BMC Pharmacol Toxicol. 2025 Apr 22;26(1):91. doi: 10.1186/s40360-025-00920-4.

ABSTRACT

BACKGROUND: Ganirelix, a third-generation GnRH antagonist, is widely used in assisted reproductive technology (ART) for rapid pituitary suppression to prevent premature luteinizing hormone (LH) surges. Despite its extensive clinical use, real-world evidence on its safety in large populations remains scarce. This study aimed to evaluate the safety profile of ganirelix by comprehensively analyzing adverse drug events (ADEs) using real-world data from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) and the Japan Adverse Drug Event Reporting (JADER) database.

METHODS: We extracted ADE data from FAERS (Q1 2004-Q2 2024) and JADER (Q1 2009-Q1 2024). Disproportionality analyses, including reporting odds ratios (ROR), proportional reporting ratios (PRR), Bayesian Confidence Propagation Neural Networks (BCPNN), and Multi-item Gamma Poisson Shrinkage (MGPS), were employed to identify significant associations between ganirelix and ADEs.

RESULTS: In the FAERS database, we identified 1,096 ganirelix-related ADE reports, spanning 26 system organ classes (SOCs). A total of 65 positive signals were detected, including ADEs consistent with drug label such as ovarian hyperstimulation syndrome (OHSS) (n = 290, ROR 2462.76, PRR 2168.48, EBGM05 1655.59, IC025 9.18), injection site pain (n = 54, ROR 3.99, PRR 3.93, EBGM05 3.13, IC025 0.31), and fetal death (n = 6, ROR 21.05, PRR 21.00, EBGM05 10.72, IC025 2.72). Additionally, unexpected signals not listed in the drug label were identified, including ectopic pregnancy (n = 7, ROR 33.02, PRR 32.93, EBGM05 17.64, IC025 3.37), maternal exposure before pregnancy (n = 30, ROR 76.09, PRR 75.16, EBGM05 74.72, IC025 6.22), dermatitis allergic (n = 4, ROR 7.98, PRR 7.97, EBGM05 3.50, IC025 1.33), and bladder tamponade (n = 4, ROR 771.47, PRR 770.3, EBGM05 311.57, IC025 7.80). The median time to ADE onset was 13 days. External validation using the JADER database (62 ganirelix-related ADE reports) confirmed four signals, including abortion (n = 19), OHSS (n = 17), missed abortion (n = 9), and fetal death (n = 8), aligning with FAERS findings.

CONCLUSION: This study provides a robust real-world safety evaluation of ganirelix, with findings corroborated by two independent pharmacovigilance databases. While consistent with clinical observations, the identification of unexpected signals warrants further pharmacoepidemiological investigations to confirm these results.

PMID:40264185 | DOI:10.1186/s40360-025-00920-4

Front Immunol. 2025 Apr 8;16:1582050. doi: 10.3389/fimmu.2025.1582050. eCollection 2025.

ABSTRACT

OBJECTIVE: Advanced cervical cancer remains associated with high mortality rates. While pembrolizumab has improved clinical outcomes in cervical cancer, the therapeutic efficacy in advanced stages is often compromised by immune-related adverse events (irAEs). This study aimed to systematically analyze pembrolizumab-associated adverse events (AEs) in cervical cancer using the FDA Adverse Event Reporting System (FAERS) database, providing new insights for optimizing clinical practice.

METHODS: AE reports related to pembrolizumab in cervical cancer were extracted from the FAERS database (Q1 2016 to Q4 2024). Disproportionality analyses were performed using multiple algorithms, including the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS). AEs were classified by system organ class (SOC) and preferred term (PT) based on the Medical Dictionary for Regulatory Activities (MedDRA), then ranked by frequency and signal strength.

RESULTS: A total of 646 pembrolizumab-related AE reports in cervical cancer were identified. Age distribution peaked at 45-65 years cohort (32.75%), followed by 18-44 years (12.85%), 66-75 years (11.76%), and >75 years (4.64%). Among 270 AE reports with documented onset timelines, events predominantly occurred 3-6 months after pembrolizumab initiation (n=114, 41.36%). Clinical outcomes were categorized as other (52.80%), hospitalization (27.00%), death (10.25%), unknown (6.06%), life-threatening (2.77%), and disability (1.12%). Predominant AEs involved hematologic, endocrine, dermatologic, neurologic, gastrointestinal, urinary, and reproductive systems.

