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Background/Aims: The purpose of the study is to investigate the associations be tween sarcopenia and health-related quality of life in elderly men and women in Korea. Methods: In a cross-sectional study using data from 2008 to 2011 Korean Na tional Health and Nutrition Examination Survey, 4,937 adults aged 60 years and older who underwent a dual-energy X-ray absorptiometry scan were included in the study. Sarcopenia is defined as an appendicular skeletal muscle index of two standard deviations or more below the mean for young, healthy reference popu lations. The health-related quality of life was measured using the EuroQol-5 di mension questionnaire. Results: The overall prevalence of sarcopenia was 6.6% in these Korean people over the age of 60 years: 11.1% for men and 3.2% for women. Sarcopenic men tended to have lower income, lower physical activity, lower body mass index, and smaller waist circumference compared with nonsarcopenic men. Sarcopenic women tended to have higher body mass index and larger waist circumference compared with nonsarcopenic women. Sarcopenic men showed higher impair ments in mobility, self-care, usual activities, and pain/discomfort compared with nonsarcopenic men. Women with sarcopenia also showed higher impairments in mobility, self-care, usual activities, and anxiety/depression compared with non sarcopenic women. Sarcopenia showed an association with impairments in self-care for men, and with impairments in self-care, usual activities, and anxiety/ depression for women, after adjusting for other confounding factors. Conclusions: There is a significant association between sarcopenia and impaired health-related quality of life in this elderly Korean population, and these results differ between men and women.

Background: Apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like (APOBEC) family is known to function in innate immune system that protects against retrovirus by deaminating cytosine to uracil in single-stranded DNA. APOBEC family has emerged as an endogenous mutator to contribute to the mutation burden in many cancers. We aimed to evaluate the expression of APOBEC3A (A3A), 3B (A3B) mRNA and APOBEC3A-3B deletion polymorphism in Korean breast cancer patients and investigate the correlation between their expression and clinicopathological characteristics. Methods: One hundred thirty-eight patients who underwent surgery for breast cancer in Uijeongbu St. Mary's Hospital between January 2013 and December 2016 were evaluated. RNA and DNA were extracted from 138 breast cancer tissues and 10 adjacent normal breast tissues. The levels of A3A and A3B mRNA transcripts were determined using real-time quantitative PCR. Insertion and deletion PCR assays were performed to detect the APOBEC3A-3B deletion allele. Mutation hotspots in exon 2-11 of TP53 and exon 9/20 of PIK3CA were evaluated using direct sequencing method. Results: The expression of A3B was increased in breast cancer tissues than in normal breast tissues. The median A3B mRNA expression levels in both triple-negative breast cancer and human epidermal growth factor 2-positive breast cancer were significantly higher than in hormone receptor-positive breast cancer. Old age and high ki-67 expression were associated with increased expression of A3A and A3B. Advanced stage, presence of lymph node involvement, and high histological grade were associated with increased expression of A3A. The APOBEC3B deletion allele was found in 78 (56%) tumor samples. There was no significant association between A3A, A3B mRNA levels and the presence of APOBEC3B deletion allele. There was no difference in clinicopathological characteristics according to the presence of APOBEC3B deletion allele except histological grade. The frequency of high histological grade was significantly higher in tumors with APOBEC3B deletion allele than tumors without APOBEC3B deletion allele. TP53 mutations were identified in 12 (8.7%) cases and PIK3CA mutations were identified in 31 (22.5%) cases. There were no significant differences in the levels of A3A and A3B mRNA expression by TP53 mutation status. The presence of a PIK3CA mutation was significantly associated with lower A3A expression. Conclusions: The levels of A3B mRNA expression showed a difference according to breast cancer subtype, and triple-negative breast cancer showed the highest levels of A3B mRNA expression. The high levels of A3A and A3B mRNA expression were associated with an aggressive phenotype including high proliferation index. The APOBEC3A-3B deletion polymorphism was found in about half of the patients, but there was no difference in clinicopathological factors according to the presence of APOBEC3B deletion allele except histological grade. Citation Format: Won HS, Sun DS, Ko YH, You SH, Kim YS, Kim JS. Clinical implication of APOBEC3A and 3B in Korean patients with breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-05-03.

PTEN hamartoma tumor syndrome is a spectrum of disorders characterized by unique phenotypic features including multiple hamartomas caused by mutations of the tumor suppressor gene PTEN. Cowden syndrome and Bannayan–Riley–Ruvalcaba syndrome are representative diseases, and both have several common clinical features and differences. Because PTEN mutations are associated with an increased risk of malignancy including breast, thyroid, endometrial, and renal cancers, cancer surveillance is an important element of disease management. We report a germline mutation of the PTEN (c.723dupT, exon 7) identified in a young woman with a simultaneous occurrence of breast cancer, dermatofibrosarcoma protuberans, and follicular neoplasm. This case suggests that it is critical for clinicians to recognize the phenotypic features associated with these syndromes to accurately diagnose them and provide preventive care.

Background/Aims: This study was conducted to identify risk factors that predict vulnerability to cancer therapy on the basis of the clinical, geriatric, and quality of life assessment before starting treatment in elderly patients. Methods: Seventy-five patients aged 65 years and over with newly diagnosed stage IV solid cancer receiving chemotherapy were analyzed. Clinical and laboratory data were collected. The geriatric assessment was performed using the Korean versions of the Modified Barthel Index, Instrumental Activities of Daily Living, Mini-Mental State Examination, and Geriatric Depression Scale. The European Organisation for Research and Treatment of Cancer Quality-of-Life Core Ques tionnaire (EORTC-QLQ-C30) was also performed. Results: Forty-one patients stopped cancer treatment during or after the end of first-line therapy and were classified as the treatment interruption group. By univariate analysis, treatment interruption was associated with metastases to ≥ 2 distant sites, lower albumin level, lower EORTC-QLQ-C30 physical and role func tioning scores, and higher EORTC-QLQ-C30 fatigue and appetite loss symptom scores. By multivariate analysis, treatment interruption was significantly associ ated with low score for the EORTC-QLQ-C30 physical functioning scale (odds ra tio [OR], 1.020; 95% confidence interval [CI], 1.002 to 1.039; p = 0.030), and ≥ 2 sites of distant metastases (OR, 2.965; 95% CI, 1.012 to 8.681; p = 0.047). Conclusions: The EORTC-QLQ-C30 physical functioning score and metastases to ≥ 2 organs, which indicate a poor physical functional status and metastatic high tumor burden, were significantly associated with interruption of first-line treat ment in elderly patients with cancer.

