Background: Barriers to treatment with intravenous thrombolysis (IVT) for patients with acute ischemic stroke (AIS) in South Korea remain incompletely characterized. We analyze a nationwide prospective cohort to determine patient-level features associated with delayed presentation and non-treatment of potential IVT-eligible patients. Methods: We identified consecutive patients with AIS from 01/2011 to 08/2023 from a multicenter and prospective acute stroke registry in Korea. Patients were defined as IVT candidates if they presented within 4.5 hours from the last known well, had no lab evidence of coagulopathy, and had National Institute of Health Stroke Scale (NIHSS) ≥ 4. Multivariable generalized linear mixed regression models were used to investigate the associations between their characteristics and the IVT candidates or the use of IVT among the candidates. Results: Among 84,103 AIS patients, 41.0% were female, with a mean age of 69 ± 13 years and presentation NIHSS of 4 [interquartile range, 1–8]. Out of these patients, 13,757 (16.4%) were eligible for IVT, of whom 8,179 (59.5%) received IVT. Female sex (adjusted risk ratio [RR], 0.90; 95% confidence interval [CI], 0.86–0.94) and lower years of education (adjusted RR, 0.90; 95% CI, 0.84–0.97 for 0–3 years, compared to ≥ 13 years) were associated with a decreased likelihood of presenting as eligible for IVT after AIS; meanwhile, young age (adjusted RR, 1.12; 95% CI, 1.01–1.24 for ≤ 44 years, compared to 75–84 years) was associated with an increased likelihood of being an IVT candidate. Among those who were eligible for IVT, only age was significantly associated with the use of IVT (adjusted RR, 1.09; 95% CI, 1.03–1.16 for age 65–74 and adjusted RR, 0.83; 95% CI, 0.76–0.90 for ≥ 85 years, respectively). Conclusion Most patients with AIS present outside IVT eligibility in South Korea, and only 60% of eligible patients were ultimately treated. We identified increased age, female sex and lower education as key features on which to focus interventions for improving IVT utilization.

Background: Healthcare-associated infections impose a significant burden on antibiotic usage, healthcare expenditures, and morbidity. Therefore, it is crucial to revise policies to minimize such losses. This nationwide survey aimed to evaluate infection prevention and control (IPC) components in healthcare facilities and encourage improvements in acute care hospitals with inadequate infection prevention settings. This study aims to enhance the infection control capabilities of healthcare facilities. Methods: From December 27, 2021, to May 13, 2022, we conducted a survey of 1,767 acute care hospitals in the Republic of Korea. A survey was conducted to evaluate the infection control components in 1,767 acute care hospitals. Infection control officers provided direct responses to a systematically developed questionnaire. Subsequently, 10% of the respondents were randomly selected for the site investigation. Results: Overall, 1,197 (67.7%) hospitals responded to the online survey. On-site investigations were conducted at 125 hospitals. Hospitals with ≥ 150 beds are advised to have an IPC team under Article 3 of the Medical Service Act; however, only 87.0% (598/687) of hospitals with ≥ 100 beds had one. Conversely, 22.7% (116/510) of hospitals with < 100 beds had an IPC team. Regulations for hand hygiene, waste management, healthcare worker protection and safety, environmental cleaning, standard precautions, and prevention of the transmission of multidrug-resistant pathogens were present in 84.2%, 80.1%, 77.4%, 76.2%, 75.8%, and 63.5% of the hospitals, respectively. Hospitals with < 100 beds had low availability of all categories of standard operating procedures. Conclusion This study is the first national survey of acute care hospitals in the Republic of Korea. The data presented in the current study will improve the understanding of IPC status and will help establish a survey system. Our survey provides a basis for improving policies related to IPC in healthcare facilities.

Objective: To establish local diagnostic reference levels (DRLs) for pediatric neck CT based on age, weight, and water-equivalent diameter (WED) across multiple university hospitals in South Korea. Materials and Methods: This retrospective study analyzed pediatric neck CT examinations from nine university hospitals, involving patients aged 0–18 years. Data were categorized by age, weight, and WED, and radiation dose metrics, including volume CT dose index (CTDIvol) and dose length product, were recorded. Data retrieval and analysis were conducted using a commercially available dose-management system (Radimetrics, Bayer Healthcare). Local DRLs were established following the International Commission on Radiological Protection guidelines, using the 75th percentile as the reference value. Results: A total of 1159 CT examinations were analyzed, including 169 scans from Institution 1, 132 from Institution 2, 126 from Institution 3, 129 from Institution 4, 128 from Institution 5, 105 from Institution 6, 162 from Institution 7, 127 from Institution 8, and 81 from Institution 9. Radiation dose metrics increased with age, weight, and WED, showing significant variability both within and across institutions. For patients weighing less than 10 kg, the DRL for CTDIvol was 5.2 mGy. In the 10–19 kg group, the DRL was 5.8 mGy; in the 20–39 kg group, 7.6 mGy; in the 40–59 kg group, 11.0 mGy; and for patients weighing 60 kg or more, 16.2 mGy. DRLs for CTDIvol by age groups were as follows: 5.3 mGy for infants under 1 year, 5.7 mGy for children aged 1–4 years, 7.6 mGy for ages 5–9 years, 11.2 mGy for ages 10–14 years, and 15.6 mGy for patients 15 years or older. Conclusion Local DRLs for pediatric neck CT were established based on age, weight, and WED across nine university hospitals in South Korea.