CONCLUSION: This real-world pharmacovigilance study systematically characterizes pembrolizumab-associated AEs in cervical cancer, identifying high-signal events such as hematologic disorders, endocrine dysfunction, and dermatologic toxicities. These findings provide critical evidence for risk stratification and safety monitoring in clinical practice, emphasizing the need for organ-specific vigilance during the 3-6 months treatment window.

PMID:40264768 | PMC:PMC12011867 | DOI:10.3389/fimmu.2025.1582050

Acta Med Indones. 2025 Jan;57(1):74-80.

ABSTRACT

BACKGROUND: Geriatric patients are often subject to polypharmacy, increasing their risk of adverse drug reactions (ADRs). This study evaluated polypharmacy practices, ADR incidence, predictive factors, and the applicability of the GerontoNet Score at a tertiary referral teaching hospital in Indonesia.

METHODS: This retrospective study included 340 geriatric inpatients at Dr. Cipto Mangunkusumo Hospital, Jakarta, in 2023. The relationship between demographic data, comorbidities, number of drugs used, and ADR events was analyzed using the Chi-square test. The association between GerontoNet ADR scores and ADR events was also assessed.

RESULTS: The study included 182 (53.5%) male and 158 (46.5%) female patients, with a mean age of 71.9±6.1 years. Of these, 70.9% were aged 65 to 74. A total of 78.8% of patients had ≥ 4 comorbidities. The number of drugs ranged from 3 to 28, with a mean of 10.7 drugs and a median of 10 drugs. ADRs were detected in 26 patients (7.6%), with 17 cases in females and 9 in males (p=0.044). Insulin- and diuretic-induced hypokalemia were the most frequent ADR (13 patients), followed by heparin-induced thrombocytopenia (3 patients). No significant correlation was found between ADRs and age (p=0.505), number of comorbidities (p=0.425), number of drugs (p=0.576), or GerontoNet ADR Score (p=0.530).

CONCLUSION: Polypharmacy is prevalent at Dr. Cipto Mangunkusumo Hospital, yet the incidence of ADRs is relatively low. Most ADRs were related to high-alert drugs, while no significant correlations were found between age, polypharmacy, comorbidities, or GerontoNet Score with ADR events.

PMID:40263686

Clin Cancer Res. 2025 Apr 21. doi: 10.1158/1078-0432.CCR-25-0206. Online ahead of print.

ABSTRACT

PURPOSE: Izalontamab (SI-B001) is a novel EGFR×HER3 bispecific antibody. This first-in-human phase I study presents the safety and pharmacokinetics of izalontamab.

PATIENTS AND METHODS: Previously treated patients with locally advanced or metastatic epithelial tumors were enrolled in the dose-escalation or dose-expansion phases. The dose-escalation phase consisted of an accelerated titration and a "3+3" design with 9 dose levels from 0.4 to 28.0 mg/kg. The dose-expansion phase included 5 dose levels from 6.0 to 21.0 mg/kg. Izalontamab was administered intravenously weekly(QW) or every two weeks(Q2W) in a four-week cycle. Available pre-treatment specimens were obtained to explore the relationship between EGFR/HER3 expression and efficacy.

RESULTS: 60 patients were enrolled. Among the 60 enrolled patients, 49 had non-small cell lung cancer(NSCLC), 6 had nasopharyngeal cancer, 3 had head and neck cancer(HNSCC), and 2 had other types of cancer. The most common treatment-related adverse events were rash (42%), paronychia (25%) and infusion-related reactions (23%). No drug-related death occurred. Izalontamab displayed non-linear pharmacokinetic behavior and clearance at steady state appeared to be approaching a dose-independent value at 6 mg/kg and above. The best response included 2 confirmed partial responses in NSCLC and HNSCC patients; 18 patients had stable disease, including NSCLC(n = 17) and colorectal cancer(n=1). The recommended phase 2 dose for izalontamab was determined as 9-16mg/kg QW weekly.

CONCLUSIONS: Izalontamab was well tolerated and demonstrated preliminary antitumor activity in patients with locally advanced or metastatic epithelial tumors, supporting it as a promising therapeutic candidate for combination therapies, with a phase 3 study currently underway.

PMID:40260627 | DOI:10.1158/1078-0432.CCR-25-0206

Oral Dis. 2025 Apr 21. doi: 10.1111/odi.15337. Online ahead of print.

