Background: Long-term growth data of very low birth weight (VLBW) infants are currently collected in the Korean Neonatal Network (KNN) and National Health Insurance Service (NHIS) database. However, variance in the number of infants, check-up time, and check-up parameters led to decreased credibility of cumulated data. We aimed to compare the data on serial growth outcomes by major morbidities from birth to 5 years in VLBW infants between the KNN and NHIS databases. Methods: We combined the NHIS and KNN data of VLBW infants born between 2013 and 2015. The check-up times in the NHIS database were at 4–6, 9–12, 18–24, 30–36, 42–48, and 54–60 months of age, whereas in the KNN were at 18–24 months of corrected age and at 36 months of age.Result: Among 8,864 VLBW infants enrolled based on the birth certificates from the Statistics Korea, 6,086 infants (69%) were enrolled in the KNN, and 5,086 infants (57%) participated in the NHIS health check-up. Among 6,068 infants, 3,428 infants (56%) were enrolled at a corrected age of 18–24 months and 2,572 infants (42%) were enrolled at a chronological age of 33–36 months according to the KNN follow-up registry. However, based on the national birth statistics data, the overall follow-up rate of the KNN at 36 months of age was as low as 29%. The NHIS screening rate was lower at first (23%); however, it increased over time to exceed the KNN follow-up rate. Growth failure (weight under 10th percentile) at corrected ages of 18–24 months and 36 months were more common in the NHIS than KNN (42% vs. 20%, 37% vs. 34.5%). Infants with bronchopulmonary dysplasia and periventricular leukomalacia showed similar rates of growth failure at 2 years but varying rates at 3 years between the KNN and NHIS. Conclusion By integrating the KNN and NHIS data indirectly at continuous time points according to morbidities, we found that there are discontinuities and discrepancies between the two databases among VLBW infants. Establishing an integrated system by patient level linking the KNN and NHIS databases can lead to better understanding and improved neonatal outcomes in VLBW infants in Korea.

Purpose: The aims of the study were to develop and evaluate a machine learning model with which to predict postnatal growth failure (PGF) among very low birth weight (VLBW) infants. Materials and Methods: Of 10425 VLBW infants registered in the Korean Neonatal Network between 2013 and 2017, 7954 infants were included. PGF was defined as a decrease in Z score >1.28 at discharge, compared to that at birth. Six metrics [area under the receiver operating characteristic curve (AUROC), accuracy, precision, sensitivity, specificity, and F1 score] were obtained at five time points (at birth, 7 days, 14 days, 28 days after birth, and at discharge). Machine learning models were built using four different techniques [extreme gradient boosting (XGB), random forest, support vector machine, and convolutional neural network] to compare against the conventional multiple logistic regression (MLR) model. Results: The XGB algorithm showed the best performance with all six metrics across the board. When compared with MLR, XGB showed a significantly higher AUROC (p=0.03) for Day 7, which was the primary performance metric. Using optimal cut-off points, for Day 7, XGB still showed better performances in terms of AUROC (0.74), accuracy (0.68), and F1 score (0.67). AUROC values seemed to increase slightly from birth to 7 days after birth with significance, almost reaching a plateau after 7 days after birth. Conclusion We have shown the possibility of predicting PGF through machine learning algorithms, especially XGB. Such models may help neonatologists in the early diagnosis of high-risk infants for PGF for early intervention.

Background: Macrosomia, as an infant with birth weight over 4 kg, can have several perinatal, and neonatal complications. This study aimed to estimate the incidence of macrosomia in Korea and to identify the growth and developmental outcomes and other neonatal complications. Methods: In total, 397,203 infants who were born in 2013 with birth weight ≥ 2.5 kg and who underwent infant health check-up between their 1 st and 7 th visit were included from the National Health Insurance Service database. The information was obtained by the International Classification of Diseases-10 codes or self-reported questionnaires in the National Health Screening Program. Results: The distribution of infants by birth weight was as follows: 384,181 (97%) infants in the 2.5–3.99 kg (reference) group, 12,016 (3%) infants in the 4.0–4.49 kg group, 772 (0.2%) infants in the 4.5–4.99 kg group, and 78 (0.02%) infants in the ≥ 5 kg group. Macrosomia showed significantly higher incidence of sepsis, male sex, and mothers with GDM and birth injury. There was a significant difference in weight, height, and head circumference according to age, birth weight group, and combination of age and birth weight, respectively (P < 0.001). The number of infants with the weight above the 90 th percentile in macrosomia at each health check-up showed higher incidence than in reference group. The mean body mass index significantly differed among the groups, as 50.6 in infants with 2.5–3.99 kg of birth weight, 63.5 with 4.0–4.49 kg, 71.0 with 4.5–4.99 kg, and 73.1 with ≥ 5 kg. There was a significant difference in the incidence of poor developmental results between infants with macrosomia and the reference group at 24, 36 and 48 month of age. Conclusion Macrosomia was significantly associated with the risk of sepsis, birth injury, obesity and developmental problem especially in a boy born from mothers with gestational diabetes mellitus. Careful monitoring and proper strategies for monitoring growth and development are needed.

