Endocr Pract. 2025 Apr 15:S1530-891X(25)00118-1. doi: 10.1016/j.eprac.2025.04.004. Online ahead of print.

ABSTRACT

OBJECTIVES: Research has increasingly explored the benefits of thiazolidinediones (TZDs) beyond diabetes management, particularly in reducing stroke and dementia risks. However, concerns about cardiovascular adverse events, especially heart failure, necessitate a re-evaluation of TZD-associated cardiovascular risks using real-world data.

METHODS: This study re-evaluates the cardiovascular risks of TZDs and their efficacy in stroke prevention. We conducted a real-world pharmacovigilance study using the FDA Adverse Event Reporting System (FAERS) database (January 2004 to December 2023) to assess cardiovascular risks associated with TZDs, including myocardial infarction, heart failure, and stroke. Multivariable logistic regression adjusted the Reporting Odds Ratio from the disproportional analysis. Additionally, a network meta-analysis of clinical studies (January 2000 to March 2024) examined the efficacy of TZDs in stroke prevention.

RESULTS: Our analysis of the FAERS database revealed significantly higher cardiovascular risks associated with TZDs. However, clear differences exist in cardiovascular risks between pioglitazone and rosiglitazone. Rosiglitazone was linked to a markedly increased incidence of myocardial infarction, heart failure, and stroke. In contrast, we didn't observe strong cardiovascular risks associated with pioglitazone. Instead, pioglitazone was shown to slightly heighten the risk of heart failure. Further, the network meta-analysis, based on SUCRA rankings and ranking probabilities also disclosed similar findings: when compared to placebo, rosiglitazone increased stroke risk, while pioglitazone reduced stroke incidence in individuals with diabetes and pre-diabetes.

CONCLUSIONS: Our analysis shows that pioglitazone has potential therapeutic effects on stroke prevention and fewer cardiovascular adverse events compared to rosiglitazone, underscoring the importance of re-assessing TZD safety for optimal patient outcomes.

PMID:40246234 | DOI:10.1016/j.eprac.2025.04.004

Lancet. 2025 Apr 11:S0140-6736(25)00628-2. doi: 10.1016/S0140-6736(25)00628-2. Online ahead of print.

ABSTRACT

BACKGROUND: Gepotidacin, a first-in-class, bactericidal, triazaacenaphthylene antibacterial that inhibits bacterial DNA replication, was shown to be efficacious and well tolerated in the treatment of uncomplicated urinary tract infections. We evaluated the efficacy and safety of gepotidacin for the treatment of uncomplicated urogenital gonorrhoea.

METHODS: EAGLE-1 (NCT04010539) was a phase 3, open-label, sponsor-blinded, multicentre, non-inferiority study evaluating oral gepotidacin (two 3000 mg doses administered 10-12 h apart) compared with 500 mg intramuscular ceftriaxone plus 1 g oral azithromycin for the treatment of gonorrhoea. Eligible participants were aged 12 years and older, had a bodyweight over 45 kg, and had suspected uncomplicated urogenital gonorrhoea (including mucopurulent discharge), a positive laboratory test for Neisseria gonorrhoeae, or both. Participants were randomly allocated in a 1:1 ratio to each treatment group, stratified by sex (original urogenital anatomy at birth) and sexual orientation (men who have sex with men [MSM], men who have sex with women [MSW], and female) in combination, and age group (age <18 years, ≥18 to 65 years, or >65 years). The primary efficacy endpoint was microbiological success, defined as culture-confirmed bacterial eradication of N gonorrhoeae from the urogenital body site at test-of-cure (days 4-8). The non-inferiority margin was prespecified at -10%. The primary outcome was assessed in the microbiological intention-to-treat (micro-ITT) population, all participants randomly allocated to a study treatment who received at least one dose of their study treatment and had confirmed ceftriaxone-susceptible N gonorrhoeae isolated from the baseline culture of their urogenital specimen. The safety population comprised all participants who received one or more doses of any study treatment.

