pH and Redox-Dual Sensitive Chitosan Nanoparticles Having Methyl Ester and Disulfide Linkages for Drug Targeting against Cholangiocarcinoma Cells

The aim of this study is to prepare pH- and redox-sensitive nanoparticles for doxorubicin (DOX) delivery against DOX-resistant HuCC-T1 human cholangiocarcinoma (CCA) cells. For this purpose, L-histidine methyl ester (HIS) was attached to chitosan oligosaccharide (COS) via dithiodipropionic acid (abbreviated as ChitoHISss). DOX-incorporated nanoparticles of ChitoHISss conjugates were fabricated by a dialysis procedure. DOX-resistant HuCC-T1 cells were prepared by repetitive exposure of HuCC-T1 cells to DOX. ChitoHISss nanoparticles showed spherical morphology with a small diameter of less than 200 nm. The acid pH and glutathione (GSH) addition induced changes in the size distribution pattern of ChitoHISss nanoparticles from a narrow/monomodal distribution pattern to a wide/multimodal pattern and increased the fluorescence intensity of the nanoparticle solution. These results indicate that a physicochemical transition of nanoparticles can occur in an acidic pH or redox state. The more acidic the pH or the higher the GSH concentration the higher the drug release rate was, indicating that an acidic environment or higher redox states accelerated drug release from ChitoHISss nanoparticles. Whereas free DOX showed decreased anticancer activity at DOX-resistant HuCC-T1 cells, DOX-incorporated ChitoHISss nanoparticles showed dose-dependent anticancer activity. Intracellular delivery of DOX-incorporated ChitoHISss nanoparticles was relatively increased at an acidic pH and in the presence of GSH, indicating that DOX-incorporated ChitoHISss nanoparticles have superior acidic pH- and redox-sensitive behavior. In an in vivo tumor xenograft model, DOX-incorporated ChitoHISss nanoparticles were specifically delivered to tumor tissues and then efficiently inhibited tumor growth. We suggest that ChitoHISss nanoparticles are a promising candidate for treatment of CCA.     

Application of Machine Learning Approaches to Predict Postnatal Growth Failure in Very Low Birth Weight Infants

PurposeThe aims of the study were to develop and evaluate a machine learning model with which to predict postnatal growth failure (PGF) among very low birth weight (VLBW) infants.Materials and MethodsOf 10425 VLBW infants registered in the Korean Neonatal Network between 2013 and 2017, 7954 infants were included. PGF was defined as a decrease in Z score >1.28 at discharge, compared to that at birth. Six metrics [area under the receiver operating characteristic curve (AUROC), accuracy, precision, sensitivity, specificity, and F1 score] were obtained at five time points (at birth, 7 days, 14 days, 28 days after birth, and at discharge). Machine learning models were built using four different techniques [extreme gradient boosting (XGB), random forest, support vector machine, and convolutional neural network] to compare against the conventional multiple logistic regression (MLR) model.ResultsThe XGB algorithm showed the best performance with all six metrics across the board. When compared with MLR, XGB showed a significantly higher AUROC (p=0.03) for Day 7, which was the primary performance metric. Using optimal cut-off points, for Day 7, XGB still showed better performances in terms of AUROC (0.74), accuracy (0.68), and F1 score (0.67). AUROC values seemed to increase slightly from birth to 7 days after birth with significance, almost reaching a plateau after 7 days after birth.ConclusionWe have shown the possibility of predicting PGF through machine learning algorithms, especially XGB. Such models may help neonatologists in the early diagnosis of high-risk infants for PGF for early intervention.     

Current Landscape and Future Perspectives of Abbreviated MRI for Hepatocellular Carcinoma Surveillance

While ultrasound (US) is considered an important tool for hepatocellular carcinoma (HCC) surveillance, it has limited sensitivity for detecting early-stage HCC. Abbreviated MRI (AMRI) has recently gained popularity owing to better sensitivity in its detection of early-stage HCC than US, while also minimizing the time and cost in comparison to complete contrast-enhanced MRI, as AMRI includes only a few essential sequences tailored for detecting HCC. Currently, three AMRI protocols exist, namely gadoxetic acid-enhanced hepatobiliary-phase AMRI, dynamic contrast-enhanced AMRI, and non-enhanced AMRI. In this study, we discussed the rationale and technical details of AMRI techniques for achieving optimal surveillance performance. The strengths, weaknesses, and current issues of each AMRI protocol were also elucidated. Moreover, we scrutinized previously performed AMRI studies regarding clinical and technical factors. Reporting and recall strategies were discussed while considering the differences in AMRI protocols. A risk-stratified approach for the target population should be taken to maximize the benefits of AMRI and the cost-effectiveness should be considered. In the era of multiple HCC surveillance tools, patients need to be fully informed about their choices for better adherence to a surveillance program.     

