Predictive Validity of a New Triage System for Outcomes in Patients Visiting Pediatric Emergency Departments: A Nationwide Study in Korea.

Triage is essential for rapid and efficient intervention in patients visiting an emergency department. In Korea, since 2016, the Pediatric Korean Triage and Acuity Scale (PedKTAS) has been implemented nationwide for the triage of patients visiting pediatric emergency departments (PEDs). The aim of this study was to evaluate the validity of the PedKTAS in patients who visit PEDs. This study was a retrospective observational study of national registry data collected from all emergency medical centers and institutions throughout Korea. We analyzed data from patients aged <15 years who visited emergency departments nationwide from January 2016 to December 2019. The hospitalization and intensive care unit (ICU) admission rates were analyzed on the basis of triage level. In total, 5,462,964 pediatric patients were included in the analysis. The hospitalization rates for PedKTAS Levels 1-5, were 63.5%, 41.1%, 17.0%, 6.5%, and 3.7%, respectively, and were significantly different (p < 0.001). The ICU admission rates for PedKTAS Levels 1-5 were 14.4%, 6.0%, 0.3%, 0.1%, and 0.1%, respectively, and were significantly different (p < 0.001). The hospitalization and ICU admission rates were highest for PedKTAS Level 1, and differences were significant based on the level. We identified that the PedKTAS is suitable for predicting the emergency status of pediatric patients who visit PEDs.

Effect of COVID-19 on Emergency Department Visits by Pediatric Burn Patients in Korea: Retrospective Observational Study.

It's been over a year since the outbreak of the coronavirus disease (COVID-19), which is still a global public health challenge. Many countries have implemented social distancing to prevent the risk of infection with COVID-19. As a result, children spend more time at home. Home is where burns among children occur predominantly. We hypothesized that the changes in lifestyle due to the COVID-19 outbreak may have affected pediatric emergency department (PED) visits by children sustaining burn injuries. This study was a long-term multicenter observational study. Pediatric burn patients were defined in accordance with International Classification of Disease, Tenth Edition (ICD-10). We investigated the trend in PED weekly visits by pediatric burn patients before and after the outbreak of COVID-19 and trends in the proportion of visits according to burn severity based on segmented regression analysis. The data were adjusted for seasonality due to seasonal variation in the visits. Over the past 3 years, the proportion of pediatric burn patients tended to decrease. However, it increased in the fourth week of January 2020, when COVID-19 was first confirmed in Korea. In particular, the proportion of PED visits to pediatric burn patients with severe burns increased after the COVID-19 epidemic. Our study showed increases in the proportion of PED visits among pediatric burn patients due to the spread of COVID-19. Many of these burn accidents mainly occur at home, suggesting the need for parental intervention to prevent the risk of burn injuries among children.

Impact of COVID-19 Pandemic on Children Visiting Emergency Department for Mental Illness: A Multicenter Database Analysis from Korea.

We aimed to identify changes in the proportion of pediatric emergency department (PED) visits due to mental illness during the coronavirus disease 2019 (COVID-19) pandemic. This was a retrospective observational study of visits to the PED at six university hospitals from January 2017 to December 2020. We included children aged 5−17 years who were diagnosed with a mental illness. We used segmented regression analysis to identify the change in the proportion of patients with mental illness. A total of 845 patients were included in the analysis. After the first case of COVID-19 was reported in Korea, the number of PED visits significantly decreased by 560.8 patients per week (95% confidence interval (CI): −665.3 to −456.3, p < 0.001). However, the proportion of patients with mental illness increased significantly, by 0.37% per week (95% CI: 0.04% to 0.70%, p = 0.03), at this time point. Subgroup analyses revealed that emotional disorders significantly increased by 0.06% per month (95% CI: 0.02% to 0.09%, p < 0.001) during the pandemic. Our study revealed that an increased proportion of patients with mental illness visited the PED during the COVID-19 pandemic. Specifically, we identified that the proportion of emotional disorders continues to rise during this pandemic.