Background: Cancer-associated fibroblasts (CAFs) reside within the tumor microenvironment, facilitating cancer progression and metastasis via direct and indirect interactions with cancer cells as well as other stromal cell types. CAFs are comprised of heterogeneous subpopulations of activated fibroblasts, including myofibroblastic, inflammatory, or immunosuppressive CAFs. In this study, we sought to identify subpopulations of CAFs isolated from human lung adenocarcinomas and describe their transcriptomic as well as functional characteristics through single-cell RNA sequencing (scRNA-seq) and subsequent bioinformatics analyses. Methods: We isolated and cultured two types of CAFs. Total CAFs were isolated after negative selection using cell-type-specific antibodies against lymphocytes (CD45), macrophages (CD68), endothelial cells (CD31), and epithelial cells (Ep-CAM). THY1+ CAFs were isolated after additional selection based on CAF-specific marker THY1. Total CAFs (n=5,139 cells) and THY1+ CAFs (n=4,038 cells) were subjected to 10X Genomics scRNA-seq. scRNA-seq data were then integrated and analyzed using the Seurat method. Results: Cell trajectory analysis of combined total and THY1+ CAFs revealed two branching points with five distinct branches. Based on Gene Ontology analysis, we denoted Branch 1 as “immunosuppressive”, Branch 2 as “neoantigen-presenting”, Branch 4 as “myofibroblastic”, and Branch 5 as “proliferative” CAFs. We selected representative branch-specific markers and measured their expression levels in total and THY1+ CAFs. We also investigated the effects of these markers on CAF activity under co-culture with lung cancer cells. Conclusions: This study describes novel subpopulations of CAFs in lung adenocarcinoma, highlighting their potential value as therapeutic targets. Citation Format: Daeseung Kim, Jeong Seon Kim, Seoree Kim, Sang Hoon Chun, Jae Jun Kim, Inyoung Cheon, Sieun Lee, Jung Sook Yoon, Soon Auck Hong, Hye Sung Won, Keunsoo Kang, Young-Ho Ahn, Yoon Ho Ko. Identification and characterization of cancer-associated fibroblast subpopulations in lung adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB043.

e12528 Background: The treatment of male breast cancer (MBC) has been extrapolated from female breast cancer (FBC) because of its rarity despite their different clinicopathologic characteristics. We aimed to investigate the distribution of intrinsic subtypes based on immunohistochemistry (IHC), their clinical impact, and treatment pattern in clinical practice through a multicenter study in Korea. Methods: We retrospectively analyzed clinical data of 248 MBC patients 18 institutions across the country from January 1995 to July 2016. Results: The median age of MBC patients was 63 years (range: 25–102 years). Among the 148 patients that underwent intrinsic subtype classification, 61 (41.2%), 44 (29.7%), 29 (19.5%), and 14 (9.5%) were luminal A, luminal B, HER2, and triple-negative breast cancer (TNBC), respectively. TNBC patients showed inferior survival compared with those with other subtypes. Of the 221 patients with operable breast cancer, 108 (48.6%) received adjuvant chemotherapy and 52 (23.5%) received adjuvant radiation therapy. Most hormone receptor-positive patients (166 patients, 82.6%) received adjuvant endocrine treatment. Five-year completion of adjuvant endocrine treatment was associated with superior disease-free survival (DFS) in patients classified with an intrinsic subtype (hazard ratio [HR] = 0.19, 95% confidence interval [CI] 0.005–0.65, P = 0.008) and in all patients (HR = 0.16, 95% CI 0.05–0.54, P = 0.003). Conclusions: Distribution of subtypes of MBC was similar to FBC and luminal type A was most common. Overall survival tended to be improved for luminal A subtype although there was no statistical significance. Completion of adjuvant endocrine treatment was associated with prolonged DFS in intrinsic subtype classified patients. MBC patients have tended to receive les treatment. MBC patients should be treated with standard guideline as FBC patients receive.

Background To assess fetal cardiac parameters predictive of postnatal operation type in fetuses with tetralogy of Fallot (TOF). Methods Echocardiographic data obtained in the second and third trimesters were retrospectively reviewed for fetuses diagnosed with TOF between 2014 and 2018 at Asan Medical Center. The following fetal cardiac parameters were analyzed: 1) pulmonary valve annulus (PVA) z-score, 2) right pulmonary artery (RPA) z-score, 3) aortic valve annulus (AVA) z-score, 4) pulmonary valve peak systolic velocity (PV-PSV), 5) PVA/AVA ratio, and 6) RPA/descending aorta (DAo) ratio. These cardiac parameters were compared between a primary corrective surgery group and a palliative shunt operation followed by complete repair group. Results A total of 100 fetuses with TOF were included. Only one neonatal death occurred. Ninety patients underwent primary corrective surgery and 10 neonates underwent a multistage surgery. The PVA z-score, RPA z-score, and RPA/DAo ratio measured in the second trimester and the PVA z-score, RPA z-score, and PVA/AVA raio measured in the third trimester were significantly lower in the multistage surgery group, while the PV-PSV as measured in both trimesters were significantly higher in the multistage surgery group. Conclusion Fetal cardiac parameters are useful for predicting the operation type necessary for neonates with TOF.

