Cuproptosis-Related 4-Gene Risk Model for Predicting Immunotherapy Drug Response and Prognosis of Kidney Renal Clear Cell Carcinoma.

Background Kidney renal clear cell carcinoma (KIRC) is one of the most common renal malignancies with a high mortality rate. Cuproptosis, a novel form of cell death, is strongly linked to mitochondrial metabolism and is mediated by protein lipoylation, leading to a proteotoxic stress response and cell death. To date, few studies have ellucidated the holistic role of cuproptosis-related genes (CRGs) in the pathogenesis of KIRC.Methods We comprehensively and completely analyzed the RNA sequencing data and corresponding clinical information from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. We screened for differentially expressed CRGs and constructed a prognostic risk model using univariate and multivariate Cox proportional regression analyses. Kaplan-Meier analysis was performed and receiver operating characteristic (ROC) curves were plotted to predict the prognosis of KIRC patients. Functional enrichment analysis was utilized to explore the internal mechanisms. Immune-related functions were analyzed using single-sample gene set enrichment analysis (ssGSEA), tumour immune dysfunction and exclusion (TIDE) scores, and drug sensitivity analysis.Results We established a concise prognostic risk model consisting of four CRGs (DBT, DLAT, LIAS and PDHB) to predict the overall survival (OS) in KIRC patients. The results of the survival analysis indicated a significantly lower OS in the high-risk group as compared to the patients in the low-risk group. The area under the time-dependent ROC curve (AUC) at 1, 3, and 5 year was 0.691, 0.618, and 0.614 in KIRC. Functional enrichment analysis demonstrated that CRGs were significantly enriched in tricarboxylic acid (TCA) cycle-related processes and metabolism-related pathways. Sorafenib, doxorubicin, embelin, and vinorelbine were more sensitive in the high-risk group.Conclusions We constructed a concise CRGs risk model to evaluate the prognosis of KIRC patients and this may be a new direction for the diagnosis and treatment of KIRC.

Performance assessment of medical service for organ transplant department based on diagnosis-related groups: A programme incorporating ischemia-free liver transplantation in China.

Background: In July 2017, the first affiliated hospital of Sun Yat-sen university carried out the world's first case of ischemia-free liver transplantation (IFLT). This study aimed to evaluate the performance of medical services pre- and post-IFLT implementation in the organ transplant department of this hospital based on diagnosis-related groups, so as to provide a data basis for the clinical practice of the organ transplant specialty. Methods: The first pages of medical records of inpatients in the organ transplant department from 2016 to 2019 were collected. The China version Diagnosis-related groups (DRGs) were used as a risk adjustment tool to compare the income structure, service availability, service efficiency and service safety of the organ transplant department between the pre- and post-IFLT implementation periods. Results: Income structure of the organ transplant department was more optimized in the post-IFLT period compared with that in the pre-IFLT period. Medical service performance parameters of the organ transplant department in the post-IFLT period were better than those in the pre-IFLT period. Specifically, case mix index values were 2.65 and 2.89 in the pre- and post-IFLT periods, respectively (p = 0.173). Proportions of organ transplantation cases were 14.16 and 18.27%, respectively (p < 0.001). Compared with that in the pre-IFLT period, the average postoperative hospital stay of liver transplants decreased by 11.40% (30.17 vs. 26.73 days, p = 0.006), and the average postoperative hospital stay of renal transplants decreased by 7.61% (25.23 vs.23.31 days, p = 0.092). Cost efficiency index decreased significantly compared with that in the pre-IFLT period (p < 0.001), while time efficiency index fluctuated around 0.83 in the pre- and post-IFLT periods (p = 0.725). Moreover, the average postoperative hospital stay of IFLT cases was significantly shorter than that of conventional liver transplant cases (p = 0.001). Conclusion: The application of IFLT technology could contribute to improving the medical service performance of the organ transplant department. Meanwhile, the DRGs tool may help transplant departments to coordinate the future delivery planning of medical service.

Overview of Clinical Trials on Type 2 Diabetes Mellitus: A Comprehensive Analysis of the ClinicalTrials.gov Database.

PURPOSE: A better understanding of the current features of type 2 diabetes mellitus (T2DM)-related clinical trials is important for improving designs of clinical trials and identifying neglected areas of research. It was hypothesized that the trial registration policy promoted the designs of T2DM-related trials over the years. Therefore, this study aimed to present a comprehensive overview of T2DM-related clinical trials registered in the ClinicalTrials.gov database. METHODS: T2DM-related clinical trials registered in the ClinicalTrials.gov database were searched and assessed the characteristics of the relevant trials. We searched PubMed and Google Scholar for the publication statuses of the primary completed trials. RESULTS: Overall, 5117 T2DM-related trials were identified for analysis. Of the interventional trials, 71.5% had a primary treatment purpose while only 8.9% were prevention or health service. There were more interventional trials registered prior to patient recruitment between 2012 and 2019 than between 2004 and 2011 (44.6% vs 19.9%, P<0.001). The period between 2012 and 2019 also had more trials that enrolled <100 participants (59.2% vs 50.9%), were single-center studies (60.7% vs 50.6%), had non-randomized allocations (11.3% vs 6.3%), were open-label (49.2% vs 45.6%), and had smaller sample sizes than the period between 2004 and 2011 (all P<0.001). The five-year cumulative publication rates after primary completion of the trials were <40%. CONCLUSION: Although the ClinicalTrials.gov database did not include all clinical trials, the trials registered in the ClinicalTrials.gov database still accounted for most of the clinical studies. Encouragingly, more interventional trials were registered prior to patient recruitment over the years. The majority of T2DM-related clinical trials focused on drug-related treatment, and trials regarding prevention in T2DM should be promoted. More attention should be paid to improve the publication and dissemination of clinical trials results.

Current landscape of type 1 diabetes mellitus-related interventional clinical trials registered on ClinicalTrials.gov: a cross-sectional study.

AIMS: A better understanding of the current features of type 1 diabetes mellitus (T1DM)-related interventional clinical trials is important for improving clinical trial designs and identifying neglected research areas. Therefore, this study aimed to comprehensively assess T1DM-related interventional clinical trials registered in the ClinicalTrials.gov database. METHODS: In this cross-sectional study, T1DM-related clinical trials registered in the ClinicalTrials.gov database were searched on July 1, 2020. The characteristics of the relevant trials were assessed. PubMed and Google Scholar were used to search for publication statuses of primary completed studies. RESULTS: Overall, 1,421 T1DM-related interventional clinical trials were identified for analysis. Of those trials, 509 (35.8%) involved children and 912 (64.2%) involved only adults. Overall, 63.2% of trials enrolled < 50 participants and 61.9% were registered after patient recruitment. Most trials were single-centered (66.0%). The proportions of trials with children were higher than those with only adults with respect to the primary purpose of health service or prevention (13.6% vs. 4.8%), intervention of device (30.8% vs. 23.9%), education or lifestyle (28.9% vs. 11.3%), and dietary supplement (5.7% vs. 2.5%) (all P < 0.01). Only 24.0% of trials had available results after primary completion. The 5-year cumulative publication rate after primary trial completion was < 40%. CONCLUSIONS: T1DM-related interventional clinical trials registered in ClinicalTrials.gov were dominated by small single-center studies. Most trials lacked the availability of results and their respective publications. Large multicenter interventional clinical trials on T1DM are needed, and more attention should be paid to improve the publication and dissemination of clinical trials results.