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75; 95% CI, 0.67-0.83, respectively) and PCa mortality (HR, 0.80; 95% CI 0.69, 0.92) and 0.64; 95% CI, d 0.51-0.81, respectively. The effects were more pronounced in post-diagnostic users combination use of metformin/statins was associated with a 32% reduction in all-cause mortality (95% CI, 0.57-0.80), and 54% reduction in PCa mortality (95% CI, 0.30-0.69). No significant association of metformin alone was observed with either all-cause mortality or PCa mortality. CONCLUSIONS Statin use alone or in combination with metformin was associated with lower all-cause and PCa mortality among high-risk patients, particularly in post-diagnostic settings; further studies are warranted. © 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.Tissue repair is a complex process that requires effective communication and coordination between cells across multiple tissues and organ systems. Two of the initial intracellular signals that encode injury signals and initiate tissue repair responses are calcium and extracellular signal-regulated kinase (ERK). However, calcium and ERK signaling control a variety of cellular behaviors important for injury repair including cellular motility, contractility, and proliferation, as well as the activity of several different transcription factors, making it challenging to relate specific injury signals to their respective repair programs. This knowledge gap ultimately hinders the development of new wound healing therapies that could take advantage of native cellular signaling programs to more effectively repair tissue damage. The objective of this review is to highlight the roles of calcium and ERK signaling dynamics as mechanisms that link specific injury signals to specific cellular repair programs during epithelial and stromal injury repair. We detail how the signaling networks controlling calcium and ERK can now also be dissected using classical signal processing techniques with the advent of new biosensors and optogenetic signal controllers. Finally, we advocate the importance of recognizing calcium and ERK dynamics as key links between injury detection and injury repair programs that both organize and execute a coordinated tissue repair response between cells across different tissues and organs. This article is categorized under Models of Systems Properties and Processes > Mechanistic Models Biological Mechanisms > Cell Signaling Laboratory Methods and Technologies > Imaging Models of Systems Properties and Processes > Organ, Tissue, and Physiological Models. © 2020 The Authors. WIREs Systems Biology and Medicine published by Wiley Periodicals, Inc.AIMS Patients hospitalized for heart failure (HF) are at increased risk for events post-discharge. Mineralocorticoid receptor antagonists (MRAs) improve the clinical course of patients with HF with reduced ejection fraction. We assessed MRA use in high-risk patients following an HF hospitalization to determine rate of MRA prescription, likelihood of drug continuation post-discharge, reasons for discontinuation, and association between MRA maintenance and outcomes. METHODS AND RESULTS Patients admitted to our hospital system between 2011 and 2013 were identified retrospectively through automated search of electronic medical records for appropriate ICD 9 and 10 codes. Patients with left ventricular ejection fraction 1 year of follow-up and no contraindication to MRA use were included. Of 271 patients meeting inclusion criteria, 105 (38.7%) were prescribed an MRA on discharge from index admission. Over a median follow-up of 3.12 ± 0.09 years, 70 (66.7%) continued MRA therapy, while 35 (33.3%) discontinued MRA therapy. Hyperkalemia, which occurred in 43 of the 105 patients (40.1%), was the most frequent cause of MRA discontinuation. Patients who maintained MRA therapy had significantly less all-cause, cardiovascular, and HF hospitalizations and significantly better survival compared with those who discontinued drug. CONCLUSIONS A minority of HF with reduced ejection fraction patients who were eligible for an MRA received them following HF hospitalization and nearly a third of them discontinued drug. Patients who discontinued an MRA were more likely to be hospitalized or die during follow-up. These findings indicate a need for better strategies to increase MRA prescription and maintain therapy following a hospitalization for HF. © 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.OBJECTIVE Follow-up data of patients with spinal metastatic tumors were analyzed to investigate the effect of separation surgery combined with SBRT on clinical outcomes. METHODS The clinical data of 52 patients with spinal metastatic tumors admitted to our hospital from January 2015 to December 2018 were retrospectively analyzed. There were 24 males and 28 females, aged 25-77 years, with an average of 56.7 ± 7.4 years. The separation surgery of all patients was successfully completed and followed up. Frankel neurological function grading, Karnofsky performance scores, VAS scores, Epidural spinal cord compression (ESCC) grading and muscle strength grading were used to assess the patients' condition. Kaplan-Meier analysis and the Log⁃rank test were used to calculate the hazard ratio (HR) and the 95% feasible interval for patients with different ages, genders, and treatments. https://www.selleckchem.com/products/3-aminobenzamide.html The multivariate Cox regression model was used to calculate the risk value HR and the 95% feasible interval in patients undergoing only seses. Frankel neurological function grading and Karnofsky performance scores of these patients were also significantly improved compared with preoperative and postoperative Frankel neurological function grading and Karnofsky performance scores (P less then 0.01). The patients who accepted separation surgery combined with SBRT were followed up for 11-38 months (mean 22.5 ± 10.2 months), and five cases died of primary tumor. Univariate and multivariate analysis showed that separation surgery combined with SBRT was an independent predictor of overall survival rate (OS). CONCLUSIONS Separation surgery combined with SBRT is an effective way to treat spinal metastatic tumors as it not only has smaller surgical trauma, but can also significantly relieve pain, improve nerve function, and relieve spinal cord compression. © 2020 The Authors. Orthopaedic Surgery published by Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.
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