Background Noggin and RNA-binding protein for multiple splicing 2 (RBPMS2) are known to regulate the expression of smooth muscle cells, endothelial cells, and osteoblasts. However, the prognostic role of combined Noggin and RBPMS2 expression in resected gastric cancer (GC) is unclear. Methods A total of 163 patients with GC who underwent gastrectomy were included in this study. The expression of Noggin and RBPMS2 proteins in tumor cells at the tumor center and invasive front of resected GC was evaluated by immunohistochemistry, and in conjunction with clinicopathological parameters the patient survival was analyzed. Results RBPMS2 protein expression was high at the tumor center (n = 86, 52.8%) and low at the invasive front (n = 69, 42.3%), while Noggin protein expression was high in both tumor center (n = 91, 55.8%) and the invasive front (n = 90, 55.2%). Noggin expression at the invasive front and tumor center was significantly decreased in advanced T stage, non-intestinal-type (invasive front, P = 0.008 and P P = 0.013 and P = 0.001). RBPMS2 expression at the invasive front was significantly decreased in non-intestinal-type and positive lymphatic invasion (P P P = 0.251). Conclusions Our study indicates that high Noggin expression is a crucial prognostic factor for favorable outcomes in patients with resected GC.

During the coronavirus disease 2019 (COVID-19) pandemic, many guidelines have recommended postponing non-emergency operations. However, cesarean sections cannot be indefinitely delayed. Our institution has established a COVID-19 screening strategy for patients undergoing cesarean section. We evaluated the usefulness of this screening strategy. Parturients undergoing cesarean section at our center during the first peak of the COVID-19 outbreak were retrospectively analyzed. Each parturient underwent a questionnaire survey evaluating epidemiological correlation and symptoms at admission. Reverse transcriptase–polymerase chain reaction (RT–PCR) testing and/or chest radiography were performed. In total, 296 parturients underwent cesarean section. All elective and 37 emergency cesarean sections were performed in general operating rooms because they were considered to have a low risk of COVID-19 infection through the screening process. However, 42 emergency cases were performed in negative-pressure operating rooms with full personal protective equipment (PPE) because the RT–PCR results could not be confirmed in a timely manner. None of them were positive for RT–PCR, and there were no cases of nosocomial infection. A comprehensive preoperative screening strategy, including symptomatic and epidemiological correlation, PCR, and/or imaging test, should be performed in patients undergoing cesarian section. Further, cesarean sections in parturients with unconfirmed COVID-19 status should be performed in a negative-pressure operating room with appropriate PPE.

Objective To evaluate the reproducibility of the fetal right modified myocardial performance index (Mod-MPI) obtained by synchronizing the inflow and outflow images of the right ventricle (RV) and to evaluate its feasibility through clinical application to twin-to-twin transfusion syndrome (TTTS). Methods We prospectively evaluated 77 normal fetuses. Two experienced operators individually measured the right Mod-MPI using two different methods: (1) separate recording of the RV inflow and outflow using pulsed-wave Doppler (conventional method) and (2) synchronization of RV inflow and outflow images using the MPI + ™ function based on the closure click of the pulmonary valve (new method). To evaluate the clinical utility of the new method, we measured the right Mod-MPI in 33 TTTS fetuses using the new method before and after the fetoscopic laser coagulation (FLC). Results There was no statistical difference in Mod-MPI values between the two methods (p = .242). For both operators, the intra- and interoperator reproducibility of Mod-MPI was high with both methods (ICCs >0.950). Among the components of Mod-MPI measured using the new method, ejection time showed the highest reproducibility, whereas isovolumetric relaxation time demonstrated the lowest reproducibility. In TTTS fetuses, the Mod-MPI significantly decreased after FLC in recipients, and there was no difference in MPI values before and after FLC in donors. Conclusion Right Mod-MPI measurement after the synchronization of RV inflow and outflow images is a reliable technique for evaluating fetal right cardiac function. This novel method can also independently evaluate the systolic and diastolic functions of the right heart.

Objective To report our experience with management of fetuses with congenital high airway obstruction syndrome (CHAOS). Methods We retrospectively reviewed the cases of fetuses who were prenatally diagnosed and postnatally confirmed with CHAOS between 2010 and 2019 at Asan Medical Center, Seoul, Korea. Results Of 13 fetuses prenatally diagnosed with CHAOS, 7 were lost to follow-up and 6 were postnatally confirmed as having CHAOS. All fetuses, except one were delivered via cesarean section with an ex utero intrapartum treatment (EXIT) procedure. Two patients had coexisting congenital heart diseases requiring several cardiac surgeries following birth. Both of these patients demonstrated developmental delay; however, the remaining 4 had a normal development except for expressive language. Two infants died of respiratory complications, and the remaining 4 were alive at the end of the follow-up period. All 4 live patients underwent tracheostomy with planned reconstruction surgery. Three children are now able to phonate, and 1 can maintain a conservation. Conclusion The proper management of CHAOS using the EXIT procedure results in high survival and low hypoxemia-induced complication rates. Therefore, an accurate prenatal diagnosis is necessary for an appropriate perinatal management.

To establish whether a correlation exists between the fetal middle cerebral artery peak systolic velocity (MCA PSV) and fetal hemoglobin levels before intrauterine transfusion (IUT) in cases of severe fetal anemia.This was a single-center, retrospective study of data from 49 fetuses treated with IUT for fetal anemia between 2003 and 2018. Severe fetal anemia was suspected when MCA PSV was or exceeded 1.55 multiples of the median.The causes of anemia were largely idiopathic, and the overall survival rate was 57%. MCA PSV and hemoglobin were correlated in all 34 fetuses with alloimmune fetal anemia, whereas the 15 fetuses with nonimmune causes showed no correlation. Of the 15 noncorrelated cases, twin pregnancy was most common, followed by idiopathic causes. All the twin pregnancies involved monochorionic twins. Fetal hydrops, especially ascites, was significantly associated with severe anemia.Fetal MCA PSV may not be a reliable independent factor for the diagnosis of severe fetal anemia in nonimmune cases, and the presence of associated hydrops implies that the fetus is more likely to have severe fetal anemia than in a fetus without hydrops.

