| 1. |
- Zhai, Yinghong, et al.
(författare)
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Cardiovascular Toxicity of Carfilzomib : The Real-World Evidence Based on the Adverse Event Reporting System Database of the FDA, the United States
- 2021
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Ingår i: Frontiers in Cardiovascular Medicine. - : Frontiers Media S.A.. - 2297-055X. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Background: Carfilzomib, an effective proteasome inhibitor agent for the therapy of relapsed and refractory multiple myeloma, has been related to a significant number of cardiovascular events. However, patterns of cardiovascular complications associated with this agent remain poorly characterized in real-world settings.Objective: To gain further insight into the frequency, spectrum, clinical features, timing, and outcomes of carfilzomib-related cardiovascular toxicities.Methods: This disproportionality (case/non-case) study was conducted leveraging records from FAERS database from 2014 to 2019. Cardiovascular events were defined and broadly categorized eight entities using narrow version of the Standardized MedDRA Queries (SMQs). Reporting odds ratios (ROR) and information component (IC) were calculated to measure disproportionality. Additionally, statistical shrinkage was applied to reduce false-positive signals.Results: The final number of records involved was 28,479,963, with 3,370 records submitted for carfilzomib related cardiovascular events. Significant disproportionality association between carfilzomib administration and cardiovascular events was captured (IC025/ROR025 = 0.85/1.95) when exploring in the entire database. Upon further analysis, all eight broad categories of cardiovascular toxicities were disproportionately associated with carfilzomib with varying frequencies, time-to-onset, and severities. Cardiomyopathy-related complications (N = 1,301, 38.61%), embolic and thrombotic events (N = 821, 24.36%), and cardiac failure (N = 765, 22.70%) largely comprised the reported problems. Notably, the strongest signal was detected for cardiac failure (IC025/ROR025 = 1.33/2.59), followed by pulmonary hypertension (IC025/ROR025 = 1.19/2.34). Median onset time of cardiovascular events was 41days (Q1-Q3: 9-114 days), with the shortest median time being 16 days (Q1-Q3: 4-85 days) for ischemic heart disease, with the longest time being 68 days (Q1-Q3: 21-139 days) for embolic and thrombotic events. Torsade de pointes/QT prolongation was identified as a new complication (IC025/ROR025 = 0.33/1.29) and was particularly noteworthy for highest death proportion (44.11%).Conclusions: Treatment with carfilzomib can lead to severe and versatile cardiovascular events. Early and intensive monitoring is important, particularly in the first 3 months after carfilzomib initiation. Maximizing the benefit while reducing potential cardiovascular harms of carfilzomib should become a priority.
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| 2. |
- Zhai, Yinghong, et al.
(författare)
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Updated Insights on Cardiac and Vascular Risks of Proton Pump Inhibitors : A Real-World Pharmacovigilance Study
- 2022
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Ingår i: Frontiers in Cardiovascular Medicine. - : Frontiers Media S.A.. - 2297-055X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Proton pump inhibitors (PPIs) are among the most widely prescribed medications in clinical practice. However, there are also concerns about the potential risks of long-term PPI use. The present study aimed to examine the safety of PPIs and summarize their potential cardiac and vascular risks in a real-world setting.Methods: This pharmacovigilance study extracted records between January 2015 and December 2019 from the FDA Adverse Event Reporting System (FAERS) database. The association of seven PPI medications with cardiac and vascular events (CVEs) were evaluated. Two established pharmacovigilance methods, reporting odds ratio (ROR) and information components (IC) based statistical shrinkage, were used to measure disproportionality.Results: In total 62,140 CVE records associated with PPI use were investigated. Women showed a higher proportion (54.37%) of PPI-associated CVEs. The median time from PPI initiation to CVE onset was 97 [interquartile range (IQR): 8-491] days, with the shortest median time of 42 days (IQR: 2-277 days) for esomeprazole, and the longest time of 389 days (IQR: 0-525 days) for dexlansoprazole. Although PPIs were not associated with elevated CVE risks compared those of the whole database (IC025/ROR025 = -0.39/0.74), various signals emerged. Despite some similarities exist between the PPIs, their cardiac and vascular safety profiles varied significantly. Pantoprazole showed the broadest spectrum of signals, from thrombotic thrombocytopenic purpura (IC025/ROR025 = 0.01/1.08) to renal haemangioma (IC025/ROR025 = 3.14/9.58). Esomeprazole showed the second-broadest spectrum of toxicities, ranging from duodenal ulcer hemorrhage (IC025/ROR025 = 0.07/1.28) to hypertensive nephropathy (IC025/ROR025 = 4.09/18.72). Vascular signals were more dominant than cardiac signals, suggesting that vascular function was more heavily affected. Hypertensive nephropathy, renal haemangioma, renal artery stenosis, and renal infarct had strong signals across most PPI regimens and merited further attention.Conclusions: PPIs may inflict various CVEs, particularly those involving the vascular system, on the users. Given the wide range of onset times and different toxicity profiles for various PPI medications, they should be prescribed with caution.
