Purpose: Considering the high disease burden and unique features of Asian patients with breast cancer (BC), it is essential to have a comprehensive view of genetic characteristics in this population. An institutional targeted sequencing platform was developed through the Korea Research-Driven Hospitals project and was incorporated into clinical practice. This study explores the use of targeted next-generation sequencing (NGS) and its outcomes in patients with advanced/metastatic BC in the real world. Materials and Methods: We reviewed the results of NGS tests administered to BC patients using a customized sequencing platform—FiRST Cancer Panel (FCP)—over 7 years. We systematically described clinical translation of FCP for precise diagnostics, personalized therapeutic strategies, and unraveling disease pathogenesis. Results: NGS tests were conducted on 548 samples from 522 patients with BC. Ninety-seven point six percentage of tested samples harbored at least one pathogenic alteration. The common alterations included mutations in TP53 (56.2%), PIK3CA (31.2%), GATA3 (13.8%), BRCA2 (10.2%), and amplifications of CCND1 (10.8%), FGF19 (10.0%), and ERBB2 (9.5%). NGS analysis of ERBB2 amplification correlated well with human epidermal growth factor receptor 2 immunohistochemistry and in situ hybridization. RNA panel analyses found potentially actionable and prognostic fusion genes. FCP effectively screened for potentially germline pathogenic/likely pathogenic mutation. Ten point three percent of BC patients received matched therapy guided by NGS, resulting in a significant overall survival advantage (p=0.022), especially for metastatic BCs. Conclusion Clinical NGS provided multifaceted benefits, deepening our understanding of the disease, improving diagnostic precision, and paving the way for targeted therapies. The concrete advantages of FCP highlight the importance of multi-gene testing for BC, especially for metastatic conditions.

Purpose: Considering the high disease burden and unique features of Asian patients with breast cancer (BC), it is essential to have a comprehensive view of genetic characteristics in this population. An institutional targeted sequencing platform was developed through the Korea Research-Driven Hospitals project and was incorporated into clinical practice. This study explores the use of targeted next-generation sequencing (NGS) and its outcomes in patients with advanced/metastatic BC in the real world. Materials and Methods: We reviewed the results of NGS tests administered to BC patients using a customized sequencing platform—FiRST Cancer Panel (FCP)—over 7 years. We systematically described clinical translation of FCP for precise diagnostics, personalized therapeutic strategies, and unraveling disease pathogenesis. Results: NGS tests were conducted on 548 samples from 522 patients with BC. Ninety-seven point six percentage of tested samples harbored at least one pathogenic alteration. The common alterations included mutations in TP53 (56.2%), PIK3CA (31.2%), GATA3 (13.8%), BRCA2 (10.2%), and amplifications of CCND1 (10.8%), FGF19 (10.0%), and ERBB2 (9.5%). NGS analysis of ERBB2 amplification correlated well with human epidermal growth factor receptor 2 immunohistochemistry and in situ hybridization. RNA panel analyses found potentially actionable and prognostic fusion genes. FCP effectively screened for potentially germline pathogenic/likely pathogenic mutation. Ten point three percent of BC patients received matched therapy guided by NGS, resulting in a significant overall survival advantage (p=0.022), especially for metastatic BCs. Conclusion Clinical NGS provided multifaceted benefits, deepening our understanding of the disease, improving diagnostic precision, and paving the way for targeted therapies. The concrete advantages of FCP highlight the importance of multi-gene testing for BC, especially for metastatic conditions.

Purpose: Considering the high disease burden and unique features of Asian patients with breast cancer (BC), it is essential to have a comprehensive view of genetic characteristics in this population. An institutional targeted sequencing platform was developed through the Korea Research-Driven Hospitals project and was incorporated into clinical practice. This study explores the use of targeted next-generation sequencing (NGS) and its outcomes in patients with advanced/metastatic BC in the real world. Materials and Methods: We reviewed the results of NGS tests administered to BC patients using a customized sequencing platform—FiRST Cancer Panel (FCP)—over 7 years. We systematically described clinical translation of FCP for precise diagnostics, personalized therapeutic strategies, and unraveling disease pathogenesis. Results: NGS tests were conducted on 548 samples from 522 patients with BC. Ninety-seven point six percentage of tested samples harbored at least one pathogenic alteration. The common alterations included mutations in TP53 (56.2%), PIK3CA (31.2%), GATA3 (13.8%), BRCA2 (10.2%), and amplifications of CCND1 (10.8%), FGF19 (10.0%), and ERBB2 (9.5%). NGS analysis of ERBB2 amplification correlated well with human epidermal growth factor receptor 2 immunohistochemistry and in situ hybridization. RNA panel analyses found potentially actionable and prognostic fusion genes. FCP effectively screened for potentially germline pathogenic/likely pathogenic mutation. Ten point three percent of BC patients received matched therapy guided by NGS, resulting in a significant overall survival advantage (p=0.022), especially for metastatic BCs. Conclusion Clinical NGS provided multifaceted benefits, deepening our understanding of the disease, improving diagnostic precision, and paving the way for targeted therapies. The concrete advantages of FCP highlight the importance of multi-gene testing for BC, especially for metastatic conditions.

