Purpose: Mutations in the PIK3CA gene occur frequently in breast cancer patients. Activating PIK3CA mutations confer resistance to human epidermal growth factor receptor 2 (HER2)-targeted treatments. In this study, we investigated whether PIK3CA mutations were correlated with treatment response or duration in patients with HER2-positive (HER2+) breast cancer. Materials and Methods: We retrospectively reviewed the clinical information of patients with HER2+ breast cancer who received HER2-targeted therapy for early-stage or metastatic cancers. The pathologic complete response (pCR), progression-free survival (PFS), and overall survival were compared between patients with wild-type PIK3CA (PIK3CAw) and those with mutated PIK3CA (PIK3CAm). Next-generation sequencing was combined with examination of PFS associated with anti-HER2 monoclonal antibody (mAb) treatment. Results: Data from 90 patients with HER2+ breast cancer were analyzed. Overall, 34 (37.8%) patients had pathogenic PIK3CA mutations. The pCR rate of the PIK3CAm group was lower than that of the PIK3CAw group among patients who received neoadjuvant chemotherapy for early-stage cancer. In the metastatic setting, the PIK3CAm group showed a significantly shorter mean PFS (mPFS) with first-line anti-HER2 mAb. The mPFS of second-line T-DM1 was lower in the PIK3CAm group than that in the PIK3CAw group. Sequencing revealed differences in the mutational landscape between PIK3CAm and PIK3CAw tumors. Conclusion Patients with HER2+ breast cancer with activating PIK3CA mutations had lower pCR rates and shorter PFS with palliative HER2-targeted therapy than those with wild-type PIK3CA. Precise targeted-therapy is needed to improve survival of patients with HER2+/PIK3CAm breast cancer.

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.

Purpose: Next-generation sequencing (NGS) can facilitate precision medicine approaches in metastatic colorectal cancer (mCRC) patients. We investigated the molecular profiling of Korean mCRC patients under the K-MASTER project which was initiated in June 2017 as a nationwide precision medicine oncology clinical trial platform which used NGS assay to screen actionable mutations. Materials and Methods: As of 22 January 2020, total of 994 mCRC patients were registered in K-MASTER project. Targeted sequencing was performed using three platforms which were composed of the K-MASTER cancer panel v1.1 and the SNUH FIRST Cancer Panel v3.01. If tumor tissue was not available, cell-free DNA was extracted and the targeted sequencing was performed by Axen Cancer Panel as a liquid biopsy. Results: In 994 mCRC patients, we found 1,564 clinically meaningful pathogenic variants which mutated in 71 genes. Anti-EGFR therapy candidates were 467 patients (47.0%) and BRAF V600E mutation (n=47, 4.7%), deficient mismatch repair/microsatellite instability–high (n=15, 1.5%), HER2 amplifications (n=10, 1.0%) could be incorporated with recently approved drugs. The patients with high tumor mutation burden (n=101, 12.7%) and DNA damaging response and repair defect pathway alteration (n=42, 4.2%) could be enrolled clinical trials with immune checkpoint inhibitors. There were more colorectal cancer molecular alterations such as PIK3CA, KRAS G12C, atypical BRAF, and HER2 mutations and even rarer but actionable genes that approved or ongoing clinical trials in other solid tumors. Conclusion K-MASTER project provides an intriguing background to investigate new clinical trials with biomarkers and give therapeutic opportunity for mCRC patients.

The aims of this study were to determine the short-term effectiveness of an internet-based lifestyle modification (LSM) program in preventing the onset of type 2 diabetes mellitus (T2DM) in prediabetes patients in community settings. A total of 415 subjects who were diagnosed with prediabetes were randomly assigned to the LSM and standard management (SM) groups. After the 6-month intervention, the LSM group had a statistically significant reduction in body weight, body mass index compared to the SM group participants. In the LSM group, blood glucose levels were significantly decreased after intervention and the clinical improvement effect was evident in the group that achieved the target weight loss of 5% or more of the initial weight for 6 months. Internet-based 6-month-intensive LSM programs conducted by public health center personnel are an effective way to provide lifestyle intervention programs and encourage maintenance of healthy behaviors in subjects with a high risk of T2DM in community settings.

