Purpose: Despite the increasing use of immediate breast reconstruction (IBR), its oncologic safety in the setting of neoadjuvant chemotherapy (NACT) needs to be comprehensively clarified in breast cancer management. The objective of the present study was to analyze the oncologic safety of IBR following NACT. Methods: In total, 587 patients with breast cancer who underwent a total mastectomy (TM) with IBR after NACT between 2008 and 2017 at a single institution were retrospectively reviewed. The reviewed patients with IBR following skin-sparing mastectomy (SSM) or nipple-sparing mastectomy (NSM) were matched 1:3 to patients who underwent TM alone after NACT. Matching variables included age, clinical T and N stages before NACT, response to NACT, pathologic T and N stages, and molecular subtypes. Results: After propensity score matching, 95 patients who underwent IBR following SSM/ NSM after NACT (IBR group) and 228 patients who underwent TM alone after NACT (TM group) were selected. The median follow-up period was 73 (range, 5–181) months after matching. After matching, there were no significant differences between the two groups in 5-year locoregional recurrence-free survival (88.8% vs. 91.2%, p = 0.516), disease-free survival (67.3% vs. 76.6%, p = 0.099), distant metastasis-free survival (71.9% vs. 81.9%, p = 0.057), or overall survival (84.1% vs. 91.5, p = 0.061) rates. In multivariate analyses, conducting IBR was not associated with increased risks for locoregional recurrence, any recurrence, distant metastasis, or overall death. Conclusion Our findings suggest that IBR following SSM/NSM elicits comparable long-term oncologic outcomes to those of TM alone in the setting of NACT.

Purpose: K-MASTER project is a Korean national precision medicine platform that screened actionable mutations by analyzing next-generation sequencing (NGS) of solid tumor patients. We compared gene analyses between NGS panel from the K-MASTER project and orthogonal methods. Materials and Methods: Colorectal, breast, non–small cell lung, and gastric cancer patients were included. We compared NGS results from K-MASTER projects with those of non-NGS orthogonal methods (KRAS, NRAS, and BRAF mutations in colorectal cancer [CRC]; epidermal growth factor receptor [EGFR], anaplastic lymphoma kinase [ALK] fusion, and reactive oxygen species 1 [ROS1] fusion in non–small cell lung cancer [NSCLC], and Erb-B2 receptor tyrosine kinase 2 (ERBB2) positivity in breast and gastric cancers). Results: In the CRC cohort (n=225), the sensitivity and specificity of NGS were 87.4% and 79.3% (KRAS); 88.9% and 98.9% (NRAS); and 77.8% and 100.0% (BRAF), respectively. In the NSCLC cohort (n=109), the sensitivity and specificity of NGS for EGFR were 86.2% and 97.5%, respectively. The concordance rate for ALK fusion was 100%, but ROS1 fusion was positive in only one of three cases that were positive in orthogonal tests. In the breast cancer cohort (n=260), ERBB2 amplification was detected in 45 by NGS. Compared with orthogonal methods that integrated immunohistochemistry and in situ hybridization, sensitivity and specificity were 53.7% and 99.4%, respectively. In the gastric cancer cohort (n=64), ERBB2 amplification was detected in six by NGS. Compared with orthogonal methods, sensitivity and specificity were 62.5% and 98.2%, respectively. Conclusion The results of the K-MASTER NGS panel and orthogonal methods showed a different degree of agreement for each genetic alteration, but generally showed a high agreement rate.

The ezrin-radixin-moesin (ERM) proteins are a family of membrane-associated proteins known to play roles in cell-shape determination as well as in signaling pathways. We have previously shown that amphetamine decreases phosphorylation levels of these proteins in the nucleus accumbens (NAcc), an important neuronal substrate mediating rewarding effects of drugs of abuse. In the present study, we further examined what molecular pathways may be involved in this process. By direct microinjection of LY294002, a PI3 kinase inhibitor, or of S9 peptide, a proposed GSK3β activator, into the NAcc core, we found that phosphorylation levels of ERM as well as of GSK3β in this site are simultaneously decreased. These results indicate that ERM proteins are under the regulation of Akt-GSK3β signaling pathway in the NAcc core. The present findings have a significant implication to a novel signal pathway possibly leading to structural plasticity in relation with drug addiction.
Amphetamine ; Animals ; Glycogen Synthase Kinases ; Humans ; Membrane Proteins ; Microinjections ; Negotiating ; Neurons ; Nucleus Accumbens ; Phosphorylation ; Phosphotransferases ; Plastics ; Proto-Oncogene Proteins c-akt ; Rats ; Reward ; Signal Transduction ; Street Drugs ; Substance-Related Disorders