FINDINGS: Between Oct 21, 2019, and Oct 10, 2023, 628 participants were randomly allocated (314 allocated to each treatment group). Overall, 39 (6%) of 628 participants discontinued the study prematurely (20 in the gepotidacin group and 19 in the ceftriaxone plus azithromycin group), with the primary reason being lost to follow-up. The micro-ITT population included 406 participants (202 in the gepotidacin group and 204 in the ceftriaxone plus azithromycin group). Most participants in the micro-ITT population were male (372 [92%] vs 34 [8%] female), and there was a higher percentage of participants who were MSM (290 [71%]) compared with participants who were MSW (82 [20%]). Participants were predominantly White (299 [74%]) or Black or African American (61 [15%]), with 70 (17%) identifying as Hispanic or Latino. Results of the primary analysis of microbiological response at test-of-cure demonstrated microbiological success rates of 92·6% (187 of 202 [95% CI 88·0 to 95·8]) in the gepotidacin group and 91·2% (186 of 204 [86·4 to 94·7]) in the ceftriaxone plus azithromycin group (adjusted treatment difference -0·1% [95% CI -5·6 to 5·5]). Gepotidacin was non-inferior to ceftriaxone plus azithromycin. No bacterial persistence of urogenital N gonorrhoeae was observed at test-of-cure for either group. The gepotidacin group had higher rates of adverse events and drug-related adverse events, mainly due to gastrointestinal adverse events, and almost all were mild or moderate. No treatment-related severe or serious adverse events occurred in either group.

INTERPRETATION: Gepotidacin demonstrated non-inferiority to ceftriaxone plus azithromycin for urogenital N gonorrhoeae, with no new safety concerns, offering a novel oral treatment option for uncomplicated urogenital gonorrhoea.

FUNDING: GSK and federal funds from the Office of the Assistant Secretary for Preparedness and Response, Biomedical Advanced Research and Development Authority.

PMID:40245902 | DOI:10.1016/S0140-6736(25)00628-2

Case Rep Rheumatol. 2025 Apr 9;2025:9276592. doi: 10.1155/crrh/9276592. eCollection 2025.

ABSTRACT

Background: Hydralazine is a commonly used arteriolar vasodilator that is associated with autoimmune side effects, including drug-induced lupus. A less well-recognized drug-induced vasculitis can be seen, often accompanying drug-induced lupus. This syndrome can cause long-standing vague symptoms, leading to missed diagnoses, and can result in permanent end-organ damage. We describe here such a case of hydralazine-induced vasculitis and lupus overlap syndrome. Case Presentation: An 85-year old male presented with chronic fatigue and weight loss associated with anemia, leukopenia, and acute renal injury in the setting of longstanding hydralazine use. Serologic studies were notable for a positive antinuclear antibody, antihistone antibody, along with anti-myeloperoxidase (MPO) and anti-proteinase 3 (PR3) antibodies. Hydralazine was discontinued, and treatment was initiated with high-dose prednisone. A renal biopsy revealed antineutrophil cytoplasmic antibody (ANCA)-associated focal necrotizing pauci-immune glomerulonephritis. The patient's clinical course was complicated by the development of oral ulcerations and recurrent hydrocele secondary to serositis. Rituximab was then employed without clinical improvement, with eventual progression to end-stage renal disease requiring hemodialysis. Conclusions: This case report helps highlight the vague symptoms that can be associated with hydralazine-induced vasculitis/lupus overlap syndrome. This case will increase clinician awareness for early recognition of such a syndrome, prompting early diagnosis, preventing end-organ damage, reducing hospitalizations and improving quality of life.

PMID:40242048 | PMC:PMC12003037 | DOI:10.1155/crrh/9276592

Pharmacol Res Perspect. 2025 Jun;13(3):e70093. doi: 10.1002/prp2.70093.

ABSTRACT

A key challenge when identifying opportunities and prioritizing strategies for quality improvement of healthcare services is an accurate design specification against which clinical performance can be assessed. This study aimed to explore evidence-based methods as a more effective framework for quality improvement in pharmacotherapeutic practices. A stakeholder management matrix was adapted to differentiate the dimensions of the theoretical construct for quality of care and establish a design specification for healthcare practice. A review of drug-related problems (DRPs) associated with preventable medication errors was carried out on individual cases of adverse drug events (ADRs) reported in the EudraVigilance database system. The potential impact of strategies aimed at preventing the underlying root cause medication error (RCME) was evaluated according to the relative frequency and severity of patient harm identified with DRPs. Out of 1750 medication errors reported in the EudraVigilance database, 1300 cases of preventable DRPs were identified, of which 531 (41%) were classified as prescribing errors, 260 (20%) as dispensing errors, and 509 (39%) as errors encountered in drug administration. The highest risk scores were associated with case-based prescribing errors and rule-based drug administration errors. The research builds on a quality risk management approach to assess how targeted interventions may reduce the risk of medication errors. The theoretical model provided a basis for establishing the strategic domains of quality in health care and comparing quality improvement strategies in drug therapy. The measures required to mitigate the highest risk of error include medication review of prescribing practices, unit dose dispensing systems and in-line quality control to avoid treatment administration errors, and patient education in dispensing practice. This framework is independent of the healthcare or institutional setting and may be applied on a broad scale for sharing best practices, harmonization of standards, and elimination of disparities in treatment outcomes.

