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.

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: Admission blood glucose (BG) level is a predictor of mortality in critically ill patients with various conditions. However, limited data are available regarding this relationship in critically ill patients with cardiovascular diseases according to diabetic status. METHODS: A total of 1,780 patients (595 with diabetes) who were admitted to cardiac intensive care unit (CICU) were enrolled from a single center registry. Admission BG level was defined as maximal serum glucose level within 24 hours of admission. Patients were divided by admission BG level: group 1 (< 7.8 mmol/L), group 2 (7.8–10.9 mmol/L), group 3 (11.0–16.5 mmol/L), and group 4 (≥ 16.6 mmol/L). RESULTS: A total of 105 patients died in CICU (62 non-diabetic patients [5.2%] and 43 diabetic patients [7.9%]; P = 0.105). The CICU mortality rate increased with admission BG level (1.7%, 4.8%, 10.3%, and 18.8% from group 1 to group 4, respectively; P < 0.001). On multivariable analysis, hypertension, mechanical ventilator, continuous renal replacement therapy, acute physiology and chronic health evaluation II (APACHE II) score, and admission BG level significantly influenced CICU mortality in non-diabetic patients (group 1 vs. group 3: hazard ratio [HR], 3.31; 95% confidence interval [CI], 1.47–7.44; P = 0.004; group 1 vs. group 4: HR, 6.56; 95% CI, 2.76–15.58; P < 0.001). However, in diabetic patients, continuous renal replacement therapy and APACHE II score influenced CICU mortality but not admission BG level. CONCLUSION: Admission BG level was associated with increased CICU mortality in critically ill, non-diabetic patients admitted to CICU but not in diabetic patients.
APACHE ; Blood Glucose ; Cardiovascular Diseases ; Critical Care ; Critical Illness ; Diabetes Mellitus ; Humans ; Hypertension ; Intensive Care Units ; Mortality ; Prognosis ; Renal Replacement Therapy ; Ventilators, Mechanical

OBJECTIVES: The shape of the flow-volume (F-V) curve is known to change to showing a prominent plateau as stenosis progresses in patients with tracheal stenosis. However, no study has evaluated changes in the F-V curve according to the degree of bronchial stenosis in patients with unilateral main bronchial stenosis. METHODS: We performed an analysis of F-V curves in 29 patients with unilateral bronchial stenosis with the aid of a graphic digitizer between January 2005 and December 2011. RESULTS: The primary diseases causing unilateral main bronchial stenosis were endobronchial tuberculosis (86%), followed by benign bronchial tumor (10%), and carcinoid (3%). All unilateral main bronchial stenoses were classified into one of five grades (I, < or =25%; II, 26%-50%; III, 51%-75%; IV, 76%-90%; V, >90% to near-complete obstruction without ipsilateral lung collapse). A monophasic F-V curve was observed in patients with grade I stenosis and biphasic curves were observed for grade II-IV stenosis. Both monophasic (81%) and biphasic shapes (18%) were observed in grade V stenosis. After standardization of the biphasic shape of the F-V curve, the breakpoints of the biphasic curve moved in the direction of high volume (x-axis) and low flow (y-axis) according to the progression of stenosis. CONCLUSION: In unilateral bronchial stenosis, a biphasic F-V curve appeared when bronchial stenosis was >25% and disappeared when obstruction was near complete. In addition, the breakpoint moved in the direction of high volume and low flow with the progression of stenosis.
Bronchi ; Carcinoid Tumor ; Constriction, Pathologic* ; Humans ; Lung ; Maximal Expiratory Flow-Volume Curves ; Spirometry ; Tracheal Stenosis ; Tuberculosis

