OBJECTIVE: In this study, we evaluated the prevalence of allergic disease in offsprings delivered via the delivery modes of vaginal delivery vs. planned Cesarean section vs. Cesarean section with labor. METHODS: This study included 175 mother-neonate pairs from Severance Hospital who were enrolled in the Cohort for Childhood Origin of Asthma and allergic diseases study. Information regarding prenatal environmental factors, delivery, and diagnosis of allergic diseases was obtained from a questionnaire and medical record review. Patients with at least 3 years of follow-up data were included in this study. Results were adjusted for sex, birth weight, gestational age at birth, season of birth, neonatal intensive care unit admission, parity, breastfeeding, and maternal factors. RESULTS: A total of 175 offsprings were eligible for analysis. Among the subjects, 52.0% were delivered by vaginal delivery, 34.3% by planned Cesarean section, and 16.6% by Cesarean section with labor. Fifty-nine offsprings (33.7%) were diagnosed with allergic disease at a median age of 1 year (range 0.5–3 years). The prevalence of allergic disease was not associated with delivery mode after adjusting for confounding variables. Time period from membrane rupture to delivery, duration of the active phase, and the beginning of the pelvic division prior to Cesarean section were not associated with allergic disease development in offsprings. CONCLUSION: Cesarean section, irrespective of the occurrence of labor before surgery, did not increase the prevalence of allergic disease in infants up to 3 years of age.
Asthma ; Birth Weight ; Breast Feeding ; Cesarean Section* ; Cohort Studies ; Confounding Factors (Epidemiology) ; Diagnosis ; Female ; Follow-Up Studies ; Gestational Age ; Humans ; Infant ; Infant, Newborn ; Intensive Care, Neonatal ; Medical Records ; Membranes ; Parity ; Parturition ; Pregnancy ; Prevalence* ; Rupture ; Seasons

To examine the effects of Populus tomentiglandulosa (PT) extract on the expressions of antioxidant enzymes and neurotrophic factors in the cornu ammonis 1 (CA1) region of the hippocampus at 5 min after inducing transient global cerebral ischemia (TGCI) in gerbils, TGCI was induced by occlusion of common carotid arteries for 5 min. Before ischemic surgery, 200 mg·kg PT extract was orally administrated once daily for 7 d. We performed neuronal nuclear antigen immunohistochemistry and Fluoro-Jade B staining. Furthermore, we determined in situ production of superoxide anion radical, expression levels of SOD1 and SOD2 as antioxidant enzymes and brain-derived neurotrophic factor (BDNF) and insulin-like growth factor I (IGF-I) as neurotrophic factors. Pretreatment with 200 mg·kg PT extract prevented neuronal death (loss). Furthermore, pretreatment with 200 mg·kg PT extract significantly inhibited the production of superoxide anion radical, increased expressions of SODs and maintained expressions of BDNF and IGF-I. Such increased expressions of SODs were maintained in the neurons after IRI. In summary, pretreated PT extract can significantly increase levels of SODs and protect the neurons against TGCI, suggesting that PT can be a useful natural agent to protect against TGCI.
Animals ; Brain-Derived Neurotrophic Factor ; genetics ; metabolism ; CA1 Region, Hippocampal ; drug effects ; metabolism ; Gerbillinae ; Humans ; Insulin-Like Growth Factor I ; genetics ; metabolism ; Male ; Neuroprotective Agents ; administration & dosage ; Plant Extracts ; administration & dosage ; Populus ; chemistry ; Pyramidal Cells ; drug effects ; metabolism ; Reperfusion Injury ; drug therapy ; genetics ; metabolism ; Superoxide Dismutase ; genetics ; metabolism ; Up-Regulation ; drug effects

