Optimal Insertion Depth of Central Venous Catheter through the Right Internal Jugular Vein, Verified by Transesophageal Echocardiography: A Prospective Observational Study.

This prospective observational study investigated the optimal insertion depth of the central venous catheter through the right internal jugular vein using transesophageal echocardiography. After tracheal intubation, the anesthesiologist inserted a probe for esophageal echocardiography into the patient's esophagus. The investigators placed the catheter tip 2 cm above the superior edge of the crista terminalis with echocardiography, which was defined as the optimal point. We measured the inserted length of the catheter. Pearson correlation tests were performed with the measured optimal depth and some patient parameters. We made a new formula for placing the catheter at the optimal position. A total of 89 subjects were enrolled in this trial. The correlation coefficient between the measured optimal depth and the patient's parameters was the highest for patient height (0.703, p < 0.001). We made a new formula of 'height (cm)/10 - 1.5 cm'. The accuracy rate of this formula for the optimal zone was 71.9% (95% confidence interval; 62.4 - 81.4%), which was the highest among the previous formulas or guidelines when we compared. In conclusion, the central venous catheter tip was evaluated with transesophageal echocardiography, and we could make a new formula of 'height (cm)/10 - 1.5', which seemed to be better than other previous guidelines.

Combined effect of changes in NO2, O3, PM2.5, SO2 and CO concentrations on small airway dysfunction.

BACKGROUND AND OBJECTIVE: When multiple complex air pollutants are combined in real-world settings, the reliability of estimating the effect of a single pollutant is questionable. This study aimed to investigate the combined effects of changes in air pollutants on small airway dysfunction (SAD). METHODS: We analysed Korea National Health and Nutrition Examination Survey (KNHANES) V-VIII database from 2010 to 2018 to elucidate the associations between annual changes in air pollutants over a previous 5-year period and small airway function. We estimated the annual concentrations of five air pollutants: NO2, O3, PM2.5, SO2 and CO. Forced expiratory flow between 25% and 75% of vital capacity (FEF25%-75%) <65% was defined as SAD. Using the quantile generalized-Computation (g-Computation) model, the combined effect of the annual changes in different air pollutants was estimated. RESULTS: A total of 29,115 individuals were included. We found significant associations between SAD and the quartiles of annual changes in NO2 (OR = 1.10, 95% CI = 1.08-1.12), O3 (OR = 1.03, 95% CI = 1.00-1.05), PM2.5 (OR = 1.03, 95% CI = 1.00-1.05), SO2 (OR = 1.04, 95% CI = 1.02-1.08) and CO (OR = 1.16, 95% CI = 1.12-1.19). The combined effect of the air pollutant changes was significantly associated with SAD independent of smoking (OR = 1.31, 95% CI = 1.26-1.35, p-value <0.001), and this trend was consistently observed across the entire study population and various subgroup populations. As the estimated risk of SAD, determined by individual-specific combined effect models, increased and the log odds for SAD increased linearly. CONCLUSION: The combined effect of annual changes in multiple air pollutant concentrations were associated with an increased risk of SAD.

Chromosomal Microarray Analysis in Fetuses With Ultrasonographic Soft Markers: A Meta-Analysis of the Current Evidence.

BACKGROUND: Ultrasonographic soft markers are normal variants, rather than fetal abnormalities, and guidelines recommend a detailed survey of fetal anatomy to determine the necessity of antenatal karyotyping. Anecdotal reports have described cases with ultrasonographic soft markers in which chromosomal microarray analysis (CMA) revealed pathogenic copy number variants (CNVs) despite normal results on conventional karyotyping, but CMA for ultrasonographic soft markers remains a matter of debate. In this systematic review, we evaluated the clinical significance of CMA for pregnancies with isolated ultrasonographic soft markers and a normal fetal karyotype. METHODS: An electronic search was conducted by an experienced librarian through the MEDLINE, Embase, and Cochrane CENTRAL databases. We reviewed 3,338 articles (3,325 identified by database searching and 13 by a hand search) about isolated ultrasonographic soft markers, and seven ultrasonographic markers (choroid plexus cysts, echogenic bowel, echogenic intracardiac focus, hypoplastic nasal bone, short femur [SF], single umbilical artery, and urinary tract dilatation) were included for this study. RESULTS: Seven eligible articles were included in the final review. Pathogenic or likely pathogenic CNVs were found in fetuses with isolated ultrasonographic soft markers and a normal karyotype. The overall prevalence of pathogenic or likely pathogenic CNVs was 2.0% (41 of 2,048). The diagnostic yield of CMA was highest in fetuses with isolated SF (9 of 225, 3.9%). CONCLUSION: CMA could aid in risk assessment and pregnancy counseling in pregnancies where the fetus has isolated ultrasonographic soft markers along with a normal karyotype.

