Int J Gynecol Cancer. 2025 May 10;35(7):101930. doi: 10.1016/j.ijgc.2025.101930. Online ahead of print.

ABSTRACT

OBJECTIVE: Chemoradiotherapy is currently the main treatment for locally advanced cervical cancer. Nevertheless, the survival profile of locally advanced cervical cancer patients remains unsatisfactory because of metastasis and recurrence. We aimed to assess the survival outcomes and safety of radiotherapy ± chemotherapy combined with nimotuzumab (a human monoclonal antibody against epidermal growth factor receptor that has anti-tumor activities) for patients with locally advanced cervical cancer.

METHODS: Patients with stage IIB to IVA (International Federation of Gynecology and Obstetrics 2018) pathological and diagnosed locally advanced cervical cancer from January 2021 to December 2022 were collected in this retrospective, multi-center, and single-arm study. All patients received platinum-based radiotherapy ± chemotherapy with nimotuzumab (200 mg once a week for 6 weeks). Primary end point was overall survival. Secondary end points were progression-free survival and safety. The adverse events were recorded. Statistical analysis was performed using Statistics Analysis System software (v 9.4).

RESULTS: A total of 60 patients were collected with a median follow-up of 17.4 months (95% CI 14.8 to 19.2). The median age was 58 years (range; 35-90). A total of 16 patients (26.7%) had stage II, 38 patients (63.3%) had stage Ⅲ, and 6 patients (10%) had stage Ⅳ. The median overall survival was not reached, and the median progression-free survival was 20.4 months (95% CI 16.3 to not evaluable). Radiotherapy ± chemotherapy with nimotuzumab achieved 90.7% 1- and 2-year overall survival. Moreover, 1-year progression-free survival was 82.1%, and the 2-year progression-free survival was 47.7%. The most common treatment-related grade 3 to 4 adverse events included neutropenia (15%), anemia (21.7%), and thrombocytopenia (5%). No drug-related severe adverse events or deaths occurred.

CONCLUSIONS: The addition of nimotuzumab to radiotherapy ± chemotherapy was associated with favorable oncologic outcomes for patients with locally advanced cervical cancer, and the toxicity was tolerable and manageable.

PMID:40450867 | DOI:10.1016/j.ijgc.2025.101930

J Affect Disord. 2025 May 29:119435. doi: 10.1016/j.jad.2025.119435. Online ahead of print.

ABSTRACT

BACKGROUND: There is insufficient understanding of the long-term studies on adverse events (ADEs) in major depressive disorder (MDD) treated with atypical antipsychotics (AAPs), risks in patients with different psychiatric disorders, and differences between male and female patients.

METHODS: This study retrieved ADE reports for aripiprazole, quetiapine XR, brexpiprazole, and cariprazine from the FDA Adverse Event Reporting System (FAERS) for the time periods of FDA approval for MDD in the first quarter (Q1) of 2007, the Q1 of 2009, the Q1 of 2015, and the Q1 of 2022 respectively to the Q1 of 2024. Four algorithms (ROR, PRR, BCPNN, and MGPS) assessed ADE signals. We compared positive signal rates between MDD and non-MDD, and assessed sex differences in drug-related risks by ROR.

RESULTS: Patients with MDD had significantly higher rates of impulse control disorders (ICDs), obsessive-compulsive disorder (OCD), weight gain, extrapyramidal symptoms, and metabolic disorders compared to non-MDD (P < 0.05). Restless legs syndrome was associated with aripiprazole (P < 0.01), brexpiprazole (P < 0.01), and quetiapine XR. Serotonin syndrome, eosinophilic myocarditis, and angle closure glaucoma were new signals of aripiprazole in patients with MDD (P < 0.05). Female patients were more likely to gain weight (P < 0.05) with using aripiprazole, quetiapine XR, and brexpiprazole, whereas male patients with aripiprazole (P < 0.01) or brexpiprazole (P < 0.05) reported higher rates of ICDs and OCD.

CONCLUSION: It is suggesting a potential increased risk of various ADEs in patients with MDD when taking AAPs. The causal relationship and the exact mechanism between drugs and ADEs remains unclear, requiring further research.

PMID:40449747 | DOI:10.1016/j.jad.2025.119435

BMC Health Serv Res. 2025 May 30;25(1):773. doi: 10.1186/s12913-025-12898-0.

