Viral load and the duration of viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important determinants of the transmission of coronavirus disease 2019.In this study, we examined the effects of viral doses on the lung and spleen of K18-hACE2 transgenic mice by temporal histological and transcriptional analyses. Approximately, 1×105 plaque-forming units (PFU) of SARS-CoV-2 induced strong host responses in the lungs from 2 days post inoculation (dpi) which did not recover until the mice died, whereas responses to the virus were obvious at 5 days, recovering to the basal state by 14 dpi at 1×102 PFU. Further, flow cytometry showed that number of CD8+ T cells continuously increased in 1×102 PFU-virusinfected lungs from 2 dpi, but not in 1×105 PFU-virus-infected lungs. In spleens, responses to the virus were prominent from 2 dpi, and number of B cells was significantly decreased at 1×105PFU; however, 1×102 PFU of virus induced very weak responses from 2 dpi which recovered by 10 dpi. Although the defense responses returned to normal and the mice survived, lung histology showed evidence of fibrosis, suggesting sequelae of SARS-CoV-2 infection. Our findings indicate that specific effectors of the immune response in the lung and spleen were either increased or depleted in response to doses of SARS-CoV-2. This study demonstrated that the response of local and systemic immune effectors to a viral infection varies with viral dose, which either exacerbates the severity of the infection or accelerates its elimination.

Objective: : Collateral circulation is associated with the differential treatment effect of endovascular thrombectomy (EVT) in acute ischemic stroke. We aimed to verify the ability of the collateral map to predict futile EVT in patients with acute anterior circulation ischemic stroke. Methods: : This secondary analysis of a prospective observational study included data from participants underwent EVT for acute ischemic stroke due to occlusion of the internal carotid artery and/or the middle cerebral artery within 8 hours of symptom onset. Multiple logistic regression analyses were conducted to identify independent predictors of futile recanalization (modified Rankin scale score at 90 days of 4–6 despite of successful reperfusion). Results: : In a total of 214 participants, older age (odds ratio [OR], 2.40; 95% confidence interval [CI], 1.56 to 3.67; p<0.001), higher baseline National Institutes of Health Stroke Scale (NIHSS) scores (OR, 1.12; 95% CI, 1.04 to 1.21; p=0.004), very poor collateral perfusion grade (OR, 35.09; 95% CI, 3.50 to 351.33; p=0.002), longer door-to-puncture time (OR, 1.08; 95% CI, 1.02 to 1.14; p=0.009), and failed reperfusion (OR, 3.73; 95% CI, 1.30 to 10.76; p=0.015) were associated with unfavorable functional outcomes. In 184 participants who achieved successful reperfusion, older age (OR, 2.30; 95% CI, 1.44 to 3.67; p<0.001), higher baseline NIHSS scores (OR, 1.12; 95% CI, 1.03 to 1.22; p=0.006), very poor collateral perfusion grade (OR, 4.96; 95% CI, 1.42 to 17.37; p=0.012), and longer door-to-reperfusion time (OR, 1.09; 95% CI, 1.03 to 1.15; p=0.003) were associated with unfavorable functional outcomes. Conclusion : The assessment of collateral perfusion status using the collateral map can predict futile EVT, which may help select ineligible patients for EVT, thereby potentially reducing the rate of futile EVT.

Background: Current international guidelines recommend against deep sedation as it is associated with worse outcomes in the intensive care unit (ICU). However, in Korea the prevalence of deep sedation and its impact on patients in the ICU are not well known. Methods: From April 2020 to July 2021, a multicenter, prospective, longitudinal, noninterventional cohort study was performed in 20 Korean ICUs. Sedation depth extent was divided into light and deep using a mean Richmond Agitation–Sedation Scale value within the first 48 hours. Propensity score matching was used to balance covariables; the outcomes were compared between the two groups. Results: Overall, 631 patients (418 [66.2%] and 213 [33.8%] in the deep and light sedation groups, respectively) were included. Mortality rates were 14.1% and 8.4% in the deep and light sedation groups (P = 0.039), respectively. Kaplan-Meier estimates showed that time to extubation (P < 0.001), ICU length of stay (P = 0.005), and death P = 0.041) differed between the groups. After adjusting for confounders, early deep sedation was only associated with delayed time to extubation (hazard ratio [HR], 0.66; 95% confidence inter val [CI], 0.55– 0.80; P < 0.001). In the matched cohort, deep sedation remained significantly associated with delayed time to extubation (HR, 0.68; 95% 0.56–0.83; P < 0.001) but was not associated with ICU length of stay (HR, 0.94; 95% CI, 0.79–1.13; P = 0.500) and in-hospital mortality (HR, 1.19; 95% CI, 0.65–2.17; P = 0.582). Conclusion In many Korean ICUs, early deep sedation was highly prevalent in mechanically ventilated patients and was associated with delayed extubation, but not prolonged ICU stay or in-hospital death.

