Human pluripotent stem cells (hPSCs) such as human embryonic stem cells (hESCs), induced pluripotent stem cells, and somatic cell nuclear transfer (SCNT)-hESCs can permanently self-renew while maintaining their capacity to differentiate into any type of somatic cells, thereby serving as an important cell source for cell therapy. However, there are persistent challenges in the application of hPSCs in clinical trials, where one of the most significant is graft rejection by the patient immune system in response to human leukocyte antigen (HLA) mismatch when transplants are obtained from an allogeneic (non-self) cell source. Homozygous SCNT-hESCs (homo-SCNT-hESCs) were used to simplify the clinical application and to reduce HLA mismatch. Here, we present a xeno-free protocol that confirms the efficient generation of neural precursor cells in hPSCs and also the differentiation of dopaminergic neurons. Additionally, there was no difference when comparing the HLA expression patterns of hESC, homo-SCNT-hESCs and hetero-SCNT-hESCs. We propose that there are no differences in the differentiation capacity and HLA expression among hPSCs that can be cultured in vitro. Thus, it is expected that homo-SCNT-hESCs will possess a wider range of applications when transplanted with neural precursor cells in the context of clinical trials.

Purpose: This multi-center, retrospective study was conducted to evaluate the long-term survival in patients who underwent surgical resection for small cell lung cancer (SCLC) and to identify the benefit of adjuvant therapy following surgery. Materials and Methods: The data of 213 patients who underwent surgical resection for SCLC at four institutions were retrospectively reviewed. Patients who received neoadjuvant therapy or an incomplete resection were excluded. Results: The mean patient age was 65.29±8.93 years, and 184 patients (86.4%) were male. Lobectomies and pneumonectomies were performed in 173 patients (81.2%), and 198 (93%) underwent systematic mediastinal lymph node dissections. Overall, 170 patients (79.8%) underwent adjuvant chemotherapy, 42 (19.7%) underwent radiotherapy to the mediastinum, and 23 (10.8%) underwent prophylactic cranial irradiation. The median follow-up period was 31.08 months (interquartile range, 13.79 to 64.52 months). The 5-year overall survival (OS) and disease-free survival were 53.4% and 46.9%, respectively. The 5-year OS significantly improved after adjuvant chemotherapy in all patients (57.4% vs. 40.3%, p=0.007), and the survival benefit of adjuvant chemotherapy was significant in patients with negative node pathology (70.8% vs. 39.7%, p=0.004). Adjuvant radiotherapy did not affect the 5-year OS (54.6% vs. 48.5%, p=0.458). Age (hazard ratio [HR], 1.032; p=0.017), node metastasis (HR, 2.190; p < 0.001), and adjuvant chemotherapy (HR, 0.558; p=0.019) were associated with OS. Conclusion Adjuvant chemotherapy after surgical resection in patients with SCLC improved the OS, though adjuvant radiotherapy to the mediastinum did not improve the survival or decrease the locoregional recurrence rate.

Background: To evaluate how intrauterine stress affects extremely premature infants in terms of intrauterine growth restriction. We hypothesized that extremely premature infants with mildly-low ponderal index (MPI) would have better neonatal outcomes. Methods: We selected 2,721 subjects of 23 to 28 weeks of gestation between 2013 and 2015 from Korean Neonatal Network database. They were divided into 4 groups based on ponderal index (PI) percentile; PI ≤ 3rd as severely-low PI (SPI, n = 82), 3rd < PI ≤ 10th as MPI (n = 190), 10th < PI ≤ 90th as adequate PI (API, n = 2,179), and PI > 90th as high PI (HPI, n = 270). Results: The mortality in MPI and API groups was comparable (16.3% vs. 16.9%). It was significantly lower than that in the SPI and HPI groups (30.5% and 24.9%, respectively;P = 0.001). The MPI and API groups had better neonatal morbidities compared with the SPI and/or HPI groups, while the MPI group (8.2%) showed a lower incidence of severe intraventricular hemorrhage (IVH) than the other groups (SPI, 21.3%; API, 15.0%; HPI, 19.7%, respectively; P = 0.004). The MPI group had a trend of a bottom in neonatal mortality and morbidities in extremely premature infants. Conclusion The MPI and API groups had lower mortality, massive pulmonary hemorrhage, severe bronchopulmonary dysplasia or death, pulmonary hypertension and neonatal seizure rates than the SPI and/or HPI groups, while the MPI group showed a lower incidence of severe IVH than the other groups. We speculate that the lower incidence of neonatal morbidities and mortality in the MPI group indicating mild intrauterine stress might accelerate fetal maturation resulting in better outcomes in extremely premature infants.

