than late tracheostomy.

The Change of Metabolic Syndrome Prevalence and Its Risk Factors in Korean Adults for Decade: Korea National Health and Nutrition Examination Survey for 2008–2017

Background@#Metabolic syndrome is a nationwide health problem, which is associated with the development of cardiovascular diseases, diabetes, and chronic renal failure. The prevalence of metabolic syndrome in Korea significantly increased from 1998 to 2007. After that, the prevalence was stable in female but still increasing in male. The objective of this study was to evaluate how the prevalence and risk factors for metabolic syndrome changed in Korean adults through the last decade. @*Methods@#Data from the Korea National Health and Nutrition Examination Survey 2008 to 2017 was used. National Cholesterol Education Program Adult Treatment Panel III were used to define metabolic syndrome. We compared how each metabolic syndrome component and the risk factors changed through the years. @*Results@#A total of 51,177 (30,092 female and 21,085 male) people were included in this study. The prevalence of metabolic syndrome in male increased from 24.5% in 2008 to 28.1% in 2017, whereas that in female was stable at 20.5% in 2008 from 18.7% in 2017. Waist circumference measurements and fasting glucose levels increased through the decade in male, whereas only fasting glucose levels increased in female. @*Conclusion@#Since the last decade, the prevalence of metabolic syndrome in Korean adults has increased in male but remained stable in female. Lifestyle intervention in male, namely ceasing smoking and drinking could prevent increasing metabolic syndrome prevalence in Korean adults.

Effect of Early Tracheostomy on Clinical Outcomes in Patients with Prolonged Acute Mechanical Ventilation: A Single-Center Study / 결핵및호흡기질환

BACKGROUND@#The purpose of this study was to investigate the effect of early tracheostomy on clinical outcomes in patients requiring prolonged acute mechanical ventilation (≥96 hours).@*METHODS@#Data from 575 patients (69.4% male; median age, 68 years), hospitalized in the medical intensive care unit (ICU) of a university-affiliated tertiary care hospital March 2008–February 2017, were retrospectively evaluated. Early and late tracheostomy were designated as 2–10 days and >10 days after translaryngeal intubation, respectively.@*RESULTS@#The 90-day cumulative mortality rate was 47.5% (n=273) and 258 patients (44.9%) underwent tracheostomy. In comparison with the late group (n=115), the early group (n=125) had lower 90-day mortality (31.2% vs. 47.8%, p=0.012), shorter stays in hospital and ICU, shorter ventilator length of stay (median, 43 vs. 54; 24 vs. 33; 23 vs. 28 days; all p<0.001), and a higher rate of transfer to secondary care hospitals with post-intensive care settings (67.2% vs. 43.5% p<0.001). Also, the total medical costs of the early group were lower during hospital stays than those of the late group (26,609 vs. 36,973 USD, p<0.001).@*CONCLUSION@#Early tracheostomy was associated with lower 90-day mortality, shorter ventilator length of stay and shorter lengths of stays in hospital and ICU, as well as lower hospital costs than late tracheostomy.

Knowledge and Anxiety Related to Hereditary Ovarian Cancer in Serous Ovarian Cancer Patients / 여성건강간호학회지

PURPOSE: The awareness of hereditary breast and ovarian cancer (HBOC) and BRCA testing is increasing in Korea. Compared to the sizable research on HBOC knowledge among breast cancer women, studies in the ovarian cancer population are limited. This paper aimed to investigate the level of knowledge of hereditary ovarian cancer and anxiety in women diagnosed with serous ovarian cancer in Korea and determine differences in the knowledge and anxiety according to whether genetic testing was undertaken and whether BRCA1 or BRCA2 mutations were present.METHODS: Using a descriptive research design, a cross-sectional survey was conducted on 100 women diagnosed with serous ovarian cancer at N hospital in Gyeonggi-do, Korea, from July to November 2018. The collected data were analyzed by descriptive statistics, independent t-tests, one-way analysis of variance, and Pearson's correlation coefficient using the SPSS 21.0 program.RESULTS: The hereditary ovarian cancer-related knowledge score was mid-level (mean score 8.90±3.29 out of a total of 17), as was the state anxiety level was mid-level (mean score 47.96±3.26 out of possible score range of 20–80). Genetic knowledge of hereditary ovarian cancer was associated with age, education, occupation, genetic counseling, and BRCA mutations. There were no statistically significant factors related to anxiety and there were no statistically significant correlations between knowledge level and anxiety.CONCLUSION: More comprehensive education on gene-related cancer is needed for ovarian cancer patients, especially for items with low knowledge scores. A genetic counseling protocol should be developed to allow more patients to alleviate their anxiety through genetic counseling.