Genome-wide polygenic risk scores for hypertensive disease during pregnancy can also predict the risk for long-term cardiovascular disease.

BACKGROUND: Hypertensive disorders during pregnancy are associated with the risk of long-term cardiovascular disease after pregnancy, but it has not yet been determined whether genetic predisposition for hypertensive disorders during pregnancy can predict the risk for long-term cardiovascular disease. OBJECTIVE: This study aimed to evaluate the risk for long-term atherosclerotic cardiovascular disease according to polygenic risk scores for hypertensive disorders during pregnancy. STUDY DESIGN: Among UK Biobank participants, we included European-descent women (n=164,575) with at least 1 live birth. Participants were divided according to genetic risk categorized by polygenic risk scores for hypertensive disorders during pregnancy (low risk, score ≤25th percentile; medium risk, score 25th∼75th percentile; high risk, score >75th percentile), and were evaluated for incident atherosclerotic cardiovascular disease, defined as the new occurrence of one of the following: coronary artery disease, myocardial infarction, ischemic stroke, or peripheral artery disease. RESULTS: Among the study population, 2427 (1.5%) had a history of hypertensive disorders during pregnancy, and 8942 (5.6%) developed incident atherosclerotic cardiovascular disease after enrollment. Women with high genetic risk for hypertensive disorders during pregnancy had a higher prevalence of hypertension at enrollment. After enrollment, women with high genetic risk for hypertensive disorders during pregnancy had an increased risk for incident atherosclerotic cardiovascular disease, including coronary artery disease, myocardial infarction, and peripheral artery disease, compared with those with low genetic risk, even after adjustment for history of hypertensive disorders during pregnancy. CONCLUSION: High genetic risk for hypertensive disorders during pregnancy was associated with increased risk for atherosclerotic cardiovascular disease. This study provides evidence on the informative value of polygenic risk scores for hypertensive disorders during pregnancy in prediction of long-term cardiovascular outcomes later in life.

Plasma Circulating Tumor Necrosis Factor Receptors at Multiple Time Points Can Predict the Outcome of Severe Acute Kidney Injury.

INTRODUCTION: This prospective cohort study investigated the clinical role of circulating tumor necrosis factor receptor (cTNFR) levels as prognostic biomarkers in severe acute kidney injury (AKI) patients requiring continuous renal replacement therapy (CRRT). METHODS: We enrolled 136 patients from 7 hospitals participating in the VENUS (VolumE maNagement Under body composition monitoring in critically ill patientS on CRRT) trial from July 2017 to October 2019. The levels of cTNFR1 and cTNFR2 were measured using plasma samples collected on days 0 (D0), 2 (D2), and 7 (D7). Patients were divided into high- and low-cTNFR groups based on their receptor concentrations. RESULTS: D0 concentrations of cTNFR1 and cTNFR2 were positively correlated with one another (R2 = 0.37, p < 0.001). The high-cTNFR1 group displayed a higher in-hospital mortality rate than the low-TNFR1 group (p = 0.002). Moreover, the mortality rate was significantly higher in the high-TNFR1 group than in the low-TNFR1 group after adjusting for age, sex, and acute physiology, and chronic health evaluation II scores (hazard ratio 1.82, 95% confidence interval 1.09-3.03, p = 0.025). D2 and D7 cTNFR1 levels were also associated with in-hospital mortality; contrastingly, cTNFR2 levels were not associated with this outcome. Additionally, patients were divided into three groups according to the change in cTNFR levels from D0 to D2 (ΔcTNFR). Those in the highest ΔcTNFR tertile had a higher mortality rate than the remaining patients (p = 0.033 for ΔcTNFR1; p = 0.025 for ΔcTNFR2). Patients who underwent AKI-to-chronic kidney disease transition had higher concentrations of cTNFR1 (p = 0.014). DISCUSSION/CONCLUSION: Plasma cTNFR1 concentrations at CRRT initiation and changes in cTNFR1 and 2 levels immediately following CRRT initiation are significant biomarkers for predicting the outcomes of patients with severe AKI.

The Current Status of Prolonged Breastfeeding and Its Related Factors in Korean Infants and Their Mothers: A Nationwide Cross-Sectional Study.