Impact of COVID-19 pandemic on patients with cardio/cerebrovascular disease who visit the emergency department.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic situation is a state that has had a great impact on the medical system and society. To respond to the pandemic situation, various methods, such as a pre-triage system, are being implemented in the emergency medical field. However, there are insufficient studies on the effects of this pandemic situation on patients visiting the emergency department (ED), especially those with cardio/cerebrovascular diseases (CVD)1 classified as time-dependent emergencies. METHODS: We performed a retrospective analysis of a cohort of patients from April 2020 to December 2020 (April 2020 was when the pre-triage system was established) compared to a parallel comparison patient cohort from 2019. The primary outcome was in-hospital mortality. CVD was defined by the patient's final diagnosis. RESULTS: During the same period, the number of patients who had visited the ED after COVID-19 had decreased to 79.1% of the number of patients who had visited the ED before COVID-19. The overall patient mortality and the mortality in the patients cardiovascular disease had both increased, while the mortality from cerebrovascular disease did not increase. Meanwhile, the ED length of stay had increased in all patients but did not increase in the patients with cardiovascular disease. CONCLUSION: As with prior studies conducted in other regions, in our study, the total number of ED visits were decreased compared to before COVID-19. The overall mortality had increased, particularly in the patients with cardiovascular disease.

Association between Stress Hyperglycemia and Adverse Outcomes in Children Visiting the Pediatric Emergency Department.

Stress hyperglycemia (SH) is often identified in patients visiting the pediatric emergency department (PED), and SH in adults has been associated with adverse outcomes, including mortality. In this retrospective study, we determined the adverse outcomes according to blood glucose (BG) levels of children visiting the PED of tertiary hospitals. Data were collected from the electronic medical records of children aged <18 years between 1 January 2011 and 31 December 2020. A total of 44,905 visits were included in the analysis. SH was identified in 1506 patients, with an incidence rate of 3.4%. Compared to those without SH, patients with SH had significantly higher ward admission rates (52.6% vs. 35.9%, p < 0.001), intensive care unit admission rates (2.6% vs. 0.7%, p < 0.001), and mortality rates (2.7% vs. 0.3%, p < 0.001). Compared to the normoglycemic group of 45 ≤ BG < 150 mg/dL, the odds ratios (95% CI) for mortality were 5.61 (3.35−9.37), 27.96 (14.95−52.26), 44.22 (17.03−114.82), and 39.94 (16.31−97.81) for levels 150 ≤ BG < 200, 200 ≤ BG < 250, 250 ≤ BG < 300 and ≥300 mg/dL, respectively. This suggests that SH is common in children visiting the PED and is associated with higher adverse outcomes. Thus, there is a need to quickly identify its cause and take prompt intervention to resolve it.

One-year changes in the pediatric emergency department caused by prolonged coronavirus disease 2019 pandemic.

BACKGROUND: With the coronavirus disease 2019 (COVID-19) pandemic lasting for more than a year, it is imperative to identify the associated changes in the use of emergency medical care for efficient operation of the pediatric emergency department (PED). This study was conducted to determine the long-term impact of the COVID-19 pandemic on patterns of PED visits. METHODS: This is a retrospective observational study of visits to the PED of six hospitals, between January 1, 2017, and December 31, 2020. We compared changes in the characteristics of patients before and during the COVID-19 pandemic. RESULTS: A total of 245 022 visits were included in this analysis. After the first case of COVID-19 was reported in Korea, we observed a significant decrease (54.2%) in PED visits compared with the annual average number of visits in the previous 3 years. Since then, the weekly number of PED visits decreased by 11.9 person/week (95% CI: -15.3--8.4, P < 0.001), which included an increase of 0.21% (95% CI: 0.15%-0.26%, P < 0.001) per week in high acuity patients. From 2017 to 2020, the proportion of infectious respiratory diseases by year was 25.9%, 27.0%, 28.6%, and 16.3%, respectively, demonstrating a significant decrease in 2020 (P < 0.001). CONCLUSIONS: During the COVID-19 pandemic, the number of patient visits to PEDs continues to decline, especially among those with infectious diseases. However, the disease severity of patients has gradually increased. There has been a change in the characteristics of visits to PEDs after COVID-19 which will require an appropriate response from a long-term perspective.

