Cellular senescence, a type of cytostasis, is the irreversible inhibition of the natural cell division in proliferating cells, resulting from various cellular stresses, including telomere shortening, DNA damage, mitochondrial dysfunctions, and pro-inflammatory responses. While cellular senescence can facilitate beneficial physiological processes such as tissue repair and wound healing, senescent cells also contribute to pathophysiological processes of agerelated diseases, including fibrotic lung diseases. The cellular senescence model and co-culture system were established to explore the underlying mechanisms associated with cellular senescence and fibrosis. Rutaecarpine is a bioactive alkaloid isolated from Evodia rutaecarpa (Rutaceae), a traditional herbal medicine. Rutaecarpine enhanced the promotor activity of E-cadherin, reduced TGF-β-induced reorganization of the actin cytoskeleton, and finally inhibited epithelialmesenchymal transition. Rutaecarpine also attenuated fibrotic and senescence features in bleomycin-induced lung fibrosis model. Here, we suggest the relevance between senescence and fibrosis, and a potential therapeutic approach of targeting senescence to attenuate lung fibrosis development.

Background: The aim of this study was to capture multifaceted clinical characteristics of congenital cytomegalovirus (CMV) infection from diagnosis to treatment using a multidisciplinary approach including obstetrics, pediatrics, pathology, and otorhinolaryngology-head and neck surgery. Methods: This is a retrospective study including 30 consecutive cases of congenital CMV infection that were diagnosed at a single tertiary hospital located in Seoul, Korea from January 2009 to December 2020. Congenital CMV infection was defined as a positive result by polymerase chain reaction from urine, saliva or cerebrospinal fluid or positive CMV IgM from neonatal blood sampled within 3 weeks after birth. All cases were analyzed with respect to whole clinical characteristics from diagnosis to treatment of congenital CMV by a multidisciplinary approach including prenatal sonographic findings, maternal immune status regarding CMV infection, detailed placental pathology, neonatal clinical manifestation, auditory brainstem response test, and antiviral treatment (ganciclovir or valganciclovir). Long-term outcomes including developmental delay and hearing loss were also investigated. Results: The total number of births during the study period in our institution was 19,385, with the prevalence of congenital infection estimated to be 0.15%. Among 30 cases of congenital CMV, the median gestational age at delivery was 32.2 weeks [range, 22.6–40.0] and 66.7% of these infants were delivered preterm at less than 37 weeks. Suspected fetal growth restriction was the most common prenatal ultrasound finding (50%) followed by ventriculomegaly (17.9%) and abnormal placenta (17.9%), defined as thick placenta with calcification. No abnormal findings on ultrasound examination were observed in one-third of births. Maternal CMV serology tests were conducted in only 8 cases, and one case each of positive and equivocal IgM were found. The most common placental pathologic findings were chronic villitis (66.7%) and calcification (63.0%), whereas viral inclusions were identified in only 22.2%. The most common neonatal manifestations were jaundice (58.6%) followed by elevation of aspartate aminotransferase (55.2%) and thrombocytopenia (51.7%). After excluding cases for which long-term outcomes were unavailable due to death (n = 4) or subsequent follow up loss (n = 3), developmental delay was confirmed in 43.5% of infants (10/23), and hearing loss was confirmed in 42.9% (9/21) during the follow-up period. In our cohort, 56.7% (17/30) of neonates were treated for congenital CMV with ganciclovir or valganciclovir. Conclusion Our data show that prenatal findings including maternal serologic tests and ultrasound have limited ability to detect congenital CMV in Korea. Given that CMV is associated with high rates of developmental delay and hearing loss in infants, there is an urgent need to develop specific strategies for the definite diagnosis of congenital CMV infection during the perinatal period by a multidisciplinary approach to decrease the risks of neurologic impairment and hearing loss through early antiviral treatment.