ABSTRACT

The high prevalence of multimorbidity in the aging population necessitates complex medication regimens, increasing the risk of adverse drug events (ADEs) and hospital admissions. This paper evaluates an intervention aimed at improving medication safety for northeastern and western Germany under real-world conditions, thereby providing a pragmatic approach to the challenges of multi-center studies with staggered intervention starts and voluntary participation. The analysis utilizes iterative Propensity Score Matching (PSM) followed by a Difference-in-Differences (DiD) estimator to navigate the methodological complexities and assess the intervention's effectiveness and cost-effectiveness. Results reveal a significant reduction in ADE-related hospital admissions by 27.5% and overall hospital admissions by 17.5%. We find that the intervention is cost-effective at an incremental cost-effectiveness ratio (ICER) of €15,169.66 per averted ADE and €4,180.61 per averted hospital admission. This study illustrates for evaluating complex health interventions in real-world settings and underscores the importance of balancing health outcomes improvements with economic considerations in aging populations.

PMID:40448133 | DOI:10.1186/s12913-025-12898-0

Lancet Haematol. 2025 Jun;12(6):e451-e462. doi: 10.1016/S2352-3026(25)00035-3.

ABSTRACT

As the therapeutic landscape in haematological malignancies has evolved from traditional chemotherapies to novel biological, targeted, and cellular therapies, adverse event profiles have accordingly shifted with emerging and newly described chronic, cumulative, and delayed symptomatic adverse events. The current standard of toxicity reporting in clinical trials, centred on maximum-grade adverse events, is wholly inadequate for characterising the tolerability of therapies in the modern era. As such, the science of adverse event measurement, analysis, and reporting in clinical trials needs to evolve with our ever-growing repertoire of therapeutics to facilitate more comprehensive and accurate toxicity assessment for treatment decision making. In this first paper in the Adverse Event Reporting Series, a follow-up of a 2018 Lancet Haematology Commission, we review advances in the reporting of newly described adverse events and toxicity domains in haematological malignancies, emerging clinical trial designs to more accurately identify optimal dosing strategies through enhanced adverse event measurement, and novel analytic and visualisation tools to facilitate interpretation of trial adverse event data.

PMID:40447353 | DOI:10.1016/S2352-3026(25)00035-3

Prim Care Companion CNS Disord. 2025 May 29;27(3):24r03857. doi: 10.4088/PCC.24r03857.

ABSTRACT

Objective: To conduct a systematic review of the available evidence on hydroxychloroquine (HCQ)-induced psychiatric side effects and their management.

Data sources: A literature search was conducted in PubMed, MEDLINE, PsycINFO, and Cochrane collaboration databases from 2000 to 2024 using the keywords "hydroxychloroquine" AND "psychiatry" OR "psychosis" OR "depression" OR "anxiety" OR "bipolar disorder" OR "delirium" OR "psychotic disorders" OR "psychiatric side effects" OR "psychiatric disorders."

Study selection: English-language articles with studies reporting HCQ-induced psychiatric/neuropsychiatric side effects were included. Duplicate records and studies reporting only chloroquine side effects were excluded.

Results: The review included 16 case reports, 8 original articles, and 3 review articles. HCQ was found to trigger symptoms of psychosis, depression, suicidal ideation, mania/hypomania, anxiety, sleep disturbances, and cognitive impairments. The onset of these psychiatric side effects varied, appearing shortly after starting the medication to a more extended period.

Conclusion: Based on the literature, HCQ may be associated with short-term psychiatric adverse effects. A psychiatric consultation for a thorough clinical and risk factor evaluation to differentiate a primary psychiatric disorder from a drug induced adverse effect would help guide the management. Dosage adjustments, discontinuing HCQ if feasible, and psychotropic medications like olanzapine or risperidone may be necessary when psychiatric side effects are secondary to HCQ. Further studies are needed to validate these findings.

Prim Care Companion CNS Disord 2025;27(3):24r03857.

Author affiliations are listed at the end of this article.

PMID:40446824 | DOI:10.4088/PCC.24r03857

Int J Immunopathol Pharmacol. 2025 Jan-Dec;39:3946320251343943. doi: 10.1177/03946320251343943. Epub 2025 May 29.

ABSTRACT

OBJECTIVE: To investigate the comprehensive landscape of hepatotoxic adverse events (AEs) associated with immune checkpoint inhibitors (ICIs), with a special focus on evaluating the potential risk of lethal hepatotoxic AEs.

INTRODUCTION: The widespread adoption of ICIs has markedly improved the prognosis for patients with advanced cancer. However, this therapeutic advance is accompanied by the risk of immune-related adverse events (irAEs), especially hepatotoxic AEs, which particularly affect patients with pre-existing liver diseases or hepatobiliary cancers.