Interrater reliability of spectrogram for detecting wheezing in children.

BACKGROUND: Auscultation is an easy way to evaluate and diagnose patients with lung conditions but has the shortcoming of being subjective. Using the spectrogram, it is possible to visualize wheezing. We therefore conducted a study to compare the efficacy of diagnosing wheezing by auscultation versus diagnosing wheezing by spectrogram. METHODS: This was an investigation of interrater reliability and agreement in which the subject population consisted of children, and the rater population consisted of pediatric pulmonologists. We recorded 55 respiratory sound files from June to November 2019. Three pediatric pulmonologists listened to the respiratory sound files and assessed whether wheezing was present. All respiratory sound files were also converted into spectrograms; the same pulmonologists viewed these and assessed whether wheezing was present. We tested for interrater reliability and agreement between the auscultation results and spectrographic results and investigated the diagnostic reliability of auscultation versus spectrogram. RESULTS: Agreement among the three raters of our auscultation respiratory recordings was 88% and reliability was good (κ = 0.76, P < 0.001). Agreement among the three raters of our spectrograms was 83% and reliability was good (κ =0.66, P < 0.001). The level of agreement between each rater's spectrographic findings and diagnosed wheezing was 91%, 75%, and 93%, respectively. Reliability was accordingly very good, moderate, and very good (κ = 0.82, 0.49, 0.85, P < 0.001), respectively. CONCLUSIONS: A spectrogram may be a valuable tool for evaluating wheezing in children. It may also be used to improve a young clinician's ability to accurately diagnose wheezing in the future.

Impact of Covid-19 on the Visit of Pediatric Patients with Injuries to the Emergency Department in Korea.

The total number of pediatric emergency department (PED) visitors has decreased worldwide since the coronavirus disease (COVID-19) outbreak. We hypothesized that this might also affect the number of PED visits due to injuries. Therefore, we investigated these changes in PED visits after the COVID-19 outbreak through a long-term multicenter observational study. We assessed the changes in the proportion of injured pediatric patients' weekly visits and the trend in the rate changes since the COVID-19 epidemic began by segmented regression analysis. We also evaluated the weekly change in the distribution of detailed diagnostic codes among pediatric patients with injuries before and after the COVID-19 pandemic. The proportion of injury-related PED visits increased when COVID-19 was first confirmed in Korea. After the COVID-19 epidemic, the proportion of foreign body ingestions and fracture patients among all pediatric patients with injuries increased significantly every week. The changes in the proportion of injured pediatric patients after the COVID-19 outbreak may have been the result of social distancing to prevent the spread of the virus. The risk of pediatric infections decreased but the risk of injury remained. Therefore, parents should take precautions to prevent infectious diseases and be careful to prevent children's injuries at home.

Virtual reality environment using a dome screen for procedural pain in young children during intravenous placement: A pilot randomized controlled trial.