CD8+ tumor-infiltrating lymphocytes (TILs) play a major role in antitumor immunity. High endothelial venules (HEVs) are related to diverse immune cells in solid tumors. We analyzed CD8+ and Foxp3+ TILs in combination with HEVs to determine their prognostic role in advanced gastric cancer (AGC). We enrolled 157 patients with AGC in this study. The densities of CD8+ TILs and Foxp3+ TILs were calculated using immunohistochemical staining. HEVs were evaluated by MECA-79 expression. HEVs were identified in 60 (38.2%) cases and was significantly associated with an increased number of CD8+ TILs (p = 0.027) but not of Foxp3+ TILs (p = 0.455) and CD20+ TILs (p = 0.163). A high CD8+/HEV+ level was significantly associated with nodal metastasis (p = 0.048). In survival analysis, patients with high CD8+/HEV+ levels demonstrated the longest overall survival (OS) (p = 0.015). Furthermore, a high CD8+/HEV+ level was an independent prognostic factor in AGC (p = 0.011, hazard ratio (HR) = 0.435, 95% confidence interval (CI) = 0.245&ndash, 0.837). HEVs were found to play an important role in antitumor immunity associated with CD8+ TILs in AGC. This analysis of HEVs and CD8+ TILs helps stratify patients with AGC and sheds light on tumor immunity.

The effects of prenatal particulate matter with an aerodynamic diameter ranging from 0.1 μm to 2.5 μm (PMTo determine the critical windows of prenatal PMMother-child pairs were enrolled from the birth cohort of the Cohort for Childhood Origin of Asthma and allergic diseases (COCOA) study. PMPMHigher PM

The cost of next-generation sequencing technologies is rapidly declining, making RNA-seq-based gene expression profiling (GEP) an affordable technique for predicting receptor expression status and intrinsic subtypes in breast cancer patients. Based on the expression levels of co-expressed genes, GEP-based receptor-status prediction can classify clinical subtypes more accurately than can immunohistochemistry (IHC). Using data from The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA BRCA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) datasets, we identified common predictor genes found in both datasets and performed receptor-status prediction based on these genes. By assessing the survival outcomes of patients classified using GEP- or IHC-based receptor status, we compared the prognostic value of the two methods. We found that GEP-based HR prediction provided higher concordance with the intrinsic subtypes and a stronger association with treatment outcomes than did IHC-based hormone receptor (HR) status. GEP-based prediction improved the identification of patients who could benefit from hormone therapy, even in patients with non-luminal breast cancer. We also confirmed that non-matching subgroup classification affected the survival of breast cancer patients and that this could be largely overcome by GEP-based receptor-status prediction. In conclusion, GEP-based prediction provides more reliable classification of HR status, improving therapeutic decision making for breast cancer patients.

Background We aimed to evaluate the expression of APOBEC3A (A3A), 3B (A3B) mRNA, and germline APOBEC3A/B deletion polymorphism in patients with breast cancers and to investigate the correlation between their expressions and clinicopathological characteristics. Methods RNA and DNA samples were extracted from 138 breast cancer tissues and adjacent normal breast tissues. The levels of A3A and A3B mRNA transcripts were determined using quantitative real-time polymerase chain reaction. Insertion and deletion PCR assays were performed to detect the A3B deletion allele. The serum concentrations of soluble programmed death-ligand 1 (sPD-L1) and interferon gamma were determined using enzyme-linked immunosorbent assays. Results A3B mRNA expression levels were significantly higher in triple-negative breast cancers compared to hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancers. Older age of the patient and high ki-67 expression were associated with increased expression levels of A3A and A3B mRNA. Advanced tumor stage, presence of lymph node involvement, and high histological grade were associated with increased expression levels of A3A mRNA. The APOBEC3A/B deletion allele was found in 77 (55.8%) patients. TP53 and PIK3CA mutations were detected in 62 (44.9%) and 31 (22.5%) patients, respectively. The presence of a PIK3CA mutation was associated with lower A3A mRNA expression levels. There was a weak positive relationship between A3A mRNA expression levels and serum sPD-L1 levels. Conclusions There was a difference in A3B mRNA expression levels according to breast cancer subtypes, and high levels of A3A and A3B mRNA expressions were associated with an aggressive phenotype. There was a high incidence of APOBEC3A/B deletion allele. Further studies are needed to identify the clinical significance of APOBEC in Asian patients with breast cancer.

Pregnancy following heart transplantation is a high-risk condition, requiring adequate maintenance of immunosuppressive drugs that enable proper graft function for optimal maternal and fetal outcomes. Here, we present the first case of successful child delivery in a patient who underwent heart transplantation in Korea. The 35-year-old female patient had become pregnant at 4 years after heart transplantation. The pregnancy progressed uneventfully, and the infant was healthy.

Objective Although corpus callosal abnormalities are among the most common brain malformations detected prenatally, few previous studies have described the neurodevelopmental outcomes of children with this condition. The aim of our study was to evaluate the neurodevelopmental outcomes and associated clinical features of children with corpus callosal abnormalities diagnosed by prenatal ultrasonography. Methods Between July 2011 and July 2016, forty-nine children with corpus callosal abnormalities were born in Asan Medical Center Children’s Hospital. Neurodevelopmental assessments were conducted in 40 patients at a median age of 24.8 months using the Bayley Scales of Infant Development II or the Korean Infant and Child Development Test. Patients were categorized according to their postnatal magnetic resonance imaging (MRI) findings and accompanying anomalies. Baseline characteristics and developmental outcomes of each group were compared. Results Isolated agenesis or hypoplasia of the corpus callosum was found in 16 (32.7%) patients, other associated central nervous system (CNS) abnormalities were found in 28 (57.1%) patients, and non-CNS abnormalities were found in 11 (22.4%) patients. Among the 40 patients who underwent developmental assessment, 18 (45.0%) showed normal development and 10 (25.0%) showed moderate-to-severe global developmental delay. Seven of the twelve (58.3%) patients with isolated corpus callosal abnormalities showed normal development. The combination of corpus callosal abnormalities with non-CNS anomalies was significantly associated with developmental delay (odds ratio 2.5, 95% confidence interval 1.6–3.9, p = 0.001). Conversely, children with isolated corpus callosal abnormalities showed relatively favorable neurodevelopmental outcomes. Conclusion Appropriate evaluation and comprehensive therapeutic approaches are strongly recommended for neonates who present with corpus callosal abnormalities combined with additional anomalies.