PMID:40241378 | DOI:10.1002/prp2.70093

Eye (Lond). 2025 Apr 16. doi: 10.1038/s41433-025-03808-z. Online ahead of print.

ABSTRACT

PURPOSE: To investigate primary suspect drugs and identify a potential association between medication use and Tubulointerstitial Nephritis and Uveitis (TINU).

METHODS: A retrospective pharmacovigilance study was conducted using the Food and Drug Administration (FDA) Adverse Events Database (FAERS) from Q1 2004 to Q2 2024, focusing on patient demographics and statistical signal detection. A qualitative analysis assessed patient demographics. To ascertain if these reports yielded statistically significant signals, we used the proportional reporting ratio (PRR), chi-squared with Yates' correction (χ2), reporting odds ratio (ROR), empirical Bayes geometric mean (EBGM), and information component (IC).

RESULTS: One hundred twenty-six adverse reports for TINU were identified, along with 37 primary suspect drugs from the FAERS database. The mean age of patients was 30.05 ± 20.88 years. Most reports were of female patients (n = 67, 53%). Of the 37 primary suspect drugs, lamotrigine (n = 35, 27%) and diclofenac (n = 15, 12%) were the most frequently reported suspect drugs. The signal detection analysis also identified positive signals and potential causality for both drugs. Lamotrigine demonstrated the strongest positive signal (PRR = 90.09, χ2 = 3001.58, ROR 95% CI: 124.35 [84.20-183.66], EBGM [EBGM05]: 70.98 [50.21], IC [IC05]: 5.32 [4.83]), followed by diclofenac (PRR = 24.21, χ2 = 312.49, ROR 95% CI: 27.35 [15.95-46.90], EBGM [EBGM05]: 4.11 [2.47], IC [IC05]: 3.79 [2.99]).

CONCLUSION: Our study identified 37 primary suspect drugs associated with TINU, with lamotrigine and diclofenac showing the strongest statistical signals. Lamotrigine demonstrated the highest association, suggesting a potential drug-related risk for developing TINU, particularly in younger patients and females. Further research is warranted to explore causality and underlying mechanisms in these associations.

PMID:40240507 | DOI:10.1038/s41433-025-03808-z

Sci Rep. 2025 Apr 16;15(1):13105. doi: 10.1038/s41598-025-95961-4.

ABSTRACT

The accurate preclinical prediction of adverse drug reactions (ADRs), such as nausea and vomiting, remains a challenge. The Gastro-Intestinal Pacemaker Activity Drug Database (GIPADD) ( http://www.gutrhythm.com/public_database ) is a new source of electrophysiological big data for drug research. Over the past 2 years, the database has doubled in size, and now contains the electrophysiological profiles of 172 drugs across 11,943 datasets. This study used a state-of-the-art deep-learning model with time-series classification to explore the feasibility of using raw electrophysiological recordings from tissues to predict ADRs. The GIPADD contains the recordings of the electrical activity of various gastrointestinal tissues (stomach, duodenum, ileum, and colon) exposed to a drug at three or more different concentrations, representing the effects of the drug on gastrointestinal pacemaker activity. Each drug in the database is associated with at least 60 recordings. The datasets are divided in a ratio of 8:2 for training and validation. A modified InceptionTime classifier (ICT) was used to predict whether a drug induces ADRs, using data from the SIDER database as the target. Concentrations and tissues were added as covariates and added to the input of the model during forward propagation. We also established a negative control with shuffled target labels, and external validation was conducted using time-shifted recording predictions. The best model for predicting nausea, vomiting, diarrhoea, and constipation achieved by-drug accuracies of 0.87, 0.89, 0.85, and 0.91, respectively; by-drug precision (class 1) of 0.88, 0.90, 0.99, and 0.89, respectively; and area under the receiver operating characteristic curve (AUROC) values of 0.84, 0.87, 0.94, and 0.96, respectively. The best model was an ensemble of five independent ICT classifiers trained on the same dataset. Models trained using shuffled labels (negative controls) exhibited significantly lower accuracy, precision, and AUROC values than models trained using correctly labelled datasets, indicating that ICT classifiers successfully identified latent features in the raw recordings associated with ADRs. The combined benefits of the GIPADD and deep learning may accelerate drug safety testing and drug development by enabling the reliable analysis of electrophysiological drug profiles during the preclinical stage.

PMID:40240387 | DOI:10.1038/s41598-025-95961-4

J Med Internet Res. 2025 Apr 16;27:e68757. doi: 10.2196/68757.