Phenotype of Asthma-COPD Overlap in COPD and Severe Asthma Cohorts

BackgroundAsthma and chronic obstructive pulmonary disease (COPD) are airway diseases with similar clinical manifestations, despite differences in pathophysiology. Asthma-COPD overlap (ACO) is a condition characterized by overlapping clinical features of both diseases. There have been few reports regarding the prevalence of ACO in COPD and severe asthma cohorts. ACO is heterogeneous; patients can be classified on the basis of phenotype differences. This study was performed to analyze the prevalence of ACO in COPD and severe asthma cohorts. In addition, this study compared baseline characteristics among ACO patients according to phenotype.MethodsPatients with COPD were prospectively enrolled into the Korean COPD subgroup study (KOCOSS) cohort. Patients with severe asthma were prospectively enrolled into the Korean Severe Asthma Registry (KoSAR). ACO was defined in accordance with the updated Spanish criteria. In the COPD cohort, ACO was defined as bronchodilator response (BDR) ≥ 15% and ≥ 400 mL from baseline or blood eosinophil count (BEC) ≥ 300 cells/μL. In the severe asthma cohort, ACO was defined as age ≥ 35 years, smoking ≥ 10 pack-years, and post-bronchodilator forced expiratory volume in 1 s/forced vital capacity < 0.7. Patients with ACO were divided into four groups according to smoking history (threshold: 20 pack-years) and BEC (threshold: 300 cells/μL).ResultsThe prevalence of ACO significantly differed between the COPD and severe asthma cohorts (19.8% [365/1,839] vs. 12.5% [104/832], respectively; P < 0.001). The percentage of patients in each group was as follows: group A (light smoker with high BEC) – 9.1%; group B (light smoker with low BEC) – 3.7%; group C (moderate to heavy smoker with high BEC) – 73.8%; and group D (moderate to heavy smoker with low BEC) – 13.4%. Moderate to heavy smoker with high BEC group was oldest, and showed weak BDR response. Age, sex, BDR, comorbidities, and medications significantly differed among the four groups.ConclusionThe prevalence of ACO differed between COPD and severe asthma cohorts. ACO patients can be classified into four phenotype groups, such that each phenotype exhibits distinct characteristics.     

Effect of Surface Modification for Carbon Cathode Materials on Charge–Discharge Performance of Li-Air Batteries

Li-air batteries have attracted considerable attention as rechargeable secondary batteries with a high theoretical energy density of 11,400 kWh/g. However, the commercial application of Li-air batteries is hindered by issues such as low energy efficiency and a short lifetime (cycle numbers). To overcome these issues, it is important to select appropriate cathode materials that facilitate high battery performance. Carbon materials are expected to be ideal materials for cathodes due to their high electrical conductivity and porosity. The physicochemical properties of carbon materials are known to affect the performance of Li-air batteries because the redox reaction of oxygen, which is an important reaction for determining the performance of Li-air batteries, occurs on the carbon materials. In this study, we evaluated the effect of the surface modification of carbon cathode materials on the charge–discharge performance of Li-air batteries using commercial Ketjenblack (KB) and KB subjected to vacuum ultraviolet (VUV) irradiation as cathodes. The surface wettability of KB changed from hydrophobic to hydrophilic as a result of the VUV irradiation. The ratio of COOH and OH groups on the KB surface increased after VUV irradiation. Raman spectra demonstrated that no structural change in the KB before and after VUV irradiation was observed. The charge and discharge capacities of a Li-air battery using VUV-irradiated KB as the cathode decreased compared to original KB, whereas the cycling performance of the Li-air battery improved considerably. The sizes and shapes of the discharge products formed on the cathodes changed considerably due to the VUV irradiation. The difference in the cycling performance of the Li-air battery was discussed from the viewpoint of the chemical properties of KB and VUV-irradiated KB.     

