Lindegaardcreech5686

Using mediation analysis, we examined whether any mechanical ventilation, blood gas or hemodynamic parameters could explain the effects of Csr on AKI. Only PEEP mediated the significant but small effect (less than 5%) of Csr on severe AKI. Amprenavir supplier The effects of PEEP, in turn, were not mediated by any other evaluated parameter. Several sensitivity analyses with (I) need of renal replacement therapy (RRT) as an alternative outcome and (II) only patients with Vt less then 8 mL/kg, confirmed our main findings. In trying to validate our DAG assumptions, we confirmed that only ΔP was associated with mortality but not with severe AKI. Conclusions Crs and PEEP are the only respiratory-related variables with a direct causal association in severe AKI. No mechanical ventilator or blood gas parameter mediated the effects of Crs. link2 Approaches reducing Vt and/or ΔP in ARDS can have limited effect on renal protection. 2019 Annals of Translational Medicine. All rights reserved.Background To examine whether MLKL participated in the invasion of radiosensitive nasopharyngeal carcinoma (NPC) cell (CNE-2) and radioresistant NPC cell (CR) through regulating epithelial-mesenchymal transition (EMT). Methods siRNA and CRISPR/Cas9 technique were used to decrease MLKL expression in NPC cell (CNE-2 and CR). Trans-well assay was conducted to evaluate invasion. Gene expression profiling was performed using Human U133 2.0 plus arrays (Affymetrix). Kyoto Encyclopedia of Genes and Genomes (KEGG) was adopted to analyze gene expression profiling. Hub genes at a functional level were accessed by protein-to-protein network (PPI). Quantitative real-time PCR and Western blot were used to access EMT markers. Results Invasion of CR was about 3~fold change higher than that of CNE-2. Silencing MLKL by siRNA inhibited invasion of CR, not CNE-2. Further, depleting MLKL by CRISPR-Cas9 in CR (CR-MLKL KO) also inhibited its invasion. KEGG pathway analysis showed invasion-related pathways were altered, such as adhonal Medicine. All rights reserved.Background According to guidelines, it is recommended that pulmonary nodules be discussed by a multidisciplinary team (MDT); however, the evidence for the effectiveness of MDT is sparse. To demonstrate the importance of the involvement of an MDT for the prediction of small solitary pulmonary nodules, we conducted this retrospective study. Methods The patient database of those who attended our MDT and the electronic medical record system of our hospital was used; we collected all the data from patients found with small solitary pulmonary nodules (≤2 cm), which were suspected as malignant and who received a resection of the nodules. We summarized their characteristics and analyzed them, and then compared the post-operation pathological diagnosis of the patients who attended an MDT to those who did not participate in an MDT during the same period (2017-2019.2). We also collected the follow-up data. Propensity-score-matching was utilized during the process of analysis to get a more reliable conclusion. Results Most of the qualified patients were female. Most of the small solitary pulmonary nodules (≤2 cm) were adenocarcinoma and located on the right upper lobe. There were no differences in the SUV value between malignant nodules and benign nodules. After propensity-score matching, the total positive prediction value of small solitary pulmonary nodules (≤2 cm) without an MDT was 69.4%, while that with MDT was 77.6%; the difference was not significant with a P value of 0.30. The negative predictive value of MDT was 76.2%. Conclusions In developing countries, small solitary pulmonary nodules tend to be more correctly diagnosed with MDT. 2019 Annals of Translational Medicine. All rights reserved.Background The activation of the renin-angiotensin system (RAS) promotes tumor progression. In this study, we aimed to assess whether RAS inhibitors (RASIs) could improve the outcome of hepatocellular carcinoma (HCC) patients with primary hypertension after curative liver resection. Methods Data on 387 consecutive patients with primary hypertension who underwent curative liver resection for HCC were reviewed. The study population was divided into two groups based on the type of anti-hypertensive medications the RASI group (patients using RASIs) and the non-RASI group (patients using other anti-hypertensive drugs but not RASIs). Kaplan-Meier curves, log-rank tests and cox proportional hazards regression models were used to analyze time to recurrence (TTR) and overall survival (OS). Results There were 144 (37.2%) patients in RASI group and 243 (62.8%) in non-RASI group. The preoperative clinicopathological features were comparable between the two groups. Kaplan-Meier curves demonstrated HCC patients with RASIs had a longer TTR and OS than the patients with non-RASIs (both P less then 0.001). On multivariate analysis, RASIs administration was identified as an independent prognostic factor for TTR [hazard ratio (HR) =0.52, 95% confidence interval (CI), 0.38-0.70, P less then 0.001] and OS (HR =0.50, 95% CI, 0.34-0.74, P less then 0.001). Patients in the RASI group had lower rates of extrahepatic metastases than patients in the non-RASI group (2.8% vs. 7.8%, P less then 0.042). Conclusions Targeting the RAS was associated with a reduced risk of recurrence, decreased rate of extrahepatic metastases and prolonged survival of HCC patients with primary hypertension after curative liver resection. 