Background: The risk of device thrombosis and device-oriented clinical outcomes with bioresorbable vascular scaffold (BVS) was reported to be significantly higher than with contemporary drug-eluting stents (DESs). However, optimal device implantation may improve clinical outcomes in patients receiving BVS. The current study evaluated mid-term safety and efficacy of Absorb BVS with meticulous device optimization under intravascular imaging guidance. Methods: The SMART-REWARD and PERSPECTIVE-PCI registries in Korea prospectively enrolled 390 patients with BVS and 675 patients with DES, respectively. The primary endpoint was target vessel failure (TVF) at 2 years and the secondary major endpoint was patientoriented composite outcome (POCO) at 2 years. Results: Patient-level pooled analysis evaluated 1,003 patients (377 patients with BVS and 626 patients with DES). Mean scaffold diameter per lesion was 3.24 ± 0.30 mm in BVS group.Most BVSs were implanted with pre-dilatation (90.9%), intravascular imaging guidance (74.9%), and post-dilatation (73.1%) at proximal to mid segment (81.9%) in target vessel.Patients treated with BVS showed comparable risks of 2-year TVF (2.9% vs. 3.7%, adjusted hazard ratio [HR], 1.283, 95% confidence interval [CI], 0.487–3.378, P = 0.615) and 2-year POCO (4.5% vs. 5.9%, adjusted HR, 1.413, 95% CI, 0.663–3.012,P = 0.370) than those with DES. The rate of 2-year definite or probable device thrombosis (0.3% vs. 0.5%, P = 0.424) was also similar. The sensitivity analyses consistently showed comparable risk of TVF and POCO between the 2 groups. Conclusion With meticulous device optimization under imaging guidance and avoidance of implantation in small vessels, BVS showed comparable risks of 2-year TVF and device thrombosis with DES.

Background: There has been no comparison of the determinants of admission route between acute ischemic stroke (AIS) and acute myocardial infarction (AMI). We examined whether factors associated with direct versus transferred-in admission to regional cardiocerebrovascular centers (RCVCs) differed between AIS and AMI. Methods: Using a nationwide RCVC registry, we identified consecutive patients presenting with AMI and AIS between July 2016 and December 2018. We explored factors associated with direct admission to RCVCs in patients with AIS and AMI and examined whether those associations differed between AIS and AMI, including interaction terms between each factor and disease type in multivariable models. To explore the influence of emergency medical service (EMS) paramedics on hospital selection, stratified analyses according to use of EMS were also performed. Results: Among the 17,897 and 8,927 AIS and AMI patients, 66.6% and 48.2% were directly admitted to RCVCs, respectively. Multivariable analysis showed that previous coronary heart disease, prehospital awareness, higher education level, and EMS use increased the odds of direct admission to RCVCs, but the odds ratio (OR) was different between AIS and AMI (for the first 3 factors, AMI > AIS; for EMS use, AMI < AIS). EMS use was the single most important factor for both AIS and AMI (OR, 4.72 vs. 3.90). Hypertension and hyperlipidemia increased, while living alone decreased the odds of direct admission only in AMI;additionally, age (65–74 years), previous stroke, and presentation during non-working hours increased the odds only in AIS. EMS use weakened the associations between direct admission and most factors in both AIS and AMI. Conclusions Various patient factors were differentially associated with direct admission to RCVCs between AIS and AMI. Public education for symptom awareness and use of EMS is essential in optimizing the transportation and hospitalization of patients with AMI and AIS.

