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.

The accuracy and convenience of continuous glucose monitoring (CGM), which efficiently evaluates glycemic variability and hypoglycemia, are improving. There are two types of CGM: professional CGM and personal CGM. Personal CGM is subdivided into real-time CGM (rt-CGM) and intermittently scanned CGM (isCGM). CGM is being emphasized in both domestic and foreign diabetes management guidelines. Regardless of age or type of diabetes, CGM is useful for diabetic patients undergoing multiple insulin injection therapy or using an insulin pump. rt-CGM is recommended for all adults with type 1 diabetes (T1D), and can also be used in type 2 diabetes (T2D) treatments using multiple insulin injections. In some cases, short-term or intermittent use of CGM may be helpful for patients with T2D who use insulin therapy other than multiple insulin injections and/or oral hypoglycemic agents. CGM can help to achieve A1C targets in diabetes patients during pregnancy. CGM is a safe and cost-effective alternative to self-monitoring blood glucose in T1D and some T2D patients. CGM used in diabetes management works optimally with proper education, training, and follow up. To achieve the activation of CGM and its associated benefits, it is necessary to secure sufficient repetitive training and time for data analysis, management, and education. Various supports such as compensation, insurance coverage expansion, and reimbursement are required to increase the effectiveness of CGM while considering the scale of benefit recipients, policy priorities, and financial requirements.

PURPOSE: This study aimed to investigate associations of central obesity with sexual maturation and metabolic parameters in Korean girls with precocious puberty. METHODS: This retrospective study evaluated data from 72 girls under 8 years of age with a chief complaint of early breast development. The patients were categorized as central precocious puberty (CPP) subjects or non-CPP subjects based on their gonadotropin-releasing hormone stimulation test results. Visceral fat thickness (VFT) was measured using ultrasonography and defined as the distance from the linea alba to the aorta. Patient anthropometric, metabolic, and hormonal parameters were also evaluated. RESULTS: Increased VFT was correlated with an earlier onset of thelarche among all study subjects (r=-0.307, P=0.034). Overweight CPP subjects showed higher insulin resistance than normal weight CPP subjects. Insulin resistance was not significantly different between overweight and normal weight non-CPP subjects. VFT was not significantly different between CPP and non-CPP subjects (2.22±0.79 cm vs. 2.74±1.47 cm, P=0.169). However, overweight and obese CPP subjects (body mass index percentile>85%) had lower VFT than non-CPP obese subjects. CONCLUSIONS: Central obesity, defined using ultrasonography-measured VFT, might be associated with early pubertal development in Korean girls. However, VFT was not higher in CPP than non-CPP patients and was not significantly correlated with insulin resistance. Further longitudinal studies with a larger cohort are needed.
Aorta ; Breast ; Cohort Studies ; Female* ; Gonadotropin-Releasing Hormone ; Humans ; Insulin Resistance ; Intra-Abdominal Fat* ; Longitudinal Studies ; Obesity, Abdominal ; Overweight ; Puberty, Precocious* ; Retrospective Studies ; Sexual Maturation ; Ultrasonography

OBJECTIVE: Although suicide is a serious public health concern for adolescents, there is a lack of studies that explore its risk factors in the Republic of Korea. The present study aims to investigate risk factors associated with suicidal behaviors in Korean adolescents. METHODS: Participants consisted of 2258 middle and high school students who completed a series of questionnaires regarding suicide ideation or attempts, non-suicidal self-injuries, depression, impulsivity, drinking behaviors, and negative life events, including peer bullying. RESULTS: Among the participants, 8.3% of students reported suicide ideation, while 3.2% reported a history of a suicide attempt in the past 12 months. Depression, peer-victimization, internet-related delinquency, and positive attitudes toward suicide were associated with suicidal ideations and attempts. Adverse life events were also associated with suicide ideation, but not attempts, while not living with both parents and poor family relationships were associated with suicide attempts, but not ideations. Non-suicidal self-injuries were associated with both suicide ideations and attempts. Students with suicidal ideations and attempts can be differentiated depending on the presence of self-injury. CONCLUSION: In addition to depression or behavioral problems, non-suicidal self-injuries and lack of support from family may also play significant roles in suicide attempts in adolescents. To facilitate the prevention of suicide in adolescents, longitudinal studies should be followed to confirm the risk factors identified in this study.
Adolescent* ; Bullying ; Depression ; Drinking Behavior ; Family Relations ; Humans ; Impulsive Behavior ; Longitudinal Studies ; Parents ; Problem Behavior ; Public Health ; Republic of Korea ; Risk Factors* ; Suicidal Ideation* ; Suicide