2019 Annals of Translational Medicine. All rights reserved.Background To study the prognostic significance in gallbladder cancer (GBC) patients of the four N stage methods of log odds of positive lymph nodes (LODDS), lymph node ratio (LNR), and N stage in the 7th and 8th editions of the American Joint Committee on Cancer (AJCC), and to establish a prognostic model of GBC based on LODDS. Methods Data of 1,321 patients with GBC who underwent surgical resection of lymph nodes from 2010 to 2014 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. We then randomly divided these data into a training set (n=925) and a validation set (n=396). C-index, Akaike information criterion (AIC), and area under the curve (AUC) were calculated to evaluate the accuracy of LODDS, LNR, and N stage in the 7th and 8th editions of the AJCC. Cox multivariate analysis was performed to determine whether LODDS was an independent prognostic factor, and a nomogram model was established. C-index was used to evaluate the accuracy of the nomogram. A receiver operating characteristic (ROC) curve was drawn and the area under the AUC was calculated to evaluate the accuracy of the nomogram in predicting patients' 1-, 3-, and 5-year overall survival (OS). Results Univariate analysis showed that the four methods were all correlated with OS. Through C-index, AIC and AUC, We found that LODDS had the best accuracy of the four methods. C-index and AUC analysis revealed that the nomogram based on LODDS had excellent prognostic ability. All the results were verified in the validation set. Conclusions LODDS is an independent prognostic factor for GBC patients, and it is the best N stage in the SEER database. This new nomogram-containing LODDS system is a great model to predict the prognosis of GBC patients. 2019 Annals of Translational Medicine. All rights reserved.Background Acute myeloid leukemia (AML) is a heterogeneous clonal disease that prevents normal myeloid differentiation with its common features. Its incidence increases with age and has a poor prognosis. Studies have shown that DNA methylation and abnormal gene expression are closely related to AML. Methods The methylation array data and mRNA array data are from the Gene Expression Omnibus (GEO) database. Through the GEO data, we identified differential genes from tumors and normal samples. Then we performed Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses on these differential genes. Protein-protein interaction (PPI) network construction and module analysis were performed to screen the highest-scoring modules. Next, we used SurvExpress software to analyze the genes in the highest-scoring module and selected potential prognostic genes by univariate and multivariate Cox analysis. Finally, the three genes screened by SurvExpress software were analyzed using the methylation analysis site MethSurv to explore AML associated methylation biomarkers. Results We found three genes that can be used as independent prognostic factors for AML. These three genes are the low expression/methylation genes ATP11A and ITGAM, and the high expression/low methylation gene ZNRF2. Conclusions In this study, we performed a comprehensive analysis of DNA methylation and gene expression to identify key epigenetic genes in AML. 2019 Annals of Translational Medicine. All rights reserved.Background Long-term survival and high-quality life of patients with gliomas depends on the extent of resection (EOR) and the protection of functional white matter fibers. link3 The navigation system provides precise positioning for surgery based on preoperative magnetic resonance imaging (MRI) but the precision decreases when intraoperative brain drift occurs. Ultrasound (US) can support real-time imaging and correct brain shift. The real-time US-MRI multimodal fusion virtual navigation system (UMNS) is a new technique for glioma surgery. In order to obtain a maximum EOR and functional protection, this study aimed to explore the feasibility, efficiency, and safety of real-time UMNS for glioma surgery, and to evaluate the benefit of the new application by UMNS presetting markers between the tumor and functional white matter fiber surgery. Methods A retrospective analysis included 45 patients who underwent glioma surgery, 19 patients with only intraoperative US, and 26 patients with UMNS. A preoperative plan was madenals of Translational Medicine. All rights reserved.Background With the increase of chimeric antigen receptor-modified T (CAR-T) cell therapy, serious complications initiated by CAR-T cells have garnered wide attention. We have previously developed a 4-1BB/CD3-ζ-costimulated CAR-T cells against CD19 (CART19) for adult acute lymphoblastic leukemia (ALL). In this study, a preclinical safety assessment of CART19 was performed on NSG mice, to evaluate the preclinical toxicity along with its efficacy and tissue distribution. Methods A total of 120 NSG mice were used for a combined pharmacodynamics and toxicity study for 56 days. Ninety-six mice of which were single dosed with Raji-Luc (5×105 per animal, i.p.) and different concentrations of CART19 (0.2×107, 0.6×107 and 1.8×107 per animal, i.v.), while the rest were assigned to the Untreated group. Optical intensity of Raji-Luc in mice, clinical symptoms, body mass, hematological analysis, humanized cytokine, lymphocyte subset counting, necropsy and histopathological examinations were performed. In addition, a singltrategies for CAR-T products for the treatment of hematological diseases or leukemia. 2019 Annals of Translational Medicine. All rights reserved.Background We used data from the National Health Insurance Research Database (NHIRD) of Taiwan to determine whether patients who develop posttraumatic parkinsonism (PTP) after traumatic brain injury (TBI) have an increased mortality risk. Methods We analyzed data from the NHIRD of patients aged ≥20 years who had received a diagnosis of and admitted for head injury with TBI (ICD-9-CM 850-854, 959.01) from 2000 to 2012. The TBI cohort was further divided into PTP and posttraumatic non-parkinsonism (PTN) cohorts and compared against a sex-, age-, comorbidity-, and index-date-matched comparison cohort. We calculated the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) of all-cause mortality risk in these cohorts after adjustment for age, sex, and comorbidities. Results There were 23,504 and 744 patients enrolled in the PTN cohort and the PTP cohort. Subsequent parkinsonism happened with an incidence of 3.07% in patients with TBI, and 11.59% in those aged over 65 years. The PTP cohort (aHR =1.67, 95% CI 1.