Large population-based studies examining differences in ICI-associated cardiotoxicity across cancer types and agents are limited. Data of 5518 cancer patients who received at least one cycle of ICIs were extracted from a large network of health care organizations. ICI treatment groups were classified by the first ICI agent(s) (ipilimumab, nivolumab, pembrolizumab, cemiplimab, avelumab, atezolizumab, or durvalumab) or its class (PD-1 inhibitors, PD-L1 inhibitors, CTLA4-inhibitors, or their combination (ipilimumab + nivolumab)). Time to first cardiac adverse event (CAE) (arrhythmia, acute myocardial infarction, myocarditis, cardiomyopathy, or pericarditis) developed within one year after ICI initiation was analyzed using a competing-risks regression model adjusting for ICI treatment groups, patient demographic and clinical characteristics, and cancer sites. By month 12, 12.5% developed cardiotoxicity. The most common cardiotoxicity was arrhythmia (9.3%) and 2.1% developed myocarditis. After adjusting for patient characteristics and cancer sites, patients who initiated on monotherapy with ipilimumab (adjusted Hazard Ratio (aHR): 2.00; 95% CI: 1.49–2.70; p < 0.001) or pembrolizumab (aHR: 1.21; 95% CI: 1.01–1.46; p = 0.040) had a higher risk of developing CAEs within one year compared to nivolumab monotherapy. Ipilimumab and pembrolizumab use may increase the risk of cardiotoxicity compared to other agents. Avelumab also estimated a highly elevated risk (aHR: 1.92; 95% CI: 0.85–4.34; p = 0.117) compared to nivolumab and other PD-L1 agents, although the estimate did not reach statistical significance, warranting future studies.
Dispersive liquid-liquid microextraction (DLLME) coupled with high-performance liquid chromatography-variable wavelength detector (HPLC-VWD) was developed for extraction and determination of thiamphenicol (THA) in honey. A mixture of extraction solvent (30 microL 1,1,2,2-tetrachloroethane) and dispersive solvent (1.0 mL of acetonitrile) was rapidly injected into 5.00 mL sample solution for the formation of cloudy solution. The analyte in the sample was extracted into the fine droplets of C(2)H(2)Cl(4). After extraction, phase separation was performed by centrifugation, and the enriched analyte in the sedimented phase was determined by HPLC-VWD. Some important parameters, such as the kind and volume of extraction solvent and dispersive solvent, extraction time, sample solution pH, sample volume, and salt effect, were investigated and optimized. Under the optimum extraction condition, the method yielded a linear calibration curve in the concentration range from 3 to 2000 microg/kg for target analyte. The enrichment factors for THA was 87.9, and the limit of detection (S/N = 3) was 0.1 microg/kg. The relative standard deviation for the extraction of 10 microg/kg of THA was 6.2% (n = 6). The main advantages of DLLME-HPLC method are simplicity of operation, rapidity, low cost, high enrichment factor, high recovery, good repeatability, and extraction solvent volume at the microL level. Honey samples were successfully analyzed using the proposed method.
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