RESUMO
Objective: This study aims to analyze adverse drug events (ADEs) associated with cenobamate from the FAERS database, covering the third quarter of 2020 to the second quarter of 2023. Methods: Data related to cenobamate-associated ADEs from the third quarter of 2020 to the second quarter of 2023 were collected. After standardizing the data, various signal quantification techniques, including ROR, MHRA, BCPNN, and MGPS, were employed for analysis. Results: Among 2535 ADE reports where cenobamate was the primary suspected drug, 94 adverse reactions involving 11 different System Organ Class (SOC) categories were identified through the application of four signal quantification techniques. More specifically, neurological disorders and injuries resultant from complications are frequent adverse reactions associated with cenobamate. Conclusion: Our research findings align with established results, affirming the favorable safety profile of cenobamate. Effective prevention of adverse reactions induced by cenobamate can be achieved through the establishment of efficient blood concentration monitoring and dose adjustments.
RESUMO
Objective: The present work aimed to assess reoxygenation and tumor inhibition during fractionated radiotherapy (FRT) in murine tumors using 18F-fluoromisonidazole (18F-FMISO) and 18F-fluorothymidine (18F-FLT) based micro positron emission tomography/computed tomography (PET/CT). Materials and Methods: A nude mouse xenograft model was established with the head and neck squamous carcinoma cell (FaDu), followed by administration of FRT. Imaging was carried out with both 18F-FMISO and 18F-FLT PET/CT, prior to FRT (Pre-FRT, 0 Gy), during FRT (Inter-FRT, 21 Gy), and after FRT (Post-FRT, 40 Gy). The maximum standardized uptake (SUVmax) and tumor-to-normal muscle ratio (TNR) were determined in regions of interest (ROIs) in 18F-FMISO and 18F-FLT PET/CT images. Then, hypoxic (HV) and proliferative tumor (PTV) volumes obtained by PET/CT were analyzed. Immunohistochemistry was performed to analyze the changes of hypoxia-inducible factor- (HIF)-1α, carbonic anhydrase 9 (CAIX), Ki67 and proliferating cell nuclear antigen (PCNA). Associations of the levels of these biomarkers with PET/CT parameters were analyzed. Results: 18F-FMISO PET/CT demonstrated markedly elevated reduction rates of SUVmax (30.3 vs. 14.5%, p = 0.012), TNR (27.9 vs. 18.3%, p = 0.032) and HV (85.0 vs. 71.4%, p = 0.047) from Pre-FRT to Inter-FRT compared with values from Inter-FRT to Post-FRT. Meanwhile, PTV reduction rate in 18F-FLT PET/CT from Pre-FRT to Inter-FRT was significantly decreased compared with that from Inter-FRT to Post-FRT (21.2 vs. 82.7%, p = 0.012). Tumor HIF-1α, CAIX, Ki67, and PCNA amounts were continuously down-regulated during radiotherapy. TNR (FMISO) showed significant correlations with HIF-1α (r = 0.692, p = 0.015) and CAIX (r = 0.801, p = 0.006) amounts in xenografts, while associations of SUVmax (FMISO) with hypoxia markers were weak (r = 0.418, p = 0.041 and r = 0.389, p = 0.037, respectively). SUVmax (FLT) was significantly correlated with Ki67 (r = 0.792, p = 0.003) and PCNA (r = 0.837, p = 0.004). Conclusions: Tumor reoxygenation occurs early during radiotherapy, while inhibition of cell proliferation by tumoricidal effects mainly takes place gradually with the course of radiotherapy. 18F-FMISO and 18F-FLT PET/CT are sensitive and non-invasive tools for the monitoring of tumor reoxygenation and proliferation during radiotherapy.