BACKGROUND: International authorities recommend prolonged breastfeeding (PBF) for 12-24 months or more with 6 months of exclusive breastfeeding (EBF). Based on the Korean National Health and Nutrition Examination Survey (KNHANES) data, this study attempted to help encourage and educate breastfeeding (BF) over 1 year by investigating long-term BF trends and related factors in Korean infants and their mothers. METHODS: This cross-sectional study was based on data on children aged 12-23 months and their mothers from 2010 to 2020. BF rates were compared between KNHANES V (2010-2012), KNHANES VI (2013-2015), KNHANES VII (2016-2018), and part of KNHANES VIII (2019-2020). In addition, data related to mothers and infants, including demographics, socioeconomic, educational, and health status, were collected, and their association with BF status was analyzed. RESULTS: Of the 933 infants included in the study, the proportions achieving full BF at 6 months of age and PBF at 12 and 18 months were 34.8%, 33.7%, and 7.1%, respectively. Over the past 10 years, the trends of all three BF practices have significantly decreased since 2016 (P < 0.001). Of the 849 infants whose maternal data were available, multiple logistic regression analysis showed that EBF for 6 months (defined as full BF at 1, 3, and 6 months of age) positively correlated with maternal and infants' factors such as unemployed status, past BF experience, no history of drinking, and infants' birth weight of ≥ 2.5 kg. The mother's education level, particularly the nutrition label impact, current employment status, and smoking and drinking status, were significantly associated with PBF for ≥ 12 months but were not related to PBF for ≥ 18 months, except for drinking status. CONCLUSIONS: In Korea, the long-term BF rate of ≥ 12 months has declined in the past 10 years, and BF becomes rare after 18 months. Higher maternal interest in nutrition information appears to be driving access to PBF over 12 months than EBF for 6 months or PBF over 18 months. To promote PBF over 12 months in Korea, it may be helpful to strengthen nutrition education that specifically emphasizes the benefits of PBF along with EBF, especially during infant health examinations.

Growth, Nutritional Status, and Dietary Intake Patterns Associated With Prolonged Breastfeeding in Young Korean Children: A Nationwide Cross-Sectional Study.

BACKGROUND: Although the optimal duration of breastfeeding remains unclear, breastfeeding is generally recommended exclusively for the first 6 months of life, which continues into late infancy. However, the awareness regarding the effects of long-term breastfeeding is relatively low compared with that of breastfeeding in early infancy. We aimed to investigate the growth and nutritional characteristics of the children with prolonged breastfeeding (PBF) over 1 year. METHODS: This cross-sectional study was based on the data of children aged 12 to 23 months from the National Health and Nutrition Examination Survey (2010-2020) conducted by the Korean Center for Disease Control and Prevention. Data on anthropometric measurements, dietary behavior, and food and nutrient intake were extracted, and the association between PBF and growth, nutritional status, and dietary patterns were analyzed. RESULTS: Of the 872 children with a birth weight of ≥ 2.5 kg in the final analysis, 34.2% continued breastfeeding over 12 months of age, and their median breastfeeding duration was 14.2 months. Children with PBF were more likely to have lower current body weight (P < 0.001) and weight gain (P < 0.001), lower daily protein (P = 0.012), calcium (P < 0.001), and iron (P < 0.001) intake per calorie compared with children weaned by 12 months of age or those who were never breastfed. Furthermore, they were started on complementary food at 6 months or later rather than 4-5 months (P < 0.001), consumed cow's milk earlier (P = 0.012), and consumed probiotics as dietary supplements (P < 0.001) significantly less commonly. When comparing the intake of food groups, children with PBF had a significantly higher intake of cereals and grains (P = 0.023) and fruits (P = 0.020) and a significantly lower intake of bean products (P = 0.020) and milk and dairy products (P = 0.003). CONCLUSION: Korean children who continued breastfeeding over 12 months of age showed distinct characteristics in terms of growth, nutritional status, and dietary patterns in the second year of life compared to children who did not. Long-term additional research on their growth and nutritional status may be needed; however, these findings are significant as important fundamental data for nutritional counseling to establish healthy PBF.

Differences in Growth and Dietary and Nutrient Intake Patterns by Breastfeeding Status Over One Year Among Korean Children Aged 24-35 Months.

