Three anti-HIV drugs, ritonavir, lopinavir and darunavir, might have therapeutic effect on coronavirus disease 2019 . In this study, the structure models of two severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proteases, coronavirus endopeptidase C30 (CEP_C30) and papain like viral protease (PLVP), were built by homology modeling. Ritonavir, lopinavir and darunavir were then docked to the models, respectively, followed by energy minimization of the protease-drug complexes. In the simulations, ritonavir can bind to CEP_C30 most suitably, and induce significant conformation changes of CEP_C30; lopinavir can also bind to CEP_C30 suitably, and induce significant conformation changes of CEP_C30; darunavir can bind to PLVP suitably with slight conformation changes of PLVP. It is suggested that the therapeutic effect of ritonavir and lopinavir on COVID-19 may be mainly due to their inhibitory effect on CEP_C30, while ritonavir may have stronger efficacy; the inhibitory effect of darunavir on SARS-CoV-2 and its potential therapeutic effect may be mainly due to its inhibitory effect on PLVP.

Background: This study investigated whether expanding waist circumference (WC) is causally associated with an elevated risk of coronary heart disease (CHD), using a two-sample Mendelian randomization (MR) study through integrating summarized data from genome-wide association study. Methods: The data included in this analysis were mainly from the Genetic Investigation of ANthropometric Traits (GIANT), Consortium and Coronary ArteryDisease Genome wide Replication, and Meta-analysis plus the Coronary Artery Disease (C4D) Genetics (CARDIoGRAMplusC4D) Consortium. Three statistical approaches, inverse-variance weighted (IVW), weighted median, and MR-Egger regression method were conducted to assess the casual relationship. The exposure was WC, measured by 46 single-nucleotide polymorphisms from GIANT and the outcome was the risk of CHD. Then, we used the genetic data from Neale Lab and TAG to infer whether WC causally affected the established risk factors of CHD. Results: The IVW method presented that genetically predicted WC was positively casually associated with CHD (odds ratio [OR]: 1.57, 95% CI = 1.33-1.84; p = 4.81e-08), which was consistent with the result of weighted median and MR-Egger regression. MR-Egger regression indicated that there was no directional horizontal pleiotropy to violate the MR assumption. Additionally, expanded WC was also associated with higher risk of hypertension and diabetes, higher cholesterol, more smoking intensity, and decreased frequency of physical activity. Conclusion: Our analysis provided strong evidence to indicate a causal relationship between WC and increased risk of CHD. K E Y W O R D Scoronary heart disease, Mendelian randomization, waist circumference 2 of 11 | CHEN Et al.

Background There has not been a well-accepted prognostic model to predict the mortality of aortic aneurysm patients in intensive care unit after open surgery repair. Otherwise, our previous study found that anion gap was a prognosis factor for aortic aneurysm patients. Therefore, we wanted to investigate the relationship between anion gap and mortality of aortic aneurysm patients in intensive care unit after open surgery repair. Methods From Medical Information Mart for Intensive Care III, data of aortic aneurysm patients in intensive care unit after open surgery were enrolled. The primary clinical outcome was defined as death in intensive care unit. Univariate analysis was conducted to compare the baseline data in different groups stratified by clinical outcome or by anion gap level. Restricted cubic spline was drawn to find out the association between anion gap level and mortality. Subgroup analysis was then conducted to show the association in different level and was presented as frost plot. Multivariate regression models were built based on anion gap and were adjusted by admission information, severity score, complication, operation and laboratory indicators. Receiver operating characteristic curves were drawn to compare the prognosis ability of anion gap and simplified acute physiology score II. Decision curve analysis was finally conducted to indicate the net benefit of the models. Results A total of 405 aortic aneurysm patients were enrolled in this study and the in-intensive-care-unit (in-ICU) mortality was 6.9%. Univariate analysis showed that elevated anion gap was associated with high mortality (P value < 0.001), and restricted cubic spline analysis showed the positive correlation between anion gap and mortality. Receiver operating characteristic curve showed that the mortality predictive ability of anion gap approached that of simplified acute physiology score II and even performed better in predicting in-hospital mortality (P value < 0.05). Moreover, models based on anion gap showed that 1 mEq/L increase of anion gap improved up to 42.3% (95% confidence interval 28.5–59.8%) risk of death. Conclusions The level of serum anion gap was an important prognosis factor for aortic aneurysm mortality in intensive care unit after open surgery.

and Huang K (2022) Machine learning-based prediction of the post-thrombotic syndrome: Model development and validation study.