Background We hypothesised that lactate concentrations are independently associated with massive transfusion in patients with primary postpartum haemorrhage. Moreover, combining lactate concentrations with the shock index, defined as the ratio of heart rate to systolic arterial blood pressure, can improve the predictive performance for massive transfusion. Methods We retrospectively analysed patients with primary postpartum haemorrhage in the emergency department of a tertiary referral centre in Korea between January 1, 2004 and December 31, 2015. Results Of the 302 patients, 101 (33.4%) patients required massive transfusion. Lactate concentration was independently associated with the requirement for massive transfusion [odds ratio, 1.56; 95% confidence interval (CI), 1.31–1.87; P 4.0 mM L−1) was associated with 86.1% specificity and 67.8% positive predictive value for massive transfusion. When combining elevated lactate concentrations (>4.0 mM L−1) with a shock index >1.0, the specificity and positive predictive value increased to 95.5% and 82.4%, respectively. Conclusions Point-of-care testing of lactate concentrations in the emergency department may be useful to predict massive transfusion requirements in primary postpartum haemorrhage. Combining initial lactate concentrations with the shock index improves the predictive performance for massive transfusion requirements and may contribute to rapid risk stratification of patients with primary postpartum haemorrhage in need of transfusion and further focus on early interventions to control bleeding.

OBJECTIVES To evaluate the perinatal survival and renal function of fetuses with lower urinary tract obstruction (LUTO) who underwent vesicoamniotic shunting using a double-basket catheter METHODS: We retrospectively reviewed 32 fetuses with LUTO who underwent vesicoamniotic shunting using a double-basket catheter between 1998 and 2013. RESULTS Among the 32 fetuses examined, 5 died because of termination of pregnancy, and 2 died in utero. The median gestational age at diagnosis was 15.5 (range, 10.0-27.3) weeks, and that at initial shunting was 17.1 (range, 12.3-32.2) weeks. Shunt dislocation or occlusion occurred in 18 of 42 procedures (42.8%). The median gestational age at delivery for the 25 live births was 35.5 (range, 28-40) weeks. Postnatal diagnosis revealed posterior urethral valves in 15 fetuses, a cloacal anomaly in 7, and urethral stenosis in 3. Three neonatal deaths occurred, resulting in an overall perinatal survival rate of 68.8% (22 of 32). The rates of normal renal function were 40.6% (13 of 32) at 28 days and 40% (10 of 25) at 2 years after birth. The absence of oligohydramnios after shunting was the only prognostic factor for normal renal function at 2 years (P

Prenatal particulate matter

Objectives To evaluate the reproducibility of the fetal right myocardial performance index determined by simultaneous recording of inflow and outflow using a dual gate pulsed-wave Doppler (DD). Methods This was a prospective study of 39 normal singleton fetuses. Two experienced operators each measured the right myocardial performance index in three ways, twice: (1) separate recording of the inflow and outflow using single-gate pulsed-wave Doppler (PD), (2) simultaneous recordings of the inflow and outflow using tissue Doppler (TD), and (3) simultaneous recordings of the inflow and outflow using DD. Intra- and interoperator reproducibility were assessed with intraclass correlation coefficients. The measurements from all three methods taken by the more experienced operator were compared using Bland-Altman plots and mean differences. Results For both operators, intra-operator reproducibility was the highest when using DD, followed by PD, and TD. Interoperator agreement was the highest for PD measurements, followed by DD, and TD. The smallest mean difference was between the PD and DD measurements by the more experienced operator. There was a positive correlation between PD and DD values (r = 0.369, P

Prenatal intervention of severe fetal aortic valve stenosis by ultrasound-guided percutaneous balloon valvuloplasty has been performed to prevent the progression to hypoplastic left heart syndrome, and achieve biventricular circulation in neonates. Here we report a case of fetal aortic valvuloplasty prenatally diagnosed with aortic stenosis at 24 weeks of gestation and showed worsening features on a follow-up echocardiography. Prenatal aortic valvuloplasty was performed at 29 weeks of gestation, and was a technical success. However, fetal bradycardia sustained, and an emergency cesarean delivery was performed. To the best of our knowledge, this is the first reported case of fetal aortic valvuloplasty which was performed in Asia.

Background/Aims.The miRNA-200 (miR-200) family may act as key inhibitors of epithelial-to-mesenchymal transition. However, the potential prognostic value of miR-200s in various human malignancies remains controversial. This meta-analysis analyzed the associations between miR-200 levels and survival outcomes in a variety of tumors.Methods.Eligible published studies were identified by searching the Embase, PubMed, CINAHL, and Google scholar databases. Patient clinical data were pooled, and pooled hazard ratios (HRs) with 95% confidence intervals (95% CI) were used to calculate the strength of this association.Results.The pooled HRs suggested that high tissue expression of miR-200 family members was associated with better survival (overall survival [OS]: HR = 0.70, 95% CI 0.54–0.91; progression-free survival [PFS]: HR = 0.63, 95% CI 0.52–0.76) in thirty-four eligible articles. In contrast, higher expression of circulating miR-200 members was significantly associated with poor clinical outcome (OS, HR = 1.68, 95% CI 1.15–2.46; PFS, HR = 2.62, 95% CI 1.68–4.07).Conclusion.The results from this meta-analysis suggest that miR-200 family members are potential prognostic biomarkers in patients with various carcinomas. To apply these findings in the clinic, large prospective studies are needed to validate the prognostic values of miR-200s in individual cancer types.