ABSTRACT

OBJECTIVE: Neuropsychiatric disorders are associated with poor oral health, with antipsychotics as potential contributors. This study aimed to analyse the oral adverse effects of antipsychotics using the EudraVigilance database.

METHODS: A case/noncase analysis was conducted to calculate reporting odds ratios (ROR) and assess the disproportionality of oral adverse events.

RESULTS: A total of 5663 reports of oral adverse effects related to antipsychotics were identified. Atypical antipsychotics had a higher overall incidence (5663 vs. 787 for typical), but typical antipsychotics showed stronger associations with specific oral issues (ROR = 2.2 vs. 1.6 for atypical). The most commonly reported effects were disturbances in salivary flow, including xerostomia and hypersalivation. Olanzapine and quetiapine were linked to dry mouth (ROR = 1.8 and 3.0) and tooth loss (ROR = 1.7 and 1.8). Clozapine had the highest number of reports (1619) and ROR (33.1) for hypersalivation. Disproportionality analysis revealed significant associations with orofacial dyskinesia for all antipsychotics, except clozapine. Aripiprazole had the highest ROR (13.7) for orofacial dyskinesia and was linked to a swollen tongue in patients aged ≤ 17 years (12 cases, ROR = 3.6). No sex-based differences were identified.

CONCLUSIONS: Antipsychotics significantly affect oral health, highlighting the need for preventive dental care and interventions to reduce these effects and improve patient well-being.

PMID:40259575 | DOI:10.1111/odi.15337

Clin Transl Sci. 2025 Apr;18(4):e70193. doi: 10.1111/cts.70193.

ABSTRACT

Medication prescribing is imperfect, and unintended side effects complicate patient care. Pharmacogenomics (PGx) is an emerging solution that associates genotypes with personalized drug-related outcomes, but it has not been widely adopted. We hypothesize that patient and provider attributes may predict and promote PGx utilization. We studied PGx using data from the ACCOuNT study, a multi-institutional prospective trial that implemented broad preemptive PGx result delivery for African American inpatients [Clinicaltrials.gov NCT03225820]. Patients were genotyped, and their PGx information was made available within an integrated informatics portal. Utilization of PGx data (defined as the active choice to review PGx information) was left to the enrolled provider's discretion. Our primary endpoint was to identify patient and care team attributes associated with PGx use. We identified statistically significant univariate predictors and utilized logistic regression to compare relative predictiveness. This study included 187 patients (60.4% female, median age 55, 75.4% treated at the University of Chicago, 17.6% at Northwestern University, and 7.0% at the University of Illinois Chicago) and 188 providers (63.8% MD, 22.3% PharmD, 6.4% PA, and 7.4% APN). In multivariate analysis, we found that the use of PGx information in a prior admission significantly predicted the use in subsequent admissions (OR 7.62, p < 0.05). Similarly, pharmacist participation on care teams significantly predicted PGx use (OR 4.52, p < 0.05). In the first systematic analysis of the impact of patient and care team factors on inpatient PGx clinical decision support (CDS) adoption, we found that actionable care team attributes, such as pharmacist participation or successful initial adoption measures, predict PGx CDS use.

PMID:40259529 | DOI:10.1111/cts.70193

Sci Rep. 2025 Apr 21;15(1):13693. doi: 10.1038/s41598-025-98528-5.

ABSTRACT

Drug-drug interaction-induced (DDI-induced) adverse drug event (ADE) is a significant public health burden. Risk of ADE can be related to timing of exposure (TOE) such as initiating two drugs concurrently or adding one drug to an existing drug. Thus, real-world data based DDI detection shall be expanded to investigate precise adverse DDI with a special awareness on TOE. We developed a Sensitive and Timing-awarE Model (STEM), which was able to optimize the probability of detection and control false positive rate for mining all two-drug combinations under case-crossover design, in particular for DDIs with TOE-dependent risk. We analyzed a large-scale US administrative claims data and conducted performance evaluation analyses. We identified signals of DDIs by using STEM, in particular for DDIs with TOE-dependent risk. We also observed that STEM identified significantly more signals than the conditional logistic regression model-based (CLRM-based) methods and the Benjamini-Hochberg procedure. In the performance evaluation, we found that STEM demonstrated proper false positive control and achieved a higher probability of detection compared to CLRM-based methods and the Benjamini-Hochberg procedure. STEM has a high probability to identify signals of DDIs in high-throughput DDI mining while controlling false positive rate, in particular for detecting signals of DDI with TOE-dependent risk.