Pericardial effusion (PCE) in neonates has various clinical presentations depending on the amount and speed of fluid accumulation and can cause cardiac tamponade (CT). We report a case of rapidly accumulating PCE and near-fatal CT with an umbilical venous catheter successfully resolved by emergent echo-guided pericardiocentesis in a term infant who had been hospitalized with meconium aspiration syndrome and persistent pulmonary hypertension. This case report suggests that if a patient with an intracardiac umbilical catheter shows sudden cardiopulmonary instability, the possibility of PCE and CT should be considered. Furthermore, if necessary, emergency drainage of the PCE and removal of the umbilical catheter should be immediately performed.

Background: Complementary and alternative medicine (CAM) has been used frequently, and its use continues to increase in lung cancer patients, despite insufficient scientific of its efficacy. To investigate this situation, we analyzed the current awareness and use of CAM in Korean lung-cancer patients. Methods: This prospective survey–based study was performed at seven medical centers in South Korea between August and October 2019. The survey assessed general patient characteristics and the awareness and use of CAM. We analyzed differences in the clinical parameters of patients aware and not aware of CAM and of CAM non-users and users. Results: Of the 434 patients included in this study, 68.8% responded that they were aware of CAM and 30.9% said they had experienced it. In univariate analysis, the patients aware of CAM were younger with poor performance status, had advanced-stage lung cancer, received more systemic therapy, and received concurrent chemoradiation therapy (CCRT). By multiple logistic regression, younger age, poor performance status, advanced stage, and prior CCRT were identified as independent risk factors for CAM awareness. There were no significant differences in the general characteristics and cancer-associated clinical parameters of CAM non-users and users. Conclusion Specific clinical parameters were associated with patients’ awareness of CAM, although there were no significantly different characteristics between CAM users and non-users.

Background: Lipopolysaccharide (LPS) exerts cytotoxic effects on brain cells, especially on those belonging to the oligodendrocyte lineage, in preterm infants. The susceptibility of oligodendrocyte lineage cells to LPS-induced inflammation is dependent on the developmental stage. This study aimed to investigate the effect of LPS on oligodendrocyte lineage cells at different developmental stages in a microglial cell and oligodendrocyte coculture model. Methods: The primary cultures of oligodendrocytes and microglia cells were prepared from the forebrains of 2-day-old Sprague–Dawley rats. The oligodendrocyte progenitor cells (OPCs) co-cultured with microglial cells were treated with 0 (control), 0.01, 0.1, and 1 µg/mL LPS at the D3 stage to determine the dose of LPS that impairs oligodendrocyte differentiation. The co-culture was treated with 0.01 µg/mL LPS, which was the lowest dose that did not impair oligodendrocyte differentiation, at the developmental stages D1 (early LPS group), D3 (late LPS group), or D1 and D3 (double LPS group). On day 7 of differentiation, oligodendrocytes were subjected to neural glial antigen 2 (NG2) and myelin basic protein (MBP) immunostaining to examine the number of OPCs and mature oligodendrocytes, respectively. Results: LPS dose-dependently decreased the proportion of mature oligodendrocytes (MBP+ cells) relative to the total number of cells. The number of MBP+ cells in the early LPS group was significantly lower than that in the late LPS group. Compared with those in the control group, the MBP+ cell numbers were significantly lower and the NG2+ cell numbers were significantly higher in the double LPS group, which exhibited impaired oligodendrocyte lineage cell development, on day 7 of differentiation. Conclusion Repetitive LPS stimulation during development significantly inhibited brain cell development by impairing oligodendrocyte differentiation. In contrast, brain cell development was not affected in the late LPS group. These findings suggest that inflammation at the early developmental stage of oligodendrocytes increases the susceptibility of the preterm brain to inflammation-induced injury.

We describe the occurrence of acute type A aortic dissection in a patient with situs inversus totalis. A 37-year-old man presented to the emergency department with acute chest pain. Initial chest X-ray findings showed a right-sided heart and a left-sided liver. Contrast-enhanced computed tomography revealed a Stanford type A acute aortic dissection, aortic root dilatation, and situs inversus totalis. All of the thoracic structures were mirror-image reversed and an abnormal coronary artery was observed. The Bentall operation was performed. This report demonstrates that computed tomography and echocardiography were useful for understanding the anatomy and the presence or absence of concurrent anomalies in a patient with situs inversus totalis. The patient’s postoperative course was uneventful.

