Neurol Ther. 2025 Apr 12. doi: 10.1007/s40120-025-00739-5. Online ahead of print.

ABSTRACT

INTRODUCTION: All large studies evaluating the role of cilostazol versus other antiplatelet agents in stroke prevention have been conducted in Asia and included patients with minor stroke or transient ischemic attack (TIA). Ours is the first-ever trial to evaluate the safety and efficacy of cilostazol versus clopidogrel in moderate and moderate-to-severe ischemic stroke in North Africa. Accordingly, in this study we assess the role of cilostazol as an alternative to clopidogrel in Egyptian patients with first-ever non-cardioembolic moderate or moderate-to-severe ischemic stroke.

METHODS: A total of 870 patients with moderate and moderate-to-severe acute ischemic stroke (AIS) were randomly assigned to administration of loading and maintenance doses of cilostazol or clopidogrel.

RESULTS: Of the 870 patients included in our trial, 37 (8.7%) in the cilostazol arm and 59 (13.6%) in the clopidogrel arm experienced a new stroke (HR 0.53; 95% CI, 0.33-0.84; P = 0.007). Twelve participants (2.8%) in the cilostazol group and 25 patients (5.7%) in the clopidogrel group experienced drug-related hemorrhagic complications (HR 0.25; 95% CI, 0.12-0.53; P = 0.001). Patients with hypertension who received cilostazol had significantly lower rates of recurrent hemorrhagic and ischemic stroke.

CONCLUSION: Egyptian patients with non-cardioembolic moderate and moderate-to-severe ischemic stroke who received cilostazol within the first 24 h of symptoms had significantly lower rates of hemorrhagic transformation of brain infarction and peripheral hemorrhagic complications than those who received clopidogrel. Patients with hypertension achieved the greatest benefit from cilostazol, as they experienced a significant reduction in recurrent ischemic and hemorrhagic infarction. There were no significant differences between the two groups regarding the modified Rankin scale (mRS) score after 3 months or in the non-hemorrhagic side effects. Our results were derived from a single-blinded study; a more extensive, double-blinded, multinational study is needed for the results to be generalizable worldwide.

TRIAL REGISTRATION: Retrospectively registered, ClinicalTrials.gov, NCT06242132, 27-01-2024.

PMID:40220202 | DOI:10.1007/s40120-025-00739-5

Clin Pharmacol Ther. 2025 Apr 11. doi: 10.1002/cpt.3674. Online ahead of print.

ABSTRACT

Patritumab deruxtecan (HER3-DXd, also known as MK-1022), an antibody-drug conjugate consisting of a human epidermal growth factor receptor 3 (HER3) antibody attached to a topoisomerase I inhibitor payload (DXd), has demonstrated efficacy in patients with metastatic breast cancer and non-small cell lung cancer (NSCLC). Exposure-efficacy was assessed in 446 patients with EGFR-mutated NSCLC; exposure-safety was assessed in 715 patients with NSCLC, breast cancer, or colorectal cancer. A range of HER3-DXd dosing regimens was evaluated, including fixed-dosing regimens (1.6-8 mg/kg every 3 weeks [Q3W]; 3.2-6.4 mg/kg Q3W), an up-titration dosing regimen, and an alternative Q2W/Q3W dosing regimen. Logistic regression or time-to-event models were used to test the relationships of each endpoint with pharmacokinetic analytes (anti-HER3-ac-DXd and DXd). Anti-HER3-ac-DXd exposure was positively associated with objective response rate, and bone metastasis was identified as a significant covariate. DXd exposure showed a stronger correlation with most safety endpoints compared with anti-HER3-ac-DXd exposure, except for grade ≥ 2 nausea/vomiting and any grade adjudicated drug-related interstitial lung disease (ILD). Dose response predictions verified a manageable safety profile for the 5.6 mg/kg Q3W regimen. This observation was supported by low predicted rates of adjudicated drug-related ILD and adverse events leading to treatment discontinuation with the 5.6 mg/kg Q3W regimen. Overall, these results support the selection of HER3-DXd 5.6 mg/kg Q3W as the recommended dosing regimen for patients with NSCLC, and these data inform the optimal dosing regimen for other tumor types.

