Severe and fatal adverse events of immune checkpoint inhibitor combination therapy in patients with metastatic renal cell carcinoma: a systematic review and meta-analysis.

Introduction: Immune checkpoint inhibitor (ICI) combination therapy has changed the treatment landscape for metastatic renal cell carcinoma (mRCC). However, little evidence exists on the treatment-related severe adverse events (SAEs) and fatal adverse events (FAEs) of ICI combination therapy in mRCC. Method: We searched PubMed, Embase, and Cochrane Library databases to evaluate randomized controlled trials (RCTs) of ICI combination therapy versus conventional tyrosine kinase inhibitor (TKI)-targeted therapy in mRCC. Data on SAEs and FAEs were analyzed using revman5.4 software. Results: Eight RCTs (n=5380) were identified. The analysis showed no differences in SAEs (60.5% vs. 64.5%) and FAEs (1.2% vs. 0.8%) between the ICI and TKI groups (odds ratio [OR], 0.83; 95%CI 0.58-1.19, p=0.300 and OR, 1.54; 95%CI 0.89-2.69, p=0.120, respectively). ICI-combination therapy was associated with less risk of hematotoxicities, including anemia (OR, 0.24, 95%CI 0.15-0.38, p<0.001), neutropenia (OR, 0.07, 95%CI 0.03-0.14, p<0.001), and thrombocytopenia (OR, 0.05, 95%CI 0.02-0.12, p<0.001), but with increased risks of hepatotoxicities (ALT increase [OR, 3.39, 95%CI 2.39-4.81, p<0.001] and AST increase [OR, 2.71, 95%CI 1.81-4.07, p<0.001]), gastrointestinal toxicities (amylase level increase [OR, 2.32, 95%CI 1.33-4.05, p=0.003] and decreased appetite [OR, 1.77, 95%CI 1.08-2.92, p=0.020]), endocrine toxicity (adrenal insufficiency [OR, 11.27, 95%CI 1.55-81.87, p=0.020]) and nephrotoxicity of proteinuria (OR, 2.21, 95%CI 1.06-4.61, p=0.030). Conclusions: Compared with TKI, ICI combination therapy has less hematotoxicity in mRCC but more specific hepatotoxicity, gastrointestinal toxicity, endocrine toxicity, and nephrotoxicity, with a similar severe toxicity profile. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023412669.

[Spatiotemporal Distribution of Aerosol Optical Depth Based on Landsat Data in the Hinterland of the Guanzhong Basin and Its Relationship with Urbanization].

Aerosol optical depth (AOD) is one of the most fundamental optical properties of aerosols that characterizes the attenuation of light by aerosols and is an indicator of regional air pollution. Based on the blue band surface reflectance database from the MOD09A1 products for the period 2000-2019 and the ASTER spectral database, AOD was estimated from Landsat TM/OLI data using the deep blue algorithm (DB). Multi-year average/annual average and seasonal AOD values for the period 2000-2019 were then calculated to analyze the spatial characteristics and temporal variations of AOD using the empirical orthogonal function method (EOF). Furthermore, the impacts of urbanization on the spatio-temporal distribution of AOD were analyzed. The obtained results are summarized as follows:① The multi-year average AOD spatial distribution in the hinterland of the Guanzhong Basin was significantly affected by topography and human activities, with higher AOD values and variationsin areas of low altitude and high-intensity human activities compared to the surrounding mountains. Thus, changes in AOD in the study area are mainly affected by anthropogenic factors. AOD also showed significant seasonal variations, whereby spring (0.34) > summer (0.33) > autumn (0.23) > winter (0.12), and the largest regional differences occurred in summer; ② The annual average AOD (from 2000-2019) showed the trend of "increase-decrease-increase", and reached a maximum in 2005, with the high AOD area gradually moving to the south. The distribution of AOD values in spring and summer was relatively discrete, while it is in a low-value agglomeration state in winter; ③ Three main AOD spatial distribution modes were identified based on the EOF, which had cumulative contribution rate of 83.0%. The spatial distribution trend of AOD showed regional consistency, with feature vectors consistent with the altitude, thus reflecting the difference of AOD at different altitudes. Taking the Qinling Mountains as the dividing line, the AOD presented the "north-south" pattern, AOD showed a "north-south" pattern, reflecting the uniqueness of the regional development in the Guanzhong Basin compared to the southern Qinling Mountains. The "southeast-northwest" distribution pattern indicated that the AOD presented a reverse change trend between urban and non-urban; and ④ The results of correlation analysis between the AOD and urbanization revealed a positive correlation with permanent population density (R2=0.707, P<0.05), impervious surface density (R2=0.377, P<0.05), and industrial POI density (R2=0.727, P<0.5). These results are significant for improving the monitoring of air quality in the Guanzhong Basin and for the construction of an urban ecological environment.