A 15-year-old boy was referred due to gynecomastia and short stature. He was overweight and showed the knuckle-dimple sign on the left hand, a short fourth toe on the left foot, and male external genitalia with a small phallus. His levels of estradiol and follicle-stimulating hormone were increased, and his testosterone concentration was normal. Other hormonal tests were within the normal range. Radiographs showed short fourth and fifth metacarpals and fourth metatarsal bones. The karyotype was reported as 46,X,+mar, and the marker chromosome was shown to originate from the Y chromosome, which was identified by fluorescence in situ hybridization. Polymerase chain reaction and direct sequencing were used to clarify the deleted loci of the Y chromosome by making use of Y-specific sequence-tagged sites (STSs). The sex-determining region Y and centromere were verified, and there were microdeletions on the long arm of the Y chromosome. The azoospermia factor (AZF) b region was partially deleted, and AZFa and AZFc were completely deleted. Two STS probes of sY143 and the Y chromosome RNA recognition motif in AZFb showed positive signals corresponding to Yq11.223. The karyotype of the patient was interpreted as 46,X,der(Y)del(Y)(q11.21q11.222)del(Y)(q11.23qter). Herein, we report a rare case of a boy presenting with gynecomastia and short stature with 46, X, +mar, which originated from the Y chromosome, which was identified to have Yq microdeletions.
Adolescent ; Arm ; Azoospermia ; Centromere ; Estradiol ; Fluorescence ; Follicle Stimulating Hormone ; Foot ; Genitalia ; Gynecomastia* ; Hand ; Humans ; In Situ Hybridization ; Karyotype ; Male* ; Metacarpal Bones ; Metatarsal Bones ; Overweight ; Polymerase Chain Reaction ; Reference Values ; RNA ; Sequence Tagged Sites ; Testosterone ; Toes ; Y Chromosome

PURPOSE: Abdominal obesity is a fundamental factor underlying the development of metabolic syndrome. Because of radiation exposure and cost, computed tomography or dual-energy X-ray absorptiometry to evaluate abdominal adiposity are not appropriate in children. Authors evaluated whether ultrasound results could be an indicator of insulin resistance and nonalcoholic fatty liver disease (NAFLD). METHODS: We enrolled 73 subjects (aged 6-16 years) who were evaluated abdominal adiposity by ultrasound. Subcutaneous fat thickness was defined as the measurement from the skin-fat interface to the linea alba, and visceral fat thickness (VFT) was defined as the thickness from the linea alba to the aorta. Anthropometric and biochemical metabolic parameters were also collected and compared. The subjects who met 2 criteria, radiologic confirmed fatty liver and alanine aminotransferase >40, were diagnosed with NAFLD. RESULTS: There was a strong positive correlation between VFT and obesity. VFT was highly correlated with the homeostasis model assessment for insulin resistance score (r=0.403, P<0.001). The area under the curve for VFT as a predictor of NAFLD was 0.875 (95% confidence interval [CI], 0.787-0.964). VFT of 34.3 mm was found to be the discriminating cutoff for NAFLD (sensitivity, 84.6%; specificity, 71.2%, respectively). CONCLUSION: Ultrasound could be useful in measuring VFT and assessing abdominal adiposity in children. Moreover, increased VFT might be an appropriate prognostic factor for insulin resistance and NAFLD.
Absorptiometry, Photon ; Adiposity ; Alanine Transaminase ; Aorta ; Child ; Fatty Liver ; Homeostasis ; Humans ; Insulin Resistance ; Intra-Abdominal Fat* ; Liver* ; Non-alcoholic Fatty Liver Disease ; Obesity ; Obesity, Abdominal ; Radiation Exposure ; Sensitivity and Specificity ; Subcutaneous Fat ; Ultrasonography*