PMID:40214010 | DOI:10.1002/cpt.3674

Front Pharmacol. 2025 Mar 27;16:1511115. doi: 10.3389/fphar.2025.1511115. eCollection 2025.

ABSTRACT

OBJECTIVE: This study aims to identify the drugs most commonly associated with kidney stone-related adverse events using data from the FDA Adverse Event Reporting System (FAERS), providing insights for clinical reference regarding the use of these drugs.

METHODS: We utilized the Medical Dictionary for Regulatory Activities (MedDRA 26.0) preferred term "nephrolithiasis" to identify drug-related adverse events (ADEs) for kidney stones reported in FAERS from Q1 2004 to Q1 2024. Reporting odds ratio (ROR) was used to quantify the signal strength of these ADEs, and new risk signals for kidney stones were compared with drug labeling information to identify any previously unreported risks.

RESULTS: Out of 21,035,995 adverse events reported in FAERS, 38,307 were associated with kidney stones. The top 5 drugs most frequently linked to kidney stone cases were adalimumab (2,636 cases), infliximab (1,266 cases), interferon beta-1a (920 cases), sodium oxybate (877 cases), and teriparatide (836 cases). Notably, certain drugs like lansoprazole (ROR 7.2, 95% CI 6.62-7.84), Xywav (ROR 7.1, 95% CI 6.03-8.35), and teduglutide (ROR 5.54, 95% CI 4.83-6.36) showed significant risk signals. Of the 50 drugs identified, 33 were not previously labeled as carrying a risk of kidney stones.

CONCLUSION: Our analysis of FAERS data revealed new risk signals for kidney stones not indicated in the labels of 33 drugs. Close monitoring is recommended when using these medications, and further research is needed to investigate the mechanisms behind drug-induced kidney stone formation.

PMID:40213702 | PMC:PMC11983471 | DOI:10.3389/fphar.2025.1511115

Prostate Int. 2025 Mar;13(1):10-14. doi: 10.1016/j.prnil.2024.10.002. Epub 2024 Oct 26.

ABSTRACT

PURPOSE: This study aimed to assess the incidence, severity, and onset of dermatologic adverse events (dAEs) in Korean patients treated with apalutamide for metastatic hormone-sensitive prostate cancer (mHSPC) and to identify clinical and laboratory predisposing factors.

MATERIALS AND METHODS: We retrospectively analyzed data of patients treated with apalutamide for mHSPC at a tertiary referral center in Korea between April 2023 and March 2024. Patients with a radical prostatectomy history or insufficient data were excluded. The onset, severity, and management of dAEs were evaluated and compared between patients with and without dAEs. Clinical and laboratory data from 1 month prior to apalutamide administration were collected. Logistic regression was performed to identify predictors of dAEs, and the predictive value of serum albumin levels was analyzed using the receiver operating characteristic (ROC) curve.

RESULTS: Twenty-six (40.0%) of the 65 patients developed dAEs, including nine (13.8%) with Grade ≥3 events. The median onset of dAEs was 66.5 (45-78) days. Patients with dAEs had significantly lower initial prostate-specific antigen levels (70.4 vs. 301.6 ng/mL), higher Eastern Cooperative Oncology Group Performance Status (ECOG-PS; 30.8% vs. 5.1%), and lower serum albumin levels (3.8 vs. 4.1 g/dL). Logistic regression identified elevated Eastern Cooperative Oncology Group-Performance Status (ECOG-PS) and hypoalbuminemia as significant predictors of dAEs. ROC analysis for serum albumin levels produced an area under the curve of 0.739, with a cutoff value of 3.85 g/dL, yielding a sensitivity and specificity of 65.4% and 74.4%, respectively.

CONCLUSION: dAEs are prevalent in Korean patients treated with apalutamide for mHSPC, with ECOG-PS and serum albumin levels identified as significant risk factors.

PMID:40213344 | PMC:PMC11979388 | DOI:10.1016/j.prnil.2024.10.002

Innov Clin Neurosci. 2025 Mar 1;22(1-3):28-50. eCollection 2025 Jan-Mar.