Objective: To evaluate the effects of maternal body mass index (BMI) and plurality on maternal and umbilical cord serum magnesium levels after antenatal magnesium sulfate treatment. Methods: This was a retrospective cohort analysis of 135 women treated with antenatal magnesium sulfate at less than 32 weeks of gestation between January 2012 and June 2018. Subjects were stratified into groups according to maternal BMI (group I [18.5–22.9 kg/m²], group II [23.0–24.9 kg/m²], and group III [≥25.0 kg/m²]) and plurality (singleton and twin). Univariable and multivariable analyses were performed to compare the umbilical cord serum magnesium levels between the groups. Results: Maternal serum magnesium levels were not significantly different between the maternal BMI groups and singleton and twin pregnancies. Umbilical cord serum magnesium levels were significantly different among the maternal BMI groups (3.3±1.2 mg/dL in group I, 3.3±1.2 mg/dL in group II, and 4.0±1.4 mg/dL in group III, P=0.003). The trend of increase in magnesium levels was statistically significant (P=0.001, Jonckheere-Terpstra test). Umbilical cord serum magnesium levels were not significantly different according to plurality. However, in the multivariable analysis, maternal BMI and plurality were not significantly associated with umbilical cord serum magnesium levels after adjusting for indication and total dose of magnesium sulfate treatment, gestational age at delivery, mode of delivery, neonatal sex, and birth weight. Conclusion Maternal BMI and plurality were not significantly associated with maternal or umbilical cord serum magnesium levels after exposure to antenatal magnesium sulfate treatment.

The decision whether or not to resuscitate extremely low gestational age (GA) infants is recommended to be individualized according to antenatal counseling with parents, neonatologists, and obstetricians. A GA of 22(0/7)–23(6/7) weeks is generally considered as the lower end of the range where infants can be candidates for selective resuscitation. Below this lower end of periviable gestation, resuscitation is usually not considered and survivors are rarely reported. To date, the youngest survivor is an infant with a GA of 21(6/7) weeks reported in the English medical literature. Here, we report the case of a female infant, the first twin conceived through in vitro fertilization, with a GA of 21(5/7) weeks, who was resuscitated initially according to strong parental wishes after antenatal counseling and is still surviving at 43 months of age with fairly good neurodevelopmental outcome.
Counseling ; Female ; Fertilization in Vitro ; Gestational Age ; Humans ; Infant ; Parents ; Pregnancy ; Resuscitation ; Survivors ; Twins

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is an autosomal dominant, fatal developmental disorder of the lungs, with a mortality rate of about 100%. ACD/MPV is caused by mutations in FOXF1. Herein, we describe a newborn boy with ACD/MPV carrying a novel pathogenic variant of FOXF1. The patient developed respiratory distress and severe pulmonary hypertension on the first day of life. Despite aggressive cardiorespiratory management, including veno-venous extracorporeal membrane oxygenation, his condition deteriorated rapidly, and he died within the first month of his life. Lung histology showed the characteristic features of ACD/MPV at autopsy. Sequence analysis of FOXF1 from genomic DNA obtained from autopsied lung tissue revealed that the patient was heterozygous for a novel missense variant (c.305T>C; p.Leu102Pro). Further analysis of both parents confirmed the de novo occurrence of the variant. To the best of our knowledge, this is the first report of genetically confirmed ACD/MPV in Korea.
Autopsy ; DNA ; Extracorporeal Membrane Oxygenation ; Female ; Humans ; Hypertension, Pulmonary ; Infant, Newborn* ; Korea ; Lung ; Male ; Mortality ; Parents ; Persistent Fetal Circulation Syndrome* ; Sequence Analysis

