Hepatotoxicity in immune checkpoint inhibitors: A pharmacovigilance study from 2014-2021.

Adverse events(AEs) related to hepatotoxicity have been reported in patients treated with immune checkpoint inhibitors (ICIs). As the number of adverse events increases, it is necessary to assess the differences in each immune checkpoint inhibitor regimen. The purpose of this study was to examine the relationship between ICIs and hepatotoxicity in a scientific and systematic manner. Data were obtained from the FDA Adverse Event Reporting System database (FAERS) and included data from the first quarter of 2014 to the fourth quarter of 2021. Disproportionality analysis assessed the association between drugs and adverse reactions based on the reporting odds ratio (ROR) and information components (IC). 9,806 liver adverse events were reported in the FAERS database. A strong signal was detected in older patients (≥65 years) associated with ICIs. hepatic adverse events were most frequently reported with Nivolumab (36.17%). Abnormal liver function, hepatitis, and autoimmune hepatitis were most frequently reported, and hepatitis and immune-mediated hepatitis signals were generated in all regimens. In clinical use, patients should be alert to these adverse effects, especially in elderly patients, who may be aggravated by the use of ICI.

Hepatobiliary calculi associated with ceftriaxone treatment: An analysis of FAERS data from 2004 to 2021.

INTRODUCTION: The role of gender, age, dose and other factors in the adverse reaction process of pseudocholelithiasis caused by ceftriaxone is controversial. In this study, we further explored potential risk factors using the FAERS database. METHODS: The reported odds ratio (ROR) and the information component (IC) of specific candidate factors were calculated by using the ROR method and the Bayesian confidence promotion neural network (BCPNN) method respectively to detect potential risk factors in adverse events(AEs) of ceftriaxone and hepatobiliary calculi(HBC). One candidate factor will be considered as a suspicious signal, or potential risk factors if its lower limit of 95% confidence interval of ROR (ROR025) is greater than 1 and its lower limit of 95% confidence interval of IC (IC025) is greater than 0. RESULTS: A total of 764 AEs of HBC were used to this analysis to evaluate candidate risk factors: Age group, Gender, Dose. Child (1-12 years): male ROR025 = 6.64, IC025 = 2.42, female ROR025 = 6.66, IC025 = 2.40. Adolescent group (12-18 years): male ROR025 = 5.47, IC025 = 2.08; elderly (≥65 years): female ROR025 = 1.25, IC025 = 0.22. CONCLUSIONS: Gender was not detected as a risk factor for HBC caused by ceftriaxone. However, Male infants, male children, female children, adolescent male, and elderly female were potential risk factors for HBC caused by ceftriaxone based on criteria ROR025 > 1 and IC025 > 0.

A Complex Heterogeneous Network Model of Disease Regulated by Noncoding RNAs: A Case Study of Unstable Angina Pectoris.

MicroRNAs (miRNAs) are important types of noncoding RNAs, and there is a lack of holistic and systematic understanding of the functions they play in disease. We proposed a research strategy, including two parts network analysis and network modelling, to analyze, model, and predict the regulatory network of miRNAs from a network perspective, using unstable angina pectoris as an example. In the network analysis section, we proposed the WGCNA & SimCluster method using both correlation and similarity to find hub miRNAs, and validation on two datasets showed better results than the methods using correlation or similarity alone. In the network modelling section, we used six knowledge graph or graph neural network models for link prediction of three types of edges and multilabel classification of two types of nodes. Comparative experiments showed that the RotatE model was a good model for link prediction, while the RGCN model was the best model for multilabel classification. Potential target genes were predicted for hub miRNAs and validation of hub miRNA-target gene interactions, target genes as biomarkers and target gene functions were performed using a three-step validation approach. In conclusion, our study provides a new strategy to analyze and model miRNA regulatory networks.

Nephrotoxicity of Immune Checkpoint Inhibitors: A Disproportionality Analysis from 2013 to 2020.

Nephrotoxicity occasionally occurs during treatment with immune checkpoint inhibitors (ICIs). Few related studies compare the differences between these drugs. This study aimed to systematically characterize nephrotoxicity after ICI initiation. Data were extracted from the US FDA Adverse Event Reporting System (FAERS) database. Disproportionality analysis, including information components (ICs) and reporting odds ratios (RORs), was performed to determine the potential renal toxicity of ICIs. A total of 7,204 reports of renal adverse events (AEs) were identified in the FAERS database. Renal AEs were most commonly reported for nivolumab (46.84%). Strong signals were detected in male patients combined with ICIs. In the clinical application of ICIs, attention should be paid to patients, especially male patients, with acute kidney injury, nephritis, autoimmune nephritis and other nephrotoxic AEs. The use of ICIs is likely to aggravate their condition.