BACKGROUND/AIMS: The outcome of local treatment for advanced non-small cell lung cancer (NSCLC) remains poor, with therapies such as induction chemotherapy (IC) yielding conflicting results. This study aimed to assess the clinicopathologic and prognostic significance of the excision repair cross-complementation group 1 (ERCC1), beclin-1, and glucose-regulated protein of molecular mass 78 (GRP78) in patients with locally advanced NSCLC receiving docetaxel-platinum IC, along with efficacy and safety. METHODS: This is a retrospective observational cohort study. We reviewed medical records of 31 NSCLC patients receiving docetaxel-platinum IC, and conducted immunohistochemical staining of ERCC1, beclin-1, and GRP78. RESULTS: Response rate was 67.8% with 10.7 months of median relapse-free survival (RFS) and 23.1 months of median overall survival (OS), and no treatment-related death was reported. High expression of ERCC1, beclin-1, and GRP78 was identified in 67.7%, 87.1%, and 67.7%, respectively. Expression of ERCC1 and GRP78 did not reveal statistical significance in survival, whereas high beclin-1 expression revealed longer OS (7.6 months vs. 23.2 months; log-rank p = 0.024). In multivariate analysis, histologic differentiation (hazard ratio [HR], 3.48; p < 0.001), stage (HR, 8.5; p = 0.024), and adjuvant treatment (HR, 16.1; p = 0.001) were related to RFS, and in OS, stage (HR, 5.4; p = 0.037), adjuvant treatment (HR, 8.6; p = 0.004), and beclin-1 expression (HR, 8.2; p = 0.011) were identified as significant prognostic factors. CONCLUSIONS Our findings suggest that high beclin-1 expression predicts longer survival in locally advanced NSCLC and docetaxel-platinum IC is a treatment option that deserves consideration.

BackgroundUntil now, various types of combined therapy with nucleotide analogs and pegylated interferon (Peg-INF) in patients with hepatitis B patients have been tried. However, studies regarding the benefits of de novo combination, late-add on, and sequential treatment are very limited. The objective of the current study was to identify the efficacy of sequential treatment of Peg-INF after short-term antiviral treatment.

MethodsBetween June 2010 and June 2015, hepatitis B e antigen (HBeAg)-positive patients (n = 162) received Peg-IFN for 48 weeks (mono-treatment group, n = 81) and entecavir (ETV) for 12 weeks with a 48-week course of Peg-IFN starting at week 5 of ETV therapy (sequential treatment group, n = 81). The primary endpoint was HBeAg seroconversion at the end of follow-up period after the 24-week treatment. The primary endpoint was analyzed using Chi-square test, Fisher's exact test, and regression analysis.

ResultsHBeAg seroconversion rate (18.2% vs. 18.2%, t = 0.03, P = 1.000) and seroclearance rate (19.7% vs. 19.7%, t = 0.03, P = 1.000) were same in both mono-treatment and sequential treatment groups. The rate of alanine aminotransferase (ALT) normalization (45.5% vs. 54.5%, t = 1.12, P = 0.296) and serum hepatitis B virus (HBV)-DNA <2000 U/L (28.8% vs. 28.8%, t = 0.10, P = 1.000) was not different in sequential and mono-treatment groups at 24 weeks of Peg-INF. Viral response rate (HBeAg seroconversion and serum HBV-DNA <2000 U/L) was not different in the two groups (12.1% vs. 16.7%, t = 1.83, P = 0.457). Baseline HBV-DNA level (7 logU/ml vs. 7.5 logU/ml, t = 1.70, P = 0.019) and hepatitis B surface antigen titer (3.6 logU/ml vs. 4.0 logU/ml, t = 2.19, P = 0.020) were lower and predictors of responder in mono-treatment and sequential treatment groups, respectively.

ConclusionsThe current study shows no differences in HBeAg seroconversion rate, ALT normalization, and HBV-DNA levels between mono-therapy and sequential therapy regimens.

Trial RegistrationClinicalTrials.gov, NCT01220596; https://clinicaltrials.gov/ct2/show/NCT01220596?term=NCT01220596&rank=1.

Smoking is the major risk factor for lung squamous cell carcinoma (SCC), although a small number of lung SCCs occurs in never-smokers. The purpose of this study was to compare 50 hotspot mutations of lung SCCs between never-smokers and smokers. We retrospectively reviewed the medical records of patients newly diagnosed with lung SCC between January 1, 2011 and December 31, 2013 in the Seoul National University Hospital. Formalin-fixed, paraffin-embedded tumor samples were used for analysis of hotspot mutations. Fifty cancer-related genes in never-smokers were compared to those in ever-smokers. Of 379 lung SCC patients, 19 (5.0%) were never-smokers. The median age of these 19 patients was 67 years (interquartile range 57–73 years), and 10 of these patients were women (52.5%). The incidence rates of stage I, II, III, and IV disease in this group were 26.4%, 5.3%, 31.6%, and 36.8%, respectively, and sequencing was performed successfully in 14 cases. In the 26 lung SCC tumor samples (12 from never-smokers and 14 from ever-smokers) sequenced using personal genome machine, the most common mutations were in TP53 (75.0%), RAS (66.7%), and STK11 (33.3%), but mutations were also found in EGFR, KIT, and PTEN. The distribution of hotspot mutations in never-smokers was similar to that in ever-smokers. There was no significant difference in overall survival between the 2 groups. The 50 hotspot mutations of lung SCC in never-smokers were similar to those of ever-smokers.
Carcinoma, Squamous Cell* ; Epithelial Cells* ; Female ; Genome ; Humans ; Incidence ; Lung Neoplasms ; Lung* ; Medical Records ; Retrospective Studies ; Risk Factors ; Seoul ; Smoke ; Smoking

