Objective: This study evaluates the impact of the coronavirus disease 2019 (COVID-19) pandemic on emergency medical service (EMS) responses and out-of-hospital cardiac arrest (OHCA) outcomes. Methods: This is a retrospective comparison study analyzing the OHCA data of a university medical center in Seoul during the COVID-19 pandemic period (January 2020-January 2021) and non-pandemic period (January 2019-January 2020). The EMS response time and OHCA outcomes were compared between both periods. Based on the weekly mean number of confirmed cases and their EMS response time, patients were classified into six groups and OHCA outcomes were compared. Results: This study evaluated 309 OHCA patients (non-pandemic period of 146, pandemic period of 163). Significant delays in the EMS response and transport time were observed during the pandemic period. However, no significant differences were obtained in the rate of return of spontaneous circulation (ROSC) and survival at discharge (12.4% in pandemic vs. 13.8% in non-pandemic; P=0.722). According to the weekly mean COVID-19 incidence when patients were over 100, there was a significant increase in the EMS response and transport time, whereas ROSC and survival rate were dramatically decreased. Conclusion During the pandemic, the EMS service for OHCA patients was worse than before, with delayed and reduced survival for OHCA patients. We further determined that an increase in the number of COVID-19 cases (especially when weekly mean numbers were over 100) dramatically delayed the EMS response time. This resulted in a very low survival rate of OHCA patients.

Objectives: . Thyroid cancer is the most common endocrine tumor, with rapidly increasing incidence worldwide. However, its transcriptomic characteristics associated with immunological signatures, driver fusions, and recurrence markers remain unclear. We aimed to investigate the transcriptomic characteristics of advanced papillary thyroid cancer. Methods: . This study included 282 papillary thyroid cancer tumor samples and 155 normal samples from Chungnam National University Hospital and Seoul National University Hospital. Transcriptomic quantification was determined by high-throughput RNA sequencing. We investigated the associations of clinical parameters and molecular signatures using RNA sequencing. We validated predictive biomarkers using the Cancer Genome Atlas database. Results: . Through a comparison of differentially expressed genes, gene sets, and pathways in papillary thyroid cancer compared to normal tumor-adjacent tissue, we found increased immune signaling associated with cytokines or T cells and decreased thyroid hormone synthetic pathways. In addition, patients with recurrence presented increased CD8+ T-cell and Th1-cell signatures. Interestingly, we found differentially overexpressed genes related to immune-escape signaling such as CTLA4, IDO1, LAG3, and PDCD1 in advanced papillary thyroid cancer with a low thyroid differentiation score. Fusion analysis showed that the PI3K and mitogen-activated protein kinase (MAPK) signaling pathways were regulated differently according to the RET fusion partner genes (CCDC6 or NCOA4). Finally, we identified HOXD9 as a novel molecular biomarker that predicts the recurrence of thyroid cancer in addition to known risk factors (tumor size, lymph node metastasis, and extrathyroidal extension). Conclusion . We identified a high association with immune-escape signaling in the immune-hot group with aggressive clinical characteristics among Korean thyroid cancer patients. Moreover, RET fusion differentially regulated PI3K and MAPK signaling depending on the partner gene of RET, and HOXD9 was found to be a recurrence marker for advanced papillary thyroid cancer.

Purpose: To find biomarkers for disease, there have been constant attempts to investigate the genes that differ from those in the disease groups. However, the values that lie outside the overall pattern of a distribution, the outliers, are frequently excluded in traditional analytical methods as they are considered to be ‘some sort of problem.’ Such outliers may have a biologic role in the disease group. Thus, this study explored new biomarker using outlier analysis, and verified the suitability of therapeutic potential of two genes (TM4SF4 and LRRK2). Materials and Methods: Modified Tukey’s fences outlier analysis was carried out to identify new biomarkers using the public gene expression datasets. And we verified the presence of the selected biomarkers in other clinical samples via customized gene expression panels and tissue microarrays. Moreover, a siRNA-based knockdown test was performed to evaluate the impact of the biomarkers on oncogenic phenotypes. Results: TM4SF4 in lung cancer and LRRK2 in breast cancer were chosen as candidates among the genes derived from the analysis. TM4SF4 and LRRK2 were overexpressed in the small number of samples with lung cancer (4.20%) and breast cancer (2.42%), respectively. Knockdown of TM4SF4 and LRRK2 suppressed the growth of lung and breast cancer cell lines. The LRRK2 overexpressing cell lines were more sensitive to LRRK2-IN-1 than the LRRK2 under-expressing cell lines Conclusion Our modified outlier-based analysis method has proved to rescue biomarkers previously missed or unnoticed by traditional analysis showing TM4SF4 and LRRK2 are novel target candidates for lung and breast cancer, respectively.