Meningitis is a common central nervous system (CNS) complication of the mumps, a viral infection, but encephalitis and meningoencephalitis are less common in mumps. We describe magnetic resonance imaging findings of acute mumps meningoencephalitis in a 32-year-old male who showed bilateral hippocampal lesions without preceding parotitis. Although it is rare, hippocampal involvement should be considered a CNS complication of mumps infection.
Adult ; Brain ; Central Nervous System ; Encephalitis ; Hippocampus ; Humans ; Magnetic Resonance Imaging* ; Male ; Meningitis ; Meningoencephalitis* ; Mumps* ; Parotitis*

A 14-year-old girl was referred for evaluation of the etiology of Cushing syndrome. During the previous 2 years, she had experienced weight gain, secondary amenorrhea, growth retardation, and back pain. Random serum cortisol level, 24-hour urinary free cortisol excretion, and overnight and low-dose dexamethasone suppression tests suggested Cushing syndrome. Midnight adrenocorticotropic hormone (ACTH) level and high-dose dexamethasone suppression test confirmed Cushing disease. Pituitary magnetic resonance imaging was suspicious for microadenoma. To eliminate ectopic ACTH syndrome, and lateralize the pituitary tumor, inferior petrosal sinus sampling (IPSS) was performed by desmopressin use to stimulate ACTH. Finally, the patient was diagnosed with Cushing disease due to ACTH-secreting pituitary microadenoma, lateralized to the left side; subsequently underwent transsphenoidal surgery. Here we report a case of a 14-year-old girl diagnosed with Cushing disease with a pituitary tumor lateralized by IPSS using desmopressin, which is very rare in pediatric Cushing disease.
ACTH Syndrome, Ectopic ; Adolescent ; Adrenocorticotropic Hormone ; Amenorrhea ; Back Pain ; Cushing Syndrome ; Deamino Arginine Vasopressin* ; Dexamethasone ; Female ; Humans ; Hydrocortisone ; Magnetic Resonance Imaging ; Petrosal Sinus Sampling* ; Pituitary ACTH Hypersecretion* ; Pituitary Neoplasms* ; Weight Gain

Simvastatin is a lipid-lowering drug that is metabolized to its active metabolite simvastatin acid (SA). We developed and validated a sensitive liquid chromatography-tandem mass spectrometry (LC/MS/MS) method to quantitate SA in human plasma using a liquid-liquid extraction method with methanol. The protonated analytes generated in negative ion mode were monitored by multiple reaction monitoring. Using 500-mL plasma aliquots, SA was quantified in the range of 0.1-100 ng/mL. Calibration was performed by internal standardization with lovastatin acid, and regression curves were generated using a weighting factor of 1/χ2. The linearity, precision, and accuracy of this assay for each compound were validated using quality control samples consisting of mixtures of SA (0.1, 0.5, 5, and 50 ng/mL) and plasma. The intra-batch accuracy was 95.3-107.8%, precision was -2.2% to -3.7%, and linearity (r2) was over 0.998 in the standard calibration range. The chromatographic running time was 3.0 min. This method sensitively and reliably measured SA concentrations in human plasma and was successfully used in clinical pharmacokinetic studies of simvastatin in healthy Korean adult male volunteers.
Adult ; Calibration ; Humans* ; Liquid-Liquid Extraction ; Lovastatin ; Male ; Mass Spectrometry* ; Methanol ; Plasma* ; Protons ; Quality Control ; Running ; Simvastatin* ; Volunteers