ABSTRACT

BACKGROUND: Acute pain (AP) is a prevalent symptom in hospital settings, affecting up to 84 percent of the patients seeking healthcare services. It significantly impacts an individual's quality of life, with inadequate management resulting in slower recovery, increased cost of care, and a greater risk of developing chronic pain. While pharmacological approaches are effective, they are associated with numerous side effects, including nausea, addiction, and the possibility of fatal overdoses. Given this, virtual reality (VR) offers an innovative avenue to manage AP effectively while minimizing the effects of drugs.

OBJECTIVES: This study aims to map the extent of literature on utilizing VR as a tool for the nonpharmacological management of AP. Specifically, this review attempts to understand the characteristics of the populations using VR for AP management, the technical specifications and mechanisms used to alleviate AP, and the overall effectiveness of VR in managing AP.

METHODS: A scoping review was conducted to identify literature from the following electronic databases: PubMed, ScienceDirect, ERIC, and Google Scholar. To be included in this review, articles had to focus on AP in both adult and pediatric populations and address AP using VR in any clinical or care setting. The search was limited to peer-reviewed, English-language, quantitative research articles published between 2000 and 2024.

RESULTS: A total of 97 studies were identified. Sixty-six percent of studies demonstrated the efficacy of VR as an analgesic, outperforming traditional nonpharmacological approaches (eg, standard of care, mobile phones). Distraction was the most effective VR mechanism for pain management, showing efficacy in 86.9 percent of studies. The most common focus was on needle-related pain (30.9%), followed by dental and perioperative pain (15.5% each). VR was most effective in wound care (87.5%), followed by labor-related (83.33%) and dental (80%) pain.

CONCLUSION: VR is a promising tool for managing AP, offering considerable benefits in terms of patient care, patient experience, and reduction in drug-related side effects. The high efficacy rates for wound care, labor-related pain, and dental pain highlight the potential for VR to be integrated into standard pain management protocols. However, further research, with rigorous research design, is required to standardize VR interventions and optimize their effectiveness across different patient populations and pain contexts.

PMID:40213121 | PMC:PMC11980906

BMC Infect Dis. 2025 Apr 10;25(1):501. doi: 10.1186/s12879-025-10915-5.

ABSTRACT

BACKGROUND: Urinary tract infection (UTI) is one of the most common infectious diseases requiring convenient and appropriate treatment. Nemonoxacin is active against the common pathogens of UTIs. However, more clinical data are required to further support the utility of 500 mg nemonoxacin once daily in treatment of acute lower UTI.

METHODS: We conducted a prospective, single-arm, open-label, multicenter clinical trial in outpatients with acute lower UTI, including uncomplicated UTI (uUTI), recurrent UTI (rUTI), and complicated UTI (cUTI). The patients were prospectively enrolled to take 500 mg nemonoxacin capsules once daily for 3 days (uUTI and rUTI) or 14 days (cUTI). The baseline data, clinical symptoms, laboratory and microbiological tests were analyzed to evaluate the efficacy and safety of nemonoxacin. The clinical and microbiological efficacy were evaluated using the modified intent-to-treat (mITT) set and microbiologically modified intent-to-treat (m-mITT) set, respectively. The comprehensive efficacy and safety were assessed using microbiologically evaluable (ME) set and safety set (SS), respectively.

RESULTS: A total of 404 patients were enrolled. Majority (90.1%) of the patients were females. More than half (66.3%) of the patients were 20 to 40 years of age, and 19.1% were elderly patients (≥ 60 years). Most (83.2%) of the patients reported two or more urinary tract symptoms. The overall clinical efficacy rate of nemonoxacin was 83.9% (292/348) in mITT set, specifically, 83.9% (186/224) in uUTI, 84.4% (81/96) in rUTI and 89.3% (25/28) in cUTI. The overall microbiological efficacy rate was 76.8% (119/155) in m-mITT set. The overall comprehensive efficacy rate was 73.4% (102/139) in ME set. The incidence of clinical adverse reactions was 7.2% (29/404) in the safety set. Most of the adverse events were mild and transient, including pruritus, nausea, dizziness, and headache. No drug-related serious adverse events were observed.