ABSTRACT

Digital health interventions (DHIs) have the potential to improve health care and health promotion. However, there is a lack of guidance in the literature for the development, refinement, and prioritization of key performance indicators (KPIs) for the evaluation of DHIs. This paper presents a 4-stage process used in the Gravitate Health project based on stakeholder consultation and consensus for this purpose. The Gravitate Health consortium, which comprises private and public partners from across Europe and the United States, is developing innovative digital health solutions in the form of Federated Open-Source Platform and G-lens to present users with individualized digital information about their medicines. The first stage of this was the consultative process for the development of KPIs involving stakeholder (Gravitate Health project leads) consultations at the planning stages of the project. This resulted in the formation of an extensive list of KPIs organized into 7 categories. The second stage was conducting a scoping review, which confirmed the need for extensive stakeholder consultation in all stages of the KPI development, refinement, and prioritization process. The third stage was a period of further consultation with all consortium members, which resulted in the elimination of 1 category of KPIs. The fourth stage involved using the Delphi technique for refining and prioritizing the remaining 6 categories of KPIs. It is unusual to use this methodology in a nonresearch exercise, but it provided a clear consultative framework and structure that facilitated the achievement of consensus within a large consortium of 250 members on a substantial list of KPIs for the project. Consortium members ranked the relevance and importance of each KPI. The final list of KPIs provides substantial indicators sensitive to the needs of a broad group of stakeholders that are being used to capture real-world data in developing and evaluating DHIs.

PMID:40239207 | DOI:10.2196/68757

Cureus. 2025 Mar 16;17(3):e80671. doi: 10.7759/cureus.80671. eCollection 2025 Mar.

ABSTRACT

We present the case of a 36-year-old man with a history of type 2 diabetes mellitus (T2DM) and prior plantar necrotizing fasciitis, who initially improved on semaglutide but later experienced weight gain and elevated hemoglobin A1C (HbA1c) levels. After switching to tirzepatide, he developed nausea, epigastric pain, and vomiting. Shortly after increasing the tirzepatide dosage, he presented to the emergency room with severe abdominal pain. Diagnostic imaging revealed an ulcer in the duodenal bulb with free air, indicating acute duodenal ulcer perforation. The patient underwent emergency surgery, and postoperative tests confirmed a Helicobacter pylori infection. He received eradication therapy and was discharged about two months later. This case highlights the potential risk of duodenal perforation associated with tirzepatide, particularly in patients with untreated Helicobacter pylori infection. The patient's worsening gastrointestinal symptoms and perforation after initiating tirzepatide suggest a potential drug-related effect, emphasizing the need for careful monitoring and further research into the mechanisms underlying gastrointestinal complications associated with tirzepatide.

PMID:40236372 | PMC:PMC11999657 | DOI:10.7759/cureus.80671

Res Sq [Preprint]. 2025 Apr 4:rs.3.rs-6271510. doi: 10.21203/rs.3.rs-6271510/v1.

ABSTRACT

The development of cholinergic neurotransmitter based cognitive enhancers for Alzheimer's disease and other neuropsychiatric disorders have focused recently on allosteric modulation of specific muscarinic acetylcholine receptor (mAChR) subtypes to reduce dose-limiting side-effects that have been the hallmark of earlier orthosteric mAChR agonists. VU0467319 (VU319) is an investigational positive allosteric modulator of the M 1 mAChR. A Phase 1 first-in-human study was conducted assessing safety and brain activity utilizing cognitive tasks and event-related potentials (ERPs) in single-ascending dose and food effect studies. VU319 was given orally to 52 healthy volunteers aged 18-55 years. The single ascending dose study tested 40 participants in five dose escalating cohorts (60, 120, 240, 400, 600 mg; 6 VU319/2 placebo per dose). The food effect study involved 12 participants, 10 VU319 (120 mg)/2 placebo. Exploratory cognitive and electrophysiological tasks were examined pre-dosing and at 5 hours post-dose. Tolerability was good with no observed dose limiting side effects throughout the full dose range tested. Drug exposure increased with dose in a less than dose-proportional manner with a half-life ranging from 36 to 43 hours. Absorption was increased with food. Exploratory cognitive/ERP testing showed evidence for drug-induced CNS activity on higher doses of VU319 compared to placebo. Single dose VU319 across five ascending cohorts appeared to have a favorable safety profile and a PK profile consistent with once daily dosing. Target engagement results suggest stimulation of the cholinergic system functioning in healthy adults following a single dose of VU319. These results provide a strong foundation for further studies of positive allosteric modulators of muscarinic M 1 receptors for potential cognitive or behavioral benefits.