PURPOSE: This study was a comparative study to understand the levels of anxiety, pain and maternal-fetal attachment between women who became pregnant after infertility treatment and became pregnant naturally. METHODS: This study used a comparative survey design. Data were collected by 50 couples of natural pregnancy and of who became pregnant after infertility treatment who visited delivery room in C Medical hospital, Seoul. These couples were to have first baby, and cervix dilatation of women was less than 3 cm regardless of diagnosis. RESULTS: The score of anxiety of infertile women was significantly higher than that of naturally pregnant women; however, that of spouses showed no difference. The pain score for infertile women was significantly higher in both the active and transition phases. Pain scores that reported by their spouses did not show differences in either phase. The score of maternal-fetal attachment showed no difference between two groups of women. CONCLUSION: The result showed the importance of nursing intervention to reduce women's anxiety and pain, through both antenatal-childbirth education programs and assertive nursing interventions. It is necessary to develop and evaluate new intervention which would be more effective for reducing pain and anxiety for couples who became pregnant after infertility treatment.
Anxiety* ; Cervix Uteri ; Delivery Rooms ; Diagnosis ; Dilatation ; Education ; Family Characteristics ; Female ; Humans ; Infertility* ; Nursing ; Pregnancy ; Pregnant Women ; Seoul ; Spouses

OBJECTIVE: To investigate long-term functional changes and its underlying factors in stroke patients. METHOD: Data were collected retrospectively from the stroke patients who had been completed at least 2 times of functional evaluation after discharge. 60 stroke patients were included and we investigated long-term change of motor, cognition and activities of daily living score at 6 months from the onset and the last score during the follow up period. The motor function included manual function test (MFT), Korean version of Berg balance scale (K-BBS), cognitive function by Korean version of mini-mental status examination (K-MMSE), activities of daily living by Korean version of modified Barthel index (K-MBI). To identify the factors influencing long-term function outcome after stroke, biographical data and risk factors were collected and bivariate correlation analysis was performed. RESULTS: The mean duration of follow-up was 23.4 months and MFT, BBS, MMSE, and K-MBI scores showed no significant difference between 6 months from the onset and final evaluation. History of recurrent stroke (p = 0.007) and hypertension (p = 0.017) were significantly related with decline of cognition during follow up period. All the other independent variables were not statistically significant. CONCLUSION: None of the function showed significant changes during the 2 year of mean follow-up period. Recurrent stroke and hypertension were significant predictor for decline of cognitive function. Our results suggest that secondary prevention including blood pressure control is important to prevent decline of cognitive function after stroke.
Activities of Daily Living ; Blood Pressure ; Cognition ; Follow-Up Studies ; Humans ; Hypertension ; Postural Balance ; Retrospective Studies ; Risk Factors ; Secondary Prevention ; Stroke ; Upper Extremity

OBJECTIVE: To investigate long-term functional changes and its underlying factors in stroke patients. METHOD: Data were collected retrospectively from the stroke patients who had been completed at least 2 times of functional evaluation after discharge. 60 stroke patients were included and we investigated long-term change of motor, cognition and activities of daily living score at 6 months from the onset and the last score during the follow up period. The motor function included manual function test (MFT), Korean version of Berg balance scale (K-BBS), cognitive function by Korean version of mini-mental status examination (K-MMSE), activities of daily living by Korean version of modified Barthel index (K-MBI). To identify the factors influencing long-term function outcome after stroke, biographical data and risk factors were collected and bivariate correlation analysis was performed. RESULTS: The mean duration of follow-up was 23.4 months and MFT, BBS, MMSE, and K-MBI scores showed no significant difference between 6 months from the onset and final evaluation. History of recurrent stroke (p = 0.007) and hypertension (p = 0.017) were significantly related with decline of cognition during follow up period. All the other independent variables were not statistically significant. CONCLUSION: None of the function showed significant changes during the 2 year of mean follow-up period. Recurrent stroke and hypertension were significant predictor for decline of cognitive function. Our results suggest that secondary prevention including blood pressure control is important to prevent decline of cognitive function after stroke.
Activities of Daily Living ; Blood Pressure ; Cognition ; Follow-Up Studies ; Humans ; Hypertension ; Postural Balance ; Retrospective Studies ; Risk Factors ; Secondary Prevention ; Stroke ; Upper Extremity