Spontaneous Splenic Rupture in a Peritoneal Dialysis Patient / 대한내과학회지

Atraumatic splenic rupture (ASR) in a patient undergoing peritoneal dialysis (PD) is uncommon, but can be life-threatening. According to recent systematic reviews, the major causes of ASR are 1) neoplastic (30.3%), 2) infectious (27.3%), 3) non-infectious inflammatory (20.0%), 4) iatrogenic (9.2%), 5) mechanical (6.8%), and 6) idiopathic (6.4%). It is diagnosed by imaging studies, most commonly ultrasonography and computed tomography (CT). Due to its rarity, the early diagnosis of ASR is difficult, and no standard treatment has been described. Here, we report a case of idiopathic ASR in a patient undergoing PD. The diagnosis was established by abdominal CT scan, and splenectomy was performed. Thus, hemoperitoneum in a PD patient should raise suspicion of ASR. Early diagnosis and appropriate treatment will lead to a better outcome.

Effects of Recumbent Bicycle Exercise on Cardiac Autonomic Responses and Hemodynamics Variables in Patients with Atrial Fibrillation

BACKGROUND: The purpose of this study is to investigate the safety and efficiency of recumbent bicycle ergometer exercise by observing heart rate variability (HRV) and hemodynamic variables in patients with atrial fibrillation.METHODS: In a balanced crossover study, 13 patients with atrial fibrillation (mean age, 62.2±5.3 years) were asked to perform a bicycle exercise twice, once in the upright position and once in the recumbent position at an angle of 30°, with a 1-week interval between both. The exercise intensity was set initially at 10 W and increased by 15 W every 2 minutes up to 70 W. HRV and hemodynamic variables were measured. All data were analyzed using one-way repeated-measures analysis of variance.RESULTS: Low-frequency normalization in HRV was increased with no intergroup differences immediately after exercise. The rate pressure product was significantly lower in the recumbent than in the upright position right after exercise (104.8±14.3 vs. 151.8±51.4 mmHg×beats/min×10⁻², P < 0.01).CONCLUSIONS: Recumbent exercise improves the safety and efficiency of cardiac rehabilitation for atrial fibrillation patients by reducing myocardial workload without compromising the activation of the autonomic nervous system that regulates cardiac activity.

Effects of Recumbent Bicycle Exercise on Cardiac Autonomic Responses and Hemodynamics Variables in Patients with Atrial Fibrillation

BACKGROUND@#The purpose of this study is to investigate the safety and efficiency of recumbent bicycle ergometer exercise by observing heart rate variability (HRV) and hemodynamic variables in patients with atrial fibrillation.@*METHODS@#In a balanced crossover study, 13 patients with atrial fibrillation (mean age, 62.2±5.3 years) were asked to perform a bicycle exercise twice, once in the upright position and once in the recumbent position at an angle of 30°, with a 1-week interval between both. The exercise intensity was set initially at 10 W and increased by 15 W every 2 minutes up to 70 W. HRV and hemodynamic variables were measured. All data were analyzed using one-way repeated-measures analysis of variance.@*RESULTS@#Low-frequency normalization in HRV was increased with no intergroup differences immediately after exercise. The rate pressure product was significantly lower in the recumbent than in the upright position right after exercise (104.8±14.3 vs. 151.8±51.4 mmHg×beats/min×10⁻², P < 0.01).@*CONCLUSIONS@#Recumbent exercise improves the safety and efficiency of cardiac rehabilitation for atrial fibrillation patients by reducing myocardial workload without compromising the activation of the autonomic nervous system that regulates cardiac activity.