PMID:40258952 | DOI:10.1038/s41598-025-98528-5

Neurol Ther. 2025 Apr 21. doi: 10.1007/s40120-025-00748-4. Online ahead of print.

ABSTRACT

INTRODUCTION: The neonatal Fc receptor (FcRn) inhibitors efgartigimod and rozanolixizumab have not long been introduced for treating generalized myasthenia gravis (MG); hence, real-world evidence for their administration in multiple cycles and switching from intravenous to subcutaneous formulation remains insufficient.

METHODS: We retrospectively assessed 17 consecutive patients with generalized MG and diverse backgrounds who were treated with FcRn inhibitors.

RESULTS: All patients initially received an intravenous efgartigimod formulation. Of 17 patients, 10 (59%) were considered responders, defined as a persistent improvement of at least two points for a minimum of four consecutive weeks in the MG activities of daily living score during the first treatment cycle. Four of the non-responders in the first cycle demonstrated an improvement in fulfilling the criteria for responders in the second cycle. One of these patients, who had thymoma metastatic lesions, experienced a significant worsening of MG symptoms during the first treatment cycle. Five patients switched from intravenous to subcutaneous formulations, which was successful in all patients. The efficacy of the subcutaneous formulations was similar to that of the intravenous formulation, even in patients who switched from efgartigimod to rozanolixizumab. The drugs were well tolerated without any drug-related serious adverse events irrespective of the formulation type.

CONCLUSION: FcRn inhibitors were effective and safe in patients with generalized MG, but their efficacy may depend on the disease activity during treatment. The transition from the intravenous formulation to more convenient subcutaneous formulations was successful, indicating the likely growth of future demand for subcutaneous formulations.

PMID:40257679 | DOI:10.1007/s40120-025-00748-4

Hum Vaccin Immunother. 2025 Dec;21(1):2489900. doi: 10.1080/21645515.2025.2489900. Epub 2025 Apr 21.

ABSTRACT

VN-0200 is an investigational β-glucan-CpG-adjuvanted respiratory syncytial virus (RSV) vaccine (antigen: VAGA-9001a [RSV F glycoprotein], adjuvant: MABH-9002b). This multicenter, randomized, double-blind, dose-finding phase 2 study explored the optimal VN-0200 dose and confirmed its humoral and cellular immunity and safety. In total, 342 healthy Japanese participants aged 60 to 80 years were randomized to one of 10 vaccination groups, each receiving a different combination of VAGA-9001a and MABH-9002a. VN-0200 was administered intramuscularly on Day 1 and Day 29. Geometric mean titer (GMT) and geometric mean fold rise (GMFR) of neutralization activity for anti-RSV subgroups A (RSV/A) and B (RSV/B), anti-VAGA-9001a antibody titer, and VAGA-9001a-specific interferon (IFN)-γ response were evaluated. Safety was monitored throughout the study. GMTs of serum anti-RSV/A neutralization activity increased from baseline to Day 57 and lower limits of the 95% confidence intervals of the corresponding GMFRs were >1.0 relative to baseline in all treatment groups (primary endpoint). Findings were similar for anti-RSV/A (Day 29) and anti-RSV/B (Day 29 and Day 57) neutralization activity, anti-VAGA-9001a antibody titer (Day 29 and Day 57), and VAGA-9001a-specific IFN-γ response (Day 29 and Day 57) (secondary endpoints). There was no clear influence of adjuvant or dose - response relationship of the antigen or adjuvant for any of the study endpoints. There were no serious vaccine-related treatment-emergent adverse events (TEAEs) or vaccine-related TEAEs leading to death. All antigen/adjuvant dose combinations of VN-0200 were well tolerated and elicited an increase in anti-RSV/A and anti-RSV/B neutralization activity from baseline to Day 29 and Day 57.

PMID:40257186 | DOI:10.1080/21645515.2025.2489900

Cureus. 2025 Mar 20;17(3):e80907. doi: 10.7759/cureus.80907. eCollection 2025 Mar.