CONCLUSIONS: Nemonoxacin capsules 500 mg once daily is effective, safe, and well-tolerated for treatment of mild-to-moderate acute lower UTIs in adult outpatients.

TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2100046585). Registered on May 22, 2021.

PMID:40211176 | DOI:10.1186/s12879-025-10915-5

Drug Ther Bull. 2025 Apr 10:dtb-2025-000013. doi: 10.1136/dtb.2025.000013. Online ahead of print.

NO ABSTRACT

PMID:40210451 | DOI:10.1136/dtb.2025.000013

Drug Ther Bull. 2025 Apr 10:dtb-2025-000014. doi: 10.1136/dtb.2025.000014. Online ahead of print.

NO ABSTRACT

PMID:40210450 | DOI:10.1136/dtb.2025.000014

Clin Lab. 2025 Apr 1;71(4). doi: 10.7754/Clin.Lab.2024.241019.

ABSTRACT

BACKGROUND: This case report presents the history, findings, and diagnostic workup of a 28-year-old woman who presented to the hospital with a yellowish, parasite-like structure in her stool.

METHODS: The patient had no significant gastrointestinal complaints other than weight loss and decreased appetite, and no parasites or leukocytes were detected on direct examination of the stool.

RESULTS: No eosinophilia, elevated C-reactive protein or leukocytosis was detected in laboratory tests. It was suggested that the structure in the stool of the patient whose symptoms occurred after taking extended-release metformin could be a ghost tablet, and further investigation was not considered necessary.

CONCLUSIONS: The report emphasizes the importance of considering drug-related side effects, especially ghost pills, in patients with atypical stool findings to avoid unnecessary investigations and anxiety.

PMID:40209786 | DOI:10.7754/Clin.Lab.2024.241019

PLoS One. 2025 Apr 10;20(4):e0321015. doi: 10.1371/journal.pone.0321015. eCollection 2025.

ABSTRACT

BACKGROUND: HIV/AIDS remains a global health challenge, with significant prevalence in sub-Saharan Africa. Highly active antiretroviral therapy (HAART) is the mainstay treatment for HIV, and the number of people living with HIV (PLWHIV) on HAART has considerably increased worldwide. The use of HAART has led to improved patient outcomes; however, it is associated with adverse drug reactions (ADRs) and drug-drug interactions (DDIs), which pose serious concerns in the management of patients with HIV. The aim of the study was to determine the prevalence and factors associated with ADRs among patients on HAART.

METHODOLOGY: This was a hospital-based cross-sectional study carried out among 312 HIV patients on HAART attending HIV clinics at Mbarara Regional Hospital. Data was collected using an interviewer-administered, semi-structured questionnaire and a review of patient charts. ADRs were assessed for causality and categorized using Naranjo ADR assessment scale into probable, possible and definite, for severity using the modified Hartwig and Siegel criteria into mild, moderate and Severe, and for preventability using Schumock and Thornton criteria into definite, probable and non-preventable. Lexicomp® Drug Interaction Checker software was used to identify and rate clinically significant drug-drug interactions. The prevalence of ADRs and potential DDI was analyzed using descriptive statistics while logistic regression analysis was used to establish the association of variables.

RESULTS: 312 patients were interviewed and their records reviewed. The prevalence of ADRs during this study was 76.0%. On assessment, 78.3% of the ADRs were mild and 76.6% of ADRs were definitely preventable. CD4 count below 200 cells/mm3 (AOR = 1.00, 95% CI: 1.00-1.02; p value = 0.04), primary education level (AOR = 3.27, 95% CI: 1.34-7.95; p value = 0.009), and secondary education level (AOR = 3.64, 95% CI: 1.39-9.52; p value = 0.009) were identified as independent risk factors. Patients who experienced a significant DDI were 5.66 times more likely to experience an ADR (p value = 0.02, 95% CI: 1.32-24.18).

CONCLUSION: There is a high prevalence of adverse drug reactions among patients with HIV on HAART. Low CD4 count and lower education levels are risk factors for ADRs in this population; therefore, tailored interventions to these subgroups should be implemented for early ADR identification and management. Significant drug-drug interactions are highly associated with the occurrence of ADRs among HIV patients on HAART, which calls for intensified pharmacovigilance and pharmaceutical care in this population.