PURPOSE: To validate and update a nomogram for predicting ductal carcinoma in situ (DCIS) upstaging in preoperative biopsy. MATERIALS AND METHODS: Medical records of 444 preoperative DCIS patients were evaluated and used to validate a previous version of the Severance nomogram for predicting DCIS upstaging in preoperative biopsy. Patients were divided into two groups according to the final postoperative pathology. Univariate and multivariate analyses with the chi-square test, Student's t-test, and binary logistic regression method identified new significant variables. The updated nomogram was evaluated with the C-index and Hosmer—Lemeshow goodness of fit test. RESULTS: The area under a receiver operating characteristic curve for comparison with the previous nomogram was 0.48. In postoperative pathology, the pure DCIS and invasive cancer groups comprised 345 and 99 cases, respectively. Approximately 22.3% of patients preoperatively diagnosed with DCIS were upstaged to invasive cancer. Significant variables in the univariate analysis were operation type, human epidermal growth factor receptor 2 overexpression, comedo necrosis, sonographic mass, mammographic mass, preoperative biopsy method, and suspicious microinvasion in preoperative biopsy. In multivariate analysis, operation type, sonographic mass, mammographic mass, and suspicious microinvasion were risk factors for upstaging. The updated model with these variables showed moderate discrimination and was appropriate in the calibration test. CONCLUSION: The previous nomogram did not effectively discriminate upstaging of preoperative DCIS in an independent cohort. An updated version of the nomogram appears to provide more accurate information for predicting preoperative DCIS upstaging.
Biopsy ; Breast Neoplasms ; Breast ; Calibration ; Carcinoma, Ductal ; Carcinoma, Intraductal, Noninfiltrating ; Cohort Studies ; Discrimination (Psychology) ; Humans ; Logistic Models ; Medical Records ; Methods ; Multivariate Analysis ; Necrosis ; Nomograms ; Pathology ; Receptor, Epidermal Growth Factor ; Risk Factors ; ROC Curve ; Ultrasonography

BACKGROUND/AIMS: Programmed death receptor 1 (PD-1) is a promising new target for treatment of patients with hepatocellular carcinoma (HCC). A high expression level of programmed death-ligand 1 (PD-L1) is a possible prognostic indicator for poor outcome in other malignancies. Here, we investigated the clinical significance of PD-1 and PD-L1 in patients with HCC. METHODS: We enrolled patients with HCC who underwent surgical resection at Severance Hospital between 2012 and 2017 and investigated the levels of PD-L1 in HCC tissues (tPD-L1) and PD-L1/PD-1 in serum (sPD-L1/sPD-1). We also aimed to determine whether expression levels correlated with clinical and histological features. RESULTS: A total of 72 patient samples were analyzed. The median sPD-L1 and sPD-1 levels were 25.72 and 341.44 pg/mL, respectively. A positive correlation was detected between tPD-L1 and sPD-1 levels (R²=0.426, P<0.001). The median sPD-1 level increased linearly with tPD-L1 score (P=0.002). During the follow-up period, HCC recurred in eight (11.1%) patients and liver-related mortality occurred in eight (11.1%) patients. Higher sPD-L1 levels (≥19.18 pg/mL) tended to be associated with liver-related mortality (hazard ratio 6.866; 95% confidence interval, 0.804–58.659, P=0.078). sPD-1 levels of patients treated with nivolumab as a second-line therapy changed serially, and a >50% reduction in sPD-1 levels was observed immediately after nivolumab administration. However, sPD-1 level was not associated directly with prognosis in patients with advanced HCC. CONCLUSIONS: The results demonstrated that PD-L1 and PD-1 levels changed according to the immunotherapy. However, no significant association with clinical outcome in patients with HCC was detected.
Carcinoma, Hepatocellular ; Follow-Up Studies ; Humans ; Immunotherapy ; Mortality ; Prognosis