Background: Pulmonary surfactant (PS) replacement therapy, as a safe and effective treatment for respiratory distress syndrome (RDS) may have further increased with the extended insurance coverage since 2011 in Korea. Thus, this study aimed to investigate the epidemiologic data of PS replacement therapy for RDS in Korea and to analyze the complications associated with RDS. Methods: We included 19,442 infants who were treated with PS and diagnosed with RDS (International Classification of Diseases-10 codes: P22.0) between 2014 and 2018 from the Health Insurance Review and Assessment database. Birth certificate data from Statistics Korea were used to estimate the incidence of RDS. Results: The average incidence of RDS within the study period was 0.99% among live births.Repeated doses of PS were administered to 1,688 infants (8.7%), ranging from 2 doses in 929 infants (4.8%) to 9 doses in 1 infant (0.01%). The incidence of RDS in term infants markedly increased over 5 years from 0.2% to 0.34%. The incidence was similarly increased among the preterm infants. The RDS mortality rate was 6.3% and showed a decreasing trend according to year. The mortality rate was significantly higher in the lower gestational age group. A decreasing trend was observed in the incidence of the complications, such as patent ductus arteriosus, intraventricular hemorrhage, and bronchopulmonary dysplasia, except for pneumothorax in term infants. The complications were also higher in the lower gestational age group and the lower birth weight group. However, pneumothorax was the most frequent complication in the term infant group and in infants with birth weight ≥ 2,500 g. Conclusion Advancements in neonatal care and extended insurance coverage have increased the use of PS replacement therapy for RDS. This, in turn, decreased neonatal mortality and the incidence of the associated complications. The appropriate therapeutic strategy for RDS should be decided according to the gestational age and lung pathology.

The ex utero intrapartum treatment (EXIT) procedure was introduced to reduce fetal hypoxic damage while establishing an airway in fetuses with upper and lower airway obstruction. Delivery of the fetal head and shoulders while maintaining the uteroplacental circulation offers time to secure the fetal airway. Here, we report two cases of EXIT procedure for fetal airway obstruction, which were successfully managed with extensive preoperative planning by a professional multidisciplinary team.
Airway Obstruction* ; Fetal Therapies ; Fetus* ; Head ; Laryngeal Diseases ; Lymphangioma ; Placental Circulation ; Prenatal Diagnosis ; Shoulder

PURPOSE: In order to suggest optimal anticancer drugs for patient-tailored chemotherapy, we developed a colorectal cancer (CRC)-liver metastasis patient-derived tumor xenograft (PDTX) model. METHODS: Tissue obtained from a patient with CRC-liver metastasis (F0) was transplanted in a nonobese female mouse with diabetic/severe combined immune deficiency (F1) and the tumor tissue was retransplanted into nude mice (F2). When tumor volumes reached ~500 mm³, the F2 mice were randomly divided into 4 groups (n = 4/group) of doxorubicin, cisplatin, docetaxel, and nontreated control groups. The tumor tissues were investigated using H&E staining, terminal deoxynucleotidyl transferase dUTP nick end labeling assays, and immunohistochemistry. To determine where the mutant allele frequencies varied across the different passages, we isolated genomic DNA from the primary tumor, liver metastasis, and PDTX models (F1/F2). RESULTS: The physiological properties of the tumor were in accord with those of the patient's tumors. Anticancer drugs delayed tumor growth, inhibited proliferation, and caused apoptosis. Histological assessments revealed no observable heterogeneity among the intragenerational PDTX models. Target exon sequencing analysis without high-quality filter conditions revealed some genetic variations in the 83 cancer-related genes across the generations. However, when de novo mutations were defined as a total count of zero in F0 and ≥5 in F2, exactly prognostic impact of clone cancer profiling (EGFR, KRAS, BRAF, PIK3CA, NRAS, APC and TP53) were detected in the paired. CONCLUSION: A CRC liver metastasis PDTX model was established for the evaluation of chemotherapeutic efficacy. This model retained the physiological characters of the patient tumors and potentially provides a powerful means of assessing chemotherapeutic efficacy.
Animals ; Apoptosis ; Cisplatin ; Clone Cells ; Colorectal Neoplasms* ; DNA ; DNA Nucleotidylexotransferase ; Doxorubicin ; Drug Therapy* ; Exons ; Family Characteristics ; Female ; Gene Frequency ; Genetic Variation ; Heterografts* ; Humans ; Immunohistochemistry ; Liver* ; Mice ; Mice, Nude ; Neoplasm Metastasis* ; Population Characteristics ; Sequence Analysis ; Xenograft Model Antitumor Assays