BACKGROUND: The purpose of this study was to compare the clinical and radiological results of 2 different tibial fixations performed using bioabsorbable screws with added hydroxyapatite (HA) and pure poly-L-lactic acid (PLLA) screws in anterior cruciate ligament (ACL) reconstruction. METHODS: A total of 394 patients who underwent arthroscopic ACL reconstruction between March 2009 and June 2012 were retrospectively reviewed. Of those, 172 patients who took the radiological and clinical evaluations at more than 2 years after surgery were enrolled and divided into 2 groups: PLLA group (n = 86) and PLLA-HA group (n = 86). Both groups were assessed by means of the Lysholm score, International Knee Documentation Committee (IKDC) subjective knee score, and Tegner activity score. Stability was evaluated using the KT-2000 arthrometer. Magnetic resonance imaging was performed to evaluate tibial tunnel widening, screw resorption, osteoingeration, and foreign body reactions. RESULTS: The PLLA-HA group showed significant reduction in the extent of tibial tunnel widening and foreign body reactions and significant increase in screw resorption compared to the pure PLLA group (p < 0.001 for both). In contrast, postoperative Lysholm score, Tegner activity score, IKDC score, and side-to-side difference on the KT-2000 arthrometer showed no significant differences between groups (p = 0.478, p = 0.906, p = 0.362, and p = 0.078, respectively). The PLLA group showed more significant widening in the proximal tibial tunnel than the PLLA-HA group (p = 0.001). In the correlation analysis, proximal tibial tunnel widening revealed a positive correlation with knee laxity (r = 0.866) and a negative correlation with Lysholm score (r = −0.753) (p < 0.01 for both). CONCLUSIONS: The HA added PLLA screws would be advantageous for tibial graft fixation by reducing tibial tunnel widening, improving osteointegration, and lowering foreign body reactions. Even though no clinically significant differences were noted between the pure PLLA group and PLLA-HA group, widening of the proximal area of the tibial tunnel showed a tendency to increase knee laxity measured using the KT-2000 arthrometer.
Anterior Cruciate Ligament ; Durapatite ; Foreign Bodies ; Humans ; Knee ; Lysholm Knee Score ; Magnetic Resonance Imaging* ; Retrospective Studies ; Transplants

PURPOSE: In Korea, registration of paraquat-containing herbicides was canceled in November 2011, and sales thereof were completely banned in November 2012. We evaluated the effect of the paraquat ban on the epidemiology and mortality of herbicide-induced poisoning. MATERIALS AND METHODS: This retrospective study analyzed patients treated for herbicide poisoning at 17 emergency departments in South Korea between January 2010 and December 2014. The overall and paraquat mortality rates were compared pre- and post-ban. Factors associated with herbicide mortality were evaluated using logistic analysis. To determine if there were any changes in the mortality rates before and after the paraquat sales ban and the time point of any such significant changes in mortality, R software, version 3.0.3 (package, bcp) was used to perform a Bayesian change point analysis. RESULTS: We enrolled 2257 patients treated for herbicide poisoning (paraquat=46.8%). The overall and paraquat poisoning mortality rates were 40.6% and 73.0%, respectively. The decreased paraquat poisoning mortality rate (before, 75% vs. after, 67%, p=0.014) might be associated with increased intentionality. The multivariable logistic analysis revealed the paraquat ban as an independent predictor that decreased herbicide poisoning mortality (p=0.035). There were two major change points in herbicide mortality rates, approximately 3 months after the initial paraquat ban and 1 year after complete sales ban. CONCLUSION: This study suggests that the paraquat ban decreased intentional herbicide ingestion and contributed to lowering herbicide poisoning-associated mortality. The change point analysis suggests a certain timeframe was required for the manifestation of regulatory measures outcomes.
Commerce ; Eating ; Emergency Service, Hospital ; Epidemiology ; Herbicides ; Humans ; Intention ; Korea ; Mortality* ; Paraquat* ; Poisoning ; Retrospective Studies