Purpose To evaluate the prenatal sonographic predictive markers of the outcome in fetuses with bronchopulmonary sequestration (BPS). Methods BPS size and diameter of the feeding artery (FA) were measured prenatally and postnatally. Velocity of the FA and the left ventricular-modified myocardial performance index (LV mod-MPI) were also evaluated prenatally. Results Forty-seven women were included in the study. Mean gestational age, mass size, diameter and velocity of the FA, and LV mod-MPI at prenatal diagnosis were 23.5 ± 2.2 weeks, 3.6 ± 8.3 cm, 2.3 ± 0.6 mm, 46.6 ± 15.4 cm/s, and 0.46 ± 0.06, respectively. Mean mass diameter and FA diameter measured on postnatal CT examinations were 3.8 ± 1.0 cm and 2.3 ± 0.7 mm, respectively. Five patients had respiratory symptoms after birth. Twenty children (43%) underwent or were scheduled to undergo mass excision, and the remaining 27 (57%) were doing well without any intervention. There was no neonatal death. LV mod-MPI at diagnosis, the FA diameter after birth and the serial change in the FA size were significantly associated with postnatal mass excision. Conclusion The FA diameter and LV mod-MPI may be additional markers for predicting whether fetuses with BPS should undergo mass excision in early childhood or conservative care.

Congenital heart disease is the leading cause of birth defect related deaths. The modified myocardial performance index of the right ventricle (R-MPI) is a sensitive and early clinical indicator of fetal cardiac health. Objective repeatable measurement of R-MPI is an important deciding factor for the clinical adaptation of the R-MPI. In this work, we describe a novel method for automatic computation of R-MPI from the Pulsed Wave Doppler (PWD) images. Our method involves a Fourier series based cardiac cycle detection followed by an adaptive windowed energy based valve click localization and weighted gradient based refinement. Using this method, we have been able to measure R-MPI reliably with a mean difference of 0.0075 ± 0.034 from 170 expert annotations on 68 fetal PWD images with an Intra-Class Correlation (ICC) of 0.9380. Furthermore, we have introduced novel methods for normalization and synchronization of PWD images acquired at two different time intervals for the assessment of iso-volume time intervals and an accurate measurement of R-MPI.

To compare the incidence of brain metastases of advanced non-small cell lung cancer (NSCLC) treated with systemic cytotoxic chemotherapy (CC) and targeted therapy (TT), we performed a large-scale, retrospective, nationwide, cohort study. The population data were extracted from the Health Insurance Review and Assessment Service of Korea database from January 1, 2011, to November 30, 2016. Of the 29,174 patients newly diagnosed with stage IIIB or IV NSCLC who received systemic treatment, we investigated the initial and subsequent incidence of brain metastases. Besides, among 22,458 patients without initial brain metastasis, the overall cumulative incidence of subsequent brain metastases was compared according to systemic treatment administered. In total, 1,126 (5.0%) patients subsequently developed brain metastasis. The overall cumulative incidence of brain metastasis was significantly higher in the TT group than in the CC group (1-year cumulative incidence: 8.7% vs. 3.8%; 3-year: 17.2% vs. 5.0%; P

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This chapter includes types, morphology, clinical manifestations, diagnosis, natural and unnatural course, treatment, and fetal diagnosis of pulmonary atresia with intact ventricular septum, including one-and-half ventricle repair and Fontan operation.

This chapter includes synonyms, definition, types, morphology, clinical manifestations, diagnosis, natural course, treatment, and fetal diagnosis of atrioventricular septal defect.

This chapter includes types, morphology, clinical manifestations, diagnosis, natural course, treatment, and fetal diagnosis of interrupted aortic arch, including DiGeorge syndrome and Berry syndrome.

This chapter includes types, morphology, clinical manifestations, diagnosis, natural course, treatment, and fetal diagnosis of coarctation of the aorta and pseudocoarctation of the aorta.

There have been few studies investigating the association between atopic dermatitis (AD) and prenatal exposure to heavy metals. We aimed to evaluate whether prenatal exposure to heavy metals is associated with the development or severity of AD in a birth cohort study. A total of 331 subjects were followed from birth for a median duration of 60.0 months. The presence and severity of AD were evaluated at ages 6 and 12 months, and regularly once a year thereafter. The concentrations of lead, mercury, chromium, and cadmium in umbilical cord blood were measured by inductively coupled plasma mass spectrometry. Cord blood mononuclear cells (CBMCs) were isolated and stimulated for analysis of cytokine production using ELISA. Heavy metal levels in cord blood were not associated with the development of AD until 24 months of age. However, a positive correlation was observed between the duration of AD and lead levels in cord blood (p=0.002). AD severity was also positively associated with chromium concentrations in cord blood (p=0.037), while cord blood levels of lead, mercury, and cadmium were not significantly associated with AD severity (p=0.562, p=0.054, and p=0.055, respectively). Interleukin-13 production in CBMCs was positively related with lead and chromium levels in cord blood (p=0.021 and p=0.015, respectively). Prenatal exposure to lead and chromium is associated with the persistence and severity of AD, and the immune reaction toward a Th2 polarization.