PMID:40208898 | DOI:10.1371/journal.pone.0321015

Int J Immunopathol Pharmacol. 2025 Jan-Dec;39:3946320251327618. doi: 10.1177/03946320251327618. Epub 2025 Apr 10.

ABSTRACT

The aim of this study was to evaluate the country-specific reporting status profile of immunomodulatory drugs (IMiDs)-related adverse events (ImrAEs) in real-world clinical practice, using data from the Japanese Adverse Drug Event Report (JADER) and Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) databases. Immunomodulatory drugs, including thalidomide and its derivatives, are a new class of anticancer and anti-inflammatory drugs. IMiD risk management programs have instituted sufficient measures to prevent fetal effects but do not address adverse effects experienced by patients themselves. To date, no study has compared ImrAE profiles across countries. Adverse events were defined using the preferred terms in the Medical Dictionary for Regulatory Activities. The number of reported adverse events related to IMiDs in each country (the United States and Japan) was investigated. In both Japan and the United States, myelosuppression, pneumonia, and neuropathy peripheral have been reported as adverse events suspected to be associated with IMiDs. Adverse event profiles differed between the countries. The number of adverse event reports for thalidomide increased transiently in the United States in 2008 following the multiple myeloma indication, and then exhibited a downward trend. The number of adverse event reports for lenalidomide and pomalidomide has increased in the United States since their launch. The number of transient reports increased in Japan in 2015, when pomalidomide was launched. In this study, the profile of ImrAEs was revealed using the FAERS and JADER databases. Our comparative safety study indicated the importance of comparing the safety profiles of IMiDs using post-marketing real-world data. It is important to focus on the adverse events experienced by patients taking IMiDs, as well as the effects of IMiDs on fetuses.

PMID:40207612 | DOI:10.1177/03946320251327618

Rev Panam Salud Publica. 2025 Apr 9;49:e27. doi: 10.26633/RPSP.2025.27. eCollection 2025.

ABSTRACT

OBJECTIVE: To quantify the occurrence of vaccine-associated paralytic poliomyelitis (VAPP) cases in Brazil from January 2013 to May 2023.

METHODS: A descriptive study was conducted on VAPP cases reported as events supposedly attributable to vaccination or immunization (ESAVI) following oral poliovirus vaccine (OPV) administration. VAPP cases were defined as acute flaccid paralysis (AFP) with isolation of vaccine-derived poliovirus in stool samples and persistence of motor deficits after 60 days.

RESULTS: A total of 200 suspected cases were identified, with two confirmed as VAPP (<1 case per 10 million doses administered) based on the isolation of the vaccine virus. Risk factors associated with VAPP included incomplete vaccination schedules, malnutrition, and/or immunodeficiency.

CONCLUSIONS: VAPP occurrence was rare and aligned with expected values. Continued surveillance of ESAVI and suspected VAPP cases is essential to support poliomyelitis eradication efforts and ensure vaccine safety.

PMID:40206565 | PMC:PMC11980524 | DOI:10.26633/RPSP.2025.27

Res Pract Thromb Haemost. 2025 Mar 3;9(2):102721. doi: 10.1016/j.rpth.2025.102721. eCollection 2025 Feb.

ABSTRACT

BACKGROUND: Factor X (FX) deficiency (FXD) significantly disrupts coagulation, potentially leading to severe bleeding. While inherited FXD is rare, with a prevalence of 1 in 500,000, acquired FXD is also uncommon and frequently linked to conditions such as light-chain amyloidosis. In rare cases, certain medications can cause FXD.

KEY CLINICAL QUESTION: Here, we present a rare case of acquired FXD induced by valproic acid (VPA). This deficiency is associated with the presence of anti-FX antibodies.

CLINICAL APPROACH: A 65-year-old man undergoing treatment for various conditions, including chronic kidney disease and type 2 diabetes, developed severe FXD (activity <2 U/L) following VPA administration for epilepsy. During FXD, the patient experienced significant bleeding episodes, necessitating FX replacement with prothrombin complex concentrate. Upon discontinuation of VPA, FX activity improved in 9 days, possibly suggesting a role of the drug in FXD. Interestingly, antibodies directed against FX have been identified.