PURPOSE: The purpose of this study is to compare the performance of the T1 3D subtraction technique and the conventional 2D dynamic contrast enhancement (DCE) technique in diagnosing Cushing's disease. MATERIALS AND METHODS: Twelve patients with clinically and biochemically proven Cushing's disease were included in the study. In addition, 23 patients with a Rathke's cleft cyst (RCC) diagnosed on an MRI with normal pituitary hormone levels were included as a control, to prevent non-blinded positive results. Postcontrast T1 3D fast spin echo (FSE) images were acquired after DCE images in 3T MRI and image subtraction of pre- and postcontrast T1 3D FSE images were performed. Inter-observer agreement, interpretation time, multiobserver receiver operating characteristic (ROC), and net benefit analyses were performed to compare 2D DCE and T1 3D subtraction techniques. RESULTS: Inter-observer agreement for a visual scale of contrast enhancement was poor in DCE (κ = 0.57) and good in T1 3D subtraction images (κ = 0.75). The time taken for determining contrast-enhancement in pituitary lesions was significantly shorter in the T1 3D subtraction images compared to the DCE sequence (P < 0.05). ROC values demonstrated increased reader confidence range with T1 3D subtraction images (95% confidence interval [CI]: 0.94–1.00) compared with DCE (95% CI: 0.70–0.92) (P < 0.01). The net benefit effect of T1 3D subtraction images over DCE was 0.34 (95% CI: 0.12–0.56). For Cushing's disease, both reviewers misclassified one case as a nonenhancing lesion on the DCE images, while no cases were misclassified on T1 3D subtraction images. CONCLUSION: The T1 3D subtraction technique shows superior performance for determining the presence of enhancement on pituitary lesions compared with conventional DCE techniques, which may aid in diagnosing Cushing's disease.
Humans ; Magnetic Resonance Imaging ; ROC Curve ; Subtraction Technique

Dectin-1 is a major receptor that recognizes fungal cell wall β-glucan. We previously reported that heat-killed Saccharomyces cerevisiae (HKSC), a Dectin-1 agonist, selectively induces IgG1 class switching in mouse B cells. Dectin-1 is also expressed on human B cells; however, Dectin-1 function in human B cells remains unknown. This study aimed to investigate the direct effect of in vitro stimulation using HKSC on Ig class switching in human B cells. HKSC selectively induced the expression of germline γ4 transcripts (GLTγ4) by human B cell line 2E2, and HKSC significantly augmented GLTγ4 promoter activity. Moreover, HKSC selectively enhanced GLTγ4 expression and IgG4 production by anti-CD40-activated human tonsillar resting B cells. Thus, these results suggest that Dectin-1 maybe involved in selective IgG4 class switching by human B cells.
Animals ; B-Lymphocytes* ; Cell Line ; Cell Wall ; Humans* ; Immunoglobulin Class Switching ; Immunoglobulin G* ; In Vitro Techniques ; Mice ; Saccharomyces cerevisiae* ; Saccharomyces*

BACKGROUNDGlehnia littoralis, as a traditional herbal medicine to heal various health ailments in East Asia, displays various therapeutic properties including antioxidant effects. However, neuroprotective effects of G. littoralis against cerebral ischemic insults have not yet been addressed. Therefore, in this study, we first examined its neuroprotective effects in the hippocampus using a gerbil model of transient global cerebral ischemia (TGCI).

METHODSGerbils were subjected to TGCI for 5 min. G. littoralis extract (GLE; 100 and 200 mg/kg) was administrated orally once daily for 7 days before ischemic surgery. Neuroprotection was examined by neuronal nuclear antigen immunohistochemistry and Fluoro-Jade B histofluorescence staining. Gliosis was observed by immunohistochemistry for glial fibrillary acidic protein and ionized calcium-binding adapter molecule 1. For neuroprotective mechanisms, immunohistochemistry for superoxide dismutase (SOD) 1 and brain-derived neurotrophic factor (BDNF) was done.

RESULTSPretreatment with 200 mg/kg of GLE protected pyramidal neurons in the cornu ammonis 1 (CA1) area from ischemic insult area (F = 29.770, P < 0.05) and significantly inhibited activations of astrocytes (F = 22.959, P < 0.05) and microglia (F = 44.135, P < 0.05) in the ischemic CA1 area. In addition, pretreatment with GLE significantly increased expressions of SOD1 (F = 28.561, P < 0.05) and BDNF (F = 55.298, P < 0.05) in CA1 pyramidal neurons of the sham- and ischemia-operated groups.

CONCLUSIONSOur findings indicate that pretreatment with GLE can protect neurons from ischemic insults, and we suggest that its neuroprotective mechanism may be closely associated with increases of SOD1 and BDNF expressions as well as attenuation of glial activation.