BACKGROUND: The lack of medical personnel has led to the employment of hospitalists in Korean hospitals to provide high-quality medical care. However, whether hospitalists' care can improve patients' outcomes remains unclear. We aimed to analyze the outcome in patients cared for by hospitalists. METHODS: A retrospective review was conducted in 1,015 patients diagnosed with pneumonia or urinary tract infection from March 2017 to July 2018. After excluding 306 patients, 709 in the general ward who were admitted via the emergency department were enrolled, including 169 and 540 who were cared for by hospitalists (HGs) and non-hospitalists (NHGs), respectively. We compared the length of hospital stay (LOS), in-hospital mortality, readmission rate, comorbidity, and disease severity between the two groups. Comorbidities were analyzed using Charlson comorbidity index (CCI). RESULTS: HG LOS (median, interquartile range [IQR], 8 [5–12] days) was lower than NHG LOS (median [IQR], 10 [7–15] days), (P < 0.001). Of the 30 (4.2%) patients who died during their hospital stay, a lower percentage of HG patients (2.4%) than that of NHG patients (4.8%) died, but the difference between the two groups was not significant (P = 0.170). In a subgroup analysis, HG LOS was shorter than NHG LOS (median [IQR], 8 [5–12] vs. 10 [7–16] days, respectively, P < 0.001) with CCI of ≥ 5 points. CONCLUSION: Hospitalist care can improve the LOS of patients, especially those with multiple comorbidities. Further studies are warranted to evaluate the impact of hospitalist care in Korea.
Comorbidity ; Emergency Service, Hospital ; Employment ; Hospital Mortality ; Hospitalists ; Humans ; Korea ; Length of Stay ; Patients' Rooms ; Pneumonia ; Retrospective Studies ; Urinary Tract Infections

Ceramide metabolism is known to be an essential etiology for various diseases, such as atopic dermatitis and Gaucher disease. Glucosylceramide synthase (GCS) is a key enzyme for the synthesis of glucosylceramide (GlcCer), which is a main ceramide metabolism pathway in mammalian cells. In this article, we developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to determine GCS activity using synthetic non-natural sphingolipid C8-ceramide as a substrate. The reaction products, C8-GlcCer for GCS, could be separated on a C18 column by reverse-phase high-performance liquid chromatography (HPLC). Quantification was conducted using the multiple reaction monitoring (MRM) mode to monitor the precursor-to-product ion transitions of m/z 588.6 → 264.4 for C8-GlcCer at positive ionization mode. The calibration curve was established over the range of 0.625–160 ng/mL, and the correlation coefficient was larger than 0.999. This method was successfully applied to detect GCS in the human hepatocellular carcinoma cell line (HepG2 cells) and mouse peripheral blood mononuclear cells. We also evaluated the inhibition degree of a known GCS inhibitor 1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) on GCS enzymatic activity and proved that this method could be successfully applied to GCS inhibitor screening of preventive and therapeutic drugs for ceramide metabolism diseases, such as atopic dermatitis and Gaucher disease.
Animals ; Calibration ; Carcinoma, Hepatocellular ; Cell Line ; Chromatography, Liquid ; Dermatitis, Atopic ; Gaucher Disease ; Humans ; Mass Screening ; Mass Spectrometry ; Metabolism ; Methods ; Mice