BACKGROUND: A previous national study found that Korean children who were breastfed for at least one year had lesser weight gain, lower protein, calcium, and iron intake relative to calories, and different dietary patterns in the second year of life, compared with children weaned before 12 months of age or those who were never breastfed. Therefore, this study aimed to investigate whether growth status, dietary and nutrient intake patterns differed by prolonged breastfeeding (PBF) experience even in the third year of life, when weaning is considered complete. METHODS: This cross-sectional study was based on the data of children aged 24 to 35 months from the National Health and Nutrition Examination Survey (2010-2020). Data on anthropometry, dietary behavior, food and nutrient intake, maternal education, and household income were extracted to analyze the association between PBF and growth, dietary and nutrient intake patterns. RESULTS: In the final analysis, 31.6% of the 931 children with a birth weight of ≥ 2.5 kg continued to breastfeed for at least 12 months of age, and their mean breastfeeding (BF) duration was 15.9 months. Children with PBF had significantly less postnatal weight gain than those without (P = 0.006). Regarding food group intake, PBF was significantly associated with lower legume and soy product intake (ß [95% confidence interval], -10.688 [-19.314, -2.062], P = 0.015) and higher fruit intake (32.978 [3.349, 62.608], P = 0.029), after adjusting for sex, age in month, total caloric intake, maternal education and household income. Regarding nutrient intake, after adjusting for these variables, PBF had significantly associated with higher dietary fiber (ß [95% CI], 1.607 [0.218, 2.996], P = 0.023), iron (0.848 [0.317, 1.380], P = 0.002) and niacin (0.728 [0.222, 1.235], P = 0.005) intake and was significantly associated with lower saturated fatty acid intake (-1.217 [-2.364, -0.071], P = 0.037) and percentage of energy from fat (-1.351 [-2.666, -0.035], P = 0.044). CONCLUSION: Even in the third year of life, children who have been breastfed for over one year continue to have relatively slow growth. However, they do appear to have better intake of some beneficial nutrients, which may be attributed to healthier dietary intake patterns in children with PBF. The results of this study can be used to support the recommendation of long-term BF for Korean infants and toddlers.

The Effect of Vanishing Twin on First- and Second-Trimester Maternal Serum Markers and Nuchal Translucency: A Multicenter Prospective Cohort Study.

BACKGROUND: The purpose of this study was to evaluate the effect of vanishing twin (VT) on maternal serum marker concentrations and nuchal translucency (NT). METHODS: This is a secondary analysis of a multicenter prospective cohort study in 12 institutions. Serum concentrations of pregnancy-associated plasma protein-A in the first trimester and alpha-fetoprotein (AFP), total human chorionic gonadotrophin, unconjugated estriol, and inhibin A in the second trimester were measured, and NT was measured between 10 and 14 weeks of gestation. RESULTS: Among 6,793 pregnant women, 5,381 women were measured for serum markers in the first or second trimester, including 65 cases in the VT group and 5,316 cases in the normal singleton group. The cases in the VT group had a higher median multiple of the median value of AFP and inhibin A than the normal singleton group. The values of other serum markers and NT were not different between the two groups. After the permutation test with adjustment, AFP and inhibin A remained significant differences. The frequency of abnormally increased AFP was also higher in the VT group than in the normal singleton group. CONCLUSION: VT can be considered as an adjustment factor for risk assessment in the second-trimester serum screening test.

Restoration of erectile function by a combination of antiapoptosis by JNK inhibitor and preservation of smooth muscle or endothelium by hepatocyte growth factor in a rat model of cavernous nerve injury.

BACKGROUND: Because of structural alterations in the corpus cavernosum after radical prostatectomy (RP), post-RP erectile dysfunction remains a very difficult condition to treat. We aimed to determine if the combined administration of a Jun-amino terminal kinase (JNK) inhibitor and hepatocyte growth factor (HGF) in the immediate post-injury period would restore erectile function by antiapoptotic and pro-regenerative effects through the rectification of molecular pathways related to the structural integrity of the penis in a rat model of bilateral cavernosal nerve crush injury (CNCI). METHODS: A total of 70 rats were divided into five groups: Sham surgery (S), CNCI (I), and once-daily intraperitoneal administration of 10.0 mg/kg JNK inhibitor + twice-weekly intracavernosal administration of low-dose (2.1 µg), medium-dose (4.2 µg), or high-dose (8.4 µg) HGF (I + J + LH or I + J + MH or I + J + HH, respectively) in the immediate post-injury period. Erectile responses to electrostimulation (1.0, 3.0, and 5.0 V), histological staining, caspase-3 activity, and Western blotting were evaluated 9 days after surgery. RESULTS: Group I showed lower intracavernosal pressure (ICP)/mean arterial pressure (MAP) after stimulation at each voltage, lower area under the curve (AUC)/MAP after stimulation at each voltage, less smooth muscle (SM) content, a lower SM/collagen ratio, higher caspase-3 activity, increased cJun phosphorylation, decreased protein expression of PECAM-1, decreased cMet phosphorylation, and decreased endothelial nitric oxide synthase (eNOS) phosphorylation compared to Group S. The SM content, SM/collagen ratio, protein expression of ICP/MAP, or AUC/MAP after stimulation at each voltage in Group I + J + LH were partially restored, despite the normalization of cJun phosphorylation and caspase-3 activity. The ICP/MAP, AUC/MAP, caspase-3 activity, SM content, protein expression of PECAM-1, cJun phosphorylation, cMet phosphorylation, and eNOS phosphorylation in both Groups I + J + MH and I + J + HH were restored to the levels observed in Group S, while the SM/collagen ratio was significantly improved but not completely normalized. CONCLUSIONS: Our data indicated that the combined administration of a JNK inhibitor and medium or high-dose HGF to nerve-injured rats in the immediate post-injury period after CNCI may restore erectile function to a level comparable to the normal level by suppressing cavernosal apoptosis and preserving the integrity of SM or endothelium via rectification of the cJun and cMet/eNOS pathways.