METHODS: Reports in the FAERS database from Q1 2014 to Q3 2024 were collected. The characteristics of ICI-related hepatotoxic AEs were summarized. Disproportionality analysis was conducted to calculate reported odds ratios for assessing signals of hepatotoxic AEs. Additionally, logistic regression was employed to evaluate patient-related factors contributing to an increased risk of these AEs.

RESULTS: Hepatotoxic AEs increased yearly and occurred primarily in patients with hepatobiliary tumors. CTLA-4 inhibitors exhibited the highest incidence of AEs. In contrast, PD-1 inhibitors had the shortest median time to AE onset. Abnormal hepatic function was a common AE, whereas Stauffer's syndrome was identified as a rare AE. The risk of hepatotoxic AEs was notably elevated by combination immunotherapy and the concurrent use of specific drugs. Despite variations in the safety profiles of different ICI regimens, these differences did not significantly influence the risk of fatal hepatotoxicity. Furthermore, older men who experienced other AEs were found to be at higher risk for developing fatal hepatotoxicity.

CONCLUSION: The safety profiles of different ICIs vary widely, necessitating individualized drug selection based on patient-specific factors.

PMID:40443110 | DOI:10.1177/03946320251343943

Future Oncol. 2025 Jun;21(15):1859-1865. doi: 10.1080/14796694.2025.2509409. Epub 2025 May 29.

ABSTRACT

AIMS: To assess hepatic safety data of pexidartinib in adult patients with tenosynovial giant cell tumor (TGCT) from the retrospective 5-year evaluation of the TURALIO® Risk Evaluation and Mitigation Strategy (tREMS) Program.

PATIENTS & METHODS: We analyzed data collected from healthcare professionals, patients, pharmacies, and distributors who participated in the tREMS Program from August 2019 to June 2024.

RESULTS: For the current reporting period, June 2022 to June 2024, of the 524 patients enrolled in the tREMS with ≥ 1 dispense of pexidartinib, 24 (4.6%) had adverse events or laboratory abnormalities suggestive of serious and potentially fatal liver injury, with a total of 45/735 (6.1%) patients over 5 years. One (0.2%) patient in the current period had confirmed vanishing bile duct syndrome (VBDS) and was recovering at last follow-up. Another patient from the previous reporting period had unconfirmed VBDS and was alive with unknown recovery status at last follow-up. For the current reporting period and cumulative 5-year tREMS assessment, the reported frequency and pattern of liver injury were consistent with the phase 3 ENLIVEN trial.

CONCLUSIONS: The tREMS Program effectively mitigates the risk of hepatotoxicity through careful monitoring and early intervention. Pexidartinib remains a viable treatment option for TGCT when managed according to recommended guidelines.

PMID:40438996 | DOI:10.1080/14796694.2025.2509409

Comput Biol Med. 2025 May 28;193:110464. doi: 10.1016/j.compbiomed.2025.110464. Online ahead of print.

ABSTRACT

OBJECTIVE: Developing search strategies for synthesizing evidence on drug harms requires specialized expertise and knowledge. The aim of this study was to evaluate ChatGPT's ability to enhance search strategies for systematic reviews of drug harms by identifying missing and generating omitted keywords.

MATERIALS AND METHODS: A literature search in PubMed identified systematic reviews of drug harms from 10 high-impact journals between 1-Nov-2013 to 27-Nov-2023. Sixteen search strategies used in these reviews were selected each with a single error of omission introduced. ChatGPT's (GPT-4) performance was evaluated based on error detection, similarity between the extracted and generated search strategies via strict and semantic keyword matching, and proportion of omitted keywords generated.

RESULTS: ChatGPT identified the introduced errors in all search strategies. Under strict matching, the mean Jaccard's similarity measure was 0.17 (range: 0.00-0.52) and with semantic matching this increased to 0.23 (range: 0.00-0.53). Similarly, the mean proportion of keywords recreated by ChatGPT was 49 % using strict matching increasing to 71 % with semantic matching.

DISCUSSION AND CONCLUSION: ChatGPT effectively detected errors and generated relevant keywords, showing potential as a tool for evidence retrieval on drug harms.

PMID:40441054 | DOI:10.1016/j.compbiomed.2025.110464

Pediatr Infect Dis J. 2025 May 23. doi: 10.1097/INF.0000000000004859. Online ahead of print.

ABSTRACT

BACKGROUND: Dispersible and immediate-release fixed-dose combinations (FDC) of abacavir, dolutegravir, and lamivudine are priority first-line antiretroviral therapy (ART) in children with HIV-1 (CWHIV). We report safety, efficacy and tolerability of these regimens through 48 weeks of treatment.