Effects of Platelet-rich Plasma on Ocular Surface in Patients with Dry Eye Syndrome: Clinico-experimental Analysis

PURPOSE@#To evaluate the effect of platelet rich plasma (PRP) on ocular surface damage caused by hyperosmotic conditions using retrospective clinical and experimental analyses.@*METHODS@#Eighty eyes of moderate dry eye syndrome patients who had no responses using conventional treatments were included in the study. Before and 1, 3, and 6 months after the use of autologous PRP, the visual acuity, intraocular pressure, tear break-up time (TBUT), ocular staining score (OSS), and ocular surface disease index (OSDI) were compared. The changes in inflammatory factors of ocular surface cells were analyzed using a corneo-limbal epithelial cell culture and a hyperosmotic stress experimental model.@*RESULTS@#Using retrospective clinical analyses, in 64 eyes (80%) after the use of autologous PRP, the symptom scores and symptoms were significantly reduced in the OSDI questionnaire when compared with the symptom scores and symptoms before treatment. The TBUT and OSS, which were objective indicators showed a significant increase of TBUT and significant decrease of OSS in 68 eyes (85%) and 72 eyes (90%), respectively. The expression of inflammatory factors such as interleukin-1, tumor necrosis factor-α, metalloproteinase (MMP)-1, and MMP-3 decreased in corneo-limbal epithelial cells under hyperosmotic conditions when PRP was added.@*CONCLUSIONS@#The use of autologous PRP showed significant improvement before and after treatment in the TBUT, OSS, symptom scores and symptoms, and OSDI. In addition, anti-inflammatory effects were demonstrated in hyperosmotic models simulating dry eye syndrome. Therefore, autologous PRP could be used effectively for the treatment of moderate dry eye syndrome.

Spontaneous Splenic Rupture in a Peritoneal Dialysis Patient / 대한내과학회지

Atraumatic splenic rupture (ASR) in a patient undergoing peritoneal dialysis (PD) is uncommon, but can be life-threatening. According to recent systematic reviews, the major causes of ASR are 1) neoplastic (30.3%), 2) infectious (27.3%), 3) non-infectious inflammatory (20.0%), 4) iatrogenic (9.2%), 5) mechanical (6.8%), and 6) idiopathic (6.4%). It is diagnosed by imaging studies, most commonly ultrasonography and computed tomography (CT). Due to its rarity, the early diagnosis of ASR is difficult, and no standard treatment has been described. Here, we report a case of idiopathic ASR in a patient undergoing PD. The diagnosis was established by abdominal CT scan, and splenectomy was performed. Thus, hemoperitoneum in a PD patient should raise suspicion of ASR. Early diagnosis and appropriate treatment will lead to a better outcome.

Factors associated with low-level physical activity in elderly patients with chronic obstructive pulmonary disease

BACKGROUND/AIMS@#In patients with chronic obstructive pulmonary disease (COPD), the extent of physical activity (PA) is correlated with disease severity and prognosis. However, factors associated with low-level PA in elderly COPD patients are not known. We assessed the levels of PA and clinical factors associated with low-level of PA in elderly COPD patients.@*METHODS@#This was a secondary analysis of a multicenter, prospective study of 245 patients with COPD. Among them, 160 patients with 65 years or more were included. Three PA groups were defined with respect to daily activity time (low, moderate, and high). Health related quality of life (HRQL) was measured using St. George's respiratory questionnaire (SGRQ) and 36-item short-form health survey. Anxiety and depression status were assessed employing the hospital anxiety and depression scale (HADS). Multivariate logistic regression was performed to identify independent predictors of low-level PA in elderly COPD patients.@*RESULTS@#Of all the 160 patients, 103 (64.4%) engaged in low-level PA. Upon univariate analysis, a decreased exercise capacity (6-minute walk test < 250 m), an increased dyspnea (the modified medical research council [MMRC] dyspnea scale ≥ 2), a decreased HRQL (total SGRQ score), and a presence of depression (HADS-D ≥ 8) were significantly associated with low-level PA. Upon multivariate analysis, an MMRC grade ≥ 2 (hazard ratio [HR], 2.550; p = 0.034), and HADS-D ≥ 8 (HR, 2.076; p = 0.045) were independently associated with low-level PA in elderly COPD patients.@*CONCLUSIONS@#Two-thirds of elderly patients with COPD reported low-level of PA. More severe dyspnea and a presence of depression were independently associated with low-level PA in elderly COPD patients.