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| 3. |
- Mu, Liwen, et al.
(författare)
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Enriching Heteroelements in Lignin as Lubricating Additives for Bioionic Liquids
- 2016
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Ingår i: ACS Sustainable Chemistry and Engineering. - : American Chemical Society (ACS). - 2168-0485. ; 4:7, s. 3877-3887
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Tidskriftsartikel (refereegranskat)abstract
- Depolymerization and modification of lignin have been achieved simultaneously in a one-pot chemical reaction. Two heteroelement-rich modifiers, imidazol-1-yl phosphonic dichloride and 1H-1,2,4-triazol-1-yl phosphonic dichloride, were selected to react with lignin in this work. The modified lignin (m-lignin) is demonstrated as an effective lubricating additive for [choline][amino acid] ([CH][AA]) bioionic liquids. Different characterization techniques have been utilized to study the lignin depolymerization, reaction between lignin and modifiers and m-lignin/[CH][AA] interaction. The effect of the molecular structure of the modifiers on the rheological and tribological properties of m-lignin/[CH][AA] lubricants was systematically investigated. Density function theory is used to calculate the electronic structure of lignin, m-lignin, and [CH][AA]. The atomic natural charge analysis revealed the most negative charge on nitrogen bonded to a phosphorus atom and the strongest capability of forming hydrogen bonding with [CH][AA]. The introduced nitrogen and phosphorus elements not only increase the hydrogen bonding density in m-lignin/[CH][AA] but also enhance the polarity of the m-lignin, both of which facilitate a strong adhesion of lubricant on a metal surface and thus promote lubrication. A larger fraction of heteroatom groups in m-lignin contributes to a better lubrication property of these lubricants
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| 4. |
- Mu, Liwen, et al.
(författare)
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Grafting Heteroelement-Rich Groups on Graphene Oxide : Tuning Polarity and Molecular Interaction with Bio-Ionic Liquid for Enhanced Lubrication
- 2017
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Ingår i: Journal of Colloid and Interface Science. - : Elsevier. - 0021-9797 .- 1095-7103. ; 498, s. 47-54
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Tidskriftsartikel (refereegranskat)abstract
- Two different heteroelement-rich molecules have been successfully grafted on graphene oxide (GO) sheets which were then used as lubricant additives in bio-ionic liquid. The grafting was processed with reactions between GO sheets and synthesized heteroelement-rich molecules (Imidazol-1-yl phosphonic dichloride and 1H-1,2,4-triazol-1-yl phosphonic dichloride, respectively). The modified GO (m-GO) was added into [Choline][Proline] ([CH][P]) bio-ionic liquid, and has been demonstrated effective additive in promoting lubrication. Different characterization techniques have been utilized to study the reaction between GO and the two modifiers. The effect of molecular structure of the modifiers on the rheological and tribological properties of m-GO/[CH][P] lubricants was systematically investigated. Both theoretical calculation and experimental results demonstrated that the introduced heteroelement-rich groups are beneficial to increase the robustness of lubrication film by intensified hydrogen bonding and enhance the lubricant/friction surface adhesion by increased polarity of the m-GO. As a result, the interfacial lubrication could be significantly improved by these newly developed m-GO/[CH][P] lubricants.