METHODS: IMPAACT 2019 was a phase I/II, international, multisite, open-label, noncomparative study of dispersible and immediate-release FDC abacavir/dolutegravir/lamivudine (ABC/DTG/3TC) in participants with HIV-1 <12 years of age weighing 6 to <40 kg. At entry, participants were ART-naive or ART-experienced and virally suppressed on stable ART for ≥6 months. Participants received weight-banded dosing and enrolled across 5 weight bands in parallel. Follow-up visits were completed at weeks 1, 4, 12, 24, 36 and 48.

RESULTS: Fifty-seven participants were enrolled; 2 participants withdrew due to poor drug tolerability. Fifty-four of 55 participants on the study at week 48 remained on the study drug. All 54 participants who remained on study drug through week 48 had viral loads of <200 copies/mL. CD4-lymphocyte counts remained stable with age over 48 weeks. Mean change (95% confidence interval) in body mass index Z-scores was 0.4 (0.2-0.6). Nine study drug-related adverse events were reported. One drug-induced liver injury attributed to abacavir and dolutegravir led to the permanent discontinuation of the study drug.

CONCLUSIONS: Dispersible FDC ABC/DTG/3TC is the first dispersible dolutegravir-containing single tablet regimen for CWHIV. Dispersible- and immediate-release ABC/DTG/3TC was observed to be generally safe, effective and well-tolerated in CWHIV through 48 weeks.

PMID:40440679 | DOI:10.1097/INF.0000000000004859

Cancer Control. 2025 Jan-Dec;32:10732748251337362. doi: 10.1177/10732748251337362. Epub 2025 May 29.

ABSTRACT

IntroductionDrug-induced myelosuppression (DIM) is a serious side effect of several medications, particularly chemotherapy, immunosuppressants, and targeted therapies, which can lead to infections, anemia, and bleeding. While these drugs are effective, their adverse effects can disrupt treatment plans and reduce quality of life. However, early identification of DIM remains challenging, as many associated drugs do not explicitly list this risk, complicating clinical monitoring.MethodsThis study utilized the FDA Adverse Event Reporting System (FAERS) database to perform signal mining and assess the risks of DIM. Reports from the first quarter of 2004 to the third quarter of 2024 were analyzed using signal detection algorithms such as Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM). These methods helped identify drug signals related to DIM and explore risk factors and occurrence patterns.ResultsThe study analyzed 21 380 adverse event reports related to DIM, showing a significant increase in the number of reports since 2019, peaking at 3501 in 2021. Among patients, 50.2% were female, 35.5% were male, and the majority (44.42%) were aged between 18 and 65. Breast cancer patients had the highest DIM incidence (10.6%). Geographically, China reported the most cases (57.4%), followed by Japan (12.4%), and the United States (6.76%). The drugs most frequently linked to DIM included trastuzumab, bevacizumab, venetoclax, methotrexate, and pertuzumab. Additionally, 12 new drug signals were identified that were not labeled for DIM risk, including PERTUZUMAB, SODIUM CHLORIDE, and MESNA, which showed particularly strong or unexpected associations.ConclusionThis study identifies new DIM-related drug signals and emphasizes the need for early detection to improve clinical management and optimize treatment regimens. The findings provide valuable evidence for drug safety monitoring and can help reduce DIM-related risks in cancer treatment.

PMID:40439714 | DOI:10.1177/10732748251337362

Ethiop J Health Sci. 2024 Nov;34(6):459-468. doi: 10.4314/ejhs.v34i6.5.

ABSTRACT

BACKGROUND: Chronic Liver Disease (CLD) is a long-term condition marked by a gradual decline in liver function. Patients with CLD often experience multimorbidity and polypharmacy, which can adversely affect their health outcomes. The objective of the current study is to identify and resolve the drug-related problems associated with chronic liver disease.

METHODS: This prospective observational study involved 150 patients with CLD over a six-month period. Eligible participants included individuals over 18 years old, diagnosed with CLD based on the Child-Pugh score, and currently receiving treatment. Drug-related problems (DRPs) were identified using the Pharmaceutical Care Network Europe (PCNE) classification version 9.1. Data analysis was conducted using Chi-square and Fisher's exact tests with SPSS software version 29.

RESULTS: A total of 212 DRPs were identified and resolved. The most frequent type of DRP was related to treatment efficacy, with 96 instances (45.29%). Within this category, the subcategory 'effect of drug treatment not optimal' was the most common, accounting for 45 patients (21.23%). Drug interactions were identified as the leading cause of DRPs, comprising 65 cases (30.66%). Most issues were addressed at the prescriber level, with 48.11% of interventions accepted by physicians.