PMID:40235479 | PMC:PMC11998771 | DOI:10.21203/rs.3.rs-6271510/v1

Drug Ther Bull. 2025 Apr 15:dtb-2024-000071. doi: 10.1136/dtb.2024.000071. Online ahead of print.

NO ABSTRACT

PMID:40234015 | DOI:10.1136/dtb.2024.000071

Neurol Sci. 2025 Apr 15. doi: 10.1007/s10072-025-08107-9. Online ahead of print.

ABSTRACT

BACKGROUND: More than one-third of all ischemic strokes are induced by large vessel occlusion (LVO). All the wide-scale trials that assessed the impacts of cilostazol versus clopidogrel in stroke management have been conducted in Asia and involved patients with minor stroke or TIA. Our trial is the first-ever study to evaluate cilostazol versus clopidogrel in acute LVO with moderate to severe ischemic stroke in North Africa.

OBJECTIVES: We assessed the efficacy and safety of cilostazol versus clopidogrel in first-ever LVO moderate and moderate to severe ischemic stroke patients.

METHODS: 580 moderate and moderate-to-severe LVO ischemic stroke participants were randomly enrolled to receive loading and maintenance doses of cilostazol or clopidogrel.

RESULTS: 580 patients were included in the intention-to-treat analysis. 29 (10.0%) participants in the cilostazol arm and 43 (14.8%) participants in the clopidogrel arm experienced a new stroke (HR 0.37; 95% CI, 0.29-0.73; P-value = 0.03). Eight participants (2.8%) in the cilostazol arm and 17 patients (5.9%) in the clopidogrel arm had drug-related hemorrhagic complications (HR 0.29; 95% CI, 0.18-0.63; P-value = 0.008).

CONCLUSION: Patients who experienced acute LVO moderate and moderate-to-severe ischemic stroke and received loading and maintenance doses of cilostazol within the first 24 h after stroke onset had better clinical outcomes based on recurrent stroke rates and better safety outcomes regarding hemorrhagic transformation of brain infarction and drug-induced peripheral hemorrhagic side effects compared to those who received loading and maintenance doses of clopidogrel. There were no significant differences between the two groups regarding death due to vascular events and unfavorable mRS after three months of stroke onset.

REGISTRATION: Retrospectively registered on ClinicalTrials.gov, NCT06242145, 27-01-2024.

PMID:40232632 | DOI:10.1007/s10072-025-08107-9

Expert Opin Drug Saf. 2025 Apr 15. doi: 10.1080/14740338.2025.2494689. Online ahead of print.

ABSTRACT

BACKGROUND: Interstitial lung disease (ILD) is a group of disorders characterized by inflammation and fibrosis of lung tissue that make it hard to carry oxygen. Our study aimed to comprehensively evaluate the risk of drug-induced ILD using data from the FDA Adverse Event Reporting System (FAERS) database.

RESEARCH DESIGN AND METHODS: We queried the ILD reports from 2004 to 2023. The reporting odds ratio (ROR) and Bayesian Confidence Propagation Neural Network (BCPNN) were calculated to detect disproportionality signals for drugs associated with ILD.

RESULTS: A total of 39,332 ILD-related reports were identified. The most frequently reported drugs were Methotrexate (N = 1245), followed by Pembrolizumab (N = 1026), Amiodarone (N = 975), Rituximab (N = 915), and Doxorubicin (N = 911). Disproportionality analysis revealed significant signals for the top 50 drugs, including Trastuzumab deruxtecan (ROR 56.25, 95% CI 51.27-61.72; IC025 5.49), Ramucirumab (ROR 27.80, 95% CI 241.6-31.99; IC025 4.50), Amiodarone (ROR 24.35, 95% CI 22.82-25.99; IC025 4.40), Gefitinib (ROR 23.02, 95% CI 20.66-25.66; IC025 4.29), and Doxorubicin (ROR 13.99, 95% CI 13.09-14.95; IC025 3.64).

CONCLUSIONS: Drug-induced ILD represents a significant challenge in clinical practice. Our findings underscore the importance of maintaining a high index of suspicion for drug-induced ILD, particularly when prescribing medications identified as having significant associations with ILD.

PMID:40232264 | DOI:10.1080/14740338.2025.2494689

Endocrinol Metab (Seoul). 2025 Apr 15. doi: 10.3803/EnM.2024.2200. Online ahead of print.