Cumulative Recurrence Rate and Risk Factors for Recurrent Abdominal Wall Endometriosis after Surgical Treatment in a Single Institution

PurposeThis study aimed to evaluate the cumulative recurrence rate and risk factors for recurrent abdominal wall endometriosis (AWE) after surgical treatment.Materials and MethodsA retrospective cohort study was conducted at a single gynecological surgery center between January 2004 and December 2020. Patients who were surgically treated and followed up for at least 6 months after surgery were selected.ResultsEighteen patients with pathologically diagnosed AWE were included in this study. The median follow-up duration was 22.5 months (range, 6–106). The median age was 37 years (range, 22–48), and 33.3% of the patients were nulliparous. Among the patients included in our study, 55.6% complained of a mass with cyclic pain, and 27.8% had a palpable mass. In addition, 22.2% of patients experienced recurrence with 17.5±9.7 months of mean time to recurrence. The cumulative recurrence rates at 24 and 60 months after surgical treatment of AWE were 23.8% and 39.1%, respectively. There were no statistically significant risk factors for the recurrence of AWE, including postoperative medical treatment.ConclusionThe recurrence rate of AWE appears to be correlated with the follow-up duration. There was no statistically significant risk factor for the recurrence of AWE. Unlike ovarian endometriosis, postoperative hormonal treatment does not seem to lower the recurrence of AWE. The findings of the current study may help healthcare providers in counselling and managing patients with AWE.     

Effect of a Boarding Restriction Protocol on Emergency Department Crowding

PurposeAccess block due to the lack of hospital beds causes crowding of emergency departments (ED). We initiated the “boarding restriction protocol” that limits the time of stay in the ED for patients awaiting hospitalization to 24 hours from arrival. The purpose of this study was to determine the effect of the boarding restriction protocol on ED crowding.Materials and MethodsThe primary outcome was ED occupancy rate, which was calculated as the ratio of the number of occupying patients to the total number of ED beds. Time factors, such as length of stay (LOS), treatment time, and boarding time, were investigated.ResultsThe mean of the ED occupancy rate decreased from 1.532±0.432 prior to implementation of the protocol to 1.273±0.353 after (p<0.001). According to time series analysis, the absolute effect caused by the protocol was -0.189 (-0.277 to -0.110) (p=0.001). The proportion of patients with LOS exceeding 24 hours decreased from 7.6% to 4.0% (p<0.001). Among admitted patients, ED LOS decreased from 770.7 (421.4–1587.1) minutes to 630.2 (398.0–1156.8) minutes (p<0.001); treatment time increased from 319.6 (198.5–482.8) minutes to 344.7 (213.4–519.5) minutes (p<0.001); and boarding time decreased from 298.9 (109.5–1149.0) minutes to 204.1 (98.7–545.7) minutes (p<0.001). In pre-protocol period, boarding patients accumulated in the ED during the weekdays and resolved on Friday, but this pattern was alleviated in post-period.ConclusionThe boarding restriction protocol was effective in alleviating ED crowding by reducing the accumulation of boarding patients in the ED during the weekdays.     

Association between weight status and recreational drug abuse in Korean adolescents

The purpose of this study was to investigate the relationship between weight status and recreational drug use in Korean adolescents. A total of 72,399 adolescent students (38,152 boys and 34,247 girls) from the middle first to high third grade participated in the 5^th Korea Youth Risk Behaviour Web-based Survey (KYRBWS-V) project in 2009. They were assessed for body mass index (BMI) and recreational drug abuse. The associations between BMI and recreational drug use were examined using multivariable logistic regression analysis after adjusting for the covariate variables of age, smoking frequency and cigarette consumption, frequency of alcohol consumption and severe alcohol intoxication, amount of alcohol consumed, parents’ education level, economic status, sedentary activities during the week, mental stress, sleep duration, frequency of vigorous and moderate physical activities, and muscular strength exercises during the week. For boys, the odds ratio (OR) (95% confidence interval [CI]) between overweight and drug use were 0.990 (0.723–1.356; p = 0.950) for almost none, 0.939 (0.521–1.693; p = 0.834) for past use, and 0.791 (0.385–1.624; p = 0.523) for present use. The OR (95% CI) between obesity and drug use was 0.731(0.508–1.052; p = 0.091) for almost none, 0.755 (0.389–1.465; p = 0.407) for past use, and 0.701 (0.314–1.565; p = 0.386) for present use. For girls, the OR (95% CI) between overweight and drug use was 1.112 (0.702–1.763; p = 0.650) for almost none, 1.103 (0.464–2.619; p = 0.825) for past use, and 0.927 (0.267–3.218; p = 0.905) for present use. The OR (95% CI) between obesity and drug abuse was 0.594 (0.261–1.352; p = 0.215) for almost none, 1.318 (0.462–3.764; p = 606) for past use, and <0.001(<0.001–<0.001; p = 0.998) for present use. We concluded that recreational drug use had no correlation with overweight and obesity in Korean adolescents.