Mannosylerythritol lipids (MELs) are glycolipids and have several pharmacological efficacies. MELs also show skin-moisturizing efficacy through a yet-unknown underlying mechanism. Aquaporin-3 (AQP3) is a membrane protein that contributes to the water homeostasis of the epidermis, and decreased AQP3 expression following ultraviolet (UV)-irradiation of the skin is associated with reduced skin moisture. No previous study has examined whether the skin-moisturizing effect of MELs might act through the modulation of AQP3 expression. Here, we report for the first time that MELs ameliorate the UVA-induced downregulation of AQP3 in cultured human epidermal keratinocytes (HaCaT keratinocytes). Our results revealed that UVA irradiation decreases AQP3 expression at the protein and messenger RNA (mRNA) levels, but that MEL treatment significantly ameliorated these effects. Our mitogen-activated protein kinase inhibitor analysis revealed that phosphorylation of c-Jun N-terminal kinase (JNK), but not extracellular signal-regulated kinase or p38, mediates UVA-induced AQP3 downregulation, and that MEL treatment significantly suppressed the UVA-induced phosphorylation of JNK. To explore a possible mechanism, we tested whether MELs could regulate the expression of peroxidase proliferator-activated receptor gamma (PPAR-γ), which acts as a potent transcription factor for AQP3 expression. Interestingly, UVA irradiation significantly inhibited the mRNA expression of PPAR-γ in HaCaT keratinocytes, whereas a JNK inhibitor and MELs significantly rescued this effect. Taken together, these findings suggest that MELs ameliorate UVA-induced AQP3 downregulation in HaCaT keratinocytes by suppressing JNK activation to block the decrease of PPAR-γ. Collectively, our findings suggest that MELs can be used as a potential ingredient that modulates AQP3 expression to improve skin moisturization following UVA irradiation-induced damage.
Down-Regulation* ; Epidermis ; Glycolipids ; Homeostasis ; Humans* ; JNK Mitogen-Activated Protein Kinases* ; Keratinocytes* ; Membrane Proteins ; Peroxidase ; Phosphorylation* ; Phosphotransferases ; PPAR gamma ; Protein Kinases ; RNA, Messenger ; Skin ; Transcription Factors ; Water

We recently reported that adeno-associated virus serotype 1 (AAV1) transduction of murine nigral dopaminergic (DA) neurons with constitutively active ras homolog enriched in brain with a mutation of serine to histidine at position 16 [Rheb(S16H)] induced the production of neurotrophic factors, resulting in neuroprotective effects on the nigrostriatal DA system in animal models of Parkinson’s disease (PD). To further investigate whether AAV1-Rheb(S16H) transduction has neuroprotective potential against neurotoxic inflammation, which is known to be a potential event related to PD pathogenesis, we examined the effects of Rheb(S16H) expression in nigral DA neurons under a neurotoxic inflammatory environment induced by the endogenous microglial activator prothrombin kringle-2 (pKr-2). Our observations showed that Rheb(S16H) transduction played a role in the neuroprotection of the nigrostriatal DA system against pKr-2-induced neurotoxic inflammation, even though there were similar levels of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-1-beta (IL-1β), in the AAV1-Rheb(S16H)-treated substantia nigra (SN) compared to the SN treated with pKr-2 alone; the neuroprotective effects may be mediated by the activation of neurotrophic signaling pathways following Rheb(S16H) transduction of nigral DA neurons. We conclude that AAV1-Rheb(S16H) transduction of neuronal populations to activate the production of neurotrophic factors and intracellular neurotrophic signaling pathways may offer promise for protecting adult neurons from extracellular neurotoxic inflammation.