CONCLUSION: This study provides valuable insights into identifying and managing DRPs that can negatively impact treatment outcomes in CLD patients. The findings can assist healthcare professionals in prioritizing strategies to enhance clinical results.

PMID:40438433 | PMC:PMC12110266 | DOI:10.4314/ejhs.v34i6.5

Chin Med J (Engl). 2025 May 29. doi: 10.1097/CM9.0000000000003672. Online ahead of print.

ABSTRACT

BACKGROUND: Chronic kidney disease (CKD)-associated anemia (CKD-anemia) is associated with poor survival, and hemoglobin targets are often not achieved with current therapies. Phase 3 trials have demonstrated the treatment efficacy of roxadustat for CKD-anemia. This phase four study aims to evaluate the long-term (52-week) safety and effectiveness of roxadustat in a broad real-world patient population with CKD-anemia with and without dialysis in China.

METHODS: This Phase 4 multicenter, open-label, prospective study, conducted from 24 November 2020 to 11 November 2022, evaluated the long-term safety and effectiveness of roxadustat for CKD-anemia in China. Patients aged ≥18 years with CKD-anemia with or without dialysis were included. The initial oral dose was 70-120 mg (weight-based followed by dose adjustment) over 52 weeks. The primary endpoint was safety based on adverse events (AEs). The secondary endpoints were hemoglobin changes from baseline and the proportion of patients who achieved mean hemoglobin ≥100 g/L. Effectiveness evaluable populations 1 (EE1) and EE2 included roxadustat-naïve and previously roxadustat-treated patients, respectively. The safety analysis set (SAF) included all patients who received ≥1 dose.

RESULTS: The EE1, EE2, and SAF populations included 1804, 193, and 2021 patients, respectively. In the SAF, the mean age was 50 ± 14 years, and 1087 patients (53.8%) were male. Mean baseline hemoglobin was 96.9 ± 14.0 g/L in EE1 and 100.3 ± 12.9 g/L in EE2. In EE1, the mean (95% confidence interval) hemoglobin changes from baseline over weeks 24-36 and 36-52 were 14.2 (13.5-14.9) g/L and 14.3 (13.5-15.0) g/L, respectively. Over weeks 24-36 and 36-52, 83.3% and 86.1% of patients in EE1 and 82.7% and 84.7% in EE2 achieved mean hemoglobin ≥100 g/L, respectively. In the SAF, 1643 patients (81.3%) experienced treatment-emergent AEs (TEAEs). Overall, 219 patients (10.8%) experienced drug-related TEAEs. Thirty-eight patients (1.9%) died of TEAEs (unrelated to the study drug). Vascular access thrombosis was uncommon.

CONCLUSIONS: Roxadustat (52 weeks) increased hemoglobin and maintained the treatment target in Chinese patients with CKD-anemia with acceptable safety, supporting its use in real-world settings.

REGISTRATION: Chinese Clinical Trial Registry (www.chictr.org.cn) ChiCTR2100046322 CDE (www.chinadrugtrials.org.cn) CTR20201568.

PMID:40437668 | DOI:10.1097/CM9.0000000000003672

Future Oncol. 2025 Jun;21(14):1787-1796. doi: 10.1080/14796694.2025.2502313. Epub 2025 May 27.

ABSTRACT

BACKGROUND: Nearly half of patients with cancer are diagnosed at 70 years or older, which presents challenges in cancer care due to their high comorbidity burden and the underrepresentation of this age group in clinical trials. This retrospective study evaluated the association between comorbidity burden and immune checkpoint inhibitors (ICIs) treatment outcomes among older adults.

METHODS: Data were collected from patients aged 70 years or older at the time of diagnosis who were treated with ICIs from 2011 to 2022. Key clinical outcomes include changes in performance status, overall survival (OS), progression-free survival (PFS), and immune-related adverse events (irAEs) and were compared between low baseline Charlson Comorbidity Index (CCI) and high CCI (<4 vs. ≥4) groups.

RESULTS: Among 1,223 patients, patients with CCI scores ≥4 (n = 300) had a significantly shorter OS (11.4 vs. 13.6 months, p = 0.0461) but similar PFS (8.0 vs. 7.7 months, p = 0.258) compared to patients with CCI scores <4. There was no significant difference in changes in performance status pre- and post-treatment (p = 0.14) or in the irAE prevalence between the two groups (39.3% vs. 38.3%, p = 0.786).

CONCLUSION: Our study suggests that ICIs are safe in patients with high comorbidity burden but that the presence of pre-treatment comorbidities decreases overall survival.