Background: Administration of adequate antibiotics is crucial for better outcomes in sepsis. Because no uniform tool can accurately assess the risk of multidrug-resistant (MDR) pathogens, a local antibiogram is necessary. We aimed to describe the antibiogram of MDR bacteria based on locations of sepsis onset in South Korea. Methods: We performed a prospective observational study of adult patients diagnosed with sepsis according to Sepsis-3 from 19 institutions (13 tertiary referral and 6 universityaffiliated general hospitals) in South Korea. Patients were divided into four groups based on the respective location of sepsis onset: community, nursing home, long-term-care hospital, and hospital. Along with the antibiogram, risk factors of MDR bacteria and drug-bug match of empirical antibiotics were analyzed. Results: MDR bacteria were detected in 1,596 (22.7%) of 7,024 patients with gram-negative predominance. MDR gram-negative bacteria were more commonly detected in long-termcare hospital- (30.4%) and nursing home-acquired (26.3%) sepsis, whereas MDR grampositive bacteria were more prevalent in hospital-acquired (10.9%) sepsis. Such findings were consistent regardless of the location and tier of hospitals throughout South Korea. Patients with long-term-care hospital-acquired sepsis had the highest risk of MDR pathogen, which was even higher than those with hospital-acquired sepsis (adjusted odds ratio, 1.42; 95% confidence interval, 1.15–1.75) after adjustment of risk factors. The drug-bug match was lowest in patients with long-term-care hospital-acquired sepsis (66.8%). Conclusion Gram-negative MDR bacteria were more common in nursing home- and long-term-care hospital-acquired sepsis, whereas gram-positive MDR bacteria were more common in hospital-acquired settings in South Korea. Patients with long-term-care hospitalacquired sepsis had the highest the risk of MDR bacteria but lowest drug-bug match of initial antibiotics. We suggest that initial antibiotics be carefully selected according to the onset location in each patient.

Purpose: The aim of this study was to investigate the efficacy of various epidermal growth factor receptor (EGFR)–tyrosine kinase inhibitors (TKIs) plus bevacizumab in advanced EGFR-mutant lung adenocarcinoma patients. Materials and Methods: From August 2016 to October 2020, we enrolled advanced lung adenocarcinoma patients harboring exon 19 deletion or L858R receiving gefitinib, erlotinib and afatinib plus bevacizumab as the first-line treatment for the purposes of analysis. Results: A total of 36 patients were included in the final analysis. Three patients received gefitinib, 17 received erlotinib, and 16 received afatinib combined with bevacizumab as the first-line treatment. The objective response rate was 77.8%, and disease control rate was 94.4%. The overall median progression-free survival (PFS) was 16.4 months, while the median PFS was 17.1 months in patients with exon 19 deletion, and 16.2 months in patients with L858R mutation (p=0.311). Regarding the use of different EGFR-TKIs, the median PFS was 17.1 months in the erlotinib group and 21.6 months in the afatinib group (p=0.617). In patients with brain metastasis at baseline, the median PFS was 18.9 months in the erlotinib group and 16.4 months in the afatinib group (p=0.747). Amongst patients harboring exon 19 deletion, the median PFS was 16.2 months in the erlotinib group and not-reached in the afatinib group (p=0.141). In patients with L858R mutation, the median PFS was 18.9 months in the erlotinib group and 16.2 months in the afatinib group (p=0.481). Conclusion Our research demonstrates that not only erlotinib combined with bevacizumab, but also afatinib plus bevacizumab as first-line treatment, provides solid clinical efficacy in advanced EGFR-mutant lung adenocarcinoma patients.