OBJECTIVES: The combination extract of four kinds of herbs, Gastrodia elata, Liriope platyphylla, Dimocarpus longan, and Salvia miltiorrhiza, has shown to have memory improving effects in mice. The aim of this study was to investigate the efficacy and safety of the herbal mixture for improving working memory as well as microstructural changes in white matter integrity in individuals with subjective memory complaints. METHODS: Seventy-five individuals with subjective memory complaints were assigned to receive either placebo (n = 15) or herbal mixture (low-dose group, n = 30 and high-dose group, n = 30) supplementation in an 8-week, randomized, double-blind, placebo-controlled clinical trial. Changes in working memory performance and fractional anisotropy (FA) values reflecting white matter integrity from baseline to 8-week endpoint were assessed. RESULTS: The herbal mixture group showed an increase in working memory performance compared to the placebo group (p for interaction = 0.001). In addition, the herbal mixture group showed an increase in FA values in the temporo-parietal regions (corrected p < 0.05), which are crucially involved in working memory function and are among the most affected regions in patients with cognitive impairments. CONCLUSIONS: Findings from this study indicate that the herbal mixture may be a promising therapeutic option for individuals with subjective memory complaints.
Animals ; Anisotropy ; Diffusion Tensor Imaging ; Gastrodia ; Humans ; Memory* ; Memory, Short-Term* ; Mice ; Salvia miltiorrhiza

Although the functional ingredient has been evaluated by the Korea Food and Drug Administration (KFDA) based on scientific evidence, the levels of scientific evidence and consistency of the results might vary according to emerging data. Therefore, periodic re-evaluation may be needed for some functional ingredients. In this study, we re-evaluated scientific evidence for the antioxidant activity of coenzyme Q10 as a functional ingredient in health functional food. Literature searches were conducted using the Medline and Cochrane, KISS, and IBIDS databases for the years 1955-2010 with the search term of coenzyme Q10 in combination with antioxidant. The search was limited to human studies published in Korean, English, and Japanese. Using the KFDA's evidence based evaluation system for scientific evaluation of health claims, 33 human studies were identified and reviewed in order to evaluate the strength of the evidence supporting a relation between coenzyme Q10 and antioxidant activity. Among 33 studies, significant effects for antioxidant activities were reported in 22 studies and their daily intake amount was 60 to 300 mg. Based on this systematic review, we concluded that there was possible evidence to support a relation between coenzyme Q10 intake and antioxidant activities. However, because inconsistent results have recently been reported, future studies should be monitored.
Asian Continental Ancestry Group ; Functional Food ; Humans ; Korea ; Ubiquinone ; United States Food and Drug Administration

Mucinous adenocarcinoma arising from a chronic anorectal fistula is a rare condition. It is often confused with a hemorrhoid or perineal abscess, which consequently delays accurate diagnosis. Here, we report the case of a 58-year-old man with blood-tinged stool who reported a rectal mass, which was diagnosed as mucinous adenocarcinoma arising from an anal fistula. After initial computed tomography-guided needle aspiration biopsy had failed to provide an accurate diagnosis, transrectal punch biopsy was performed to obtained adequate tissue sample for confirmative histological diagnosis. The patient was successfully treated with neoadjuvant concurrent chemoradiotherapy followed by surgical intervention.
Abscess ; Adenocarcinoma, Mucinous* ; Biopsy* ; Biopsy, Needle ; Chemoradiotherapy* ; Fistula* ; Hemorrhoids ; Humans ; Middle Aged ; Mucins* ; Needles ; Neoadjuvant Therapy ; Rectal Fistula

OBJECTIVE: The aim of this study was to identify apoptosis-related genes of ovarian cancer cell lines following cisplatin treatment. METHODS: We used IC50 values and fluorescence-activated cell sorting analysis to compare cell death in 2 ovarian cancer cell lines, namely, SKOV-3 and OVCAR-3, upon treatment with cisplatin. Moreover, the change in transcriptional levels of apoptosis-associated genes was measured with a dendron-modified DNA microarray. RESULTS: The protein levels for the up-regulated genes in each cell line were validated to identify the molecules that may determine the cellular behavior of cisplatin resistance. Eight genes were over-expressed in the 2 cell lines. The cisplatin-induced up-regulation of DAD1 in transcriptional and protein levels contributed to the cisplatin resistance of OVCAR-3, and the up-regulation of FASTK and TNFRSF11A in SKOV-3 resulted in its higher sensitivity to cisplatin than that of OVCAR-3. CONCLUSION: In the present study, we have identified a set of genes responsible for apoptosis following cisplatin treatment in ovarian cancer cell lines. These genes may give information about the understanding of cisplatin-induced apoptosis in ovarian cancer.
Apoptosis ; Cell Death ; Cell Line ; Cisplatin ; DNA ; Flow Cytometry ; Inhibitory Concentration 50 ; Ovarian Neoplasms ; RNA, Messenger ; Up-Regulation