PMID:40432298 | DOI:10.1080/14796694.2025.2502313

Future Oncol. 2025 Jun;21(13):1639-1645. doi: 10.1080/14796694.2025.2497257. Epub 2025 May 28.

ABSTRACT

BACKGROUND: Alleviating the toxic and adverse reactions associated with chemotherapy is crucial for improving patient outcomes. This study aimed to assess the impacts of positive emotion, engagement, relationships, meaning, and accomplishment (PERMA) model-based psychological interventions and predictive chemotherapy reaction nursing on patients with malignant tumors following chemotherapy.

RESEARCH DESIGN AND METHODS: The control group (n = 43) received conventional care, while the observation group (n = 43) received psychological intervention based on PERMA model alongside predictive nursing care. Chemotherapy-induced toxicity and side effects, fatigue levels, coping mode, psychological status, and quality of life were assessed.

RESULTS: Compared to the control group, the observation group exhibited a lower incidence of gastrointestinal adverse reactions, myelosuppression, alopecia, and oral ulcers (p < 0.05), reduced behavioral, cognitive, somatic, and emotional fatigue (p < 0.001), lower scores in avoidance and yielding coping styles (p < 0.001), higher scores in confrontation coding mode (p = 0.056), improved quality of life, and better outcomes in anxiety, depression, and overall psychological state of patients (p < 0.001).

CONCLUSION: PERMA model-based psychological interventions and predictive chemotherapy reaction nursing interventions effectively reduce the incidence of chemotherapy-induced toxicity, alleviate fatigue, enhance quality of life, and improve psychological well-being in cancer patients.

PMID:40432478 | DOI:10.1080/14796694.2025.2497257

BMC Pharmacol Toxicol. 2025 May 28;26(1):112. doi: 10.1186/s40360-025-00951-x.

ABSTRACT

BACKGROUND: Hepatic injury is a common pathological process for a wide spectrum of liver diseases. Quercetin has been found to counteract this process by scavenging free radicals, but its therapeutic effect is limited due to poor water-solubility. Thus, the question of how to deliver quercetin to a target organ effectively with minimal side effects has remained a clinical challenge. Our previous research findings indicate that when quercetin is delivered in the form of liposomal nanoparticles, its targeting efficiency to the liver is significantly enhanced. Although quercetin liposomal nanoparticles have been shown to improve the therapeutic effect on liver damage compared to traditional quercetin treatment, the optimal dosage of liposomal quercetin still warrants further exploration. The aim of this study was therefore to ascertain whether there are differences in the therapeutic effects on liver damage at different dosages of quercetin liposomes and to determine the optimal dosage.

METHODS: 62 rats modeled with liver injury were enrolled and distributed into 4 groups, where they were treated with quercetin liposome nanoparticles, blank liposome nanoparticles, simple quercetin, and normal saline accordingly. Serum samples were measured for liver function indicators, and tissue samples were analyzed by pathohistological examination. Statistical analysis was performed to quantify the difference between the experimental and control groups.

RESULTS: Both liver function and histopathological examinations demonstrated enhanced therapeutic effects as the concentration of quercetin liposome drugs increased. Moreover, compared to traditional quercetin treatments, liposomal quercetin nanoparticles of varying concentrations uniformly provide better liver protection, with the highest dose group showing the best therapeutic effect. In addition, low concentration carrier liposome nanoparticles also showed a certain protective effect on the liver damage in rats.

CONCLUSION: Liposomal quercetin nanoparticles exhibit superior efficacy in liver protection and repair compared to pure quercetin, with the highest dose group showing the best therapeutic effect.

PMID:40437639 | DOI:10.1186/s40360-025-00951-x

Sci Rep. 2025 May 28;15(1):18645. doi: 10.1038/s41598-025-02723-3.