OBJECTIVES: The goal of this study was to investigate trends in admission to the emergency department and the use of invasive or surgical procedures during hospitalization for acute myocardial infarction (AMI) in Korea. METHODS: The National Health Insurance (NHI) claims database between 2007 and 2011 was used. We identified all admission claims that included codes from the tenth revision of the International Classification of Diseases beginning with I21 as the primary or secondary diagnosis. Information about the admission route, admission date, discharge date, and whether coronary artery angiography, angioplasty, or bypass surgery was performed was also obtained from the NHI database. RESULTS: Of the 513,886 relevant admission claims over the five years encompassed by this study, 295,001 discrete episodes of admission for AMI were identified by analyzing the date and length of each admission and the interval between admissions. The number of AMI admissions gradually decreased from 66,883 in 2007 to 47,656 in 2011. The number and proportion of admissions through the emergency department also decreased from 38,118 (57.0%) in 2007 to 24,001 (50.4%) in 2011. However, during the same period, admissions in which invasive or surgical procedures were performed increased from 15,342 (22.9%) to 17,505 (36.7%). CONCLUSIONS: The reported numbers of emergency department visits and admissions for AMI decreased from 2007 to 2011. However, only a small portion of the patients underwent invasive or surgical procedures during hospitalization, although the number of admissions involving invasive or surgical procedures has increased. These findings suggest that simply counting the number of admission claims cannot provide valid information on trends in AMI occurrence.
Angiography ; Angioplasty ; Coronary Vessels ; Diagnosis ; Emergency Service, Hospital ; Hospitalization* ; Humans ; International Classification of Diseases ; Korea ; Myocardial Infarction* ; National Health Programs* ; Vascular Surgical Procedures

BACKGROUND: In many countries, nephrologists follow clinical practice guidelines for mineral bone disorders to control secondary hyperparathyroidism (SHPT) associated with abnormal serum calcium (Ca) and phosphorus (P) levels in patients undergoing maintenance hemodialysis (MHD). The Kidney Disease Outcomes Quality Initiative (KDOQI) Guidelines have long been used in Korea, and this study was undertaken to investigate the current status of serum Ca and P control in MHD patients. METHODS: Data were collected from a total of 1,018 patients undergoing MHD without intercurrent illness, in 17 hemodialysis centers throughout the country. Serum levels of Ca, P, and intact parathyroid hormone (iPTH) were measured over 1 year, and the average values were retrospectively analyzed. RESULTS: Serum levels of Ca, P, and the CaxP product were 9.1+/-0.7mg/dL, 5.3+/-1.4mg/dL, and 48.0+/-13.6mg2/dL2, respectively. However, the percentages of patients with Ca, P, and Ca x P product levels within the KDOQI guideline ranges were 58.7%, 51.0%, and 70.7%, respectively. Of the 1,018 patients, 270 (26.5%) had iPTH >300pg/mL (uncontrolled SHPT), whereas 435 patients (42.7%) showed iPTH <150pg/mL. Patients with uncontrolled SHPT had significantly higher values of serum Ca, P, and CaxP product than those with iPTH < or =300pg/mL. CONCLUSION: Despite the current clinical practice guidelines, SHPT seems to be inadequately controlled in many MHD patients. Uncontrolled SHPT was associated with higher levels of serum Ca, P, and Ca x P product, suggestive of the importance of SHPT management.
Calcium* ; Humans ; Hyperparathyroidism, Secondary ; Kidney Diseases ; Korea ; Parathyroid Hormone ; Phosphorus* ; Renal Dialysis* ; Retrospective Studies

PURPOSE: The Tox-Info system is a poisonous substance information database developed by the Korean National Institute of Food and Drug Safety Evaluation. The aim of this study was to estimate the coverage effectiveness of the Tox-Info system by comparing the toxic substances included in the database with the distribution of the toxic substances implicated in the cases of intoxicated patients presenting to emergency departments. The secondary aim of the study was to propose any additional substances that should be added to the database. METHODS: We retrospectively reviewed the medical records of patients suffering with toxic exposure who had visited any of 12 selected emergency departments in Korea from January 2010 to December 2011. The identified toxic substances were classified into groups including prescription drugs, agricultural chemicals, household products, animals or plants, herbal drugs, and others. We calculated the coverage rate of the Tox-Info database relative to the number of intoxication cases and the type of toxic substances involved. RESULTS: A total of 5,840 intoxicated patient records were collected. Their mean age was 46.6+/-20.5 years and 56.2% were female. Of the total intoxication cases, 87.8% of the identified toxic substances were included in the Tox-Info database, while only 41.6% of all of the types of identified toxic substances were included. Broken down by category, 122 prescription drugs, 15 agricultural chemicals, 12 household products, 14 animals or plants and 2 herbal drugs involved in poisoning cases were not included in the Tox-info database. CONCLUSION: This study demonstrated the clinical usefulness of the Tox-Info system. While 87.8% of the substances involved in the cases were included in the Tox-Info database, the database should be continuously updated in order to include even the most uncommon toxic substances.
Agrochemicals ; Animals ; Emergencies ; Female ; Household Products ; Humans ; Korea ; Medical Records ; Prescription Drugs ; Retrospective Studies ; Stress, Psychological