The aim of this study was to investigate the relationship between survival and incidence of bronchopulmonary dysplasia (BPD) in extremely premature infants, and identify clinical factors responsible for this association. Medical records of 350 infants at 23-26 weeks gestation from 2000 to 2005 (period I, n = 137) and 2006 to 2010 (period II, n = 213) were retrospectively reviewed. The infants were stratified into 23-24 and 25-26 weeks gestation, and the survival, BPD incidence, and clinical characteristics were analyzed. BPD was defined as oxygen dependency at 36 weeks postmenstrual age. The overall survival rate was significantly improved in period II compared to period I (80.3% vs. 70.0%, respectively; P = 0.028), especially in infants at 23-24 weeks gestation (73.9% vs. 47.4%, respectively; P = 0.001). The BPD incidence in survivors during period II (55.0%) was significantly decreased compared to period I (67.7%; P = 0.042), especially at 25-26 weeks gestation (41.7% vs. 62.3%, respectively; P = 0.008). Significantly improved survival at 23-24 weeks gestation was associated with a higher antenatal steroid use and an improved 5-minute Apgar score. A significant decrease in BPD incidence at 25-26 weeks gestation was associated with early extubation, prolonged use of less invasive continuous positive airway pressure, and reduced supplemental oxygen. Improved perinatal and neonatal care can simultaneously lead to improved survival and decreased BPD incidence in extremely premature infants.
Adult ; Bronchopulmonary Dysplasia/epidemiology/*mortality ; Demography ; Female ; Gestational Age ; Humans ; Incidence ; Infant, Extremely Premature ; Infant, Newborn ; Intensive Care Units, Neonatal ; Male ; Multivariate Analysis ; Odds Ratio ; Pregnancy ; Retrospective Studies ; Severity of Illness Index ; Survival Rate/*trends

PURPOSE: We investigated the prognostic factors for distant metastasis (DM) in patients with locally advanced oropharyngeal cancer (OPC) treated with surgery and adjuvant radiotherapy with or without concurrent chemotherapy. MATERIALS AND METHODS: Eighty-five patients treated between January 1995 and August 2014 were evaluated retrospectively. Data regarding the pathological tumour and nodal status, human papillomavirus (HPV) status, treatment characteristics, and pretreatment maximum standardized uptake value (SUVmax) of 18-fluoro-2-deoxyglucose positron emission tomography–computed tomography scan (¹⁸F-FDG PET-CT) were evaluated, and their influence on DM and survival outcomes were analyzed. RESULTS: Median follow-up period was 48.0 months. Recurrence was observed in 20 patients, including locoregional recurrence and DM. DM was observed in 13 patients. A multivariate analysis confirmed that the presence of lymphovascular invasion (p=0.031), lower neck lymph node (LN) involvement (p=0.006), SUVmax ≥ 9.7 (p=0.014), and tumour size ≥ 3 cm (p=0.037) significantly affected DM. HPV status was not associated with DM. Perineural invasion (p=0.048), lower neck LNinvolvement (p=0.008), SUVmax ≥ 9.7 (p=0.019), and tumour size ≥ 3 cm (p=0.033) were also significant factors for the DM-free survival rate. CONCLUSION: Lower neck LN involvement, high SUVmax in pretreatment ¹⁸F-FDG PET-CT, and large tumour size were predictive factors for DM in patients of OPC.
Drug Therapy* ; Electrons ; Follow-Up Studies ; Humans ; Lymph Nodes ; Multivariate Analysis ; Neck ; Neoplasm Metastasis* ; Oropharyngeal Neoplasms* ; Radiotherapy* ; Radiotherapy, Adjuvant ; Recurrence ; Retrospective Studies ; Survival Rate

PURPOSE: To evaluate the safety and feasibility of delayed cord clamping compared with umbilical cord milking in premature infants less than 32 weeks of gestation. METHODS: This study was performed by 1:2 case-control match. Infants received delayed cord clamping (DCC) for one minute (DCC group, n=10, May 2014-October 2015) were compared with perinatal factors-matching controls, who received umbilical cord milking (CM, CM group, n=20, May 2014-October 2015) or who received immediate cord clamping (ICC, ICC group, n=20, January 2008-December 2008). The primary outcome was hematocrit during the first 28 days. Secondary outcomes included delivery room management, selected neonatal morbidities and mortality. RESULTS: Baseline characteristics were comparable in all the three groups. The median hematocrit level at 1st day and 3rd day was significantly higher in the DCC group (54.3±6.2%, 53.6±5.6%) as compared with the CM group (48.0±7.7%, 43.2±7.8%) or ICC group (47.2±7.5%, 45.8±6.3%). The DCC group had reductions in red blood cell transfusion within the first two weeks of life compared to the CM group (10% vs. 50%, P=0.03). The DCC group compared to the CM group had no increment in respiratory intervention in the delivery room and hypothermia on admission. There was no difference between DCC and CM in mortality, intraventricular hemorrhage, bronchopulmonary dysplasia, necrotizing enterocolitis, severe retinopathy of prematurity and sepsis. CONCLUSION: Delayed cord clamping for 1 minute in preterm infants may be a safe and feasible method to increase initial hematocrit and reduce transfusion compared with umbilical cord milking.
Bronchopulmonary Dysplasia ; Case-Control Studies ; Constriction* ; Delivery Rooms ; Enterocolitis, Necrotizing ; Erythrocyte Transfusion ; Hematocrit ; Hemorrhage ; Humans ; Hypothermia ; Infant ; Infant, Newborn* ; Infant, Premature ; Methods ; Milk* ; Mortality ; Pregnancy ; Retinopathy of Prematurity ; Sepsis ; Umbilical Cord