e16172 Background: Despite recent advancements in the understanding of the molecular biology of biliary tract cancer (BTC), target therapy and immunotherapy have demonstrated only limited efficacy, with cytotoxic systemic therapy still being the most effective treatment in BTC, except for surgery. Thus, this study aimed to analyze the role of DKK1 or β-catenin as a prognostic factor in BTC and determine the clinical association of ß-catenin and DKK1 with CD8+ tumor-infiltrating lymphocyte (TIL). Methods: We used data in The Cancer Genome Atlas (TCGA) Research Network and the clinicopathological data of 145 patients with BTC who had undergone primary radical resection between 2006 and 2016. Immunohistochemistry was performed on formalin-fixed, paraffin-embedded tissue sections, and whole tissue sections of representative tumor samples were used for antigen retrieval. Results: CD8+TIL expression was a significant predictor of favorable overall survival (OS) and recurrence-free survival (RFS) (median OS, 34.9months in TIL-high, 16.7months in TIL-low, P < 0.0001 respectively; median RFS, 27.1months in TIL-high, 10months in TIL-low, P < 0.0001 respectively). Positive ß-catenin expression and high DKK1 expression was also associated with a shorter OS (median OS, 23.95months in positive ß-catenin, 26.1months in negative ß-catenin, P = 0.1009 respectively; median OS, 19.4months in high DKK1, 31.65months in Low DKK1, P = 0.0093 respectively), but not RFS (p = 0.1466, at ß-catenin respectively; p = 0.2924, in DKK1 respectively). In the CD8+TIL-high BTC group, the tumor expression of β-catenin and DKK1 had a significant negative impact on either OS or RFS (p = 0.0146 and p = 0.0112, at ß-catenin respectively; p = 0.0950 and p = 0.3904, in DKK1 respectively). However, in the TIL-low BTC group, there were no differences in OS or RFS according to ß-catenin and DKK1 expression (p = 0.5108 and p = 0.8431, at ß-catenin respectively; p = 0.1127 and p = 0.1095, in DKK1 respectively). Cox regression multivariate analysis demonstrated that CD8+ TIL (hazard ratio [HR], 0.490; 95% confidence interval (CI), 0.303-0.791; p = 0.004) and β-catenin (HR, 1.652; 95% CI, 1.035-2.639; p = 0.036) retained significant association with OS after adjustment for all variables. Conclusions: Among patients with resected BTC, β-catenin and DKK1 protein levels are associated with poor clinical outcomes, whereas high CD8+ TIL levels are associated with good clinical outcomes. This confirms the differential clinical role of Wnt/β-catenin and DKK1 proteins according to TIL expression in BTC.

Fetal ventricular tachycardia (VT) is an extremely rare condition. Because sustained VT is highly associated with perinatal morbidity and mortality, prenatal management with antiarrhythmic drugs is crucial. A 33-year-old woman was referred to our hospital for fetal bradycardia at 25.2 weeks of gestation. Initial echocardiography showed bradycardia with irregular atrial beats, which was suspected as blocked atrial bigeminy. Four weeks later, the fetal tachycardia was accompanied by no atrioventricular conduction. Therefore, VT was diagnosed. The fetus developed hydrops. Despite the use of antiarrhythmic drug, the neonate died a few hours after birth because of persistent VT. Only few cases of fetal VT have been reported worldwide, and no case has been reported in Korea. Here, we report a case of fetal VT and discuss the prenatal management using antiarrhythmic drugs, reviewing previous reports.

Background The effects of prenatal particulate matter with an aerodynamic diameter ranging from 0.1 μm to 2.5 μm (PM2.5) and vitamin D on atopic dermatitis (AD) phenotypes have not been evaluated. DNA methylation and cord blood (CB) vitamin D could represent a plausible link between prenatal PM2.5 exposure and AD in an offspring. Objective To determine the critical windows of prenatal PM2.5 exposure on the AD phenotypes, if vitamin D modulated these effects, and if placental DNA methylation mediated these effects on AD in offspring. Methods Mother–child pairs were enrolled from the birth cohort of the Cohort for Childhood Origin of Asthma and allergic diseases (COCOA) study. PM2.5 was estimated by land-use regression models, and CB vitamin D was measured by chemiluminescence immunoassay. AD was identified by the parental report of a physician’s diagnosis. We defined the following 4 AD phenotypes according to onset age (by the age of 2 years) and persistence (by the age of 3 years): early-onset transient and persistent, late onset, and never. Logistic regression analysis and Bayesian distributed lag interaction model were used. DNA methylation microarray was analyzed using an Infinium Human Methylation EPIC BeadChip (Illumina, San Diego, California) in placenta. Results PM2.5 exposure during the first trimester of pregnancy, especially during 6 to 7 weeks of gestation, was associated with early-onset persistent AD. This effect increased in children with low CB vitamin D, especially in those with PM2.5 exposure during 3 to 7 weeks of gestation. AHRR (cg16371648), DPP10 (cg19211931), and HLADRB1 (cg10632894) were hypomethylated in children with AD with high PM2.5 and low CB vitamin D. Conclusion Higher PM2.5 during the first trimester of pregnancy and low CB vitamin D affected early-onset persistent AD, and the most sensitive window was 6 to 7 weeks of gestation. Placental DNA methylation mediated this effect.

Aim Some recent studies have reported that early intervention by a medical emergency team (MET) for clinical deterioration before intensive care unit (ICU) admission was associated with a survival benefit in critically ill cancer patients. We hypothesized that early MET intervention for an obstetric crisis in the general wards would be related to favorable outcomes in critically ill obstetric patients. Methods Data of obstetric patients who were managed by a MET were collected retrospectively from 1 March 2008 to 30 April 2015. A total of 69 obstetric patients were enrolled. Among them, 48 (69.6%) were treated successfully in the general wards and 21 (30.4%) were transferred to the ICU. Results Major causes of MET activation were pulmonary edema (n = 23, 33.3%), hypovolemic shock (n = 19, 27.5%), and septic shock (n = 8, 11.6%). Compared with the patients treated in the general ward, the patients transferred to the ICU had significantly higher severity of illness score. Sequential Organ Failure Assessment score was the most useful for prediction of ICU admission of obstetric patients (AUC, 0.810, P < 0.001), and the ideal cut-off was 4 (sensitivity, 81%; specificity, 60%). During the study period, in-hospital mortality of the obstetric patients was 2.9% (2/69). Conclusion After MET activation many obstetric patients could be successfully treated in the general wards without mortality. Therefore, MET may reduce ICU admissions in critically ill obstetric patients.

