Background: This systematic review and network meta-analysis aimed to provide a complete hepatotoxicity profile, hepatotoxicity spectrum, and safety ranking of immune checkpoint inhibitor drugs for cancer treatment. Methods: PubMed, Embase, Scopus, CINAHL, Web of Science, psycINFO, Cochrane Library, and ClinicalTrials.gov. websites were searched, and a manual search of relevant reviews and trials up to January 1, 2022, was undertaken. Head-to-head III randomized controlled trials comparing any 2 or 3 of the following treatments or different doses of the same immune checkpoint inhibitor drug were included: programmed death 1 (PD-1), programmed death ligand 1, and cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) inhibitors and conventional therapy. We included 106 randomized trials (n=164,782) containing 17 treatment arms. Results: The overall incidence of hepatotoxicity was 4.06%. The rate of fatal liver adverse events was 0.07%. The programmed death ligand 1 inhibitor+targeted therapy drug+chemotherapy group had the highest risk of treatment-related increases in all-grade alanine aminotransferase and aspartate aminotransferase levels, and the differences were significant. For immune-related hepatotoxicity, no significant difference was found between PD-1 and CTLA-4 inhibitors for all-grade hepatotoxicity; however, CTLA-4 inhibitors were associated with a higher risk of grade 3–5 hepatotoxicity than PD-1 inhibitors. Conclusions: The highest incidence of hepatotoxicity and fatality was observed with triple therapy. The overall incidence of hepatotoxicity was similar between different dual regimens. For immune checkpoint inhibitor monotherapy, the overall risk of immune-mediated hepatotoxicity related to CTLA-4 inhibitors did not differ significantly from that of PD-1 inhibitors. There was no direct relationship between the risk of liver injury and drug dose, whether monotherapy or combination therapy was used.

Aim: We evaluated whether acute drug-induced liver injury (DILI) caused by adjuvant chemotherapy with epirubicin plus cyclophosphamide for early breast cancer was associated with estradiol (E2), luteinizing hormone (LH), and follicle-stimulating hormone (FSH).Methods: Reproductive hormone test results of breast cancer patients were collected in the first chemotherapy cycle. E2, LH, and FSH levels were loge-transformed to normally distributed variables and were assessed using Student’s t-test to determine significant differences between the case and control groups. Hormone levels were classified according to the interquartile range and analyzed by logistic regression to determine their association with DILI caused by chemotherapy.Results: Among the 915 enrolled patients (DILI group: 204; control group: 711), menopausal status, along with serum E2, LH, and FSH levels, did not substantially differ between case and control groups. However, in the premenopause subgroup (n = 483), we found a significant difference in the E2 level between the case and control groups (p = 0.001). After adjusting for age and body mass index, premenopausal patients with 152–2,813 pg/mL E2 showed a lower risk of chemotherapy-induced DILI than patients with ≤20 pg/mL E2 (odds ratio: 0.394; 95% confidence interval: 0.207–0.748). The linear trend χ2 test revealed that E2 levels in premenopausal patients with breast cancer were inversely associated with the development of DILI.Conclusion: High serum E2 levels are associated with a reduced DILI risk in premenopausal patients with breast cancer undergoing epirubicin plus cyclophosphamide adjuvant chemotherapy.

Background Patients undergoing heart surgery may experience a range of physiological changes, and the postoperative recovery time is long. Patients and their families often have concerns about quality of life (QoL) after discharge. eHealth interventions may improve patient participation, ensure positive and effective health management, improve the quality of at-home care and the patient's quality of life, and reduce rates of depression. Objective The purpose of this study was to evaluate the effects of eHealth interventions on the physiology, psychology, and compliance of adult patients after cardiac surgery to provide a theoretical basis for clinical practice. Methods We conducted systematic searches of the following 4 electronic databases: PubMed, Embase, CINAHL, and the Cochrane Central Register of Controlled Trials. Mean (SD) values were used to calculate the pooled effect sizes for all consecutive data, including QoL, anxiety, and depression. Where the same results were obtained using different instruments, we chose the standardized mean difference with a 95% CI to represent the combined effect size; otherwise, the mean difference (MD) with a 95% CI was used. Odds ratios were used to calculate the combined effect size for all dichotomous data. The Cohen Q test for chi-square distribution and an inconsistency index (I2) were used to test for heterogeneity among the studies. We chose a fixed-effects model to estimate the effect size if there was no significant heterogeneity in the data (I2≤50%); otherwise, a random-effects model was used. The quality of the included studies was assessed using the Cochrane risk-of-bias tool for randomized trials (RoB 2). Results The search identified 3632 papers, of which 19 met the inclusion criteria. In terms of physical outcomes, the score of the control group was lower than that of the intervention group (MD 0.15, 95% CI 0.03-0.27, I2=0%, P=.02). There was no significant difference in the mental outcomes between the intervention and control groups (MD 0.10, 95% CI –0.03 to 0.24, I2=46.4%, P=.14). The control group’s score was lower than that of the intervention group for the depression outcomes (MD –0.53, 95% CI –0.89 to –0.17, I2=57.1%, P=.004). Compliance outcomes improved in most intervention groups. The results of the sensitivity analysis were robust. Nearly half of the included studies (9/19, 47%) had a moderate to high risk of bias. The quality of the evidence was medium to low. Conclusions eHealth improved the physical component of quality of life and depression after cardiac surgery; however, there was no statistical difference in the mental component of quality of life. The effectiveness of eHealth on patient compliance has been debated. Further high-quality studies on digital health are required. Trial Registration PROSPERO CRD42022327305; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=327305