Fungi are a major cause of human infections with diverse clinical manifestations. The incidence of fungal infections has increased over time, particularly in patients who have risk factors such as neutropenia, immune suppression, an intravascular catheter, parenteral nutrition, a prosthetic device, and prior broad spectrum antibiotic therapy. Here, we present an unusual case of co-infection by 2 distinct fungi, Candida parapsilosis and Trichosporon asahii, isolated from a patient who did not have any known risk factors initially, except active pulmonary tuberculosis. Despite the negative conversion of sputum acid-fast bacilli (AFB) culture test after treatment, clinical symptoms were refractory to therapy. The patient developed symptoms suggesting septic shock, and 2 distinct colonies were isolated from a blood specimen, which were identified as C. parapsilosis and T. asahii by MALDI-TOF and rRNA sequencing. Fever and hypotension were relieved after anti-fungal agent injection, and pulmonary lesions identified by imaging also improved.
Candida ; Catheters ; Coinfection ; Fever ; Fungemia ; Fungi ; Humans ; Hypotension ; Incidence ; Neutropenia ; Parenteral Nutrition ; Risk Factors ; Shock, Septic ; Sputum ; Trichosporon ; Tuberculosis, Pulmonary

BACKGROUND: Several factors contribute to differences in Streptococcus pneumoniae serotype distribution. We investigated the serotype distribution and antimicrobial resistance of S. pneumoniae isolated between 2014 and 2016 in Korea. METHODS: We collected a total of 1,855 S. pneumoniae isolates from 44 hospitals between May 2014 and May 2016, and analyzed the serotypes by sequential multiplex PCR. We investigated the distribution of each serotype by patient age, source of the clinical specimen, and antimicrobial resistance pattern. RESULTS: The most common serotypes were 11A (10.1%), followed by 19A (8.8%), 3 (8.5%), 34 (8.1%), 23A (7.3%), and 35B (6.2%). The major invasive serotypes were 3 (12.6%), 19A (7.8%), 34 (7.8%), 10A (6.8%), and 11A (6.8%). Serotypes 10A, 15B, 19A, and 12F were more common in patients ≤5 years old, while serotype 3 was more common in patients ≥65 years old compared with the other age groups. The coverage rates of pneumococcal conjugate vaccine (PCV)7, PCV10, PCV13, and pneumococcal polysaccharide vaccine 23 were 11.8%, 12.12%, 33.3%, and 53.6%, respectively. Of the 1,855 isolates, 857 (46.2%) were multi-drug resistant (MDR), with serotypes 11A and 19A predominant among the MDR strains. The resistance rates against penicillin, cefotaxime, and levofloxacin were 22.8%, 12.5%, and 9.4%, respectively. CONCLUSIONS: There were significant changes in the major S. pneumoniae serotypes in the community. Non-PCV13 serotypes increased in patients ≤5 years old following the introduction of national immunization programs with the 10- and 13-polyvalent vaccines.
Cefotaxime ; Humans ; Immunization Programs ; Korea ; Levofloxacin ; Multiplex Polymerase Chain Reaction ; Penicillins ; Pneumococcal Vaccines ; Pneumonia ; Serogroup ; Streptococcus pneumoniae ; Streptococcus ; Vaccines

BACKGROUND: Hemorheologic indices are known to be related to vascular complications in variable clinical settings. However, little is known about the associations between hemorheologic parameters and acute myocardial infarction (AMI) in type 2 diabetes mellitus (T2DM). The purpose of this study was to demonstrate the changes of hemorheologic environment inside of blood using hemorheologic parameters, especially the elongation index (EI) and critical shear stress (CSS) in diabetics with versus without AMI. METHODS: A total of 195 patients with T2DM were enrolled. Patients were divided into the study group with AMI (AMI+, n = 77) and control group (AMI−, n = 118) who had no history of coronary artery disease. Hemorheologic parameters such as EI and CSS were measured and compared between the two groups. RESULTS: The EI was lower (30.44%±1.77% in AMI+ and 31.47%±1.48% in AMI−, P < 0.001) but the level of CSS was higher (316.13±108.20 mPa in AMI+ and 286.80±85.34 mPa in AMI−, P = 0.040) in the AMI+. The CSS was significantly related to the erythrocyte sedimentation rate (R² = 0.497, P < 0.001) and use of dipeptidyl peptidase-4 inhibitors (R² = 0.574, P = 0.048). CONCLUSION: Diabetics with AMI resulted in adverse hemorheologic changes with lower EI and higher CSS compared to diabetic subjects without AMI. Evaluation of the hemorheologic parameters may provide valuable supplementary information for managing patients with AMI and T2DM.
Blood Sedimentation ; Coronary Artery Disease ; Diabetes Mellitus, Type 2* ; Erythrocyte Deformability ; Hemorheology ; Humans ; Myocardial Infarction*