CONCLUSION: This case emphasizes the necessity for clinicians to be vigilant of hemostasis disorders associated with VPA, even though such occurrences are rare.

PMID:40206323 | PMC:PMC11981724 | DOI:10.1016/j.rpth.2025.102721

Cancer Innov. 2025 Apr 9;4(3):e70008. doi: 10.1002/cai2.70008. eCollection 2025 Jun.

ABSTRACT

BACKGROUND: The phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB or AKT)/mammalian target of rapamycin (mTOR) signaling pathway (PAM pathway) plays a critical role in breast cancer pathogenesis and progression, and is closely linked with resistance to endocrine therapy in advanced breast cancer. Randomized clinical trials have shown that PI3K/AKT/mTOR inhibitors deliver significant clinical benefits, particularly for patients with advanced hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer.

METHODS: In 2022, the Breast Cancer Expert Committee of the National Cancer Quality Control Center convened specialists in related fields to draft the "Expert Consensus on the Clinical Application of PI3K/AKT/mTOR Inhibitors in the Treatment of Advanced Breast Cancer." This consensus raised awareness of these inhibitors among oncologists in China and improved the precision of clinical decision-making. In recent years, growing evidence has emphasized the importance of targeting the PAM pathway, reflected in the approval of several innovative agents. This consensus is an updated 2025 edition that retains the foundational structure of the 2022 edition while incorporating notable updates.

RESULTS: Updates to the consensus include the introduction of newly approved PAM pathway inhibitors, updated data from recent clinical trials, and expanded therapeutic applications. The revised guidance also offers updated recommendations for genetic testing to detect alterations in relevant pathways. The section on managing drug-related adverse events has been significantly expanded, providing detailed insights into different types of adverse events and their management. These updates aim to enhance the clinical application of PAM pathway inhibitors, promote precision medicine, and ultimately, improve survival outcomes for patients with breast cancer.

PMID:40206206 | PMC:PMC11981814 | DOI:10.1002/cai2.70008

Front Pharmacol. 2025 Mar 26;16:1565480. doi: 10.3389/fphar.2025.1565480. eCollection 2025.

ABSTRACT

BACKGROUND: Herpes zoster severely impacts patients' quality of life and therapeutic results. This research utilized data from the FDA Adverse Event Reporting System (FAERS) to examine the prevalence and attributes of drug-induced herpes zoster.

METHODS: We analyzed FAERS reports about zoster from Q1 2004 to Q3 2024 and developed a list of possible pathogenic agents. Ranked the 30 medicines with the greatest incidence of reported herpes zoster cases. Statistical disproportionality analysis was employed to identify an elevated reporting frequency of herpes zoster linked to a particular medication.

RESULTS: Herpes zoster was referenced in 50,164 FAERS reports from 2004 to 2024. The majority of the implicated drugs were immunosuppressants. Anifrolumab exhibited the greatest ROR and PRR ratings among the drugs evaluated. Furthermore, rozanolixizumab, tozinameran, elapegademase, and other medications not indicated for inducing herpes zoster were recognized, underscoring the necessity for increased clinical vigilance and awareness. Nonetheless, these correlations should be regarded with caution, as they do not establish a direct causative relationship.

CONCLUSION: This study underscores the need of pharmacovigilance in recognizing and comprehending drug-induced herpes zoster. Additional research is required to validate these findings and to design strategies for risk management and reduction to enhance treatment outcomes in patients.

PMID:40206093 | PMC:PMC11979123 | DOI:10.3389/fphar.2025.1565480

Front Pharmacol. 2025 Mar 26;16:1508290. doi: 10.3389/fphar.2025.1508290. eCollection 2025.

ABSTRACT

BACKGROUND: Drug-induced liver injury (DILI) is the most common cause of acute liver injury. Anoectochilus roxburghii (Wall.) Lindl. (AR) and its polysaccharide fractions (ARPs) have been shown to have effective therapeutic effects with minimal side effects on a wide range of diseases including hepatopathy. This study aims to determine the therapeutic effects of ARPs on acetaminophen (APAP)-induced liver injury and to explore the mechanistic pathways involved.