PURPOSE: Abdominal obesity is a fundamental factor underlying the development of metabolic syndrome. Because of radiation exposure and cost, computed tomography or dual-energy X-ray absorptiometry to evaluate abdominal adiposity are not appropriate in children. Authors evaluated whether ultrasound results could be an indicator of insulin resistance and nonalcoholic fatty liver disease (NAFLD). METHODS: We enrolled 73 subjects (aged 6-16 years) who were evaluated abdominal adiposity by ultrasound. Subcutaneous fat thickness was defined as the measurement from the skin-fat interface to the linea alba, and visceral fat thickness (VFT) was defined as the thickness from the linea alba to the aorta. Anthropometric and biochemical metabolic parameters were also collected and compared. The subjects who met 2 criteria, radiologic confirmed fatty liver and alanine aminotransferase >40, were diagnosed with NAFLD. RESULTS: There was a strong positive correlation between VFT and obesity. VFT was highly correlated with the homeostasis model assessment for insulin resistance score (r=0.403, P<0.001). The area under the curve for VFT as a predictor of NAFLD was 0.875 (95% confidence interval [CI], 0.787-0.964). VFT of 34.3 mm was found to be the discriminating cutoff for NAFLD (sensitivity, 84.6%; specificity, 71.2%, respectively). CONCLUSION: Ultrasound could be useful in measuring VFT and assessing abdominal adiposity in children. Moreover, increased VFT might be an appropriate prognostic factor for insulin resistance and NAFLD.
Absorptiometry, Photon ; Adiposity ; Alanine Transaminase ; Aorta ; Child ; Fatty Liver ; Homeostasis ; Humans ; Insulin Resistance ; Intra-Abdominal Fat* ; Liver* ; Non-alcoholic Fatty Liver Disease ; Obesity ; Obesity, Abdominal ; Radiation Exposure ; Sensitivity and Specificity ; Subcutaneous Fat ; Ultrasonography*

In males, precocious puberty (PP) is defined as the development of secondary sexual characteristics before age 9 years. PP is usually idiopathic; though, organic abnormalities including tumors are more frequently found in male patients with PP. However, advanced puberty in male also can be an important clinical manifestation in tumors. We report 2 cases of rapidly progressive puberty in males, each associated with a germ-cell tumor. First, an 11-year-old boy presented with mild fever and weight loss for 1 month. Physical examination revealed a pubertal stage of G3P3 with 10-mL testes. Investigations revealed advanced bone age (16 years) with elevated basal luteinizing hormone and testosterone levels. An anterior mediastinal tumor was identified by chest radiography and computed tomography, and elevated α-fetoprotein (AFP) and β-human chorionic gonadotropin (β-hCG) levels were noted. Histopathologic analysis confirmed a yolk-sac tumor. Second, a 12-year-old boy presented with diplopia, polydipsia, and polyuria for 4 months. Physical examination revealed a pubertal stage of G3P3 with 8-mL testes. Bone age was advanced (16 years) and laboratory tests indicated panhypopituitarism with elevated testosterone level. A mixed germ-cell tumor was diagnosed with elevated AFP and β-hCG levels. Of course, these patients also have other symptoms of suspecting tumors, however, rapidly progressive puberty can be the more earlier screening sign of tumors. Therefore, in male patients with accelerated or advanced puberty, malignancy should be considered, with evaluation of tumor markers. In addition, advanced puberty in male should be recognized more widely as a unique sign of neoplasm.
Adolescent ; Child ; Chorionic Gonadotropin ; Diplopia ; Fever ; Humans ; Luteinizing Hormone ; Male* ; Mass Screening ; Physical Examination ; Polydipsia ; Polyuria ; Puberty* ; Puberty, Precocious ; Radiography ; Testis ; Testosterone ; Thorax ; Tumor Markers, Biological ; Weight Loss

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

Turner syndrome (TS) is a relatively common chromosomal disorder and is associated with a range of comorbidities involving the cardiovascular system. Vascular abnormalities, in particular, are a common finding in cases of TS. However, dissection involving the vertebral arteries is rare. Here, we report the case of a 9-year-old girl with TS who had been treated with growth hormone replacement therapy for the past 3 years. She presented with weakness of both lower legs, and was ultimately diagnosed with spinal hemorrhage due to vascular malformation. We treated her with intravenous high dose dexamethasone (0.6 mg/kg) and she could walk without assistance after 6 days of treatment. In conclusion, when a patient with TS shows sudden weakness of the lower limbs, we should consider the possibility of spinal vessel rupture and try to take spine magnetic resonance imaging as soon as possible. We suggest a direction how to make a proper diagnosis and management of sudden vertebral artery hemorrhage in patients with TS.
Cardiovascular System ; Child ; Chromosome Disorders ; Comorbidity ; Dexamethasone ; Diagnosis ; Female ; Growth Hormone ; Hemorrhage* ; Humans ; Leg ; Lower Extremity ; Magnetic Resonance Imaging ; Rupture ; Spine ; Turner Syndrome* ; Vascular Malformations* ; Vertebral Artery ; Vertebral Artery Dissection