Purpose: As preterm infants have shown advances in survival rate, many very-lowbirth-weight (VLBW) infants have shown developmental delay even without a major brain injury. Thus, the incidence of and risk factors associated with poor neurodevelopmental outcome should be evaluated. Methods: A multicenter nationwide prospective longitudinal cohort study of VLBW infants born in South Korea between 2013 and 2015 was conducted. Poor neurodevelopmental outcome was diagnosed if the Bayley Scales of Infant and Toddler Development (BSID)-III composite score was ≤85 (cognition, language, motor). We analyzed the associations of baseline neonatal characteristics, environmental characteristics and neonatal morbidities with poor neurodevelopmental outcome. Results: The study included 285 infants, of whom 34 (11.9%) exhibited cognition delay; 59 (20.7%), showed language delay and 32 (11.2%) showed motor delay. The mean gestational age and birth weight were 29 weeks and 1,130 g, respectively. Moderate and severe bronchopulmonary dysplasia (P=0.056) and intraventricular hemorrhage grade I (P=0.079) were marginally associated with cognition delay. Higher paternal educational level (P<0.05) was significantly associated with the language outcome. Birth weight (P<0.05) and head circumference at discharge (P<0.05) were the major predictors of motor delay. Conclusion The population-based nationwide cohort study shows that approximately 20% of VLBW infants without major brain injury have developmental delay. Several factors that are not directly associated with major brain injury were significantly associated with poor neurodevelopmental outcome.

Objectives: Osteoporosis and fracture are known complications of systemic lupus erythematosus (SLE). We assessed the prevalence and risk factors for osteoporosis in patients with SLE. Methods: A total of 155 female SLE patients were recruited retrospectively in 5 university hospitals. The bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry, and the fracture risk assessment tool (FRAX) for high-risk osteoporotic fractures was calculated with and without BMD. Results: The mean age was 53.7 ± 6.8 years, and osteoporotic fractures were detected in 19/127 (15.0%) patients. The proportion of patients having a high-risk for osteoporotic fractures in the FRAX with and without BMD, and osteoporosis by the World Health Organization (WHO) criteria were 25 (16.1%), 24 (15.5%), and 51 (32.9%), respectively, and 48.0–68.6% of them were receiving treatment. On multivariate logistic analysis, nephritis (odds ratio [OR] 11.35) and cumulative dose of glucocorticoid (OR 1.1) were associated with high-risk by the FRAX with BMD, and low complement levels (OR 4.38), erythrocyte sedimentation rate (ESR) (OR 1.04), and cumulative dose of glucocorticoid (OR 1.05) were associated with osteoporosis by the WHO criteria in patients with SLE. Conclusions Among Korean female patients with SLE, the proportion of patients having a high-risk of osteoporotic fractures by the FRAX tool was 15.5%–16.1% and the proportion of patients having osteoporosis by the WHO criteria was 32.9%. In SLE, nephritis, low level of complement, ESR, and cumulative dose of glucocorticoids may contribute to fracture risk.

Purpose: As preterm infants have shown advances in survival rate, many very-lowbirth-weight (VLBW) infants have shown developmental delay even without a major brain injury. Thus, the incidence of and risk factors associated with poor neurodevelopmental outcome should be evaluated. Methods: A multicenter nationwide prospective longitudinal cohort study of VLBW infants born in South Korea between 2013 and 2015 was conducted. Poor neurodevelopmental outcome was diagnosed if the Bayley Scales of Infant and Toddler Development (BSID)-III composite score was ≤85 (cognition, language, motor). We analyzed the associations of baseline neonatal characteristics, environmental characteristics and neonatal morbidities with poor neurodevelopmental outcome. Results: The study included 285 infants, of whom 34 (11.9%) exhibited cognition delay; 59 (20.7%), showed language delay and 32 (11.2%) showed motor delay. The mean gestational age and birth weight were 29 weeks and 1,130 g, respectively. Moderate and severe bronchopulmonary dysplasia (P=0.056) and intraventricular hemorrhage grade I (P=0.079) were marginally associated with cognition delay. Higher paternal educational level (P<0.05) was significantly associated with the language outcome. Birth weight (P<0.05) and head circumference at discharge (P<0.05) were the major predictors of motor delay. Conclusion The population-based nationwide cohort study shows that approximately 20% of VLBW infants without major brain injury have developmental delay. Several factors that are not directly associated with major brain injury were significantly associated with poor neurodevelopmental outcome.