PURPOSE: The aim of this study was to evaluate serum and urinary nephrin levels of normal pregnancy to establish a standard reference value and to compare them with patients who subsequently developed preeclampsia (PE). MATERIALS AND METHODS: In this prospective study, 117 healthy singleton pregnancies were enrolled between 6 to 20 weeks of gestation at 2 participating medical centers during October 2010 to March 2012. Urine and serum samples were collected at the time of enrollment, each trimester, and at 4 to 6 weeks postpartum. Enzyme-linked immunosorbent assay for nephrin was performed and samples from patients who subsequently developed PE were compared to the normal patients. RESULTS: Of 117 patients initially enrolled, 99 patients delivered at the study centers and of those patients, 12 (12.1%) developed PE at a median gestational age of 34⁺⁴ weeks (range 29⁺⁵–36⁺⁶). In the normal patients (n=68), serum nephrin level decreased and urinary nephrin level increased during the latter of pregnancy. In 12 patients who subsequently developed PE, a significant rise in the 3rd trimester serum and urinary nephrin levels, compared to the controls, was observed (p<0.001), and this increase occurred 9 days prior to the onset of clinical disease. CONCLUSION: As the onset of PE was preceded by the rise in the serum and urinary nephrin in comparison to normal pregnancy, serum and urinary nephrin may be a useful predictive marker of PE.
Enzyme-Linked Immunosorbent Assay ; Gestational Age ; Humans ; Postpartum Period ; Pre-Eclampsia* ; Pregnancy* ; Prospective Studies ; Reference Values

Estrogens are commonly used in gynecologic area, such as oral contraception, hormone replacement therapy, and in vitro fertilization-embryo transfer. Although estrogen is a common cause of acute drug-induced pancreatitis, there has been paucity of report in Korea. Clinical course of estrogen-induced acute pancreatitis is usually mild to moderate, but fetal case can occur. In addition, there can be a latency from the first administration to the symptom. Therefore, physicians should consider the possibility of the disease when a woman taking estrogen or previous history of taking estrogen presents with acute abdominal pain. Here, we report a case of estrogen-induced acute pancreatitis that occurred during the preparation for embryo transfer.
Abdominal Pain ; Contraception ; Embryo Transfer ; Estrogens ; Female ; Hormone Replacement Therapy ; Humans ; In Vitro Techniques ; Korea ; Pancreatitis*

OBJECTIVE: To evaluate the risk of emergency cesarean section according to the prepregnancy body mass index (BMI) and gestational weight gain per the 2009 Institute of Medicine guidelines. METHODS: A retrospective analysis of data from 2,765 women with singleton full-term births (2009 to 2012) who attempted a vaginal delivery was conducted. Pregnancies with preeclampsia, chronic hypertension, diabetes, planned cesarean section, placenta previa, or cesarean section due to fetal anomalies or intrauterine growth restriction were excluded. Odds ratios (ORs) and confidence intervals (CIs) for emergency cesarean section were calculated after adjusting for prepregnancy BMI or gestational weight gain. RESULTS: Three-hundred and fifty nine (13.0%) women underwent emergency cesarean section. The adjusted OR for overweight, obese, and extremely obese women indicated a significantly increased risk of cesarean delivery. Gestational weight gain by Institute of Medicine guidelines was not associated with an increased risk of cesarean delivery. However, inadequate and excessive weight gain in obese women was highly associated with an increased risk of emergency cesarean section, compared to these in normal BMI (OR, 5.56; 95% CI, 1.36 to 22.72; OR, 3.63; 95% CI, 1.05 to 12.54; respectively), while there was no significant difference between normal BMI and obese women with adequate weight gain. CONCLUSION: Obese women should be provided special advice before and during pregnancy for controlling weight and careful consideration should be needed at the time of vaginal delivery to avoid emergency cesarean section.
Body Mass Index* ; Cesarean Section* ; Emergencies* ; Female ; Humans ; Hypertension ; Institute of Medicine (U.S.)* ; Odds Ratio ; Overweight ; Parturition ; Placenta Previa ; Pre-Eclampsia ; Pregnancy ; Retrospective Studies ; Weight Gain*