Regulation of synaptic architecture and synaptic vesicle pools by Nervous wreck at Drosophila Type 1b glutamatergic synapses

Nervous wreck (Nwk), a protein that is present at Type 1 glutamatergic synapses that contains an SH3 domain and an FCH motif, is a Drosophila homolog of the human srGAP3/MEGAP protein, which is associated with mental retardation. Confocal microscopy revealed that circles in Nwk reticulum enclosed T-shaped active zones (T-AZs) and partially colocalized with synaptic vesicle (SV) markers and both exocytosis and endocytosis components. Results from an electron microscopic (EM) analysis showed that Nwk proteins localized at synaptic edges and in SV pools. Both the synaptic areas and the number of SVs in the readily releasable (RRPs) and reserve (RPs) SV pools in nwk2 were significantly reduced. Synergistic, morphological phenotypes observed from eag¹;nwk² neuromuscular junctions suggested that Nwk may regulate synaptic plasticity differently from activity-dependent Hebbian plasticity. Although the synaptic areas in eag¹;nwk² boutons were not significantly different from those of nwk², the number of SVs in the RRPs was similar to those of Canton-S. In addition, three-dimensional, high-voltage EM tomographic analysis demonstrated that significantly fewer enlarged SVs were present in nwk² RRPs. Furthermore, Nwk formed protein complexes with Drosophila Synapsin and Synaptotagmin 1 (DSypt1). Taken together, these findings suggest that Nwk is able to maintain synaptic architecture and both SV size and distribution at T-AZs by interacting with Synapsin and DSypt1.

Prevalence of Osteoporosis in Korean Patients with Chronic Obstructive Pulmonary Disease and Their Health-related Quality of Life According to the Korea National Health and Nutrition Examination Survey 2008–2011

BACKGROUND: In this study, we evaluated the prevalence of osteoporosis, risk factors associated with osteoporosis, and health-related quality of life (HRQOL) in clinically stable chronic obstructive pulmonary disease (COPD) patients. METHODS: A total of 1,081 COPD patients were recruited from the Korea National Health and Nutrition Examination Survey (KNHANES) from July 2008 to May 2011. Bone mineral densities at the lumbar spine, femoral neck, and total proximal femur were measured using dual energy X-ray absorptiometry. HRQOL was assessed using the EuroQOL-5 dimensions (EQ-5D) questionnaire. To identify factors associated with osteoporosis and HRQOL in patients with COPD, multivariate regression analyses was performed. RESULTS: Of the 1,081 COPD patients, 191 (17.7%) were diagnosed with osteoporosis. There were significant differences in age, sex, smoking status, education level, house income, and body mass index (BMI) between the osteoporotic and non-osteoporotic groups. COPD patients with osteoporosis had significantly lower EQ-5D scores than the controls. In multivariate analyses, older age (odds ratio [OR]=1.10, P < 0.001) was risk factor for osteoporosis. And patients of male sex (OR=0.06, P < 0.001), high house income (OR=0.75, P=0.045), and high BMI (OR=0.74, P < 0.001) were less likely to have osteoporosis. In addition, osteoporosis was associated with poor HRQOL (β=−0.21, P=0.023). CONCLUSIONS: The prevalence of osteoporosis in COPD patients based on the 2008 to 2011 KNHANES data were relatively lower than that in physician-diagnosed COPD patients. In these COPD patients, older age, female sex, low household income, and low BMI increased the risk for osteoporosis.

Analysis of Serum Cytokine Profile in Pemphigus

BACKGROUND: Pemphigus is a group of autoimmune blistering diseases affecting skin and mucous membranes. While pemphigus is an autoantibody mediated disease, the role of T cells and cytokines in the pathogenesis is being increasingly recognized. OBJECTIVE: This study was conducted to observe alterations in the serum cytokine levels of patients with pemphigus vulgaris (PV), pemphigus foliaceous (PF), paraneoplastic pemphigus (PNP) and compare with bullous pemphigoid (BP) and healthy subjects. METHODS: A total of 75 subjects (28 PV, 13 PF, 7 PNP, 7 BP, and 20 healthy controls) were included, all patients in active disease state. Serum levels of interferon (IFN)-γ, interleukin (IL)-4, IL-6, IL-17A, IL-10, tumor necrosis factor (TNF)-α, and IL-8 were measured by enzyme-linked immunosorbent assay. RESULTS: The median concentration of IFN-γ was lower in PV and BP patients compared to control (0.77, 0.34 and 1.63 pg/ml, respectively). IL-6 and IL-10 was significantly higher in PNP patients compared to control (4.92 and 0.24 pg/ml for IL-6, 0.86 and <0.12 pg/ml for IL-10, respectively). IL-8 was increased significantly in PV and PNP patients compared with control (11.85, 31.5 and 8.31 pg/ml, respectively). For IL-4, IL-17A and TNF-α, no significant difference was observed between the five groups. CONCLUSION: The decreased level of IFN-γ in PV may imply suppressed Th1 response in the active disease stage. A Th2 predominant response is suggested in the active stage of PNP, with elevated serum levels of IL-6 and IL-10. Increased level of proinflammatory cytokine IL-8 is observed in the sera of PV and PNP patients.