ABSTRACT

Most patients who undergo percutaneous coronary intervention (PCI) to address coronary artery disease receive antiplatelets and anticoagulants to lower the risk of postoperative thrombotic events. Tirofiban, a glycoprotein IIb/IIIa inhibitor (GPI), has demonstrated remarkable efficacy in reducing morbidity and mortality rates in PCI postoperative care. However, it is crucial to be vigilant about potential complications associated with tirofiban, particularly thrombocytopenia. Thrombocytopenia is a serious complication that requires close monitoring of the patients' platelet count after initiation of the therapy. Regularly monitoring levels in two- to six-hour increments during the initial 24-48 hours after exposure can detect most cases of acute and potentially life-threatening thrombocytopenia. Prompt discontinuation of GPI and timely implementation of other supportive measures can help prevent further adverse events. We present a case of a 70-year-old male who presented to the Emergency Department with chest pain. Following a thorough evaluation, the patient underwent angiography, during which stent placement was performed. Administration of tirofiban resulted in profound thrombocytopenia, with platelets decreasing to 1 g/L within 24 hours. Tirofiban was promptly withdrawn, and a platelet transfusion was initiated in order to stabilize the patient's platelet level.

PMID:40255833 | PMC:PMC12009166 | DOI:10.7759/cureus.80907

Cureus. 2025 Mar 19;17(3):e80832. doi: 10.7759/cureus.80832. eCollection 2025 Mar.

ABSTRACT

Orlistat is an FDA-approved medication for obesity management that functions as a pancreatic lipase inhibitor. This medication is accessible without a prescription in numerous developed nations. As its utilization rises, the likelihood of experiencing adverse events also increases. A thorough understanding of these events is crucial for making informed decisions and ensuring effective management. We describe the case of a 23-year-old female who presented with acute pancreatitis after she started orlistat. We reviewed the association between orlistat use and acute pancreatitis, analyzing clinical cases and potential risk factors. By examining available medical literature and case studies, our study aims to provide insights into the correlation between orlistat therapy and the manifestation of acute pancreatitis.

PMID:40255727 | PMC:PMC12007682 | DOI:10.7759/cureus.80832

Can J Gastroenterol Hepatol. 2025 Apr 10;2025:2702089. doi: 10.1155/cjgh/2702089. eCollection 2025.

ABSTRACT

CKD-495 is a newly developed drug extracted from Cinnamomum cassia Presl. This phase II study assessed the clinical benefits of CKD-495 in the treatment of acute and chronic gastritis. This study randomly assigned 250 patients with endoscopically-proven gastric mucosal erosion to five groups. The groups received either 75 mg or 150 mg of CKD-495, 100 mg of rebamipide, 60 mg of Artemisiae argyi folium 95% ethanol ext. (20 ⟶ 1) (Stillen; Dong-A ST Co., Ltd., Seoul, Korea), or placebo for 2 weeks, respectively. The primary endpoint was the erosion improvement rate, and the secondary endpoints were erosion cure rates, improvement rates of gastrointestinal symptoms, edema, redness, and hemorrhage. Drug-related adverse events were evaluated. The endoscopic erosion improvement rate was significantly higher in the 75 mg CKD-495 group than in the other groups in both the full analysis set (73% vs. 41%, 45%, 52%, 48% for the 75 mg CKD-495, 150 mg CKD-495, placebo, 60 mg Stillen, and 100 mg rebamipide groups, respectively) and the per-protocol set (PPS) (75% vs. 37%, 45%, 51%, 50%). The cure rate of gastric erosion was significantly higher in the 75 mg CKD-495 group than in the other groups. The improvement rates of hemorrhage erosion were significantly higher in the 150-mg CKD-495 group. No significant differences were observed in the safety profiles. No serious adverse events or drug reactions were observed. These results demonstrate that 75 mg of CKD-495 has excellent efficacy for the treatment of endoscopic and symptomatic improvements for acute and chronic gastritis. Trial Registration: ClinicalTrials.gov identifier: NCT03437785.

PMID:40255536 | PMC:PMC12006708 | DOI:10.1155/cjgh/2702089

Age Ageing. 2025 Mar 28;54(4):afaf095. doi: 10.1093/ageing/afaf095.

ABSTRACT

BACKGROUND: Ageing increases the risk of treatment-related toxicities (TRT) in patients with cancer. This systematic review provided an overview of existing prediction models for TRT in this population and evaluated their predictive performances.

METHODS: A systematic search was conducted in MEDLINE (Ovid), Embase, PubMed, CINAHL and CENTRAL (Cochrane Central Register of Controlled Trials) databases for studies developing severe TRT prediction models in older cancer patients published between 1 January 2000 and 31 October 2023. The included models were summarised and assessed using the Prediction Model Risk of Bias Assessment Tool (PROBAST).