Background We aimed to use the Medical Information Mart for Intensive Care III database to build a nomogram to identify 30-day mortality risk of deep vein thrombosis (DVT) patients in intensive care unit (ICU). Methods Stepwise logistic regression and logistic regression with least absolute shrinkage and selection operator (LASSO) were used to fit two prediction models. Bootstrap method was used to perform internal validation. Results We obtained baseline data of 535 DVT patients, 91 (17%) of whom died within 30 days. The discriminations of two new models were better than traditional scores. Compared with simplified acute physiology score II (SAPSII), the predictive abilities of two new models were improved (Net reclassification improvement [NRI] > 0; Integrated discrimination improvement [IDI] > 0; P < 0.05). The Brier scores of two new models in training set were 0.091 and 0.108. After internal validation, corrected area under the curves for two models were 0.850 and 0.830, while corrected Brier scores were 0.108 and 0.114. The more concise model was chosen to make the nomogram. Conclusions The nomogram developed by logistic regression with LASSO model can provide an accurate prognosis for DVT patients in ICU.

Background: Catheter-related thrombosis may lead to catheter infections and failure, further deep venous thrombosis, and pulmonary embolism. Recognizing the risk factors for catheter-related thrombosis is extremely important to inform the development of catheter care guidelines. Methods: Data were collected from a total of 1,532 patients who had undergone venous catheterization, including indwelling catheterization from 19 March 2019 to 30 March 2019 in the Sun Yat-sen Memorial Hospital. The factors for which data were to be collected included the patients’ physical characteristics, catheter-related factors, and catheter care-related factors. Logistic regression analysis, the chi-squared test, Fisher’s exact test, and the t-test were used to analyze the data. Results: Of the 1,532 patients studied, 28 developed intraductal thrombi, and of the factors analyzed, malignancy, a catheterization history, a history of thrombophilia, surgery during the week before catheterization, the catheterization duration, and anticoagulant therapy were significant risk factors associated with catheter-related thrombosis (all p < 0.05). There were no significant associations between the catheter brand, the number of lumens, the insertion direction, or the factors associated with catheter care and catheter-related thrombosis (all p > 0.05). Conclusion: Our study incorporated clear and systematic risk factors associated with catheter-related thrombosis. Malignancy, history of thrombophilia, history of catheterization, surgery during the week before catheterization, and catheterization duration were associated with increased risks of catheter-related thrombosis. Prophylactic anticoagulation was effective for preventing and treating catheter-related thrombosis.

Background It has been observed that cancer and venous thromboembolism (VTE) are associated, but anticancer therapy may violate the causality. Therefore, this study aimed to elucidate the causal relationship of various cancers to VTE using Mendelian randomization (MR). Methods Three MR methods were used to estimate causal effects: Inverse variance weighted (IVW), MR‐Egger and weighted median. Sensitivity analyses included Cochran's Q‐test, MR‐Egger intercept test and MR‐PRESSO. Gene ontology enrichment analysis was performed to elucidate the underlying mechanisms of VTE development in cancer patients. Results The primary IVW approach showed that non‐Hodgkin's lymphoma (NHL) might increase the risk of VTE (odds ratio [OR]: 1.20, 95% confidence interval [95% CI]: 1.00–1.44, p = 0.045), while melanoma possibly reduced the risk of VTE (OR: 0.89, 95% CI: 0.82–0.97, p = 0.006), although there was no significance after adjustment for multiple testing. No association was observed between VTE risk and other site‐specific cancers. Gene ontology enrichment analysis revealed that vitamin D played an important role in the development of VTE in cancer patients. Conclusions Our findings suggested that genetically predicted NHL was associated with higher VTE risk, whereas melanoma had lower VTE risk compared with other site‐specific cancers. Moreover, this study suggested that anticancer therapy and increased extensive examination might play a more important role in VTE development than the nature of cancer.

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