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: Mac-2 binding protein glycosylation isomer (M2BPGi) has been established as a non-invasive biomarker for liver fibrosis. We evaluated the diagnostic efficacy of M2BPGi compared with those of other liver fibrosis markers in liver fibrosis in non-alcoholic fatty liver disease (NAFLD). Methods: We analyzed serum M2BPGi levels in 113 NAFLD patients. A pathologist graded liver fibrosis histopathologically. The diagnostic efficacies of serum M2BPGi and other liver fibrosis markers (aspartate aminotransferase to platelet ratio index, fibrosis index based on four factors, and NAFLD fibrosis score [NFS]) were evaluated using correlation, area under the ROC curve (AUC), logistic regression, and C-statistics. Results: Serum M2BPGi level and other liver fibrosis markers showed a moderate correlation with fibrosis grade. The AUC values of M2BPGi were 0.761, 0.819, 0.866, and 0.900 for diagnosing fibrosis (F) > 0, F > 1, F > 2, and F > 3, respectively. Logistic regression analysis showed M2BPGi as the only independent factor associated with F > 2 and F > 3. Although C-statistics showed that NFS was the best diagnostic factor for F > 2 and F > 3, M2BPGi with NFS had an increased C-statistics value, indicating that it is a better diagnostic model. Conclusions The serum M2BPGi level increased with liver fibrosis severity and could be a good biomarker for diagnosing advanced fibrosis and cirrhosis in NAFLD patients. A well-controlled, prospective study with a larger sample size is needed to validate the diagnostic power of M2BPGi and other fibrosis markers in NAFLD.

PURPOSE: Many recent studies have reported that successful percutaneous coronary intervention (PCI) with drug-eluting stents (DESs) for chronic total occlusion (CTO) has more beneficial effects than failed CTO-PCI; however, there are only limited data available from comparisons of successful CTO-PCI with medical therapy (MT) in the Korean population. MATERIALS AND METHODS: A total of 840 consecutive CTO patients who underwent diagnostic coronary angiography, receiving either PCI with DESs or MT, were enrolled. Patients were divided into two groups according to the treatment assigned. To adjust for potential confounders, propensity score matching (PSM) analysis was performed using logistic regression. Individual major clinical outcomes and major adverse cardiac events, a composite of total death, myocardial infarction (MI), stroke, and revascularization, were compared between the two groups up to 5 years. RESULTS: After PSM, two propensity-matched groups (265 pairs, n=530) were generated, and the baseline characteristics were balanced. Although the PCI group showed a higher incidence of target lesion and vessel revascularization on CTO, the incidence of MI tended to be lower [hazard ratio (HR): 0.339, 95% confidence interval (CI): 0.110 to 1.043, p=0.059] and the composite of total death or MI was lower (HR: 0.454, 95% CI: 0.224 to 0.919, p=0.028), compared with the MT group up to 5 years. CONCLUSION: In this study, successful CTO PCI with DESs was associated with a higher risk of repeat PCI for the target vessel, but showed a reduced incidence of death or MI.
Coronary Angiography ; Drug-Eluting Stents* ; Humans ; Incidence ; Logistic Models ; Myocardial Infarction ; Percutaneous Coronary Intervention* ; Propensity Score ; Stroke

Therapeutic plasma exchange (TPE) is one possible treatment for patients resistant to conventional antithyroid drugs or requiring urgent attention for thyrotoxicosis. We report a 35-yr-old man with thyrotoxicosis, ultimately attributed to Graves' disease in whom antithyroid drug used initially was soon discontinued, due to abnormal liver function, and replaced by Lugol's solution. Three weeks later, an escape phenomenon (to Lugol's solution) was apparent, so we performed TPE to control the thyrotoxicosis. Two courses of TPE by a centrifugal type machine resulted in diminished levels of thyroid hormone levels, which then rebounded after another two courses of membrane filtration type TPE. However, the patient could be treated with radioactive iodine therapy without any complications at present.
Adult ; Antithyroid Agents/adverse effects/therapeutic use ; Cetirizine/adverse effects/therapeutic use ; Graves Disease/*radiotherapy ; Hepatitis B, Chronic/complications ; Humans ; Iodides/therapeutic use ; Iodine Radioisotopes/*therapeutic use ; Male ; Methimazole/adverse effects/therapeutic use ; Plasmapheresis/*methods ; Thyroid Gland/*pathology ; Thyrotoxicosis/*therapy

This paper aims to introduce, summarize, and emphasize the importance of the 'Evidence-Based, Pharmacological Treatment Guideline for Depression in Korea, Revised Edition'. The guideline broadly covers most aspects of the pharmacological treatment of patients in Korea diagnosed with moderate to severe major depression according to the DSM-IV TR. The guideline establishment process involved determining and answering a number of key questions, searching and selecting publications, evaluating recommendations, preparing guideline drafts, undergoing external expert reviews, and obtaining approval. A guideline adaptation process was conducted for the revised edition. The guideline strongly recommends pharmacological treatment considered appropriate to the current clinical situation in Korea, and should be considered helpful when selecting the appropriate pharmacological treatment of patients diagnosed with major depressive disorder. Therefore, the wide distribution of this guideline is recommended.
Antidepressive Agents/*therapeutic use ; Antipsychotic Agents/therapeutic use ; Databases, Factual ; Depression/complications/diagnosis/*drug therapy ; Drug Tolerance ; Evidence-Based Practice ; Humans ; Monoamine Oxidase Inhibitors/therapeutic use ; Neurotransmitter Uptake Inhibitors/therapeutic use ; Placebo Effect ; Psychotic Disorders/complications/drug therapy ; Republic of Korea ; Severity of Illness Index