Artificial intelligence-based identification of octenidine as a Bcl-xL inhibitor.

Apoptosis plays an essential role in maintaining cellular homeostasis and preventing cancer progression. Bcl-xL, an anti-apoptotic protein, is an important modulator of the mitochondrial apoptosis pathway and is a promising target for anticancer therapy. In this study, we identified octenidine as a novel Bcl-xL inhibitor through structural feature-based deep learning and molecular docking from a library of approved drugs. The NMR experiments demonstrated that octenidine binds to the Bcl-2 homology 3 (BH3) domain-binding hydrophobic region that consists of the BH1, BH2, and BH3 domains in Bcl-xL. A structural model of the Bcl-xL/octenidine complex revealed that octenidine binds to Bcl-xL in a similar manner to that of the well-known Bcl-2 family protein antagonist ABT-737. Using the NanoBiT protein-protein interaction system, we confirmed that the interaction between Bcl-xL and Bak-BH3 domains within cells was inhibited by octenidine. Furthermore, octenidine inhibited the proliferation of MCF-7 breast and H1299 lung cancer cells by promoting apoptosis. Taken together, our results shed light on a novel mechanism in which octenidine directly targets anti-apoptotic Bcl-xL to trigger mitochondrial apoptosis in cancer cells.

Long-term cardiovascular outcomes of gestational diabetes mellitus: a prospective UK Biobank study.

BACKGROUND: Previous studies showed that gestational diabetes mellitus (GDM) can be a risk factor for subsequent atherosclerotic cardiovascular disease. However, there is a paucity of information regarding diverse cardiovascular outcomes in elderly women after GDM. In the current study, we examined whether women with a history of GDM have an increased risk for long-term overall cardiovascular outcomes. METHODS: Among the UK participants, we included 219,330 women aged 40 to 69 years who reported at least one live birth. The new incidence of diverse cardiovascular outcomes was compared according to GDM history by multivariable Cox proportional hazard models. In addition, causal mediation analysis was performed to examine the contribution of well-known risk factors to observed risk. RESULTS: After enrollment, 13,094 women (6.0%) developed new overall cardiovascular outcomes. Women with GDM history had an increased risk for overall cardiovascular outcomes [adjusted HR (aHR) 1.36 (95% CI 1.18-1.55)], including coronary artery disease [aHR 1.31 (1.08-1.59)], myocardial infarction [aHR 1.65 (1.27-2.15)], ischemic stroke [aHR 1.68 (1.18-2.39)], peripheral artery disease [aHR 1.69 (1.14-2.51)], heart failure [aHR 1.41 (1.06-1.87)], mitral regurgitation [aHR 2.25 (1.51-3.34)], and atrial fibrillation/flutter [aHR 1.47 (1.18-1.84)], after adjustment for age, race, BMI, smoking, early menopause, hysterectomy, prevalent disease, and medication. In mediation analysis, overt diabetes explained 23%, hypertension explained 11%, and dyslipidemia explained 10% of the association between GDM and overall cardiovascular outcome. CONCLUSIONS: GDM was associated with more diverse cardiovascular outcomes than previously considered, and conventional risk factors such as diabetes, hypertension, and dyslipidemia partially contributed to this relationship.

Diagnostic effect of artificial intelligence solution for referable thoracic abnormalities on chest radiography: a multicenter respiratory outpatient diagnostic cohort study.