Background: Chronic pain significantly affects daily activities, mental health, and the interpersonal relationships of patients. Consequently, physicians use various treatments to manage pain. This study investigated the perceptions of treatment, accompanying symptoms, and other problems in patients with chronic pain. Methods: The authors enrolled patients with chronic pain from 19 university hospitals in South Korea. Data was collected on age, gender, diagnosis, disease duration, severity of pain, perception of pain treatment, and accompanying symptoms or problems using an anonymous survey comprising 19 questions. Results: In total, 833 patients with chronic pain completed the survey, and 257 (31.0%) and 537 (64.5%) patientsexpressed concerns about the potential adverse effects of medication and opioid addiction, respectively. Personalitychanges such as irritability or anger were the most frequent accompanying symptoms in 507 (63.8%) patients, followed by depression and sleep disturbance in 462 (58.1%) and 450 (54.5%) patients, respectively. Depression (P = 0.001) and anxiety (P = 0.029) were more common among women, whereas divorce (P = 0.016), family conflict (P < 0.001), unemployment (P < 0.001), suicide attempts (P < 0.001), and restrictions on economic activity (P < 0.001) were more common among men. The frequency of accompanying symptoms, except for suicidal ideation,was higher in the younger patients aged ≤ 40 years than in the older patients aged > 40 years. Conclusions Many patients with chronic pain had concerns about adverse effects or medication tolerance and experienced anxiety, depression, or sleep disturbances. The prevalence of accompanying problems varies according to age and gender.

Auricular vagus nerve stimulation (aVNS) is one of the promising neuromodulation techniques due to its non-invasiveness, convenience, and effectiveness. aVNS has been suggested as a potential treatment for neurodegenerative diseases showing impaired cerebrospinal fluid (CSF) dynamics. Improving CSF flow has been proposed as a key mechanism of the therapeutic effect on neurodegenerative diseases. However, aVNS parameters have been set empirically and the effective parameter that maximize the effect remains elusive. Here we show that 30 minutes of low-frequency aVNS increased arterial vasomotion events and enhanced cortical CSF influx along the branches of middle cerebral arteries. By using in vivo two photon imaging or widefield fluorescence microscopy with plasma and CSF tracers for visualizing blood vessels and perivascular spaces, arterial vasomotion and cortical CSF influx dynamics were acquired. The low-frequency (2 Hz) aVNS, but not middleand high-frequency (40 and 100 Hz) aVNS, significantly increased the number of vasomotion events compared to the sham group. Accordingly, in the CSF imaging, 2 Hz of aVNS markedly enhanced the CSF influx. Our findings demonstrate that lowfrequency aVNS is the effective parameter in respect to modulating vasomotion and CSF influx, resulting in brain clearance effect.

Background: Kelch-like ECH-associated protein 1 (KEAP1)–nuclear factor erythroid- 2-related factor 2 (NRF2) pathway is a major regulator protecting cells from oxidative and metabolic stress. Studies have revealed that this pathway is involved in mediating resistance to cytotoxic chemotherapy and immunotherapy; however, its implications in oncogene-addicted tumors are largely unknown. This study aimed to elucidate whether this pathway could be a potential therapeutic target for epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer. Methods: We measured the baseline expression of NRF2 using EGFR-mutant parental cells and acquired gefitinib resistant cells. We investigated whether NRF2 inhibition affected cell death in vitro and tumor growth in vivo using a xenograft mouse model, and compared the transcriptional changes before and after NRF2 inhibition. Results: Baseline NRF2 expression was enhanced in PC9 and PC9 with gefitinib resistance (PC9/GR) cells than in other cell lines, with a more prominent expression in PC9/ GR. The NRF2 inhibitor induced NRF2 downregulation and cell death in a dose-dependent manner. Cotreatment with an NRF2 inhibitor enhanced osimertinib-induced cell death in vitro, and potentiated tumor growth inhibition in a PC9/GR xenograft model. Finally, RNA sequencing revealed that NRF2 inhibition resulted in the altered expression of multiple genes involved in various signaling pathways. Conclusion We identified that NRF2 inhibition enhanced cell death and inhibited tumor growth in tyrosine kinase inhibitor (TKI)-resistant lung cancer with EGFR-mutation. Thus, NRF2 modulation may be a novel therapeutic strategy to overcome the resistance to EGFR-TKIs.