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| 5. |
- Mu, Liwen, et al.
(författare)
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Non-corrosive green lubricants : strengthened lignin–[choline][amino acid] ionic liquids interaction via reciprocal hydrogen bonding
- 2015
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Ingår i: RSC Advances. - 2046-2069. ; 5:81, s. 66067-66072
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Tidskriftsartikel (refereegranskat)abstract
- A series of novel green lubricants with dissolved lignin in [choline][amino acid] ([CH][AA]) ionic liquids (ILs) have been synthesized in this work. The effect of lignin on the thermal and tribological properties of the lignin/[CH][AA] lubricants was systematically investigated by means of thermogravimetric analysis, differential scanning calorimetry, and a friction and wear tester. The lignin in [CH][AA] has been demonstrated to be an effective additive to improve thermal stability, reduce the wear rates and stabilize the friction coefficients of lignin/[CH][AA] lubricants. Density function theory calculations on the electronic structure of [CH][AA] ILs reveal the atomic natural charge of ILs and their hydrogen bonding capability with lignin. Moreover, these green lubricants show excellent anti-corrosive properties against commercial aluminum and iron boards. The strong physical adsorption of [CH][AA] ILs onto the steel surface and the reciprocal hydrogen bonding between [CH][AA] ILs and lignin synergistically contribute to the enhanced lubrication film strength and thus the tribological properties of these new lubricants. This work provides a new perspective on utilizing complete bio-products in advanced tribological lubrication systems. In addition, this will open a new application venue for lignin to improve product value in lignocellulosic biomass utilization.
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| 6. |
- Mu, Liwen, et al.
(författare)
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Structural strategies to design bio-ionic liquid : Tuning molecular interaction with lignin for enhanced lubrication
- 2019
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Ingår i: Journal of Molecular Liquids. - : Elsevier. - 0167-7322 .- 1873-3166. ; 280, s. 49-57
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Tidskriftsartikel (refereegranskat)abstract
- Lignin strengthened ionic liquids (ILs) have shown high potential to be used as high performance green lubricants. Strengthened lignin-ILs molecular interaction is an effective approach to improve their lubrication properties. The molecular interactions of ILs’ cation and anion containing different functional groups with lignin and efficiency on the lubricating properties have rarely been studied yet. In this work, a series of novel green lubricants with dissolved lignin in [Choline][Amino Acid] ([CH][AA]), [Tetramethylammonium][Glycine] ([N 1111 ][Gly]) and [Tetrabutylammonium][Glycine] ([N 4444 ][Gly]) ILs have been synthesized and their tribological properties were systematically investigated. The longer alkyl chain in cation without reciprocal H-bond interaction between ILs’ cation and anion has the positive effect on the anti-wear properties. In addition, the less steric effect and more negative natural charges of amino acid anion synergistically contribute to the stronger H-bond interaction between lignin and choline base ILs, which enhances lubrication film strength and thus resulting in the better tribological property of ILs/lignin green lubricants. Specifically, the wear volume loss of the steel disc lubricated by [N 4444 ][Gly] with the addition of 15% lignin is only 12% of the one lubricated by pure [N 4444 ][Gly]. This work presents a method to tune molecular interaction between lignin and ILs via the structural design of ILs’ cation and anion, which are revealed as the key factor that bridges the individual components and improves overall lubricating properties.
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| 7. |
- Zhai, Yinghong, et al.