METHODS: C57BL/6J male mice at 8 weeks were used to construct a model of APAP-induced liver injury. The acute hepatic injury was induced by oral administration of APAP (300 mg/kg) before 16 h fasting. For therapeutic experiment, mice were gavaged with the water extract of AR (AR.WE) or the purified ARPs before and after APAP administration. Biochemical analyses, ELISA analyses, H&E staining, RT-PCR, and Quantitative proteomic analysis were used to investigate the effects and mechanisms of AR on DILI.

RESULTS: Both AR.WE. and the purified ARPs treatment reduced APAP-induced liver injury, decreased hepatic glutathione and TNF-α levels, alleviated oxidative stress and inflammation. Quantitative proteomic analysis revealed that ARPs downregulated the protein levels involved in apoptosis, inflammation, oxidative stress, necroptosis, while upregulated the protein levels involved in autophagy. These protective effects of ARPs are possibly related to the downregulation of vATPase activity and thus participating in the autophagic process and ferroptosis.

CONCLUSION: ARPs can protect mice against APAP-induced liver injury, alleviate oxidative stress and inflammation. Our study reveals a potential therapeutic effect for ARPs in protecting APAP-induced liver injury.

PMID:40206085 | PMC:PMC11979217 | DOI:10.3389/fphar.2025.1508290

Breast Cancer Res. 2025 Apr 9;27(1):54. doi: 10.1186/s13058-025-02013-w.

ABSTRACT

OBJECTIVE: There are three categories of drugs that treat human epidermal growth factor receptor type 2 (HER-2) positive breast cancer: monoclonal antibodies (mAbs), antibody-drug conjugates (ADCs), and tyrosine kinase inhibitors (TKIs). The purpose of this study is to analyze and compare the adverse reactions of three classes of anti-HER-2 drugs to various body systems in patients based on the FDA Adverse Event Reporting System (FAERS).

METHODS: All data reports were extracted from the FAERS between 2004 and 2024. Data mining of adverse events associated with anti-HER-2 drugs was carried out using disproportionality analysis. A multivariate logistic regression analysis was conducted to explore the risk factors associated with AEs leading to hospitalization.

RESULTS: A total of 47,799 patients were screened for the three classes of drugs, among which ADC drugs caused the largest proportion of deaths. MAb has the strongest ADR signals associated with "cardiac disorders". Moreover, trastuzumab was associated with a greater risk of cardiotoxicity. Logistic regression analysis revealed that the treatment with mAbs should be wary of serious adverse reactions in "infections and infestations" and "metabolism and nutrition disorders". Moreover, "endocrine disorders" were the factor associated with the highest risk of prolonged hospitalization due to trastuzumab deruxtecan (T-DXd). The safety of tucatinib among TKI drugs is greater than that of other drugs.

CONCLUSION: In general, from the perspective of the effects of the three classes of drugs on the various body systems of patients, we should focus on mAb-associated "cardiac disorders", ADC-associated "hepatobiliary disorders", "respiratory, thoracic and mediastinal disorders", and TKI-associated "gastrointestinal disorders.

PMID:40205546 | DOI:10.1186/s13058-025-02013-w

Stud Health Technol Inform. 2025 Apr 8;323:149-153. doi: 10.3233/SHTI250067.