Purpose: This study aimed to evaluate the prognosis of the not evaluated (NE) group by comparing it with the lost to follow-up (LTFU) group among patients with multidrug/rifampin-resistant tuberculosis (MDR/RR-TB). Materials and Methods: This was a retrospective longitudinal follow-up study using an integrated database constructed by data linkage of the three national databases. This database included 7226 cases of MDR/RR-TB notified between 2011 and 2017 in South Korea. Results: Among the 7226 MDR/RR-TB cases, 730 (10.1%) were classified as LTFU group, and 353 (4.9%) as NE group. When comparing NE group with LTFU group, there were no significant differences in the all-cause mortality rate (18.1% vs. 13.8%, p=0.065), median time to death [404 days (interquartile range, IQR 46–850) vs. 443 days (IQR 185–1157), p=0.140], and retreatment rate (26.9% vs.22.2%, p=0.090). After adjusting for potential confounders, the adjusted hazard ratio (aHR) for all-cause mortality (aHR 1.11; 95% confidence interval 0.80-1.53; p=0.531) in NE group was not significantly different than that in LTFU group. Among retreated cases, NE group had a higher treatment success rate (57.9% vs 43.8%, p=0.029) and a lower LTFU rate (11.6% vs 38.3%, p<0.001) compared to LTFU group. Conclusion NE group had an unfavorable outcome comparable to LTFU group, suggesting undetected cases of LTFU or deaths during the referral process. Establishing an efficient patient referral system would contribute to reducing the incidence of NE cases.

Background: and Purpose Previous research on patients with acute ischemic stroke (AIS) has shown a 0.5% incidence of major gastrointestinal bleeding (GIB) requiring blood transfusion during hospitalization. The existing literature has insufficiently explored the long-term incidence in this population despite the decremental impact of GIB on stroke outcomes. Methods: We analyzed the data from a cohort of patients with AIS admitted to 14 hospitals as part of a nationwide multicenter prospective stroke registry between 2011 and 2013. These patients were followed up for up to 6 years. The occurrence of major GIB events, defined as GIB necessitating at least two units of blood transfusion, was tracked using the National Health Insurance Service claims data. Results: Among 10,818 patients with AIS (male, 59%; mean age, 68±13 years), 947 (8.8%) experienced 1,224 episodes of major GIB over a median follow-up duration of 3.1 years. Remarkably, 20% of 947 patients experienced multiple episodes of major GIB. The incidence peaked in the first month after AIS, reaching 19.2 per 100 person-years, and gradually decreased to approximately one-sixth of this rate by the 2nd year with subsequent stabilization. Multivariable analysis identified the following predictors of major GIB: anemia, estimated glomerular filtration rate <60 mL/min/1.73 m2 , and a 3-month modified Rankin Scale score of ≥4. Conclusion Patients with AIS are susceptible to major GIB, particularly in the first month after the onset of AIS, with the risk decreasing thereafter. Implementing preventive strategies may be important, especially for patients with anemia and impaired renal function at stroke onset and those with a disabling stroke.

Background: Complete revascularization has demonstrated better outcomes in patients with acute myocardial infarction (AMI) and multivessel disease. However, in the case of left main (LM) culprit lesion AMI with multivessel disease, there is limited evidence to suggest that complete revascularization is better. Methods: We reviewed 16,831 patients in the Korea Acute Myocardial Infarction Registry who were treated from July 2016 to June 2020, and 399 patients were enrolled with LM culprit lesion AMI treated with percutaneous coronary intervention. We categorized the patients as those treated with complete revascularization (n=295) or incomplete revascularization (n=104). The study endpoint was major adverse cardiac and cerebrovascular events (MACCE), a composite of all-cause death, myocardial infarction, ischemia-driven revascularization, stent thrombosis, and stroke. We performed propensity score matching (PSM) and analyzed the incidence of MACCE at 1 year. Results: After PSM, the two groups were well balanced. There was no significant difference between the two groups in MACCE at 1 year (12.1% vs. 15.2%; hazard ratio, 1.28; 95% confidence interval, 0.60–2.74; p=0.524) after PSM. The components of MACCE and major bleeding were also not significantly different. Conclusion There was no significant difference in clinical outcomes between the groups treated with complete or incomplete revascularization for LM culprit lesion AMI with multivessel disease.