OBJECTIVES: We aim ed to evaluate a commercial artificial intelligence (AI) solution on a multicenter cohort of chest radiographs and to compare physicians' ability to detect and localize referable thoracic abnormalities with and without AI assistance. METHODS: In this retrospective diagnostic cohort study, we investigated 6,006 consecutive patients who underwent both chest radiography and CT. We evaluated a commercially available AI solution intended to facilitate the detection of three chest abnormalities (nodule/masses, consolidation, and pneumothorax) against a reference standard to measure its diagnostic performance. Moreover, twelve physicians, including thoracic radiologists, board-certified radiologists, radiology residents, and pulmonologists, assessed a dataset of 230 randomly sampled chest radiographic images. The images were reviewed twice per physician, with and without AI, with a 4-week washout period. We measured the impact of AI assistance on observer's AUC, sensitivity, specificity, and the area under the alternative free-response ROC (AUAFROC). RESULTS: In the entire set (n = 6,006), the AI solution showed average sensitivity, specificity, and AUC of 0.885, 0.723, and 0.867, respectively. In the test dataset (n = 230), the average AUC and AUAFROC across observers significantly increased with AI assistance (from 0.861 to 0.886; p = 0.003 and from 0.797 to 0.822; p = 0.003, respectively). CONCLUSIONS: The diagnostic performance of the AI solution was found to be acceptable for the images from respiratory outpatient clinics. The diagnostic performance of physicians marginally improved with the use of AI solutions. Further evaluation of AI assistance for chest radiographs using a prospective design is required to prove the efficacy of AI assistance. KEY POINTS: • AI assistance for chest radiographs marginally improved physicians' performance in detecting and localizing referable thoracic abnormalities on chest radiographs. • The detection or localization of referable thoracic abnormalities by pulmonologists and radiology residents improved with the use of AI assistance.

Effects of intravenous iron therapy on mortality and hospitalization of hemodialysis patients: A prospective cohort study in Korea.

Iron replacement therapy is necessary for anemia treatment in patients with advanced chronic kidney disease. Intravenous (IV) iron therapy is an efficient method for iron replacement. However, there are concerns regarding its considerable side effects, including increased risks of infection or major adverse cardiovascular events (MACE). This is a longitudinal study from a multicenter prospective cohort study conducted in the Korean end-stage renal disease population. All-cause mortality, death due to infection or MACE, hospitalization due to infection or MACE, and all adverse event of death or hospitalization due to infection or MACE were compared according to the iron replacement methods during the first 3 months of enrollment. Among 1,680 hemodialysis patients, 29.3% of patients received IV iron therapy, and 38% of patients received oral iron therapy. During the median 632 days follow-up, all-cause mortality, mortality or hospitalization due to infection or MACE, and all adverse events did not differ among iron replacement groups. There were significant differences related to the risk of all adverse events among iron replacement therapies in the log-rank test and univariate Cox regression analysis only in the prevalent dialysis patients; however, the significance was lost in multivariate Cox regression analysis. Similar results were observed in the 1-year short-term outcome analysis. High-dose IV iron did not increase adverse outcomes. All-cause mortality or all adverse events due to infection or MACE were not higher with the current clinical regimen of IV iron replacement therapy than with oral or no iron therapy in Korean hemodialysis patients.

Psychological Impact of Type of Breast Cancer Surgery: A National Cohort Study.

BACKGROUND: The present study assessed the impact of different types of breast surgery on rates of psychological disorders in breast cancer patients. METHODS: This nationwide cohort study, based on Korean Health Insurance Review and Assessment Service claims data, included 26,259 breast patients who underwent surgery from June 1, 2017, to December 31, 2018. Associations between the incidence of psychological disorders and variables were evaluated by time dependent Cox regression analyses. RESULTS: Of the 26,259 patients, 9394 (35.8%) underwent total mastectomy (TM) and 16,865 (64.2%) underwent partial mastectomy (PM); of the former, 4056 (43.2%) underwent breast reconstruction surgery (RS). A total of 4685 patients (17.84%) were newly diagnosed with psychological disorders after surgery. Multivariable analysis showed that axillary lymph node dissection was significantly associated with increased rates of overall psychological disorders (p < 0.0001), depression (p = 0.0462), anxiety (p < 0.0001) and insomnia (p < 0.0001). The rates of overall psychological disorders (p = 0.0002) and insomnia (p = 0.01) were significantly lower in patients who underwent TM than PM. RS tended to associated with reduced rates of overall psychological disorders in patients who underwent TM. Subgroup analysis showed that, compared with PM, RS after TM significantly associated with a reduced incidence of overall psychological disorders and insomnia in younger patients (< 50 years) and those who underwent sentinel lymph node biopsy. CONCLUSION: In contrast to general belief, rates of overall psychological disorders and insomnia were lower in patients who underwent TM than PM. Moreover, RS after TM confers psychological benefit in younger patients with early stage breast cancer compared with PM.