ABSTRACT

BACKGROUND: Despite their efficacy, statin-related adverse events (AEs) may interfere with statin treatment and contribute to negative outcomes in patients with cardiovascular diseases. In this study, we evaluated the safety and effectiveness of pravastatin in Korea.

METHODS: Pooled data were collected from four multicenter prospective observational studies conducted in Korea between 2011 and 2020. Finally, 7,334 and 2,022 participants were included in the safety and effectiveness analyses, respectively. Overall safety, particularly muscle-related, incidence of new-onset diabetes mellitus (DM), changes in fasting plasma glucose and hemoglobin A1c level, achievement of target low-density lipoprotein cholesterol (LDL-C) level, and changes in LDL-C level were analyzed.

RESULTS: At week 24, after 20 or 40 mg pravastatin treatment, safety results showed that AEs and adverse drug reactions (ADRs) were 8.7% and 1.3%, respectively, and that muscle-related AEs and ADRs were 0.5% and 0.3%, respectively, with no statistically significant difference in risk factors for statin-associated muscle symptoms. No patients developed DM during the study period. Additionally, at week 24, the achievement rates of target LDL-C levels were 87.9%, 78.4%, 57.8%, and 11.6% in low-, moderate-, high-, and very high-risk groups, respectively.

CONCLUSION: This study found that 20 or 40 mg pravastatin had minimal side effects and was safe for use in real-world clinical settings in Korea. Specifically, these doses effectively achieved the target LDL-C levels in patients with dyslipidemia in low-, moderate-, and high-risk groups for atherosclerotic cardiovascular disease (ASCVD). These results demonstrate that pravastatin can be safely administered continuously to patients with low-, moderate-, and high-risk ASCVD in a real-world clinical setting.

PMID:40229969 | DOI:10.3803/EnM.2024.2200

Hum Exp Toxicol. 2025 Jan-Dec;44:9603271251332914. doi: 10.1177/09603271251332914. Epub 2025 Apr 14.

ABSTRACT

IntroductionNephrotoxicity and hepatotoxicity are substantial side effects triggered in individuals injected with 5-fluorouracil (5-FU), an anticancer drug. This study aimed to investigate the impact of the natural antioxidant and anti-inflammatory phenolic compound; protocatechuic acid (PCA) on 5-FU-provoked renal and hepatic injury in rats.MethodsRats were allocated to 4 groups: control, 5-FU, 5-FU + PCA (50 mg/kg), and 5-FU + PCA (100 mg/kg). Rats were intraperitoneally injected 5-FU (75 mg/kg; once a week for 21 days. Protocatechuic acid (50 and 100 mg/kg/day; orally) was administered for 3 weeks.ResultsRats co-treated with PCA had lower serum kidney and liver function markers than those receiving 5-FU alone. Furthermore, co-treatment with PCA successfully modulated kidney and liver contents of TNF-α, NF-κB p65, active caspase-1, IL-1β, p-p38 MAPK, SOD, GSH, Nrf-2, HO-1 and MDA. Moreover, PCA improved histopathological alterations of both kidney and liver tissues.ConclusionPCA exerts its hepatoprotective and nephroprotective effects against 5-FU-triggered toxicity through modulation of oxidative stress and inflammatory pathways, particularly via Nrf-2 activation and NF-κB inhibition.

PMID:40228806 | DOI:10.1177/09603271251332914

Vox Sang. 2025 Apr 14. doi: 10.1111/vox.70032. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: Granulocyte-colony stimulating factor (G-CSF) is commonly used for peripheral blood stem cell harvesting (PBSCH). Although its well-documented adverse effects include thrombocytopaenia and bone pain, drug-induced liver injury (DILI) is rare.

MATERIALS AND METHODS: We present the case of a 40-year-old male donor who developed DILI 4 days after G-CSF administration for PBSCH.

RESULTS: Laboratory results indicated elevated hepatobiliary enzymes, with aspartate aminotransferase (AST) peaking at 171 U/L (×6 the upper limit of normal [ULN]) on Day 7 of G-CSF administration, alanine aminotransferase (ALT) at 244 U/L (×6 ULN) on Day 11, alkaline phosphatase (ALP) at 371 U/L (×3 ULN) on Day 5 and gamma-glutamyl transpeptidase (γ-GTP) 93 U/L (×1.5 ULN) on Day 9. The hepatobiliary dysfunction became evident after G-CSF administration had ended, despite other parameters-including white blood cell and platelet counts-remaining within acceptable ranges. DILI was confirmed by positive drug lymphocyte stimulation test results. The donor's liver function normalized within 1 month of supportive treatment, and the recipient achieved successful engraftment without G-CSF administration.

