Frontiers in pharmacology
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Frontiers in pharmacology · Jan 2019
Comparative Efficacy of Preoperative, Postoperative, and Perioperative Treatments for Resectable Colorectal Liver Metastases: A Network Meta-Analysis.
Background: Several treatment strategies are used for management of resectable colorectal liver metastases. We performed a Bayesian network meta-analysis to compare preoperative, postoperative, or perioperative treatments, identifying the optimal approach. Methods: We searched reports of randomized controlled trials through the relevant databases. ⋯ According to the results for the rank probabilities of the 11 treatments, the combination of HAI and bevacizumab plus postoperative CT showed the highest probability of benefitting OS, and PHRAC plus preoperative CT was most likely to benefit DFS. Conclusions: The combination of HAI and bevacizumab plus postoperative CT exhibited the greatest odds of being the most effective treatment for improving OS, and PHRAC plus preoperative CT exhibited the greatest odds of improving DFS. Further clinical studies are needed and justified.
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Frontiers in pharmacology · Jan 2019
The Differences in the Safety and Tolerability of Immune Checkpoint Inhibitors as Treatment for Non-Small Cell Lung Cancer and Melanoma: Network Meta-Analysis and Systematic Review.
Background: Immune checkpoint inhibitors (ICIs) have evolved for the treatment of solid tumors. In addition to the efficacy of ICIs for cancer, the adverse events (AEs) of ICIs are also noteworthy for gradually more extensive clinical use. Objective: To conduct a systematic review and network meta-analysis to evaluate the treatment-related AEs that occurred in clinical trials using different kinds of ICIs, to explore the differences in AEs among ICIs for treating non-small cell lung cancer (NSCLC) and melanoma, and to compare select immune-related AEs. ⋯ A combination of nivolumab and ipilimumab had the highest risk for colitis, while pembrolizumab and atezolizumab had a lower possibility than the other ICIs. Conclusion: Atezolizumab 1,200 mg and pembrolizumab 2 mg/kg every 3 weeks were ordinarily safer than other ICIs. When treating NSCLC, nivolumab had the lowest risk; when treating melanoma, pembrolizumab had the lowest toxicity.
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Frontiers in pharmacology · Jan 2019
ReviewAdapting Proteostasis and Autophagy for Controlling the Pathogenesis of Cystic Fibrosis Lung Disease.
Cystic fibrosis (CF), a fatal genetic disorder predominant in the Caucasian population, is caused by mutations in the cystic fibrosis transmembrane conductance regulator (Cftr) gene. The most common mutation is the deletion of phenylalanine from the position-508 (F508del-CFTR), resulting in a misfolded-CFTR protein, which is unable to fold, traffic and retain its plasma membrane (PM) localization. The resulting CFTR dysfunction, dysregulates variety of key cellular mechanisms such as chloride ion transport, airway surface liquid (ASL) homeostasis, mucociliary-clearance, inflammatory-oxidative signaling, and proteostasis that includes ubiquitin-proteasome system (UPS) and autophagy. ⋯ There is emerging experimental and clinical evidence that supports the notion that impaired cellular proteostasis and autophagy plays a central role in regulating pathogenesis of chronic CF lung disease. Thus, correcting the underlying proteostasis and autophagy defect in controlling CF pulmonary disease, primarily via correcting the protein processing defect of F508del-CFTR protein has emerged as a novel intervention strategy. Hence, we discuss here both the rationale and significant therapeutic utility of emerging proteostasis and autophagy modulating drugs/compounds in controlling chronic CF lung disease, where targeted delivery is a critical factor-influencing efficacy.
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Frontiers in pharmacology · Jan 2019
Pharmacokinetics of Intranasally Administered Dexmedetomidine in Chinese Children.
Background: Intranasal application is a comfortable, effective, nearly non-invasive, and easy route of administration in children. To date, there is, however, only one pharmacokinetic study on intranasal dexmedetomidine in pediatric populations and none in Chinese children available. Therefore, this study aimed to characterize the pharmacokinetics of intranasally administered dexmedetomidine in Chinese children. ⋯ The estimated absorption rate constant was Ka = 0.038 (0.004) min-1. Conclusions: When compared with studies in Caucasians, Chinese children showed a similar time to peak plasma concentration after intranasal administration, but the achieved plasma concentrations were about three times higher. Possible reasons are differences in age, ethnicity, and mode of administration.
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Frontiers in pharmacology · Jan 2019
Terlipressin Versus Norepinephrine for Septic Shock: A Systematic Review and Meta-Analysis.
Purpose: The meta-analysis aims to evaluate the efficacy and safety of terlipressin compared with norepinephrine for septic shock. Materials and Methods: The relevant studies from MEDLINE, Cochrane Library, Embase were searched by two independent investigators. A variety of keywords were used to search the studies. ⋯ Conclusions: Current results suggest that terlipressin showed no added survival benefit for septic shock when compared with norepinephrine, while terlipressin could decrease heart rate in the late phase of septic shock compared with norepinephrine without further liver and kidney injury. Systematic Review Registration: PROSPERO (ID: CRD42019128743). Available online at: http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42019128743.