We investigated the inhibitory effect of escitalopram, a selective serotonin reuptake inhibitor (SSRI), on voltage-dependent K⁺ (Kv) channels in freshly separated from rabbit coronary arterial smooth muscle cells. The application of escitalopram rapidly inhibited vascular Kv channels. Kv currents were progressively inhibited by an increase in the concentrations of escitalopram, suggesting that escitalopram inhibited vascular Kv currents in a concentration-dependent manner. The IC₅₀ value and Hill coefficient for escitalopram-induced inhibition of Kv channels were 9.54±1.33 µM and 0.75±0.10, respectively. Addition of escitalopram did not alter the steady-state activation and inactivation curves, suggesting that the voltage sensors of the channels were not affected. Pretreatment with inhibitors of Kv1.5 and/or Kv2.1 did not affect the inhibitory action of escitalopram on vascular Kv channels. From these results, we concluded that escitalopram decreased the vascular Kv current in a concentration-dependent manner, independent of serotonin reuptake inhibition.
Citalopram* ; Coronary Vessels ; Muscle, Smooth* ; Myocytes, Smooth Muscle* ; Serotonin*

We demonstrated the effect of nortriptyline, a tricyclic antidepressant drug and serotonin reuptake inhibitor, on voltage-dependent K⁺ (Kv) channels in freshly isolated rabbit coronary arterial smooth muscle cells using a whole-cell patch clamp technique. Nortriptyline inhibited Kv currents in a concentration-dependent manner, with an apparent IC₅₀ value of 2.86±0.52 µM and a Hill coefficient of 0.77±0.1. Although application of nortriptyline did not change the activation curve, nortriptyline shifted the inactivation current toward a more negative potential. Application of train pulses (1 or 2 Hz) did not change the nortriptyline-induced Kv channel inhibition, suggesting that the effects of nortiprtyline were not use-dependent. Preincubation with the Kv1.5 and Kv2.1/2.2 inhibitors, DPO-1 and guangxitoxin did not affect nortriptyline inhibition of Kv channels. From these results, we concluded that nortriptyline inhibited Kv channels in a concentration-dependent and state-independent manner independently of serotonin reuptake.
Coronary Vessels ; Muscle, Smooth* ; Myocytes, Smooth Muscle* ; Nortriptyline* ; Serotonin

PURPOSE: This study evaluated the effect of surgery-radiotherapy interval (SRI) on outcomes in patients treated with adjuvant radiotherapy (RT) after breast-conserving surgery (BCS) and adjuvant four cycles of doxorubicin/cyclophosphamide (AC) followed by four cycles of taxane. MATERIALS AND METHODS: From 1999 to 2007, 397 eligible patients were diagnosed. The effect of SRI on outcomes was analyzed using a Cox proportional hazards model, and a maximal chi-square method was used to identify optimal cut-off value of SRI for each outcome. RESULTS: The median SRI was 6.7 months (range, 5.6 to 10.3 months). A SRI of 7 months was the significant cut-off value for distant metastasis-free survival (DMFS) and disease-free survival (DFS) using a maximal chi-square method. For overall survival, a significant cut-off value was not found. The patients with SRI > 7 months had worse 6-year DMFS and DFS than those with SRI ≤ 7 months on univariate analysis (DMFS, 81% vs. 91%, p=0.003; DFS, 78% vs. 89%, p=0.002). On multivariate analysis, SRI > 7 months did not affect DMFS and DFS. CONCLUSION: RT delayed for more than 7 months after BCS and adjuvant four cycles of AC followed by four cycles of taxane did not compromise clinical outcomes.
Breast Neoplasms* ; Breast* ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Humans ; Mastectomy, Segmental* ; Multivariate Analysis ; Proportional Hazards Models ; Radiotherapy ; Radiotherapy, Adjuvant ; Time-to-Treatment