CONCLUSION: As G-CSF allergy screening is not mandatory in current Japanese protocols, DILI due to G-CSF could present a risk during PBSCH. This case emphasizes the importance of vigilant monitoring and comprehensive risk assessment to ensure the safety of healthy donors.

PMID:40228804 | DOI:10.1111/vox.70032

Front Immunol. 2025 Mar 28;16:1539373. doi: 10.3389/fimmu.2025.1539373. eCollection 2025.

ABSTRACT

The use of immune checkpoint inhibitors (ICI) can lead to immune-related adverse events (irAE), of which skin irAE is common, affecting up to 50% of ICI-treated patients. Although only a few cases of subacute cutaneous lupus erythematosus (SCLE) have been reported in patients receiving anti-programmed death-1(anti-PD-1) immunotherapy, it is important to identify ICI-induced SCLE because it may cause delayed and/or prolonged skin reactions even after treatment discontinuation. To date, no cases of cutaneous lupus associated with Camrelizumab treatment have been reported.

CASE REPORT: We report a case of a patient with advanced non-small cell lung cancer (NSCLC) who gradually developed erythematous rashes on sun-exposed skin with pruritus after one course of anti-PD-1 antibody Camrelizumab combined with chemotherapy. The rashes were initially considered as eczema, but did not improve after symptomatic treatment. The rashes continued to worsen after the third course of treatment, and the pruritus was unbearable. After antibody testing, the patient was found to have positive anti-SS-A/Ro antibody, and the histological changes were consistent with subacute cutaneous lupus erythematosus. SCLE was controlled with local and systemic glucocorticoids, hydroxychloroquine, and discontinuation of anti-PD-1 therapy.

CONCLUSION: Camrelizumab treatment may be associated with the appearance of subacute cutaneous lupus erythematosus in sun-exposed skin regions, which can be rapidly relieved by local and systemic glucocorticoids and hydroxychloroquine. It is recommended to perform early antibody testing and skin biopsy for diagnosis and treatment. Unlike classic drug-related SCLE, patients may develop multiple autoimmune diseases, and caution should be taken when using immune checkpoint inhibitors for subsequent treatment.

PMID:40226630 | PMC:PMC11985835 | DOI:10.3389/fimmu.2025.1539373

Kidney Int Rep. 2024 Dec 6;10(3):720-729. doi: 10.1016/j.ekir.2024.12.002. eCollection 2025 Mar.

ABSTRACT

INTRODUCTION: Pegmolesatide has been recently approved for treating anemia in chronic kidney disease (CKD) patients in China. We presented the results of the pivotal study conducted in patients with nondialysis-dependent (NDD)-CKD with anemia.

METHODS: This randomized, active-controlled, open-label, noninferiority phase 3 study was conducted across 38 centers in China. Eligible patients were randomly assigned to receive subcutaneous injection of pegmolesatide in the upper arm once every 4 weeks or epoetin alfa weekly or biweekly, with doses adjusted to maintain hemoglobin (Hb) level of 100 to 120 g/l. The primary outcome was the mean change in Hb level from the baseline during the efficacy evaluation period. Noninferiority of pegmolesatide to epoetin alfa was established if the lower limit of the 2-sided 95% confidence interval (CI) was ≥ -10 g/l.

RESULTS: A total of 173 patients received at least 1 dose of pegmolesatide (115 patients) or epoetin alfa (58 patients). During the efficacy evaluation period, the mean change in Hb from baseline level was 19.2 g/l in the pegmolesatide group and 15.4 g/l in the epoetin alfa group with a between-group difference of 3.8 g/l (95% CI: 0.7-6.9). The incidence of adverse events (AEs) and serious AEs (SAEs) were similar between groups, with hypertension being the most reported AE related to the study drug. No drug-related hypersensitivity reactions or fatal events were observed.

CONCLUSION: Pegmolesatide demonstrated comparable efficacy to epoetin alfa in elevating and maintaining Hb levels in patients with NDD-CKD with anemia without new safety concerns (ClinicalTrials.gov identifier: NCT03903809).

PMID:40225393 | PMC:PMC11993201 | DOI:10.1016/j.ekir.2024.12.002

Front Pharmacol. 2025 Mar 28;16:1460338. doi: 10.3389/fphar.2025.1460338. eCollection 2025.

ABSTRACT

BACKGROUND: The influence of butylphthalide on atherosclerotic plaque burden remains underexplored. This pooled analysis was aimed to evaluate its efficacy and safety in carotid atherosclerosis.