RESULTS: Out of the 6192 studies identified through literature searching, 12 studies involving 90 819 participants met the inclusion criteria. About 15 prediction models (9 (60%) for diverse cancer types; 6 (40%) for specific cancer types) were analysed. The models included between 4 and 11 variables. The most common predictors were physical function (n = 12, 80%), performance status (n = 5, 33.3%) and the MAX2 index (n = 5, 33.3%). About 2 models (13.3%) had external validation, 9 (60.0%) had internal validation and 6 (40.0%) lacked any validation. All studies were assessed to have a high risk of bias according to the PROBAST criteria.

CONCLUSION: This systematic review demonstrated that existing prediction models for TRT exhibited moderate discrimination ability in older patients with cancer, with significant heterogeneity in clinical settings and predictive variables. Standardised procedures for developing and validating prediction models are essential to improve the prediction of severe TRT in this vulnerable population.

PMID:40253686 | DOI:10.1093/ageing/afaf095

Neurotherapeutics. 2025 Apr 18:e00581. doi: 10.1016/j.neurot.2025.e00581. Online ahead of print.

ABSTRACT

Cognitive impairment is common in people with multiple sclerosis (PwMS). There is an urgent need to identify/develop novel therapies that can help cognitive function in MS. Insulin is critical for helping with regulation of multiple CNS functions, including learning and memory. Insulin administrated intranasally has shown to improve memory and learning in healthy people and in those with some neurodegenerative disorders. Hence, there was rationale for investigating intranasal insulin in PwMS who experience cognitive impairment. We completed a phase Ib/II, randomized, double-blind, placebo-controlled trial; participants were randomized in a 1:1:1 fashion, stratified by relapsing versus progressive MS, to intranasal insulin 10 ​international units (IU) twice a day, 20 IU twice a day, or placebo for 24 weeks. One-hundred and five PwMS were enrolled, 69 of whom had at least one follow up visit during the active treatment phase of the trial (baseline to week 24). The cohort's mean age was 52.4 ​± ​9.7years, 62 ​% were female, and ∼60 ​% had relapsing-remitting MS. The most common side effects amongst treatment groups included headache, rhinorrhea, and dizziness. There were 13 SAEs which were not deemed study drug related; there were no deaths. The main clinical outcome measure, SDMT, did not demonstrate any difference between intranasal insulin and placebo. Similar findings were noted for all secondary outcome measures. Intranasal insulin appeared safe and well-tolerated in PwMS. However, it was not superior to placebo in any of the clinical outcome measures assessed, which could have been impacted by the duration of the trial, small sample size for a three-arm trial design, data missingness (particularly during COVID-19), outcome measure insensitivity to change, baseline cognitive reserve, or other factors. Nonetheless, intranasally-administered therapeutics may be of interest to develop further as a way to get across the blood brain barrier.

PMID:40253245 | DOI:10.1016/j.neurot.2025.e00581

Eur J Cancer. 2025 Apr 15;222:115427. doi: 10.1016/j.ejca.2025.115427. Online ahead of print.

ABSTRACT

AIM OF THE STUDY: The antibody-drug conjugate enfortumab vedotin (EV) received approval in patients with metastatic urothelial carcinoma (mUC). EV-related cutaneous toxicities are frequently reported, whether EV-related AEs association with survival may exist is still unknown. We aim to report the association between cutaneous toxicities and survival in patients receiving EV.

METHODS: This retrospective study enrolled patients treated with monotherapy EV from two oncology centers, followed up for at least 3-months, and data collection demographics, treatments, toxicities, and outcomes. The primary endpoint was progression-free survival (PFS) in patients experiencing cutaneous toxicities or not. Overall survival (OS) was the secondary endpoint.

RESULTS: Data from 63 patients treated with EV from July 19, 2019, to March 12, 2024, were collected. Among them, the 18 (28.6 %) patients experiencing any-grade cutaneous toxicities during EV treatment showed significantly longer median PFS (mPFS: 9.2 vs. 4.7 months, hazard ratio [HR] 0.35; p = 0.0041) and OS (mOS: not reached vs. 8.4 months, HR 0.38; p = 0.0253). The multivariate analysis showed a significant association of cutaneous toxicities with improved PFS (HR 0.40, p = 0.0319), and did not demonstrate significant association with OS even if tendency was kept (HR 0.41, p = 0.067).