Background: As the number of large-scale studies involving multiple organizations producing data has steadily increased, an integrated system for a common interoperable format is needed. In response to the coronavirus disease 2019 (COVID-19) pandemic, a number of global efforts are underway to develop vaccines and therapeutics. We are therefore observing an explosion in the proliferation of COVID-19 data, and interoperability is highly requested in multiple institutions participating simultaneously in COVID-19 pandemic research. Results: In this study, a laboratory information management system (LIMS) approach has been adopted to systemically manage various COVID-19 non-clinical trial data, including mortality, clinical signs, body weight, body temperature, organ weights, viral titer (viral replication and viral RNA), and multiorgan histopathology, from multiple institutions based on a web interface. The main aim of the implemented system is to integrate, standardize, and organize data collected from laboratories in multiple institutes for COVID-19 non-clinical efficacy testings. Six animal biosafety level 3 institutions proved the feasibility of our system. Substantial benefits were shown by maximizing collaborative high-quality non-clinical research. Conclusions This LIMS platform can be used for future outbreaks, leading to accelerated medical product development through the systematic management of extensive data from non-clinical animal studies.

Background: The purpose of the study was to translate and linguistically validate a Korean language version of the PROMIS (K-PROMIS) for the six profile adult domains: Fatigue, Pain Intensity, Pain Interference, Physical Function, Sleep Disturbance, and Ability to Participate in Social Roles and Activities. Methods: A total of 268 items were translated into Korean according to the Functional Assessment of Chronic Illness Therapy multilingual translation methodology. Participants first completed approximately 27 to 35 items and were then interviewed to evaluate the conceptual equivalence of the translation to the original English language source.The K-PROMIS items that met the a priori threshold of ≥ 20% of respondents with comprehension difficulties in the cognitive interview. Results: 54 of the 268 items were identified as difficult items to comprehend for at least 20% of respondents in Round 1. The most frequently identified K-PROMIS domain on difficult items to comprehend was the Physical function (24.5%). Most items with linguistic difficulties were Fatigue and Physical function. Cultural difficulties were only included the Physical function and Ability to Participate in Social Roles and Activities domains. 25 of 54 items were slightly revised, and then these revised items were tested with additional six participants in Round 2, and most participants had no problems to understand modified items. Conclusion The six profile adult domains of K-PROMIS have been linguistically validated.Further psychometric validation of the K-PROMIS items will provide additional information of meaningful outcomes for chronic disease and clinical setting.

Background: The purpose of the study was to translate and linguistically validate a Korean language version of the PROMIS (K-PROMIS) for the six profile adult domains: Fatigue, Pain Intensity, Pain Interference, Physical Function, Sleep Disturbance, and Ability to Participate in Social Roles and Activities. Methods: A total of 268 items were translated into Korean according to the Functional Assessment of Chronic Illness Therapy multilingual translation methodology. Participants first completed approximately 27 to 35 items and were then interviewed to evaluate the conceptual equivalence of the translation to the original English language source.The K-PROMIS items that met the a priori threshold of ≥ 20% of respondents with comprehension difficulties in the cognitive interview. Results: 54 of the 268 items were identified as difficult items to comprehend for at least 20% of respondents in Round 1. The most frequently identified K-PROMIS domain on difficult items to comprehend was the Physical function (24.5%). Most items with linguistic difficulties were Fatigue and Physical function. Cultural difficulties were only included the Physical function and Ability to Participate in Social Roles and Activities domains. 25 of 54 items were slightly revised, and then these revised items were tested with additional six participants in Round 2, and most participants had no problems to understand modified items. Conclusion The six profile adult domains of K-PROMIS have been linguistically validated.Further psychometric validation of the K-PROMIS items will provide additional information of meaningful outcomes for chronic disease and clinical setting.

Objective: To investigate differences in the heritability of skeletodental characteristics between twin pairs with skeletal Class I and Class II malocclusions. Methods: Forty Korean adult twin pairs were divided into Class I (C-I) group (0° ≤ angle between point A, nasion, and point B [ANB]) ≤ 4°; mean age, 40.7 years) and Class II (C-II) group (ANB > 4°; mean age, 43.0 years). Each group comprised 14 monozygotic and 6 dizygotic twin pairs. Thirty-three cephalometric variables were measured using lateral cephalograms and were categorized as the anteroposterior, vertical, dental, mandible, and cranial base characteristics. The ACE model was used to calculate heritability (A > 0.7, high heritability). Thereafter, principal component analysis (PCA) was performed. Results: Twin pairs in C-I group exhibited high heritability values in the facial anteroposterior characteristics, inclination of the maxillary and mandibular incisors, mandibular body length, and cranial base angles. Twin pairs in C-II group showed high heritability values in vertical facial height, ramus height, effective mandibular length, and cranial base length. PCA extracted eight components with 88.3% in the C-I group and seven components with 91.0% cumulative explanation in the C-II group. Conclusions Differences in the heritability of skeletodental characteristics between twin pairs with skeletal Class I and II malocclusions might provide valuable information for growth prediction and treatment planning.