ABSTRACT

Endometrial cancer (EC) is one of the most common malignancies in women. In recent years, immunotherapy has gradually become a significant treatment option. However, the mechanisms underlying immune checkpoint inhibitor (ICI)-related Adverse Events (AEs) remain poorly understood, posing significant challenges for optimizing clinical treatment strategies. This study aims to integrate the FAERS database and single-cell transcriptomic data to investigate potential mechanisms underlying PD-1 inhibitor-related AEs in EC immunotherapy, with a focus on exploring the PD-1-associated cell communication network and its potential compensatory activation pathways. Data related to AEs were extracted from the FAERS database. Disproportionality analyses, including Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS), were used to quantify signals of immune-related AEs (irAEs) associated with ICIs. We compared the occurrence timing and characteristics of AEs across different drugs. Subsequently, scRNA-seq was performed to analyze the tumor microenvironment of EC, focusing on PD-1-high expressing cell populations. Cell Communication was analyzed and key receptor-ligand pairs were identified. From Q1 2004 to Q3 2024, 21,838,627 drug-related reports were retrieved from FAERS, including 2,202 related to ICIs. ICI-associated irAEs involved 26 organ systems, with general disorders, gastrointestinal disorders, and injury/poisoning as the top System Organ Class (SOC). Fatigue, product use issues, and diarrhea were the most reported Preferred Terms (PTs). PD-1 inhibitors were associated with faster onset of AEs compared to PD-L1 inhibitors and Weibull modeling indicated an early failure-type AE pattern for both treatments. Single-cell analysis further demonstrated that PD-1 was highly expressed in CD8 + cytotoxic T cells and Tfh cells, which communicated with other cells within the tumor microenvironment through key receptor-ligand pairs such as CXCL12-CXCR4 and CXCL16-CXCR6. These findings suggested that PD-1 inhibitors may induce AEs through compensatory activation of the CXCR4 and CXCR6 pathways. This study suggested that PD-1 inhibitors may contribute to irAEs in EC, potentially through compensatory activation of the CXCR4 and CXCR6 pathways. By integrating FAERS and scRNA-seq data, key receptor-ligand interactions were identified, providing preliminary insights that could inform future efforts to optimize immunotherapy efficacy and mitigate AEs. However, further validation through clinical studies and mechanistic research is needed to confirm these findings.

PMID:40436981 | DOI:10.1038/s41598-025-02723-3

Sci Rep. 2025 May 28;15(1):18738. doi: 10.1038/s41598-025-02426-9.

ABSTRACT

Pemetrexed, a multi-target antifolate chemotherapeutic widely used in non-small cell lung cancer (NSCLC) and malignant pleural mesothelioma (MPM), is associated with various adverse drug events (ADEs), some of which may be underrecognized in clinical trials. This study conducted a comprehensive pharmacovigilance analysis using two major spontaneous reporting systems-FAERS (2004Q1-2024Q3) and JADER (2007Q1-2024Q3)-to evaluate pemetrexed-related ADEs. Disproportionality analysis was performed using four algorithms: Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-Item Gamma Poisson Shrinker (MGPS). Time-to-onset (TTO) patterns were assessed using Weibull distribution modeling. A total of 12,026 and 4,522 pemetrexed-related ADE reports were retrieved from FAERS and JADER, respectively. The most frequently reported ADEs included hematologic toxicities (anemia, neutropenia, thrombocytopenia), gastrointestinal disorders (nausea, vomiting, diarrhea), and renal impairment. Strong safety signals were consistently identified for these events. Notably, novel ADE signals such as hepatobiliary injury, endocrine dysfunction, and thromboembolic events were observed in both databases. Subgroup analyses revealed sex- and age-specific ADE patterns, with younger patients and males showing distinct toxicity profiles. Sensitivity analysis excluding combination therapies confirmed the robustness of primary signals. TTO analysis revealed that most ADEs occurred within the first two months after pemetrexed initiation, with a median TTO of 27 days and a predominance of early failure patterns (Weibull β < 1), highlighting the importance of close monitoring during early treatment. Rare but severe ADEs, including myocarditis, sepsis, cholestasis, and pseudocellulitis, were identified, several of which are not currently listed in official drug labeling. This study provides a comprehensive safety assessment of pemetrexed, confirming known toxicities and identifying new safety signals. Continuous pharmacovigilance is essential to optimize its clinical use and improve patient safety.

PMID:40436917 | DOI:10.1038/s41598-025-02426-9

R I Med J (2013). 2025 Jun 2;108(6):60-65.

ABSTRACT

Immune checkpoint inhibitors (ICIs) have significantly improved the overall survival of patients with many different types of cancer since they were first approved by the United States in 2011. However, patients who are treated with ICIs can develop a variety of toxicities, known as immunotherapy-related adverse events (irAEs), that have the potential to affect essentially any organ system. Due to the growing use of ICIs in the field of oncology, it is likely that non-oncologist clinicians will increasingly encounter irAEs in both inpatient and outpatient environments. This review will provide an overview of both common and rare irAEs for the non-oncologist clinician, in addition to providing information about several guidelines developed by multiple organizations that can aid the non-oncologist clinician with the initial work-up and diagnosis of irAEs.

PMID:40435146

J Neurol. 2025 May 28;272(6):429. doi: 10.1007/s00415-025-13172-3.

ABSTRACT

BACKGROUND: Many women are exposed to antiseizure medications (ASMs) during pregnancy, raising concerns about pregnancy and offspring health risks. The current safety data remain insufficient, necessitating further investigation.