BACKGROUND: Non-invasive positive pressure ventilation (NPPV) ensures adequate gas exchange during bronchoscopy in spontaneously breathing, hypoxemic patients, thus avoiding endotracheal intubation. However, in some patients, endotracheal intubation is eventually required after bronchoscopy. This study investigated the incidence of intubation and predictors of a need for emergency intubation prior to NPPV bronchoscopy initiation. METHODS: On a retrospective basis, we reviewed the medical records of 36 patients (median age, 55 years; interquartile range [IQR], 43~65 years) with acute hypoxemic respiratory failure who required NPPV during bronchoscopy between January 2005 and October 2007. RESULTS: All patients were hypoxemic (median PaO2/FiO2 ratio 155; IQR 90~190), but tolerated bronchoscopy with NPPV support. SOFA score and SAPS II score immediately before NPPV initiation were 4 (3~7) and 36 (30~42), respectively. Seventeen (47%) patients needed endotracheal intubation at a median time of 22 (2~50) hours after bronchoscopy. Patients who needed intubation after bronchoscopy had a higher in-hospital mortality (11 [65%] vs. 4 [21%], p=0.017). Upon multiple logistic regression analysis, the need for intubation after bronchoscopy was independently associated with a PaO2/FiO2 ratio (OR, 0.961; 95% CI, 0.924~0.999; p=0.047) immediately before NPPV initiation for bronchoscopy. CONCLUSION: The severity of the hypoxemia immediately prior to NPPV initiation for bronchoscopy was associated with the need for intubation after bronchoscopy in patients with hypoxemic respiratory failure.
Anoxia ; Bronchoscopy ; Emergencies ; Hospital Mortality ; Humans ; Incidence ; Intubation ; Intubation, Intratracheal ; Logistic Models ; Medical Records ; Positive-Pressure Respiration ; Respiration ; Respiratory Insufficiency ; Retrospective Studies

This study was conducted to observe effects of two methods of setting positive endexpiratory pressure (PEEP) based on the pressure-volume (PV) curve. After lung injury was induced by oleic acid in six mongrel adult dogs, the inflation PV curve was traced and the lower inflection point (LIP) was measured. The 'PEEP(INF)' was defined as LIP+2 cmH2O. After recruitment maneuver to move the lung physiology to the deflation limb of PV curve, decremental PEEP was applied. The lowest level of PEEP that did not result in a significant drop in PaO2 was defined as the 'PEEP(DEF)'. Arterial blood gases, lung mechanics, hemodynamics, and lung volumes (measured on computed tomography during end-expiratory pause) were measured at PEEP of 0 cmH2O, PEEP(INF) and PEEP(DEF) sequentially. The median PEEP(INF) was 13.4 cm H2O (interquartile range, 12.5-14.3) and median PEEP(DEF) was 12.0 cm H2O (10.0-16.5) (p=0.813). PEEP(DEF) was associated with significantly higher PaO2 and lung volumes, and significantly lower shunt fraction and cardiac index when compared to PEEP(INF) (p<0.05). Setting the PEEP based on the deflation limb of the PV curve was useful in improving oxygenation and lung volumes in a canine lung injury model.
Animals ; Dogs ; Lung/pathology ; *Lung Injury ; Lung Volume Measurements/*methods ; Male ; Oxygen/metabolism ; Positive-Pressure Respiration/*methods ; Pressure ; Pulmonary Gas Exchange ; Radiography, Thoracic/methods ; Tomography, X-Ray Computed/*methods

BACKGROUND: The propose of this study was to identify the level of medical technologists' perception of and compliance with hospital infection control guidelines. METHODS: A questionnaire survey was conducted for 65 medical technologists working at three university hospitals in Seoul and Kyunggi areas. The questionnaire was composed of 34 questions on the general characteristics (14 items) of individual responders and about infection control guidelines (20 items). Their response was marked on the basis of 5 points for each question. RESULTS: The mean scores of the perception of and compliance with the infection control guidelines were 4.62+/-0.34 and 3.85+/-0.42, respectively. The female technologists scored significantly higher than did the male counterparts in the participation level of the infection control guidelines (P<0.05). The medical technologists who had participated in an infection control educational program were more likely than those who had not to show a higher compliance level on the infection control guidelines (P<0.05). CONCLUSION: The study demonstrated that the development of infection control educational programs for medical technologists and a supportive policy of the hospital administration should contribute to the prevention of nosocomial infections.
Compliance* ; Cross Infection* ; Female ; Gyeonggi-do ; Hospital Administration ; Hospitals, University ; Humans ; Infection Control ; Male ; Medical Laboratory Personnel ; Seoul ; Surveys and Questionnaires

PURPOSE: To compare the results of open fixation and closed percutaneous pinning in managing Jakob stage II lateral condylar fractures of children's elbow. MATERIALS AND METHODS: Since Febuary 2000, We operated 21 children with Jakob stage II lateral condylar fractures of elbow. Eleven of the 21 were treated with closed percutaneous pinning, open fixation was done to the other 10 children. Each patient was evaluated about range of motion, carrying angle, scar satisfaction and radiologic findings for comparison between closed pinning and open fixation groups. RESULTS: Open fixation group showed 3.8 degrees decrease of elbow motion while closed pinning group showed no significant decrease. Carrying angle and radiologic findings were not different between the two groups. Open fixation group expressed dissatisfaction to their scars (average 5.2 cm) whereas all the patients of closed pinning group were satisfied with their functional and cosmetic outcomes. CONCLUSION: In managing Jakob stage II lateral condyle fractures of children's elbow, closed percutaneous pinning was thought to be superior to open fixation because of the same functional outcome and much better cosmetic results.
Child* ; Cicatrix ; Elbow ; Humans ; Range of Motion, Articular