BACKGROUND/AIMS: The meaning of specialized intestinal metaplasia (SIM) in the diagnosis of Barrett's esophagus (BE) is not clear. This study was designed to determine the clinical significance of SIM in the diagnosis of Barrett's esophagus. MATERIALS AND METHODS: Biopsies were taken from 601 subjects with endoscopically suspected columnar-lined esophagus. Under light microscopy with Alcian-blue stain, SIM was identified. Demographic characteristics, gastroesophageal (GE) reflux symptoms and endoscopic findings were compared between the SIM-present group and the SIM-absent group. RESULTS: Among 601 subjects, 184 (30.6%) were confirmed by pathology to have SIM. Age over 40 years (P<0.001) and a medication history of proton pump inhibitor or H2 blocker were found more frequently in the SIM-present group (P=0.01) than in the SIM-absent group. Any of 7 GE reflux symptoms (heartburn, acid regurgitation, chest pain, hoarseness, globus sensation, cough and epigastric soreness) were more frequent in the SIM-present group than SIM-absent group (P<0.001). Specifically, heartburn, chest pain and cough were significantly more common in the SIM-present group. There was no clinically significant difference associated with endoscopic findings or other clinical characteristics. CONCLUSIONS: When subjects with endoscopically suspected BE are analyzed based on the presence or absence of SIM, the SIM-present group was significantly associated with GE reflux symptoms suggestive of frequent GE reflux. However, the presence of SIM did not correlate with endoscopic findings.
Barrett Esophagus ; Biopsy ; Chest Pain ; Cough ; Esophagus ; Gastroesophageal Reflux ; Heartburn ; Hoarseness ; Light ; Metaplasia ; Microscopy ; Prospective Studies ; Proton Pumps ; Sensation

BACKGROUND/AIMS: Chronic gastritis is a common finding during endoscopy and it is very important to describe it correctly. This study was designed to evaluate the distribution of endoscopic gastritis and the differences according to age, sex or area. MATERIALS AND METHODS: A clinical analysis was conducted on 25,536 subjects who had undergone an upper endoscopy for routine health check-up. Endoscopic gastritis was classified into four types, superficial gastritis, erosive gastritis, atrophic gastritis and intestinal metaplasia. The distribution of the four types of gastritis was evaluated according to sex, age and area. RESULTS: 51.6% of the patients had experienced at least one of the symptoms (epigastric pain or discomfort, soarness, dyspepsia, abdominal pain) on at least a few occasions during the previous year. The incidence of normal gastric finding was 3,593 (14.1%). 21,943 (85.9%) subjects have at least more than one of endoscopic gastritis. The number of cases with superficial gastritis was 7,983 (31.3%), erosive gastritis 6,054 (23.7%), atrophic gastritis 6,918 (27.1%), and intestinal metaplasia 1,181 (7.1%). Erosive gastritis, atrophic gastritis and intestinal metaplasia were more frequent in men than women (P<0.001) and in the older age group (> or =60 years) than younger age group (P<0.001). CONCLUSIONS: The prevalence of endoscopic gastritis was very common, 85.9%. In addition, erosive gastritis, atrophic gastritis and intestinal metaplasia were more frequent in men and in the older age group, which is similar to gastric cancer or peptic ulcer. Cautious regular endoscopic follow-up might be necessary regardless of gastrointestinal symptoms in Korea.
Dyspepsia ; Endoscopy ; Female ; Gastritis ; Gastritis, Atrophic ; Helicobacter pylori ; Humans ; Incidence ; Korea ; Male ; Metaplasia ; Peptic Ulcer ; Prevalence ; Stomach Neoplasms