We assessed the feasibility and potential efficacy of a virtual reality (VR) environment using a dome screen as a distraction method in young children during intravenous (IV) placement in the pediatric emergency department. This randomized controlled pilot study enrolled children aged 2 to 6 years who underwent IV placement into either the intervention group or the control group. Children in the intervention group experienced VR using a dome screen during IV placement. The child's pain intensity was measured using the Face, Legs, Activity, Cry, and Consolability (FLACC) scale at four time points of IV placement: immediately after arrival to the blood collection room (base); immediately after the child laid down on the bed (preparation); when the tourniquet was applied (tourniquet); and the moment at which the needle penetrated the skin (venipuncture). The guardian's satisfaction and rating of the child's distress were assessed using a 5-point Likert-type questionnaire. We recruited 19 children (9 in the intervention group and 10 in the control group). Five children in the control group were excluded from the analysis because of missing video recordings (n = 3), failed first attempt at IV placement (n = 1), and the child's refusal to lie on the bed during the procedure (n = 1). No side effects of VR were reported during the study period. Although the average FLACC scale score at each time point (preparation, tourniquet, venipuncture) was lower in the intervention group than the control group, the difference was not statistically significant (2.3, interquartile range [IQR]: 2.0-3.0; vs. 3.3, IQR: 2.7-6.7, P = 0.255). There were no statistically significant differences between the groups in the guardian's satisfaction and anxiety or his/her rating of the child's pain and anxiety. The guardians and emergency medical technicians reported satisfaction with the use of VR with a dome screen and considered it a useful distraction during the procedure. VR using a dome screen is a feasible distraction method for young children during IV placement. A larger clinical trial with further development of the VR environment and study process is required to adequately evaluate the efficacy of VR using a dome screen.

Nucleotide Excision Repair, XPA-1, and the Translesion Synthesis Complex, POLZ-1 and REV-1, Are Critical for Interstrand Cross-Link Repair in Caenorhabditis elegans Germ Cells.

Interstrand cross-links (ICLs) are adducts of covalently linked nucleotides in opposing DNA strands that obstruct replication and prime cells for malignant transformation or premature cell death. ICLs may be caused by alkylating agents or ultraviolet (UV) irradiation. These toxic lesions are removed by diverse repair mechanisms such as the Fanconi anemia (FA) pathway, nucleotide excision repair (NER), translesion synthesis (TLS), and homologous recombination (HR). In mammals, the xeroderma pigmentosum group F (XP-F) protein participates in both the FA pathway and NER, while DNA polymerase ζ (POLZ-1) and REV-1 mediate TLS. Nevertheless, little is known regarding the genetic determinants of these pathways in ICL repair and damage tolerance in germ cells. In this study, we examined the sensitivity of Caenorhabditis elegans germ cells to ICLs generated by trimethylpsoralen/ultraviolet A (TMP/UV-A) combination, and embryonic mortality was employed as a surrogate for DNA damage in germ cells. Our results show that XPA-1, POLZ-1, and REV-1 were more critical than FA pathway mediators in preserving genomic stability in C. elegans germ cells. Notably, mutant worms lacking both XPA-1 and POLZ-1 (or REV-1) were more sensitive to ICLs compared to either single mutant alone. Moreover, knockdown of XPA-1 and REV-1 leads to the retarded disappearance of RPA-1 and RAD-51 foci upon ICL damage. Since DNA repair mechanisms are broadly conserved, our findings may have ramifications for prospective therapeutic interventions in humans.

Distribution of Pediatric Vital Signs in the Emergency Department: A Nationwide Study.

To effectively use vital signs as indicators in children, the magnitude of deviation from expected vital sign distribution should be determined. The purpose of this study is to derive age-specific centile charts for the heart rate and respiratory rate of the children who visited the emergency department. This study used the Korea's National Emergency Department Information System dataset. Patients aged <16 years visiting the emergency department between 1 January 2016 and 31 December 2017 were included. Heart rate and respiratory rate centile charts were derived from the population with normal body temperature (36 to <38 °C). Of 1,901,816 data points retrieved from the database, 1,454,372 sets of heart rates and 1,458,791 sets of respiratory rates were used to derive centile charts. Age-specific centile charts and curves of heart rates and respiratory rates showed a decline in heart rate and respiratory rate from birth to early adolescence. There were substantial discrepancies in the reference ranges of Advanced Paediatric Life Support and Pediatric Advanced Life Support guidelines. Age-based heart rate and respiratory rate centile charts at normal body temperature, derived from children visiting emergency departments, serve as new evidence-based data and can be used in follow-up studies to improve clinical care for children.

Hypersensitivity to DNA double-strand breaks associated with PARG deficiency is suppressed by exo-1 and polq-1 mutations in Caenorhabditis elegans.