OBJECTIVE: This study assessed the outcomes of using vascular closure devices following percutaneous transfemoral endovascular procedures in the patients who were treated with heparin, abciximab or thrombolytics (urokinase or t-PA) during the procedures. MATERIALS AND METHODS: From March 28, 2003 to August 31, 2004, we conducted a prospective and randomized study in which 1,676 cases of 1,180 patients were treated with one of the two different closure devices (the collagen plug device was Angio-SealTM; the suture-mediated closure device was The Closer STM) at the femoral access site after instituting percutaneous endovascular procedures. Among the 1,676 cases, 108 cases (the drug group) were treated with heparin only (n = 94), thrombolytics only (n = 10), heparin and thrombolytics (n = 3), or abciximab and thrombolytics (n = 1) during the procedures; 1,568 cases (the no-drug group) were treated without any medication. We compared the efficacy and complications between the two groups. Of the drug group, 42 cases underwent arterial closures with the collagen plug devices and 66 cases underwent arterial closures with the suture-mediated closure devices. We also compared the efficacy and complications between these two groups. RESULTS: The immediate hemostasis rates were 92.9% (1,456/1,568) in the no-drug group and 91.7% (99/108) in the drug group. Early complications occurred in four cases of the drug group. These included two episodes of rebleeding with using the Closer S, which required manual compression for at least 10 minutes, and two episodes of minor oozing with using one Angio-Seal and one Closer S, which required two hours of additional bed rest. There was no late complication. So, the total success rates were 90.8% (1,423/1,568) in the no-drug group and 88.0% (95/108) in the drug group. These results were not significantly different between the two groups (p = 0.34). In the drug group, the difference of the successful hemostasis rate between the collagen plug devices and the suture-mediated devices was also not statistically significant (92.9% vs. 84.8%, respectively; p = 0.21). CONCLUSION: Arterial closure of the femoral access site with using vascular closure devices is both safe and effective, even in the patients who received heparin, abciximab or thrombolytics.
Sutures ; Prospective Studies ; Postoperative Complications ; Middle Aged ; Male ; Immunoglobulin Fab Fragments/pharmacology/*therapeutic use ; Humans ; Hemostatic Techniques/*instrumentation ; Hemostasis/*drug effects ; Fibrinolytic Agents/pharmacology/*therapeutic use ; Femoral Artery/*surgery ; Female ; Collagen ; Anticoagulants/pharmacology/*therapeutic use ; Antibodies, Monoclonal/pharmacology/*therapeutic use

OBJECTIVE: Rapid and effective hemostasis at femoral puncture sites minimizes both the hospital stay and patient discomfort. Therefore, a variety of arterial closure devices have been developed to facilitate the closure of femoral arteriotomy. The objective of this prospective study was to compare the efficacy of two different closure devices; a collagen plug device (Angio-Seal) and a suture-mediated closure device (the Closer S). MATERIALS AND METHODS: From March 28, 2003 to August 31, 2004, we conducted a prospective study in which 1, 676 cases of 1, 180 patients were treated with two different types of closure device. Angio-Seal was used in 961 cases and the Closer S in 715 cases. The efficacy of the closure devices was assessed, as well as complications occurring at the puncture sites. RESULTS: Successful immediate hemostasis was achieved in 95.2% of the cases treated with Angio-Seal, and in 89.5% of the cases treated with the Closer S (p < 0.05). The rates of minor and major complications occurring between the two groups were not significantly different. In the Closer S group, we observed four major complications (0.6%), that consisted of one massive retroperitoneal hemorrhage (surgically explored) and three pseudoaneurysms. In the Angio-Seal group, we observed three major complications (0.3%) that consisted of one femoral artery occlusion, one case of infection treated with intravenous antibiotics and one pseudoaneurysm. CONCLUSION: The use of Angio-Seal was found to be more effective than that of the Closer S with regard to the immediate hemostasis of the femoral puncture sites. However, we detected no significant differences in the rate at which complications occurred.
Treatment Outcome ; *Sutures ; Prospective Studies ; Postoperative Complications ; Middle Aged ; Male ; Humans ; Hemostatic Techniques/*instrumentation ; Femoral Artery/*surgery ; Female ; *Collagen ; Aged ; Adult ; Adolescent