CONCLUSION: These results support that patients experiencing any-grade cutaneous toxicity (skin rash) had a prolonged PFS. With the recent expansion of combined treatment using EV plus pembrolizumab in first-line in mUC patients, cutaneous toxicities need to be carefully monitored and optimized dedicated management provided, considering that cutaneous toxicity may be predictive of patient outcome.

PMID:40252634 | DOI:10.1016/j.ejca.2025.115427

Int Wound J. 2025 Apr;22(4):e70513. doi: 10.1111/iwj.70513.

ABSTRACT

Tyrosine kinase inhibitors (TKIs) can treat various cancers, primarily through their antiangiogenic effects. However, as angiogenesis is crucial for successful wound healing, TKIs may adversely impact wound repair. This review analysed all 63 FDA-approved TKIs and identified evidence for wound healing and repair implications in 24 agents. The primary mechanism contributing to impaired wound healing appears to be the inhibition of vascular endothelial growth factor receptors, with secondary targets, such as epidermal growth factor receptors and platelet-derived growth factor receptors, potentially playing a role. Information from safety package inserts, preclinical studies, case reports and clinical trials suggests that these TKIs can cause delayed or impaired wound healing. The safety information generally recommends discontinuing treatment for at least one to 2 weeks before elective surgery and resuming treatment only after adequate wound healing has occurred. Neoadjuvant therapy with TKIs may be feasible if sufficient time is allowed between the cessation of the TKI and the onset of surgery. As the use of TKIs continues to increase, healthcare professionals should be aware of their potential impact on wound healing and take appropriate precautions to minimise the risk of wound-related complications.

PMID:40251464 | DOI:10.1111/iwj.70513

Sci Rep. 2025 Apr 18;15(1):13407. doi: 10.1038/s41598-025-92796-x.

ABSTRACT

Drug-related conjunctivitis can compromise ocular health and quality of life. To evaluate its epidemiology, we analyzed reports from the FDA Adverse Event Reporting System (FAERS) spanning January 2004 to June 2024. The control group in this study comprised individuals using non-target drugs, while the experimental group consisted of individuals using target drugs. Using disproportionality analysis, we identified drugs with a positive signal for conjunctivitis and stratified their risk levels; we also examined induction periods to assess the speed of onset. Among 38 drugs most frequently reported for conjunctivitis, two ophthalmic agents-brimonidine (ROR = 23.04) and latanoprost (ROR = 10.55)-and eight non-ophthalmic drugs, including tralokinumab (ROR = 83.3), dupilumab (ROR = 18.92), and allopurinol (ROR = 5.04), were associated with positive signals. Tralokinumab, brimonidine, dupilumab, and latanoprost were identified as high-association medications. Notably, ophthalmic agents had a significantly shorter induction period than non-ophthalmic drugs (mean 125.9 vs. 298.4 days). These findings underscore the need for vigilant pharmacovigilance and further investigation into the etiology and prevention of drug-related conjunctivitis.

PMID:40251175 | DOI:10.1038/s41598-025-92796-x

Eur J Hosp Pharm. 2025 Apr 18:ejhpharm-2025-004475. doi: 10.1136/ejhpharm-2025-004475. Online ahead of print.

ABSTRACT

Cefoperazone/sulbactam is a third-generation cephalosporin commonly used for severe infections. This case report presents a case of a 68-year-old woman who developed severe coagulation dysfunction and significant active bleeding after starting cefoperazone/sulbactam therapy following aortic dissection surgery. After discontinuing cefoperazone/sulbactam and administering vitamin K1, the patient's coagulation function returned to normal, with no further abnormalities after changing antibiotics. On assessing causality of the adverse drug reaction, the Naranjo scale for cefoperazone/sulbactam was 6. This case highlights the risks of cefoperazone/sulbactam in patients with underlying conditions such as renal insufficiency and malnutrition, emphasising the need for carefully monitoring coagulation parameters and dose adjustment to reduce the occurrence of drug-induced coagulopathy and healthcare-associated complications. Additionally, this case serves as a reminder of the vital contributions that clinical pharmacists make in monitoring and managing medication therapy, stressing the importance of fostering collaboration between clinical pharmacists and other healthcare workers.

PMID:40250970 | DOI:10.1136/ejhpharm-2025-004475

Curr Med Chem. 2025 Apr 17. doi: 10.2174/0109298673327575250331145643. Online ahead of print.