ABSTRACT

PM-TOM (Personalized Medicine-Therapy Optimization Method) is a clinical decision-support tool designed to optimize polypharmacy treatments by minimizing their adverse drug reactions (ADRs) caused by individual drugs or drug interactions (DDIs, DCIs, DFIs, DGIs), along with the risks identified by the STOPP and Beers criteria. On the other hand, AI tools like ChatGPT 4.0, trained on medical literature texts, can provide broader clinical reasoning and insights tailored to individual patient contexts. By referring to a documented deprescribing case, this study demonstrates the synergistic power of PM-TOM and ChatGPT in optimizing potentially inappropriate medication (PIM) treatments. A malnourished older woman was admitted to a deprescribing facility with recurrent falls, hypertension, ischemic heart disease, depression, osteoarthritis, osteoporosis, and GERD. She was initially prescribed acetaminophen, alendronate, omeprazole, lisinopril, metoprolol, aspirin, citalopram, and vitamin D, which were assessed as inadequate. While the discharge regimen improved some conditions by replacing alendronate with zoledronic acid and reducing some drug dosages, PM-TOM revealed that key risks, stemming primarily from omeprazole, aspirin, and citalopram, remained unaddressed. The discharge treatment was optimized with PM-TOM after considering alternative drug classes suggested by ChatGPT and elaborated in the available medical literature. In the optimized treatment, omeprazole (PPI) was replaced with famotidine (H2-blocker), citalopram (SSRI) with agomelatine (atypical antidepressant), zoledronic acid (bisphosphonate) with denosumab (RANK ligand inhibitor), aspirin (NSAID) with ticagrelor (antiplatelet), and lisinopril with benazepril (ACE inhibitor). These changes significantly reduced possible ADRs and the geriatric care criteria risks. Finally, ChatGPT validated the proposed adjustments, confirming their alignment with the guidelines and highlighting the potential for longer-term benefits. This case study illustrates how a combined use of PM-TOM and AI tools can effectively support the clinical decision-making process by optimizing polypharmacy treatments and minimizing their PIMs, major contributors to morbidity in older adults and high healthcare costs.

PMID:40200464 | DOI:10.3233/SHTI250067

Alzheimers Res Ther. 2025 Apr 8;17(1):77. doi: 10.1186/s13195-025-01728-4.

ABSTRACT

In this article, we have carefully read the author's comments on our published article regarding the post-marketing safety concerns of lecanemab based on the Food and Drug Administration Adverse Event Reporting System (FAERS) database. Pharmacovigilance studies based on the disproportionality analysis through the case/non-case design are common, and the details of this method deserve attention. We acknowledged the author's perspectives on the term "signal of disproportionate reporting (SDR)", and make some explanations on the SDR results for pancreatic carcinoma and the deduplication methods.

PMID:40200347 | DOI:10.1186/s13195-025-01728-4

BMC Endocr Disord. 2025 Apr 8;25(1):94. doi: 10.1186/s12902-025-01914-3.

ABSTRACT

BACKGROUND AND AIM: Hypothyroidism (HoT) treatment involves lifelong thyroxine replacement therapy and regular monitoring. The objective of this study was to assess the impact of clinical pharmacist (CP) intervention in managing drug-related problems (DRPs) on outcomes among patients with HoT receiving levothyroxine (LT4) therapy.

METHOD: A randomized controlled trial involved patients with HoT attending a university hospital's endocrinology and metabolism outpatient clinic from March 2022 to September 2022. Participants were randomly assigned to control (CG) and intervention groups (IG). CP identified and classified DRPs based on Pharmaceutical Care Network Europe (PCNE) v9.1 criteria. The validated version of the Morisky-Green-Levine (MGL) 4-question scale was used to measure adherence. All patients included in the study were assessed during their first visit and again two months later at their second visit.

RESULTS: 43 patients were assigned to the CG (n = 25) and IG (n = 18). Diabetes (21.6 vs. 20.5%) and hypertension (16.2% vs. 11.7%) were the most prevalent comorbidities in both the CG and IG, respectively. A total of 118 DRPs belonging to both groups were detected. In the IG group, the total number of DRPs significantly decreased from 66 to 24, and the total potential drug-drug interactions (pDDIs) decreased from 21 to 0 between the first and second visits (p < 0.001). CG and IG patients had no difference in adherence levels at the first and second visits (p > 0.05). A statistically significant increase in adherence to the time of taking the medication was observed between the first and second visits in IG (55.5% vs. 94.4%, p = 0.008).

CONCLUSION: This study highlights the frequent occurrence of DRPs and LT4 therapy adherence problems in patients with HoT. The findings suggest that the intervention of CPs, by increasing adherence to LT4 therapy and decreasing DRPs, could significantly contribute to improving patients' treatment outcomes.

TRIAL REGISTRATION: This study protocol has been retrospectively registered at ClinicalTrials.gov (NCT06408909) at 06/05/2024.

PMID:40200273 | DOI:10.1186/s12902-025-01914-3