METHODS: Using data from the FDA Adverse Event Reporting System (2010-2023), this study employed both the Reporting Odds Ratio (ROR) and Bayesian Confidence Propagation Neural Network (BCPNN) for disproportionality analysis of pregnancy and offspring toxicity related to maternal ASM exposure. In addition, we performed signal adjustment by excluding polytherapy cases, and drug-drug interaction (DDI) signals of two ASMs were identified using Ω Shrinkage measures and Chi-square tests.

RESULTS: 3,459 mothers were exposed to 23 ASMs, resulting in 10,910 adverse events. 59 malformation signals, 27 adverse perinatal outcome signals, and 35 dysplasia signals were identified. Among traditional ASMs, valproic acid (VPA) and carbamazepine (CBZ) exhibited the highest number of signals, while levetiracetam (LEV), lamotrigine (LTG), lacosamide, gabapentin, and topiramate (TPM) predominated among newer ASMs. Signals for cardiac malformations, adverse neurodevelopment, and adverse offspring growth outcomes were widespread, with the strongest signals for specific outcomes observed for zonisamide [ROR = 14.82, 95% CI: 5.43-40.41], gabapentin [ROR = 52.52, 95% CI: 15.68-175.95], and brivaracetam [ROR = 22.96, 95% CI: 8.42-62.61], respectively. Six DDI signals displayed ≥ 3, including LTG + LEV/VPA associated with malformation, CBZ + lacosamide/LTG, and VPA + clonazepam associated with fetal loss.

CONCLUSIONS: The potential risks associated with LEV and LTG surpass expectations, warranting further evaluation, particularly in combination therapy. In addition, ASMs with widespread signals, such as VPA, CBZ, TPM, and lacosamide, warrant heightened attention.

PMID:40434447 | DOI:10.1007/s00415-025-13172-3

Front Cell Infect Microbiol. 2025 May 13;15:1455735. doi: 10.3389/fcimb.2025.1455735. eCollection 2025.

ABSTRACT

BACKGROUND: Probiotics are recognized as beneficial foods, but adverse reactions reported by individuals still exist. This study aims to analysis adverse events (AE) related to probiotics from the FAERS database from the first quarter (Q1) of 2005 to the fourth quarter (Q4) of 2023.

METHODS: The AE data related to probiotic from the 2005 Q1 to the 2023 Q4 were collected. R language was applied to analyze the standardized AE data and three algorithms including the reporting odds ratio (ROR), the proportional reporting ratio (PRR) and the empirical Bayes geometric mean (EBGM) were used to identify AE signals.

RESULTS: In this study, 10,698,312 reports were collected from the FAERS database, of which 74 probiotic-related adverse events were reported. About one third of the reported cases were older than 60 years.36.36% of the reported cases required Hospitalization. A total of 285 preference terms (PTS) and 15 system organ classes (SOC) were identified. In the overall analysis, only 9 PTs and 2 SOCs met significant disproportionality for all three algorithms simultaneously. SOCs included Gastrointestinal disorders (N=97, ROR=5.3, PRR=3.84, EBGM=3.84) and Hepatobiliary disorders (N=9, ROR =3.39, PRR=3.32, EBGM=3.32). PTs included Gastrointestinal pain (ROR=77.76, PRR=76.69, EBGM=76.63), Hypophagia (ROR=24.13, PRR=23.88, EBGM=28.88), and Hepatobiliary disorders (N=97, ROR=5.3, PRR=3.84, EBGM=3.84) and Flatulence (ROR=23.75, PRR=23.28, EBGM=23.27) were the top four highest. Meanwhile, s found new unique adverse signals such as Agitation (ROR=12.48, PRR=12.32, EBGM=12.32) and Anxiety (ROR=4.10, PRR=4.04, EBGM=4.04). Additionally, subgroup analyses were performed to identify AE signals based on gender and age. Metabolism and nutrition disorders (N=6, ROR=3.21, PRR=3.04, EBGM=3.04) and Asthenia (N=3, ROR=5.9, PRR=5.71, EBGM=5.71) were unique AE signal for the male group.

CONCLUSION: Although, the risk of adverse reactions arising from the application of probiotics cannot be ignored. However, However, the results of this FAERS-based study continue to support the overall safety of probiotic preparations. It is necessary to pay attention to the potential influence of factors such as gender and age on the effects and adverse reactions of probiotic application in basic research and clinical application.

PMID:40433664 | PMC:PMC12106448 | DOI:10.3389/fcimb.2025.1455735