ABSTRACT

Panax ginseng (PG), a staple in traditional medicine in Korea and China, holds a rich history of application for various diseases. Notably, its primary active components, ginsenosides, exhibit diverse therapeutic effects. Chemotherapy-induced side effects pose significant challenges to the treatment outcomes of cancer patients. Current strategies for managing the adverse effects of chemotherapy exhibit limited efficacy and have the potential to induce various detrimental side effects. In the realm of complications, cardiotoxicity poses a serious threat, ranking as the second major contributor to illness and death in individuals suffering cancer. It is linked to various cellular mechanisms such as oxidative stress, inflammation, apoptosis, autophagy, endoplasmic reticulum stress, and aberrant myocardial energy metabolism. Both in vivo and in vitro experiments confirm that ginsenosides undeniably present non-toxic and efficacious alternatives for addressing chemotherapy-induced side effects, including cardiotoxicity, neurotoxicity, nephrotoxicity, hepatotoxicity, immunotoxicity, and hematopoietic inhibition. Hence, there is a need to produce novel and potent drugs sourced from natural, non-toxic compounds to address the side effects induced by chemotherapy. The emphasis should be on the underlying mechanisms targeting mentioned cellular pathways. In this comprehensive review, we consolidate current knowledge and summarization with this aim and shed light on the future research of PG in cardio-oncology.

PMID:40248929 | DOI:10.2174/0109298673327575250331145643

Lancet Child Adolesc Health. 2025 May;9(5):325-336. doi: 10.1016/S2352-4642(25)00067-7.

ABSTRACT

BACKGROUND: Respiratory syncytial virus (RSV) is a particularly dangerous infection in some populations, including very young infants. This study examined the efficacy and safety of ziresovir in hospitalised infants aged 6 months or younger with RSV infection.

METHODS: In this double-blind, randomised, placebo-controlled trial conducted across 28 hospitals in China, patients aged 1-24 months hospitalised for virologically confirmed RSV infection were randomly allocated (2:1) to receive ziresovir (10-40 mg by weight twice daily) or placebo orally for 5 days, with 2 years of follow-up. Patients were included if they had a Wang bronchiolitis clinical score (WBCS) of at least 5 at first dosing and were administered their first dose of study drug within 7 days of the onset of symptoms of RSV infection. In this prespecified subanalysis of patients aged 6 months and younger at randomisation, we analysed the primary endpoint (change from baseline in WBCS on day 3 [48 h post-baseline]) in the intention-to-treat infected (ITT-i) population (comprising patients who received at least one dose of study drug and who had PCR-confirmed RSV infection). Safety endpoints were assessed in all patients who received at least one dose. This study is registered with ClinicalTrials.gov (NCT04231968) and is completed.

FINDINGS: Participants were recruited from Sept 22, 2020, to Jan 19, 2022, and followed up to Feb 4, 2024. Among patients aged 6 months or younger, 188 participants (125 in the ziresovir group and 63 in the placebo group) received at least one dose of study drug and were included in the safety analysis, while the ITT-i population included 150 patients (100 in the ziresovir group and 50 in the placebo group). In the ziresovir group, 33 (26%) of 125 patients were female, 92 (74%) were male, mean age was 3·4 months (SD 1·4), and mean baseline WBCS was 6·8 (SD 1·7). In the placebo group, 15 (24%) of 63 patients were female, 48 (76%) were male, mean age was 3·3 months (1·5), and mean baseline WBCS was 6·9 (1·8). The least-squares mean change in WBCS from baseline to day 3 was -3·5 points (95% CI -3·9 to -3·1) with ziresovir versus -2·2 points (-2·8 to -1·7) with placebo (difference -1·2 [95% CI -1·9 to -0·6], p=0·0004). Drug-related treatment-emergent adverse events occurred in 22 (18%) of 125 patients who received ziresovir and seven (11%) of 63 patients who received placebo. No drug-related serious adverse events were observed and no deaths occurred.

INTERPRETATION: Ziresovir had a favourable safety profile and was associated with a significant clinical benefit during the treatment period compared with placebo in patients aged 6 months or younger.

FUNDING: Shanghai Ark Biopharmaceutical, National Clinical Research Center for Respiratory Diseases, and National Major Science and Technology Projects of China.

PMID:40246359 | DOI:10.1016/S2352-4642(25)00067-7