Deficiency of either of the two homologs of poly(ADP-ribose) glycohydrolase (PARG), PARG-1 and PARG-2, in Caenorhabditis elegans leads to hypersensitivity to ionizing radiation (IR). In the germ cells of parg-2 mutant worms, the dissipation of recombinase RAD-51 foci was slower than in wild-type (WT) cells, suggesting defects in DNA double-strand break (DSB) repair via homologous recombination (HR). Nevertheless, RPA-1, the large subunit of replication protein A, accumulated faster in parg-2 worms and disappeared earlier than in WT worms. This accelerated RPA-1 accumulation may result from the enhanced expression of exonuclease-1 (EXO-1) after IR treatment. Accordingly, an exo-1 mutation reduced IR sensitivity and accumulation of RPA-1 in parg-2 worms. A mutation of polq-1, encoding for a key factor in the alternative end-joining (Alt-EJ) pathway, suppressed the IR hypersensitivity phenotype of parg-2 worms and normalized the kinetics of RAD-51 dissipation. This indicates that error-prone Alt-EJ may mediate DSB repair in parg-2 worms, causing hypersensitivity to IR. In summary, PARG-2 deficiency in C. elegans causes hyperactive DSB end resection likely through EXO-1 overproduction. DSBs with long single-stranded DNA ends in parg-2 worms are thought to be repaired by Alt-EJ instead of HR, causing genomic instability.

Single-strand annealing mediates the conservative repair of double-strand DNA breaks in homologous recombination-defective germ cells of Caenorhabditis elegans.

A missense mutation in C. elegans RAD-54, a homolog of RAD54 that operates in the homologous recombination (HR) pathway, was found to decrease ATPase activity in vitro. The hypomorphic mutation caused hypersensitivity of C. elegans germ cells to double-strand DNA breaks (DSBs). Although the formation of RAD-51 foci at DSBs was normal in both the mutant and knockdown worms, their subsequent dissipation was slow. The rad-54-deficient phenotypes were greatly aggravated when combined with an xpf-1 mutation, suggesting a conservative role of single-strand annealing (SSA) for DSB repair in HR-defective worms. The phenotypes of doubly-deficient rad-54;xpf-1 worms were partially suppressed by a mutation of lig-4, a nonhomologous end-joining (NHEJ) factor. In summary, RAD-54 is required for the dissociation of RAD-51 from DSB sites in C. elegans germ cells. Also, NHEJ and SSA exert negative and positive effects, respectively, on genome stability when HR is defective.

Evaluating the Memory Enhancing Effects of Angelica gigas in Mouse Models of Mild Cognitive Impairments.

(1) Background: By 2050, it is estimated that 130 million people will be diagnosed with dementia, and currently approved medicines only slow the progression. So preventive intervention is important to treat dementia. Mild cognitive impairment is a condition characterized by some deterioration in cognitive function and increased risk of progressing to dementia. Therefore, the treatment of mild cognitive impairment (MCI) is a possible way to prevent dementia. Angelica gigas reduces neuroinflammation, improves circulation, and inhibits cholinesterase, which can be effective in the prevention of Alzheimer's disease and vascular dementia and the progression of mild cognitive impairment. (2) Methods: Angelica gigas (AG) extract 1 mg/kg was administered to mildly cognitive impaired mice, models based on mild traumatic brain injury and chronic mild stress. Then, spatial, working, and object recognition and fear memory were measured. (3) Result: Angelica gigas improved spatial learning, working memory, and suppressed fear memory in the mild traumatic brain injury model. It also improved spatial learning and suppressed cued fear memory in the chronic mild stress model animals. (4) Conclusions: Angelica gigas can improve cognitive symptoms in mild cognitive impairment model mice.

Apoptosis-Inducing Activity of Marine Sponge Haliclona sp. Extracts Collected from Kosrae in Nonsmall Cell Lung Cancer A549 Cells.