The Impact of the CHA₂DS₂-VASc Score on Recurrence of Atrial Fibrillation after a Single Catheter Ablation and Atrial Remodeling in Patients with Non-Valvular Atrial Fibrillation

BACKGROUND AND OBJECTIVES: This study aimed to evaluate the impact of the CHA₂DS₂-VASc score on atrial fibrillation (AF) recurrence after a single catheter ablation procedure in patients with non-valvular AF. We also investigated the correlation between CHA₂DS₂-VASc score and atrial substrate. SUBJECTS AND METHODS: This study evaluated 151 patients who underwent catheter ablation of non-valvular AF. The study population was stratified into group 1 (<2, n=72) and group 2 (≥2, n=79) by CHA₂DS₂-VASc score. The CHA₂DS₂-VASc score was analyzed as a continuous and categorical value for evaluating its impact on AF recurrence after catheter ablation. The left atrial voltage data were analyzed by the categorical values of this score. RESULTS: Post-ablation recurrence (31.6% vs. 18.1%, p=0.046) was observed more frequently in group 2. The mean area of the lowvoltage zone was 75.64±24.81 cm² and 94.44±28.09 cm² in groups 1 and 2, respectively (p=0.005). The left atrial mean voltage in group 2 was 0.99±0.31 mV, significantly lower than that (1.49±0.67 mV, p=0.001) in group 1. The CHA₂DS₂-VASc score was the independent predictor with a modest predictive value for AF recurrence after catheter ablation. CONCLUSION: Our study showed that CHA₂DS₂-VASc score was associated with atrial remodeling and could be useful in stratifying post-ablation recurrence in patients with non-valvular AF.

The Prognostic Value of the Charlson's Comorbidity Index in Patients with Prolonged Acute Mechanical Ventilation: A Single Center Experience / 결핵및호흡기질환

BACKGROUND: The aim of our study was to evaluate the prognostic value of Charlson's weighted index of comorbidities (WIC) in patients with prolonged acute mechanical ventilation (PAMV, ventilator care ≥96 hours). METHODS: We retrospectively enrolled 299 Korean PAMV patients who were admitted in a medical intensive care unit (ICU) of a university-affiliated tertiary care hospital between 2008 and 2013. Survivors were defined as patients who survived for 60 days after ICU admission. RESULTS: The patients' mean age was 65.1±14.1 years and 70.6% were male. The mean ICU and hospital length of stay was 21.9±19.7 and 39.4±39.1 days, respectively. In addition, the 60-day mortality rate after ICU admission was 35.5%. The mean WIC was 2.3±1.8, with significant differences between nonsurvivors and survivors (2.7±2.1 vs. 2.1±1.7, p<0.05). The area under the curve of receiver-operating-characteristics curve for WIC was 0.593 (95% confidence interval [CI], 0.523–0.661; p<0.05). Based on Kaplan-Meier curves of 60-day survival, WIC ≥5 had statistically lower survival than WIC <5 (log-rank test, p<0.05). In a multivariate Cox proportional hazard model, WIC ≥5 was associated with poor prognosis (hazard ratio, 1.901; 95% CI, 1.140–3.171; p<0.05). The mortality rate of patients with WIC ≥5 was 54.2%. CONCLUSION: Our study showed a WIC score ≥5 might be helpful in predicting 60-day mortality in PAMV patients.

Inflammatory Pseudotumor of the Liver Mimicking an Infiltrative Malignancy / 계명의대학술지

Inflammatory pseudotumor (IPT) is a relatively rare and benign disease characterized by chronic inflammatory cell infiltration with fibrosis. It is difficult to diagnose IPT because of the absence of specific symptoms or unique radiological findings. IPT can be mistaken for a malignant tumor, such as cholangiocarcinoma or hepatocellular carcinoma, due to their similar clinical and radiological findings. Unfortunately, hepatic resection is often performed due to misdiagnosis. Presented here is a case of a woman aged over 60 years who presented with general weakness lasting more than one month and unexplained body weight loss.