Short-term and long-term outcomes of trichorionic triplet pregnancies with expectant management.

INTRODUCTION: Reproductive endocrinologists recommend selective multifetal pregnancy reduction (MFPR) to save at least one or two babies, because triplet pregnancy is known to increase the risk of miscarriage and preterm delivery. However, recently improved obstetric and neonatal care may affect pregnancy outcomes differently in triplet pregnancies, which could alter practice. We compared the maternal, perinatal, and long-term outcomes of triplet pregnancies managed expectantly with those of pregnancies reduced to twins. MATERIAL AND METHODS: In this retrospective cohort study, we reviewed the clinical records of 552 trichorionic triplet pregnancies for obstetric, perinatal, and neurodevelopmental outcomes, which consisted of the expectant management (EM) group (n = 225) and MFPR group (n = 327), in Seoul National University Hospital and CHA Bundang Medical Center from January 2006 to December 2018. Neuromotor development was evaluated using the Korean-Ages and Stages Questionnaire, Bayley-III tests, and/or Gross Motor Function Measure. The two groups were compared for the following outcomes: (1) nonviable pregnancy loss before 23 weeks, (2) preterm birth before 32 weeks of gestation, (3) fetal and neonatal survival and (4) long-term neurodevelopmental outcomes. RESULTS: There were no differences in maternal age, body mass index, nulliparity or previous preterm birth between the two groups. The risk of nonviable pregnancy loss was lower in the EM group than that in the MFPR group (2 [0.9%] vs 21 [6.4%], p = 0.001). The risk of preterm delivery before 34 weeks of gestation was lower in the MFPR group (adjusted odds ratios [aOR] = 0.47, 95% confidence interval [CI] 0.30-0.73, p = 0.001). The survival rate of neonates until discharge (644 [95.4%] vs 572 [87.5], p < 0.001) and the rate of pregnancies with at least one survivor (220 [97.8%] vs 301 [92.0], p = 0.002) were higher in the EM group than those in the MFPR group. In the MFPR group, the risk of developmental delay (aOR = 2.89, 95% CI 1.38-6.02, p = 0.005) was higher. CONCLUSIONS: In trichorionic triplet pregnancies, the possibility of EM to improve survival and reduce the risk of developmental delay has been shown.

Tertiary RNA Folding-Targeted Drug Screening Strategy Using a Protein Nanopore.

Bacterial riboswitch RNAs are attractive targets for novel antibiotics against antibiotic-resistant superbacteria. Their binding to cognate metabolites is essential for the regulation of bacterial gene expression. Despite the importance of RNAs as therapeutic targets, the development of RNA-targeted, small-molecule drugs is limited by current biophysical methods. Here, we monitored the specific interaction between the adenine-sensing riboswitch aptamer domain (ARS) and adenine at the single-molecule level using α-hemolysin (αHL) nanopores. During adenine-induced tertiary folding, adenine-bound ARS intermediates exhibited characteristic nanopore events, including a two-level ionic current blockade and a ∼ 5.6-fold longer dwell time than that of free RNA. In a proof-of-concept experiment, tertiary RNA folding-targeted drug screening was performed using a protein nanopore, which resulted in the discovery of three new ARS-targeting hit compounds from a natural compound library. Taken together, these results reveal that αHL nanopores are a valuable platform for ultrasensitive, label-free, and single-molecule-based drug screening against therapeutic RNA targets.

Relationship between Three-Dimensional Magnetic Resonance Imaging Eyeball Shape and Optic Nerve Head Morphology.

