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The COVID-19 pandemic has posed a significant challenge to global public health. In response, the search for specific antiviral drugs that can effectively treat the disease caused by the SARS-CoV-2 virus has become a priority. While significant progress has been made in this regard, much work remains to address this ongoing crisis effectively. Favipiravir is an antiviral drug initially developed for the treatment of influenza and has received approval for emergency use for COVID-19 in many countries. A better understanding of the biodistribution and pharmacokinetics of Favipiravir in vivo would facilitate the development and translation of clinical antiviral drugs for COVID-19. Herein, we report the evaluation of [18F]Favipiravir in naive mice, transgenic mice models of Alzheimer's disease, and nonhuman primates (NHP) with positron emission tomography (PET). The [18F]Favipiravir was obtained in an overall decay-corrected radiochemical yield of 29% with a molar activity of 25 GBq/µmol at the end of synthesis (EOS). PET imaging in naive mice, transgenic mice models of Alzheimer's disease, and nonhuman primates revealed a low initial brain uptake, followed by a slow washout of [18F]Favipiravir in vivo. The [18F]Favipiravir was eliminated by a combination of hepatobiliary and urinary excretion. The low brain uptake was probably attributed to the low lipophilicity and low passive permeability of the drug. We hope this proof-of-concept study will provide a unique feature to study antiviral drugs using their corresponding isotopologues by PET.
RESUMEN
BACKGROUNDS: Advanced schistosomiasis is the late stage of schistosomiasis, seriously jeopardizing the quality of life or lifetime of infected people. This study aimed to develop a nomogram for predicting mortality of patients with advanced schistosomiasis japonica, taking Dongzhi County of China as a case study. METHOD: Data of patients with advanced schistosomiasis japonica were collected from Dongzhi Schistosomiasis Hospital from January 2019 to July 2022. Data of patients were randomly divided into a training set and validation set with a ratio of 7:3. Candidate variables, including survival outcomes, demographics, clinical features, laboratory examinations, and ultrasound examinations, were analyzed and selected by LASSO logistic regression for the nomogram. The performance of the nomogram was assessed by concordance index (C-index), sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). The calibration of the nomogram was evaluated by the calibration plots, while clinical benefit was evaluated by decision curve and clinical impact curve analysis. RESULTS: A total of 628 patients were included in the final analysis. Atrophy of the right liver, creatinine, ascites level III, N-terminal procollagen III peptide, and high-density lipoprotein were selected as parameters for the nomogram model. The C-index, sensitivity, specificity, PPV, and NPV of the nomogram were 0.97 (95% [CI]: [0.95-0.99]), 0.78 (95% [CI]: [0.64-0.87]), 0.97 (95% [CI]: [0.94-0.98]), 0.78 (95% [CI]: [0.64-0.87]), 0.97 (95% [CI]: [0.94-0.98]) in the training set; and 0.98 (95% [CI]: [0.94-0.99]), 0.86 (95% [CI]: [0.64-0.96]), 0.97 (95% [CI]: [0.93-0.99]), 0.79 (95% [CI]: [0.57-0.92]), 0.98 (95% [CI]: [0.94-0.99]) in the validation set, respectively. The calibration curves showed that the model fitted well between the prediction and actual observation in both the training set and validation set. The decision and the clinical impact curves showed that the nomogram had good clinical use for discriminating patients with high risk of death. CONCLUSIONS: A nomogram was developed to predict prognosis of advanced schistosomiasis. It could guide clinical staff or policy makers to formulate intervention strategies or efficiently allocate resources against advanced schistosomiasis.
RESUMEN
After one-month of oral treatment with traditional Chinese medicine decoction, without using other drugs, the lung inflammatory exudate, pulmonary fibrosis and quality of life of a 61-year-old female patient with corona virus disease 2019 (COVID-19) were significantly improved. No recurrence or deterioration of the patient's condition was found within seven weeks of treatment and follow-up, and no adverse events occurred, indicating that oral Chinese medicine decoction was able to improve the pulmonary inflammation and fibrosis in a patient recovering from COVID-19, but further research is still needed.