PURPOSE: The aim of this study is to determine the clinical characteristics of early onset sepsis (EOS) in micropreemie. METHODS: We retrospectively reviewed medical records of 107 extremely preterm infants born at 25 or less than 25 weeks of gestation and admitted to the neonatal intensive care unit of Samsung Medical Center from January 2013 to August 2015. Infants were divided into two groups based on the presence of culture-proven EOS in the first 7 days of life. Retrospective analysis of perinatal factors and laboratory findings within the first week of life was done between two groups. We compared the neonatal outcomes among two groups. RESULTS: Culture-proven EOS was diagnosed in 11 of 107 infants (10.3%). Main pathogen of EOS was Staphylococcus epidermidis (45.5%). There were no significant differences between control group and EOS group in gestational age, birth weight, Apgar score, delivery type and pathologic chorioamnionitis. Among 11 infants with EOS, 9 showed fetal tachycardia (P=0.001). And EOS group presented lower platelet count at 3rd day and 7th day of life than that of control group (P=0.033, P=0.045). Neonatal outcomes in EOS group were compatible with control group. Main cause of death was sepsis in EOS group. CONCLUSION: In micropreemie, EOS is important factor of mortality. Our data suggest that fetal tachycardia and low platelet count during the first 7 days of life were associated with EOS.
Apgar Score ; Birth Weight ; Cause of Death ; Chorioamnionitis ; Female ; Gestational Age* ; Humans ; Infant ; Infant, Extremely Premature ; Infant, Newborn ; Intensive Care, Neonatal ; Medical Records ; Mortality ; Platelet Count ; Pregnancy ; Retrospective Studies ; Sepsis* ; Staphylococcus epidermidis ; Tachycardia

PURPOSE: The aim of this study is to determine the clinical characteristics of early onset sepsis (EOS) in micropreemie. METHODS: We retrospectively reviewed medical records of 107 extremely preterm infants born at 25 or less than 25 weeks of gestation and admitted to the neonatal intensive care unit of Samsung Medical Center from January 2013 to August 2015. Infants were divided into two groups based on the presence of culture-proven EOS in the first 7 days of life. Retrospective analysis of perinatal factors and laboratory findings within the first week of life was done between two groups. We compared the neonatal outcomes among two groups. RESULTS: Culture-proven EOS was diagnosed in 11 of 107 infants (10.3%). Main pathogen of EOS was Staphylococcus epidermidis (45.5%). There were no significant differences between control group and EOS group in gestational age, birth weight, Apgar score, delivery type and pathologic chorioamnionitis. Among 11 infants with EOS, 9 showed fetal tachycardia (P=0.001). And EOS group presented lower platelet count at 3rd day and 7th day of life than that of control group (P=0.033, P=0.045). Neonatal outcomes in EOS group were compatible with control group. Main cause of death was sepsis in EOS group. CONCLUSION: In micropreemie, EOS is important factor of mortality. Our data suggest that fetal tachycardia and low platelet count during the first 7 days of life were associated with EOS.
Apgar Score ; Birth Weight ; Cause of Death ; Chorioamnionitis ; Female ; Gestational Age* ; Humans ; Infant ; Infant, Extremely Premature ; Infant, Newborn ; Intensive Care, Neonatal ; Medical Records ; Mortality ; Platelet Count ; Pregnancy ; Retrospective Studies ; Sepsis* ; Staphylococcus epidermidis ; Tachycardia