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PURPOSE: The fourth state of matter, plasma is known as an ionized gas with electrons, radicals and ions. The use of non-thermal plasma (NTP) in cancer research became possible because of the progresses in plasma medicine. Previous studies on the potential NTP-mediated cancer therapy have mainly concentrated on cancer cell apoptosis. In the present study, we compared the inhibitory effect of NTP on cell migration and invasion in the oral squamous cancer cell lines. MATERIALS AND METHODS: We used oral squamous cancer cell lines (SCC1483, MSKQLL1) and different gases (N₂, He, and Ar). To investigate the mechanism of plasma treatment, using different gases (N₂, He, and Ar) which induces anti-migration and anti-invasion properties, we performed wound healing assay, invasion assay and gelatin zymography. RESULTS: The results showed that NTP inhibits cancer cell migration and invasion of oral squamous cancer cell. In addition, focal adhesion kinase expression and matrix metalloproteinase-2/9 activity were also inhibited. CONCLUSION: The suppression of cancer cell invasion by NTP varied depending on the type of gas. Comparison of the three gases revealed that N₂ NTP inhibited cell migration and invasion most potently via decreased expression of focal adhesion kinase and matrix metalloproteinase activity.
Apoptosis ; Cell Line ; Cell Movement ; Epithelial Cells* ; Focal Adhesion Protein-Tyrosine Kinases ; Gases ; Gelatin ; Ions ; Neoplasms, Squamous Cell* ; Paxillin ; Plasma ; Plasma Gases* ; Wound Healing

PURPOSE: To determine the effects of nonthermal plasma (NTP) induced by helium (He) alone or He plus oxygen (O2) on the generation of reactive oxygen species (ROS) and cell death in anaplastic thyroid cancer cells. MATERIALS AND METHODS: NTP was generated in He alone or He plus O2 blowing through a nozzle by applying a high alternating current voltage to the discharge electrodes. Optical emission spectroscopy was used to identify various excited plasma species. The apoptotic effect of NTP on the anaplastic thyroid cancer cell lines, such as HTH83, U-HTH 7, and SW1763, was verified with annexin V/propidium staining and TUNEL assay. ROS formation after NTP treatment was identified with fluorescence-activated cell sorting with DCFDA staining. The mitogen-activated protein kinase pathways and caspase cascade were investigated to evaluate the molecular mechanism involved and cellular targets of plasma. RESULTS: NTP induced significant apoptosis in all three cancer cell lines. The plasma using He and O2 generated more O2-related species, and increased apoptosis and intracellular ROS formation compared with the plasma using He alone. NTP treatment of SW1763 increased the expression of phosphor-JNK, phosphor-p38, and caspase-3, but not phosphor-ERK. Apoptosis of SW1763 as well as expressions of elevated phosphor-JNK, phosphor-p38, and caspase-3 induced by NTP were effectively inhibited by intracellular ROS scavengers. CONCLUSION: NTP using He plus O2 induced significant apoptosis in anaplastic cancer cell lines through intracellular ROS formation. This may represent a new promising treatment modality for this highly lethal disease.
Apoptosis/*drug effects ; Caspase 3/*metabolism ; Flow Cytometry ; Humans ; Male ; Plasma Gases/*pharmacology ; Reactive Oxygen Species/*metabolism ; Spectrometry, X-Ray Emission ; Thyroid Carcinoma, Anaplastic ; p38 Mitogen-Activated Protein Kinases/*metabolism

OBJECTIVE: The aim of this study was to document the natural course of asymptomatic adult moyamoya disease (MMD) and the factors related to disease progression to aid in treatment decisions. MATERIALS AND METHODS: Among 459 adult MMD patients (aged > or = 20 years), 42 patients were included in this retrospective cohort study. Clinical records of adult asymptomatic MMD patients (n = 42) and follow-up data from September 2013 were reviewed to determine the factors related to disease progression. RESULTS: The mean age of patients at the time of diagnosis was 41.2 years (range, 23-64 years), and the mean follow-up period was 37.3 months (range, 7.4-108.7 months). Of the 42 patients and 75 hemispheres, there were 12 patients (28.6%) and 13 hemispheres (17.3%) with disease progression. There were four hemispheres (5.3%) with symptomatic progression (three hemorrhage, one transient ischemic attack) and nine hemispheres (12.0%) with asymptomatic radiographic progression. There were no relationships with sex, diabetes, hypertension, thyroid disease, family history of MMD, or family history of stroke. However, reduced initial cerebrovascular reserve capacity was observed in seven hemispheres (9.3%) in patients with disease progression. A relationship was found between disease progression and initial cerebrovascular reserve capacity (p = 0.05). None of the patients underwent bypass surgery during the follow-up period. CONCLUSION: It appears that asymptomatic adult MMD is not a permanent stable disease. In particular, reduced cerebrovascular reserve capacity is an indication of MMD progression, so close regular observation is needed.
Adult* ; Asymptomatic Diseases ; Cerebrovascular Disorders ; Cohort Studies ; Diagnosis ; Disease Progression ; Follow-Up Studies ; Hemorrhage ; Humans ; Hypertension ; Moyamoya Disease* ; Retrospective Studies ; Stroke ; Thyroid Diseases