Although various anticancer drugs have been developed for the treatment of nonsmall cell lung cancer, chemotherapeutic efficacy is still limited. Natural products such as phytochemicals have been screened as novel alternative materials, but alternative funds such as marine bioresources remain largely untapped. Of these resources, marine sponges have undergone the most scrutiny for their biological activities, including antiinflammatory, antiviral, and anticancer properties. However, the biological mechanisms of the activities of these marine sponges are still unclear. We investigated the anticancer activity of marine sponges collected from Kosrae in Micronesia and examined their mechanisms of action using nonsmall cell lung cancer A549 cells as a model system. Of 20 specimens, the Haliclona sp. (KO1304-328) showed both dose- and time-dependent cytotoxicity. Further, methanol extracts of Haliclona sp. significantly inhibited cell proliferation and cell viability. A549 cells treated with Haliclona sp. demonstrated induced expression of c-Jun N-terminal kinase (JNK), p53, p21, caspase-8, and caspase-3. The percentage of apoptotic cells significantly increased in A549 cultures treated with Haliclona sp. These results indicate that Haliclona sp. induces apoptosis via the JNK-p53 pathway and caspase-8, suggesting that this marine sponge is a good resource for the development of drugs for treatment of nonsmall cell lung cancer.

Anticancer activity of marine sponge Hyrtios sp. extract in human colorectal carcinoma RKO cells with different p53 status.

Drug development using marine bioresources is limited even though the ocean occupies about 70% of the earth and contains a large number of biological materials. From the screening test of the marine sponge extracts, we found Hyrtios sp. sponge collected from Chuuk island, Micronesia. In this study, the Hyrtios sp. extract was examined for anticancer activity against human colorectal carcinoma RKO cells that are wildtype for p53 and RKO-E6 that are p53 defective. The Hyrtios sp. extract dose-dependently inhibited viability in both cell lines. Multinucleation as an indication of mitotic catastrophe was also observed. Cytotoxicity tests gave significantly different results for RKO and RKO-E6 cells after 48 h exposure to Hyrtios sp. extract. In RKO cells treated with Hyrtios sp. extract, cell death occurred by induction of p53 and p21 proteins. In p53-defective RKO-E6 cells, Hyrtios sp. extract decreased expression of JNK protein and increased p21 protein. These results indicate that Hyrtios sp. extract induced apoptosis via different pathways depending on p53 status and could be a good natural product for developing new anticancer drugs.

Fluorescence detection of cationic amyloid fibrils in human semen.

Cationic amyloid fibrils, including the Semen Enhancer of Virus Infection (SEVI), have recently been described in human semen. Simple methods for quantitating these fibrils are needed to improve our understanding of their biological function. We performed high-throughput screening to identify molecules that bind SEVI, and identified a small molecule (8E2), that fluoresced brightly in the presence of SEVI and other cationic fibrils. 8E2 bound SEVI with almost 40-fold greater affinity than thioflavin-T, and could efficiently detect high molecular weight fibrils in human seminal fluid.

Real-time observation of multiple-protein complex formation with single-molecule FRET.

Current single-molecule techniques do not permit the real-time observation of multiple proteins interacting closely with each other. We here report an approach enabling us to determine the single-molecule fluorescence resonance energy transfer (FRET) kinetics of multiple protein-protein interactions occurring far below the diffraction limit. We observe a strongly cooperative formation of multimeric soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complexes, which suggests that formation of the first SNARE complex triggers a cascade of SNARE complex formation.

Single-molecule FRET study of SNARE-mediated membrane fusion.

Membrane fusion is one of the most important cellular processes by which two initially distinct lipid bilayers merge their hydrophobic cores, resulting in one interconnected structure. Proteins, called SNARE (soluble N-ethylmaleimide-sensitive factor-attachment protein receptor), play a central role in the fusion process that is also regulated by several accessory proteins. In order to study the SNARE-mediated membrane fusion, the in vitro protein reconstitution assay involving ensemble FRET (fluorescence resonance energy transfer) has been used over a decade. In this mini-review, we describe several single-molecule-based FRET approaches that have been applied to this field to overcome the shortage of the bulk assay in terms of protein and fusion dynamics.