(författare)
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Metabolic and Nutritional Disorders Following the Administration of Immune Checkpoint Inhibitors : A Pharmacovigilance Study
- 2021
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Ingår i: Frontiers in Endocrinology. - : Frontiers Media S.A.. - 1664-2392. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Although several metabolic and nutritional disorders (MNDs) have been reported in the recipients of immune checkpoint inhibitors (ICIs), these events have not been fully captured and comprehensively characterized in real-world population.Objectives: To provide complete metabolic and nutritional toxicity profiles after ICIs (single and combined) initiation through an integrated big database.Methods: Reporting odds ratios (ROR) and information component (IC) based on statistical shrinkage transformation were utilized to perform disproportionality analysis using the US Food and Drug Administration Adverse Events Reporting System. Both ROR and IC were used to calculate disproportionality when compared with the whole database, but only ROR was used when comparison was made for different ICI strategies. Only when both the lower limits of 95% confidence intervals (CIs) for ROR (ROR025) and IC (IC025) exceeded specified threshold values (1 and 0, respectively) was regarded as a signal.Results: A total of 29,294,335 records were involved and 8,662 records were for MNDs in patients exposed to ICIs. Statistically significant association was detected between ICIs use and total MNDs (IC025/ROR025 = 1.06/2.19). For monotherapy, three ICI monotherapies (anti-PD-1, anti-PDL-1, and anti-CTLA-4) were all disproportionately associated with MNDs. Statistically significant differences in reporting frequencies also emerged when comparing anti-PD-1 with anti-PD-L1/anti-CTLA-4 monotherapy, with RORs of 1.11 (95%CI 1.01-1.21), and 1.35 (95%CI 1.23-1.48), respectively. Notably, combination therapy was associated with a higher reporting frequency of theses toxicities compared to monotherapy with a ROR of 1.56 (95%CI 1.48-1.64). Additionally, disproportionality analysis at High-level Group Term level highlighted eight broad entities of MNDs. Further disproportionality analysis at Preferred Term level indicated a wide range and varied strength of signals. For ICI monotherapy, nivolumab and pembrolizumab showed the broadest spectrum of MNDs. For combination therapy, a variety of signals were detected for nivolumab + ipilimumab therapy even comparable to two PD-1 monotherapies.Conclusion: Metabolic and nutritional complications could be provoked by ICI monotherapy (especially anti-PD-1) and further reinforced by combination therapy. Clinicians and patients should be informed about these potential risks that might be encountered in real-world practice. Aforehand education and regular monitoring of related biochemical parameters (calcium, sodium, potassium, protein) are recommended to ensure better cancer survivorship.
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| 8. |
- Zhai, Yinghong, et al.
(författare)
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Pharmacovigilance analysis of cardiac risks associated with Bruton tyrosine kinase inhibitors
- 2023
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Ingår i: Expert Opinion on Drug Safety. - : Ashley Mark Publishing Company. - 1474-0338 .- 1744-764X. ; 22:9, s. 857-869
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Bruton tyrosine kinase inhibitors (BTKIs) can be associated with several cardiac risks.RESEARCH DESIGN AND METHODS: This study was conducted based on records from a large spontaneous reporting database, the Food and Drug Administration Adverse Event Reporting System, for cardiac events reported for several BTKI agents. Reporting odds ratio and information components based on statistical shrinkage transformation were utilized to measure disproportionality.RESULTS: The final number of records for BTKI-related cardiac events was 10 320. Death or life-threatening events occurred in 17.63% of all associated cardiac records. Significant reporting was captured between BTKI (total/specific) and cardiac events, with the strongest association for ibrutinib. A total of 47 positive signals were evacuated for ibrutinib, with atrial fibrillation being the most commonly reported one. Concomitantly, cardiac failure congestive, cardiac disorder, arrhythmia, pericardial effusion, and atrial flutter, were also noticed for relatively stronger signal and disproportionality. Atrial fibrillation was over-reported in the 3 groups (ibrutinib, acalabrutinib, zanubrutinib), and acalabrutinib had statistically significant lower reporting compared with ibrutinib.CONCLUSIONS: Receiving ibrutinib, acalabrutinib or zanubrutinib might increase the chance of cardiac complications, with ibrutinib posing the highest risk. The type of cardiotoxicity involved in ibrutinib was highly variable.
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