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Objective: Bendamustine was approved for treating chronic lymphocytic leukemia and indolent B-cell non-Hodgkin lymphoma. Despite its therapeutic benefits, the long-term safety of bendamustine in a large population remains inadequately understood. This study evaluates the adverse events (AEs) associated with bendamustine, using a real-world pharmacovigilance database to support its clinical application. Methods: We conducted a post-marketing risk analysis to assess the association between bendamustine and its AEs. Data were extracted from the US FDA's Adverse Event Reporting System (FAERS), covering the period from January 2017 to September 2023. The characteristics of bendamustine-associated AEs and the onset time were further analyzed. Statistical analysis was performed using MYSQL 8.0, Navicat Premium 15, Microsoft EXCEL 2016, and Minitab 21.0. Results: 9,461,874 reports were collected from the FAERS database, 9,131 identified bendamustine as the "primary suspected" drug. We identified 331 significant disproportionality preferred terms (PTs). Common AEs included pyrexia, neutropenia, infusion site reaction, progressive multifocal leukoencephalopathy (PML), injection site vasculitis, and pneumonia-all documented on bendamustine's label. Notably, 16 unexpected and significant AEs were discovered, including hypogammaglobulinemia, which is concerning due to its potential to increase infection susceptibility following bendamustine treatment. Other significant findings were anaphylactic reactions, PML, and cutaneous malignancies, suggesting updates to the drug's label may be necessary. Physicians should monitor for neurological and skin changes in patients and discontinue treatment if PML is suspected. Moreover, the median onset time for bendamustine-associated AEs was 13 days, with an interquartile range [IQR] of 0-59 days, predominantly occurring on the first day post-initiation. The ß of bendamustine-related AEs suggested risk reduction over time. Conclusion: Our study uncovered some potential pharmacovigilance signals for bendamustine, providing important insights for its safe and effective clinical use.
RESUMO
The chrysanthemum black spot caused by Alternaria alternata significantly reduced the quality and yield of chrysanthemum. The crude toxin secreted by A. alternata in the metabolic process have elopathic effects on plants, which is the main pathogenic factor for the occurrence of chrysanthemum black spot. The pathogenic fungi A. alternate was isolated from chrysanthemum black spot leaves, The effects of crude toxin on plant height, stem diameter, root length, resistant material content, membrane relative permeability, polyphenol oxidase (PPO), peroxidase (POD), phenylalanine ammonia-lyase (PAL) in different treatments of chrysanthemum 'Jinba' seedlings were investigated. The results showed that the crude toxin of A. alternata had an inhibition effect on plant height, stem diameter and root length. The toxin concentration was positively correlated with the inhibitory effect. 14 days after crude toxin treatment, plant height, stem diameter and root length were significantly inhibited, with an reduction of 28.9%, 21.4% and 23.3%, respectively. The cell membrane permeability of leaf increased with the toxin concentration. Under the same toxin concentration, the cell membrane permeability first increased and then decreased with the treatment duration. The contents of soluble protein, malondialdehyde (MDA) and proline in leaves were significantly increased after treatment with the toxin solution. The increases of PAL, POD and PPO were the most significant in 10 times A. alternatacrude toxin treatment. The pathogenicity of A. alternate crude toxin to the chrysanthemum 'Jinba' seedlings was mainly through inhibi-ting the normal growth of roots and stems, destructing the root cell membrane permeability and increasing the contents of MDA, normal soluble sugar and proline, and promoting the activities of PAL, POD, PPO in leaf tissues.