PURPOSE: To determine if the 3-dimensional (3D) eyeball shape is associated with the positions of the central retinal vascular trunk (CRVT) and the externally oblique border (EOB) in the optic nerve head (ONH). DESIGN: Prospective, cross-sectional study. PARTICIPANTS: Fifty-six subjects (112 eyes) with a diagnosis of glaucoma or glaucoma suspect. METHODS: The eyeball shape on 3D magnetic resonance imaging (MRI) scans was classified according to the dimension of the longest diameter: axial dimension (prolate sphere), group 1; horizontal dimension (horizontally oblate sphere), group 2; and vertical dimension (vertically oblate sphere), group 3. The deviation of the CRVT, as a surrogate of lamina cribrosa (LC) shift, was measured from the center of the Bruch's membrane opening (BMO) demarcated by OCT imaging, with the horizontal midline as 0° and the superior location as a positive value. The angular location of the longest EOB was also measured. MAIN OUTCOME MEASURE: Positions of CRVT and EOB according to the 3D eyeball shape. RESULTS: Among 112 eyes, 54 (48%) had a prolate shape (group 1), 23 (21%) had a horizontally oblate shape (group 2), and 35 (31%) had a vertically oblate shape (group 3). The angular deviation of the CRVT differed among the groups: to the nasal side in group 1, to the temporal side in group 2, and along the vertical meridian in group 3. In cases of asymmetric eyeball shape, the CRVT was deviated toward the undergrown side from the overgrown side, regardless of grouping. The angular location of the longest EOB was in the direction opposite to the CRVT position (P < 0.001). A generalized estimating equation analysis revealed that the temporal location of the CRVT was associated with older age (P = 0.001), nasal location of the longest EOB (P < 0.001), and oblate shape of the eyeball (P < 0.001, group 2; P = 0.007, group 3). CONCLUSIONS: The position of the CRVT and EOB were associated with the 3D eyeball shape. Considering that infant ONH morphology is highly uniform, various modes of eyeball expansion during growth can result in diverse directionalities of offset between the LC and the BMO in adults.

Can sodium fluorescein cause contrast-induced nephropathy?

BACKGROUND: Contrast-induced nephropathy (CIN) is a common cause of acute kidney injury (AKI), and can be diagnosed when the etiology of AKI is unclear other than via a contrast agent. Fluorescent angiography (FAG) with fluorescein sodium dye is generally considered to be safe for patients with kidney diseases. However, it remains unresolved whether or not FAG can induce CIN. METHODS: Patients from two tertiary hospitals who underwent FAG and had serum creatinine results within 4 weeks before FAG and 3 days after FAG between 2001 and 2017 were retrieved. Cases with concurrent iodinated contrast imaging or undergoing dialysis were excluded from the analysis. CIN was defined by two criteria: CIN criteria as >0.5 mg/dL or >25% increase in serum creatinine (sCr) level within 3 days after FAG, and contrast-induced acute kidney injury (CIAKI) criteria as ≥0.3 mg/dL increase within 2 days or ≥50% increase within 7 days after FAG. RESULTS: A total of 979 patients were screened, and we found 124 patients with AKI after FAG. After excluding 32 patients with clear causes of AKI other than FAG, the incidence rates of CIN were 7.3% by CIN criteria and 6.4% by CIAKI criteria. CIN incidence had a U-shaped distribution according to chronic kidney disease (CKD) stages in CIN criteria, while linear association between CIN incidence and CKD stages were found in CIAKI criteria. Kaplan-Meier curves showed the CIN group was significantly associated with end-stage renal disease (ESRD) progression (log-rank P < 0.001, in both CIN criteria and CIAKI criteria), and adjusted hazard ratios by multivariable Cox regression were 2.23 [95% confidence interval (CI) 1.468-3.378] in CIN criteria and 2.17 (95% CI 1.462-3.232) in CIAKI criteria. CONCLUSIONS: According to CIN and CIAKI criteria, FAG may cause CIN and appeared to be a possible risk factor for ESRD progression. However, CIN or CIAKI criteria themselves may overestimate AKI and require meticulous attention to the interpretation of results.

Complete and transparent reporting of primary end points of randomized trials in the dermatology literature: A comparison of registered and published primary end points.

BACKGROUND: Appropriate primary end points in randomized controlled trials (RCTs) improve the quality of the measurement and enable comparison of the findings with those of other trials. OBJECTIVE: To assess the quality of reporting primary end points in RCTs recently published in dermatology journals. METHODS: We identified 134 primary reports of RCTs among original articles in 4 dermatology journals published from January 2016 to December 2018. Details were extracted from articles, supplements, and trial registries. A multivariable logistic regression analysis was conducted to identify factors associated with adequate primary end point reporting. RESULTS: Adequate primary end point reporting was conducted in 76 of 134 RCTs (56.7%). Nine missed the definition of primary end points, and 13 did not define the timing of primary end points in the publications. Among 113 RCTs reporting primary end points explicitly in the articles, 16 showed discrepancies between registration and publication, and 21 were not able to valuate prespecification of primary end points. Multicenter studies and sponsor-initiated trials were significantly associated with adequate reporting quality after adjusting for covariates. LIMITATIONS: Prespecification was evaluated based on a comparison of the article and registry. CONCLUSIONS: The quality of primary end point reporting, particularly in prespecification, has remained unsatisfactory in the recent dermatology literature.