Necrotizing fasciitis is one of the few true emergencies in orthopedic surgery that has a very high mortality rate unless recognized promptly and treated aggressively. The authors report a case of a patient with necrotizing fasciitis on the thigh that developed secondary to an unrecognized rectal cancer perforation through the short external rotator muscles. Clinicians should always be alert to the potential that rectal cancer perforations can cause necrotizing fasciitis in rare cases.
Emergencies ; Fasciitis ; Fasciitis, Necrotizing ; Humans ; Muscles ; Orthopedics ; Rectal Neoplasms ; Thigh

OBJECTIVES: The aim of this study is to establish Korean pharmacological treatment guidelines for the initial choice of antidepressant for treatment of moderate or severe depression. METHODS: The process for establishment of guidelines involved determination of important key questions, selection of 12 international and domestic clinical practice guidelines for depression, drawing of recommendation drafts, and peer review. RESULTS: Selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), norepinephrine-dopamine reuptake inhibitors (NDRI), and noradrenergic and specific serotonergic antidepressants (NaSSA) were strongly recommended as the first-line antidepressants for treatment of moderate or severe depression. SSRIs were weakly recommended for patients who had problems with tolerability. Consideration of not only efficacy but also provisional adverse effects, drug-drug interactions, history of treatment response, preference, acceptability, cost, comorbid illnesses, and other factors in the choice of first-line antidepressants was strongly recommended. The treatment recommendations for specific clinical features of depression were as follows. SSRIs were weakly recommended for atypical depression. Augmented use of antipsychotics to antidepressants was strongly recommended for psychotic depression. Bupropion and SSRIs were weakly recommended for seasonal depression. CONCLUSION: The results of this study may contribute toward improving the quality of depression treatment by providing clear and definite recommendations for the initial choice of antidepressant for treatment of moderate or severe depression.
Antidepressive Agents ; Antipsychotic Agents ; Bupropion ; Depression ; Humans ; Seasons ; Serotonin Uptake Inhibitors

OBJECTIVES: The aim of this study was to demonstrate the recommendations for antidepressant treatment strategy of dose increment, switching, combination, and augmentation therapy derived from Evidence-Based Korean Pharmacological Treatment Guideline for Depression, Revised Edition. METHODS: The guideline was developed through adaptation of 12 domestic and foreign clinical guidelines for depression, with key questions concerning pharmacotherapy of depression, and drawing of recommendations. RESULTS: The guideline strongly recommended dose increment, switching, and combination and augmentation therapy of antidepressant when patients with depression showed inadequate treatment outcomes from initial antidepressant treatment. The dose increment was strongly recommended when the patients had insufficient response from treatment with tricyclic antidepressants (TCAs), monoamine oxidase inhibitors, selective serotonin reuptake inhibitors (SSRIs), and serotonin and norepinephrine reuptake inhibitors (SNRIs). Switching from SSRI to non-SSRI was also strongly recommended. The combination of initial medication and other classes of antidepressants could benefit from treatment with TCAs, SSRIs, SNRIs, and noradrenergic and specific serotonergic antidepressants. Combination with norepinephrine and dopamine reuptake inhibitors or serotonin-2 antagonist/reuptake inhibitors was weakly recommended. The guideline strongly recommended use of the augmentation strategy of adding lithium or benzodiazepine to initial antidepressants. Augmentation of lamotrigine, T3, methylphenidate, and modafinil was weakly recommended. CONCLUSION: If the initial outcomes of antidepressant therapy are unsatisfactory to the patients the next-step strategies of dose increment, switching, combination and augmentation of antidepressants should be considered after rechecking the patients' drug compliance, dose, and diagnosis.
Antidepressive Agents ; Antidepressive Agents, Tricyclic ; Benzhydryl Compounds ; Benzodiazepines ; Compliance ; Depression* ; Depressive Disorder, Major ; Dopamine Uptake Inhibitors ; Drug Therapy ; Humans ; Lithium ; Methylphenidate ; Monoamine Oxidase Inhibitors ; Norepinephrine ; Serotonin ; Serotonin Uptake Inhibitors ; Triazines

OBJECTIVES: The purpose of this study was to suggest recommendations of antidepressant efficacy compared with placebo, difference in efficacy of antidepressants, and appropriate time of efficacy judgment in antidepressant therapy. METHODS: Using recommendations from 12 international and domestic clinical practice guidelines for depression, drawing of recommendation drafts, and peer review, the executive committee developed the guideline. RESULTS: Tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOI), selective serotonin reuptake inhibitors (SSRI), serotonin and norepinephrine reuptake inhibitors (SNRIs), norepinephrine and specific serotonergic antidepressants (NaSSAs), norepinephrine and dopamine reuptake inhibitors (NDRIs), and serotonin antagonist and reuptake inhibitors (SARIs) were strongly recommended as having antidepressant efficacy compared with placebo. Difference in efficacy of antidepressants was as follows. TCAs, MAOI, SSRI, SNRIs, and NaSSAs were strongly recommended, however, NDRIs, SARIs were weakly recommended. If there was no or minimal improvement with treatment, appropriate time of efficacy judgment in antidepressant therapy was estimated to be after two to four weeks. CONCLUSION: We hope that the results of this study will be helpful in encouraging the optimal treatment by understanding antidepressant efficacy compared with placebo, difference in efficacy of antidepressants, and appropriate time of efficacy judgment in antidepressant therapy.
Antidepressive Agents* ; Antidepressive Agents, Tricyclic ; Depression* ; Depressive Disorder, Major ; Dopamine Uptake Inhibitors ; Judgment* ; Monoamine Oxidase Inhibitors ; Norepinephrine ; Peer Review ; Serotonin ; Serotonin Uptake Inhibitors