Ethnically specific data on genetic variation are crucial for understanding human biology and for clinical interpretation of variant pathogenicity. We analyzed data obtained by deep sequencing 1303 Korean whole exomes; the data were generated by three independent whole exome sequencing projects (named the KOEX study). The primary focus of this study was to comprehensively analyze the variant statistics, investigate secondary findings that may have clinical actionability, and identify loci that should be cautiously interpreted for pathogenicity. A total of 495 729 unique variants were identified at exonic regions, including 169 380 nonsynonymous variants and 4356 frameshift insertion/deletions. Among these, 76 607 were novel coding variants. On average, each individual had 7136 nonsynonymous single-nucleotide variants and 74 frameshift insertion/deletions. We classified 13 pathogenic and 13 likely pathogenic variants in 56 genes that may have clinical actionability according to the guidelines of the American College of Medical Genetics and Genomics, and the Association for Molecular Pathology. The carrier frequency of these 26 variants was 2.46% (95% confidence interval 1.73–3.46). To identify loci that require cautious interpretation in clinical sequencing, we identified 18 genes that are prone to sequencing errors, and 671 genes that are highly polymorphic and carry excess nonsynonymous variants. The catalog of identified variants, its annotation and frequency information are publicly available (https://koex.snu.ac.kr). These findings should be useful resources for investigating ethnically specific characteristics in human health and disease.
Biology ; Clinical Coding ; Exome ; Exons ; Genetic Variation ; Genetics, Medical ; Genomics ; High-Throughput Nucleotide Sequencing ; Humans ; Pathology, Molecular ; Virulence

In 2010, we proposed the first Korean Guidelines for the Prevention of Venous Thromboembolism (VTE). It was applicable to Korean patients, by modifying the contents of the second edition of the Japanese guidelines for the prevention of VTE and the 8th edition of the American College of Chest Physicians (ACCP) evidence-based clinical practice guidelines. From 2007 to 2011, we conducted a nationwide study regarding the incidence of VTE after major surgery using the Health Insurance Review and Assessment Service (HIRA) database. In addition, we have considered the 9th edition of the ACCP Evidenced-Based Clinical Practice Guidelines, published in 2012. It emphasized the importance of clinically relevant events as opposed to asymptomatic outcomes with preferences for both thrombotic and bleeding outcomes. Thus, in the development of the new Korean guidelines, three major points were addressed: 1) the new guidelines stratify patients into 4 risk groups (very low, low, moderate, and high) according to the actual incidence of symptomatic VTE from the HIRA databases; 2) the recommended optimal VTE prophylaxis for each group was modified according to condition-specific thrombotic and bleeding risks; 3) guidelines are intended for general information only, are not medical advice, and do not replace professional medical care and/or physician advice.
Age Factors ; Anticoagulants/adverse effects/*therapeutic use ; Asian Continental Ancestry Group ; Evidence-Based Medicine ; Heparin, Low-Molecular-Weight/therapeutic use ; Humans ; *Mechanical Thrombolysis ; Neoplasms/complications/surgery ; Republic of Korea ; Risk Assessment ; Surgical Procedures, Operative/adverse effects ; Venous Thromboembolism/etiology/prevention & control/*therapy

PURPOSE: This study was performed in order to determine the changes over time in preventable and potentially preventable traumatic death rates, and to assess the factors that affected the deaths of trauma patients which occurred in Korean pre-hospital and hospital settings. METHODS: All trauma deaths occurring either in the emergency department (ED) or after admission at twenty Korean hospitals between August 2009 and July 2010 were retrospectively analyzed. The deaths were initially reviewed by a team of multidisciplinary specialists and classified into non-preventable, potentially preventable, and preventable deaths. Only preventable and potentially preventable deaths were the subject of our analysis. Structured data extraction included patient demographics, vital signs, injury severity, probability of survival, preventability of mortality, reported errors in the evaluation and management of the patient, and classification of error types (system, judgment, knowledge). RESULTS: During the study period, 446 trauma victims died in the ED or within 7 days after admission. The mean age was 52 years, 74.1% were men and the mean time from injury to death was 35.6 hours. The most common cause of death was head injury (44.7%) followed by hemorrhage (30.8%) and multi-organ failure (8.0%). The rates of preventable/potentially preventable deaths were 35.2% overall and 29.8% when limited to patients surviving to admission. Of all death classifications, 31.2% were potentially preventable and 4.0% were preventable. Errors leading to preventable death occurred in the emergency department (51.2%), pre-hospital setting (30.3%) and during inter-hospital transfer (60.8%). Most errors were related to clinical management (48.4%) and structural problems in the emergency medical system (36.5%). CONCLUSION: The preventable death rates for Korean trauma victims were higher than those found in other developed countries, possibly due to poorly established emergency medical systems for trauma victims in pre-hospital and hospital settings. A system wide approach based on the emergency medical system and well-developed in-hospital trauma teams should be adopted in order to improve the quality of care of trauma victims in Korea.
Cause of Death ; Craniocerebral Trauma ; Demography ; Developed Countries ; Emergencies ; Emergency Medical Services ; Hemorrhage ; Humans ; Judgment ; Korea ; Male ; Retrospective Studies ; Specialization ; Vital Signs