Purpose Breast cancer treatment has progressed significantly over the past 20 years. However, knowledge regarding male breast cancer (MBC) is sparse because of its rarity. This study is an investigation of the clinicopathologic features, treatments, and clinical outcomes of MBC. Materials and methods Clinical records of 59 MBC patients diagnosed during 1995-2014 from seven institutions in Korea were reviewed retrospectively. Results Over a 20-year period, MBC patients accounted for 0.98% among total breast cancer patients, and increased every 5 years. The median age of MBC patientswas 66 years (range, 24 to 87 years). Forty-three patients (73%) complained of a palpable breast mass initially. The median symptom duration was 5 months (range, 1 to 36 months). Mastectomy was performed in 96% of the patients. The most frequent histology was infiltrating ductal carcinoma (75%). Ninety-one percent of tumors (38/43) were estrogen receptor-positive, and 28% (11/40) showed epidermal growth factor receptor 2 (HER-2) overexpression. After curative surgery, 42% of patients (19/45) received adjuvant chemotherapy; 77% (27/35) received hormone therapy. Five out of ten patients with HER-2 overexpressing tumors did not receive adjuvant anti-HER-2 therapy, while two out of four patients with HER-2 overexpressing tumors received palliative trastuzumab for recurrent and metastatic disease. Letrozole was used for one patient in the palliative setting. The median overall survival durations were 7.2 years (range, 0.6 to 17.0 years) in patients with localized disease and 2.9 years (range, 0.6 to 4.3 years) in those with recurrent or metastatic disease. Conclusion Anti-HER-2 and hormonal therapy, except tamoxifen, have been underutilized in Korean MBC patients compared to female breast cancer patients. With the development of precision medicine, active treatment with targeted agents should be applied. Further investigation of the unique pathobiology of MBC is clinically warranted.

전신홍반루푸스 환자에서 드물게 자가면역용혈빈혈과 순수적혈구무형성증이 함께 발생할 수 있다. 따라서 본 증례에서와 같이 자가면역용혈빈혈 환자가 치료 도중 스테로이드에 저항성을 보이고 빈혈이 악화된다면 순수적혈구무형성증과 같은 다른 빈혈의 원인을 검토해보아야 한다. 또한 자가면역용혈빈혈 또는 순수적혈구무형성증 환자에서 다른 기저질환의 동반 가능성을 고려하여 이에 대한 검사를 진행해야 한다.

Objectives The purpose of this study was to determine the type of an imperforate anus by using sonography in the prenatal period. Methods This retrospective study evaluated the fetal anus in all pregnant women, including low- and high-risk populations, between February 2010 and November 2013. High-type imperforate anuses were diagnosed by prenatal sonography when the anal sphincter muscles and anal canal mucosa were not visible. Low-type imperforate anuses were prenatally suspected when at least 1 of the following was present: (1) a small anus; (2) no visible anal mucosa; or (3) close location of the genitalia by the anus without a visible perineal body, particularly in a female fetus. Results Among the 9499 fetuses, 41 were prenatally suspected of having an imperforate anus, and 32 were confirmed to have this disorder. During the same study period, there were 11 false-negative cases, for a diagnostic sensitivity rate of 74%. All 9 fetuses who were confirmed to have a normal anus were prenatally suspected of having a low-type imperforate anus. Among the 32 fetuses with a confirmed imperforate anus, 19 were confirmed to have a high or intermediate type and 13 to have a low type. The type in 3 fetuses was incorrectly determined prenatally. Conclusions Although an imperforate anus is not always diagnosed prenatally, its type can be determined by prenatal sonography.

Objectives To establish normal reference ranges for the fetal left modified myocardial performance index (Mod-MPI) measured by the Auto Mod-MPI system and evaluate Mod-MPI changes in recipients of twin-to-twin transfusion syndrome (TTTS) before and after fetoscopic laser coagulation. Methods This was a prospective longitudinal study of normal singleton fetuses from 12.0 to 40.0 weeks of gestation. TTTS cases treated by laser coagulation were reviewed for Mod-MPI measurements of recipients. All measurements were performed using the Auto Mod-MPI system by a single experienced operator. Results Among a total 447 examinations from 222 fetuses, we were unable to measure the Mod-MPI in two cases, and therefore, 445 examinations were analyzed. The median Mod-MPI consistently increased from 0.44 to 0.56 throughout gestation. The median isovolumetric contraction time (ICT) and isovolumetric relaxation time (IRT) also increased with advancing gestational age. The ejection time (ET) increased until 27 weeks of gestation and decreased thereafter. In the 30 recipients, Mod-MPI, ICT, and IRT increased before laser coagulation and significantly decreased after laser coagulation. Conclusion Normal reference values for left Mod-MPI were established using the Auto Mod-MPI system, and these might be useful for assessing cardiac function in TTTS. © 2016 John Wiley & Sons, Ltd.

To evaluate safety and clinical outcomes of uterine artery embolisation (UAE) for bleeding after dilatation and curettage (DC) performed for abortion or termination.The outcomes were analysed in 11 patients who underwent UAE for bleeding after DC for missed abortions (n=8), caesarean scar pregnancies (n=2), or planned termination (n=1) between October 2001 and December 2013. Angiograms and medical records were retrospectively reviewed in order to obtain the patients' baseline characteristics, technical/clinical success rate, complications, and follow-up data regarding menstruation.Technical success, defined as successful catheterisation of both uterine arteries with embolisation to haemostasis, was 100%, whereas clinical success, defined as cessation of bleeding after the initial session of UAE and without the need for additional UAE or surgery for the purpose of haemostasis, was 81.8% (nine of 11). In the two patients with clinical failure due to recurrent vaginal bleeding after UAE, one patient underwent repeat UAE and showed a successful outcome, whilst the other patient required hysterectomy with pathological results of placenta increta. Two other patients underwent hysterectomy for placenta percreta or hydatidiform mole-mimicking remnant placenta. None of the patients included in the present series had procedure-related complications. Menstruation resumed in all eight patients with an intact uterus during the mean follow-up period.UAE may be a safe and effective treatment for bleeding after DC, especially for women who wish to preserve their fertility; however, hysterectomy may be indicated for patients with a placental abnormality.

The Jra antigen of the JR blood group system is a highly prevalent red blood cell antigen. Although anti-Jra-associated hemolytic disease of the fetus and newborn (HDFN) is generally considered mild-to-moderate, a rare fatal case was recently reported. We report the third example of HDFN-related anti-Jra with fatal outcomes. The clinical significance of anti-Jra antibody as a cause of HDFN should be reassessed.