METHODS: The literature were retrieved in online databases. Carotid intima-media thickness (IMT), plaque size, Crouse score, National Institute of Health Stroke Scale (NIHSS), circulating biomarkers, and drug-related adverse events were extracted and compared between the butylphthalide group and the control group without butylphthalide.

RESULTS: Nine randomized controlled trials with 892 subjects were included. Compared with the control group, butylphthalide significantly reduced carotid IMT (MD -0.24 mm, 95% CI [-0.31, -0.16], P < 0.00001), plaque size (MD -3.83 mm2, 95% CI [-5.64, -2.01], P < 0.0001), Crouse score (MD -0.48, 95% CI [-0.89, -0.08], P = 0.02), hs-CRP (MD -1.65 mg/L, 95% CI [-2.99, -0.30], P = 0.02) and MMP-9 (MD -12.29 μg/L, 95% CI [-16.24, -8.33], P < 0.00001). Neurological improvement (NIHSS reduction: MD -2.94, 95% CI [-4.15, -1.73], P < 0.00001) and comparable safety profiles (OR 0.93, 95% CI [0.37, 2.37], P = 0.89) were observed.

CONCLUSION: Butylphthalide treatment reduces carotid plaque burden, improves neurological recovery and has a high safety profile, supporting its role in stroke prevention.

PMID:40223926 | PMC:PMC11986422 | DOI:10.3389/fphar.2025.1460338

Orphanet J Rare Dis. 2025 Apr 12;20(1):176. doi: 10.1186/s13023-025-03676-6.

ABSTRACT

BACKGROUND: Treatment satisfaction can be described as the patient's experience in patients with cystic fibrosis (CF). It can be influenced using modulators and clinical characteristics. The aims of this study were to evaluate and compare adult CF patients with and without modulators regarding treatment satisfaction, related factors and to manage their drug related problems (DRPs).

METHODS: A single-center prospective cohort study was conducted between June 2023 and January 2024. Treatment Satisfaction Questionnaire for Medication (TSQM 1.4), including effectiveness, side effects, convenience, global satisfaction domains, CF Questionnaire-Revised (CFQ-R), and Medication Adherence Report Scale were applied and assessed with and without modulator therapy groups. The relationship between clinical characteristics and TSQM was analyzed by correlations and regression analysis. Recommendations on DRPs identified by clinical pharmacists were made to the physicians and patients and classified according to Pharmaceutical Care Network Europe (PCNE v9.1).

RESULTS: A total of 110 patients with 51 modulator therapy and 59 without modulator therapy were included. The mean global satisfaction score of modulator users was found to be 19.733 (p < 0.001) points higher than non-users. When the CFQ-R treatment burden score improved by 1point, global satisfaction score increased by 0.233 points (p < 0.001). When the number of hospitalizations increased by 1 day, the global satisfaction score decreased by 4.751 points (p < 0.001). A total of 84 DRPs were identified, and 69 (82.1%) of them were resolved.

CONCLUSIONS: Treatment satisfaction in adult CF patients is influenced by modulators, treatment burden, and clinical factors, so access to modulators is important. This is the first study to classify DRPs according to PCNE in CF. Clinical pharmacists contribute to the management of CF.

PMID:40221761 | DOI:10.1186/s13023-025-03676-6

Expert Opin Drug Saf. 2025 Apr 12. doi: 10.1080/14740338.2025.2493781. Online ahead of print.

ABSTRACT

BACKGROUND: Guillain-Barré Syndrome (GBS) is a rare but severe neurological disorder often precipitated by infections, vaccines, and potentially by certain medications. Drug-induced GBS, though less commonly reported, presents significant diagnostic and therapeutic challenges. This study investigates the correlation between various medications and the onset of GBS.

RESEARCH DESIGN AND METHODS: We conducted a retrospective pharmacovigilance analysis using data from the FDA Adverse Event Reporting System (FAERS) from Q1 2004 to Q1 2024. The analysis focused on identifying drugs frequently associated with GBS and examining the time-to-onset and severity of these events.

RESULTS: From over 17 million adverse events, 1,869 cases were identified as drug-induced GBS. Monoclonal antibodies and immunomodulators were the most frequently implicated drug classes. The median time-to-onset for GBS was within the first 30 days following drug exposure. Approximately 51.8% of the cases resulted in severe outcomes, such as hospitalization or disability. Drugs like brentuximab vedotin and efalizumab showed strong associations with GBS occurrences.

CONCLUSIONS: This study highlights the importance of monitoring for GBS symptoms following the administration of certain medications, particularly those that affect immune function, and underscores the need for healthcare providers to be aware of the potential neurological risks associated with these medications.

PMID:40220275 | DOI:10.1080/14740338.2025.2493781