Repeated administration of amphetamine (AMPH) produces behavioral sensitization, a proposed model for the escalation of drug use characteristic of human addicts. beta-Phenylethylamine (PEA) is an endogenous trace amine found in mammalian brain and resembles AMPH both structurally and behaviorally. Previously, it has been reported that chronic PEA administration produces behavioral sensitization to the challenges of AMPH. However, these data were obtained with very high amount of PEA for a relatively long period of time. Further, the effect of PEA challenge on the expression of behavioral sensitization developed by AMPH pre-exposures has not been tested yet. Thus, we examined in the present experiment the expression of behavioral sensitization with AMPH challenge after a mild chronic PEA treatment. Rats were repeatedly administered with systemic injections of saline, beta-phenylethylamine (PEA) (10 or 50 mg/kg), or amphetamine (AMPH) (1.5 mg/kg). When challenged a week after the last pre-injection, rats pre-exposed to either PEA or AMPH showed behavioral sensitization to AMPH (1.0 mg/kg), while these effects were not observed to PEA (50 mg/kg) itself. These results demonstrate that repeated exposure to PEA produces behavioral sensitization to AMPH challenge, while PEA challenge has no effect on the expression of behavioral sensitization developed by AMPH pre-exposures, suggesting that PEA may play a role in the development of locomotor sensitization to AMPH, but not in the expression of it.
Amphetamine ; Animals ; Brain ; Humans ; Peas ; Phenethylamines ; Rats ; Schizophrenia

OBJECTIVE: Patients with lung cancer have a relative high risk of developing secondary primary lung cancers. This study examined the additional value of autofluorescence bronchoscopy (AFB) for diagnosing synchronous lung cancers and premalignant lesions. METHODS: Patients diagnosed with lung cancer from January 2005 to December 2005 were enrolled in this study. The patients underwent a lung cancer evaluation, which included white light bronchoscopy (WLB), followed by AFB. In addition to the primary lesions, any abnormal or suspicious lesions detected during WLB and AFB were biopsied. RESULTS: Seventy-six patients had non-small cell lung cancer (NSCLC) and 23 had small cell lung cancer (SCLC). In addition to the primary lesions, 84 endobronchial biopsies were performed in 46 patients. Five definite synchronous cancerous lesions were detected in three patients with initial unresectable NSCLC and in one with SCLC. The secondary malignant lesions found in two patients were considered metastatic because of the presence of mediastinal nodes or systemic involvement. One patient with an unresectable NSCLC, two with a resectable NSCLC, and one with SCLC had severe dysplasia. The detection rate for cancerous lesions by the clinician was 6.0% (6/99) including AFB compared with 3.0% (3/99) with WLB alone. The prevalence of definite synchronized cancer was 4.0% (4/99) after using AFB compared with 2.0% (2/99) before, and the staging-up effect was 1.0% (1/99) after AFB. Since the majority of patients were diagnosed with advanced disease, the subjects with newly detected cancerous lesions did not have their treatment plans altered, except for one patient with a stage-up IV NSCLC who did not undergo radiotherapy. CONCLUSIONS: Additional AFB is effective in detecting early secondary cancerous lesions and is a more precise tool in the staging workup of patients with primary lung cancer than with WLB alone.
Biopsy ; Bronchoscopy* ; Carcinoma, Non-Small-Cell Lung ; Humans ; Lung Neoplasms* ; Lung* ; Prevalence ; Radiotherapy ; Small Cell Lung Carcinoma