Retrospective Review of 19 Patients with Lentigo Maligna Melanoma / 대한피부과학회지

BACKGROUND: Lentigo maligna melanoma (LMM) is a subtype of melanoma that typically develops on sun-damaged skin. LMM is estimated to comprise 4~15% of melanomas, but the prevalence is known to be relatively lower in the Korean population than in the Caucasian population. OBJECTIVE: To review the clinico-pathologic features and treatment outcomes of Korean patients with LMM. METHODS: Nineteen patients diagnosed with LMM during 2003~2015, in the Yonsei University Health System, were included in this study. The age and sex of the patients, lesion location, thickness (Breslow), stage, treatment methods, BRAF, NRAS, and KIT mutation status, and survival rates were analyzed. RESULTS: Among the 19 Korean patients, 11 were male and 8 were female. The median age was 59.2 years. The most common site was the cheek (47.4%), followed by the scalp, eyelid, nose, forehead, lip, and neck. At the time of diagnosis, 13 patients were in localized stages (5 patients, stage 0; 3 patients, stage I; and 5 patients, stage II) and 6 patients were in advanced stages (3 patients, stage III; and 3 patients, stage IV). Patients in the localized stages showed better overall survival (OS) than those in the advanced stages (p=0.012). Nine patients were treated with a wide excision, and 6 using Mohs micrographic surgery. Three patients received high-dose interferon-α therapy; 6, chemotherapy; and 4, radiotherapy. Two patients in stage 0 were treated with topical ingenol mebutate. Two patients had BRAF V600E mutation; 1, NRAS G12R mutation; and 1, KIT mutation. Median OS of the patients was 40.8 months. CONCLUSION: Our analysis provides additional information about clinical characteristics, treatment, and prognosis of LMM in Korean patients.

Genetic Variation of SCN5A in Korean Patients with Sick Sinus Syndrome

BACKGROUND AND OBJECTIVES: Due to recent studies that have shown an association between the genetic variation of SCN5A and sick sinus syndrome (SSS), we sought to determine if a similar correlation existed in Korean patients with SSS. SUBJECTS AND METHODS: We enrolled 30 patients with SSS who showed a sinus pause (longer than 3.0 s) in Holter monitoring, in addition to 80 controls. All exons including the putative splicing sites of the SCN5A gene were amplified by polymerase chain reaction and sequenced either directly or following subcloning. Wild-type and single nucleotide polymorphisms were expressed in human embryonic kidney cells, and the peak sodium current (I(Na)) was analyzed using the whole-cell patch-clamp technique. RESULTS: A total of 9 genetic variations were identified: 7 variations (G87A-A29A, IVS9-3C>A, A1673G-H558R, G3823A-D1275N, T5457C-D1819D, T5963G-L1988R, and C5129T-S1710L) had been previously reported, and 2 variants (A3075T-E1025D and T4847A-F1616Y) were novel; the potential structural effects of F1616Y were analyzed in a three-dimensional model of the SCN5A domain. Patch-clamp studies at room temperature demonstrated that the peak I(Na) was significantly increased by 140% in HEK cells transfected with F1616Y compared with wild-type (-335.13 pA/pF+/-24.04, n=8 vs. -139.95 pA/pF+/-23.76, n=7, respectively). Furthermore, the voltage dependency of the activation and steady-state inactivation of F1616Y were leftward-shifted compared with wild-type (V(h) activation=-55.36 mv+/-0.22, n=8 vs. V(h) activation=-44.21 mV+/-0.17, n=7; respectively; V(h) inactivation=-104.47 mV+/-0.21, n=7 vs. V(h) inactivation=-84.89 mV+/-0.09, n=12, respectively). CONCLUSION: F1616Y may be associated with SSS.

PTEN Methylation Dependent Sinonasal Mucosal Melanoma / Journal of the Korean Cancer Association, 대한암학회지

Sinonasal mucosal melanoma (SMM) is an aggressive and rare type of melanoma. Although the classic RAS-RAF-MEK pathway is thought to be the main pathway involved in melanoma pathogenesis, genetic alterations in the phosphatidylinositol 3-kinase-AKT pathway, including PTEN-regulated signaling, are also thought to contribute. So far, data regarding altered PTEN expression and epigenetic mechanism of PTEN silencing in development of SMM is extremely limited. Herein we report on a case of SMM with liver and bone metastases with an epigenetic alteration of PTEN. Results of mutation analysis for BRAF, NRAS, HRAS, KRAS, PIK3CA, c-Kit, and PTEN were negative; however, methylation of PTEN CpG islands was observed. Our case not only supports PTEN as a major tumor suppressor involved in melanoma tumorigenesis, but also a potential epigenetic mechanism of PTEN silencing in development of SMM.