ABSTRACT
BACKGROUND: The aim of this study was to examine risk factors of respiratory complications at the diagnosis and establish an algorithm of clinical management in children and adolescents with mediastinal tumors. METHODS: We retrospectively collected clinical information of all children and adolescents who presented with mediastinal tumors at Saitama Children's Medical Center from 1999 to 2019, including age, sex, pathological diagnosis, eight major clinical symptoms (cough, dyspnea, hypoxia, orthopnea, chest pain, wheeze, superior vena cava syndrome, and stridor), chest computed tomography (CT) findings (tumor location, mediastinal mass ratio, pleural fluid, pericardial effusion, and compression of trachea and bronchi), types of diagnostic procedure and anesthesia, respiratory complications (severe hypoxia, difficult ventilation, respiratory failure, and cardiopulmonary arrest), and clinical outcome. Subsequently, we calculated the risk score for predicting respiratory complications by combining clinical and radiological findings. RESULTS: Of the 57 patients, 7 (12%) developed respiratory complications. Cough, dyspnea, hypoxia, and orthopnea were significantly more common in patients with complications (p = 0.02, p = 0.02, p < 0.01, p = 0.03, respectively). The reduction of percentage of tracheal cross-sectional area (%TCA) and compression of the carina in chest CT were also significantly more common in patients with complications (p < 0.01 and <0.01, respectively). We calculated the risk score of respiratory complications by combining cough, wheeze, stridor, orthopnea, dyspnea, hypoxia, %TCA < 0.5, and compression of the carina. A risk score ≥ 7 showed high predictive accuracy for complications (sensitivity: 100%, specificity: 97.7%, positive likelihood ratio: 43.0). CONCLUSION: The risk score combining clinical symptoms with radiological findings is a promising predictive tool for respiratory complications in children with mediastinal tumors.
Subject(s)
Mediastinal Neoplasms , Superior Vena Cava Syndrome , Adolescent , Humans , Child , Mediastinal Neoplasms/complications , Mediastinal Neoplasms/diagnostic imaging , Case-Control Studies , Retrospective Studies , Respiratory Sounds , Cough , Superior Vena Cava Syndrome/complications , Risk Factors , Dyspnea/complications , Hypoxia/complicationsABSTRACT
The pandemic of coronavirus disease 2019 (COVID-19) has urgently necessitated the development of antiviral agents against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The 3C-like protease (3CLpro) is a promising target for COVID-19 treatment. Here, we report the new class of covalent inhibitors for 3CLpro possessing chlorofluoroacetamide (CFA) as a cysteine reactive warhead. Based on the aza-peptide scaffold, we synthesized the series of CFA derivatives in enantiopure form and evaluated their biochemical efficiencies. The data revealed that 8a (YH-6) with R configuration at the CFA unit strongly blocks the SARS-CoV-2 replication in the infected cells and this potency is comparable to that of nirmatrelvir. The X-ray structural analysis shows that 8a (YH-6) forms a covalent bond with Cys145 at the catalytic center of 3CLpro. The strong antiviral activity and sufficient pharmacokinetics property of 8a (YH-6) suggest its potential as a lead compound for treatment of COVID-19.
ABSTRACT
SARS-CoV-2 precipitates respiratory distress by infection of airway epithelial cells and is often accompanied by acute kidney injury. We report that Kidney Injury Molecule-1/T cell immunoglobulin mucin domain 1 (KIM-1/TIM-1) is expressed in lung and kidney epithelial cells in COVID-19 patients and is a receptor for SARS-CoV-2. Human and mouse lung and kidney epithelial cells express KIM-1 and endocytose nanoparticles displaying the SARS-CoV-2 spike protein (virosomes). Uptake was inhibited by anti-KIM-1 antibodies and TW-37, a newly discovered inhibitor of KIM-1-mediated endocytosis. Enhanced KIM-1 expression by human kidney tubuloids increased uptake of virosomes. KIM-1 binds to the SARS-CoV-2 Spike protein in vitro. KIM-1 expressing cells, not expressing angiotensin-converting enzyme 2 (ACE2), are permissive to SARS-CoV-2 infection. Thus, KIM-1 is an alternative receptor to ACE2 for SARS-CoV-2. KIM-1 targeted therapeutics may prevent and/or treat COVID-19.
