Naunyn Schmiedebergs Arch Pharmacol. 2025 Feb 22. doi: 10.1007/s00210-025-03899-1. Online ahead of print.

ABSTRACT

Studies on the assessment of anticancer efficacy of plant-derived phytochemicals by targeting signaling pathways have drawn a lot of attention recently for human health. Multiple investigations have proposed an involvement of Notch pathway in the processes of cancer angiogenesis and metastasis, and drug resistance. Moreover, overexpression of Notch signaling is associated with increased prostate cancer (PrCa) cell growth and development. A number of chemotherapeutic agents are reported to become resistant over a period of time and have severe side effects. To increase efficacy and lessen drug-induced toxicity, a variety of bioactive compounds have been utilized alone or as adjuncts to traditional chemotherapy. Therefore, in the present study, the potential of AKBA in inhibiting the proliferation of PrCa cells by modulating Notch signaling components and its efficacy in combination with cisplatin was investigated. The results exhibited a substantial reduction in cell survival (IC50 = 25.28 µM at 24 h and 16.50 µM at 48 h) and cellular alterations in AKBA-treated PrCa cells. Additionally, AKBA caused nuclear condensation, increased reactive oxygen species (ROS) generation, mitochondrial membrane depolarization, and caspase activation, ultimately leading to apoptosis in PrCa cells. Moreover, AKBA-elicited apoptosis was evidenced by an augmentation in the Bax to Bcl2 ratio. AKBA was also found to induce G0/G1 arrest which was substantiated by reduced cyclin D1 and CDK4 expression levels concomitantly with increased expression of p21 and p27 genes. Intriguingly, AKBA demonstrated significant downregulation of Notch signaling mediators. Furthermore, the isobolograms of the combination treatment indicated that AKBA has the potential to synergistically enhance the cytotoxic efficacy of cisplatin in DU145 cells, as evidenced by CI < 1 across all tested combinations. Overall, the results of this study suggest strong antiproliferative, apoptotic, and chemo-sensitizing potential of AKBA. Thus, AKBA holds a promising drug candidature warranting further investigation as a probable therapeutic option for both the prevention and treatment of PrCa and other solid tumors.

PMID:39985578 | DOI:10.1007/s00210-025-03899-1

Sci Rep. 2025 Feb 21;15(1):6310. doi: 10.1038/s41598-025-91102-z.

ABSTRACT

Immune related adverse events (irAEs) occur due to the inflammatory side effects of immune check point inhibitors (ICIs) and irAEs have been associated with improved efficacy in advanced non-small lung cancer (NSCLC) patients. Corticosteroids can reduce the efficacy of ICIs due to their immunosuppressive effects. In this study, we aimed to show the effects of the development of irAEs and the use of ≥ 10 mg prednisone and equivalent steroids on treatment response. We analyzed the outcomes of patients with NSCLC treated with ICIs as monotherapy or ICIs in combination with chemotherapy (ChT) at a single academic center based on the presence of irAEs and the use of corticosteroids. A landmark analysis was performed due to the time-dependent nature of irAEs. 90 patients were included in the study. irAEs were seen in a total of 45 (50%) patients. In the landmark analysis, the median overall survival (OS) was 52.1 months in those who developed irAEs and 14.4 months in those who did not (HR 2.71, 95% CI (1.55-4.73), p < 0.001), and the median progression-free survival (PFS) was also higher in the patients with irAEs (25.9 vs. 8.4 months, HR 2.54, 95% CI (1.52-4.25), p < 0.001). The objective response rate (ORR) was significantly higher in patients experiencing irAEs than without irAEs: 60% versus 33.3%, respectively (p = 0.011). The number of patients using steroids was 22 (24%), while 68 patients (76%) were not using steroids. There was no significant difference in mOS: 26.5 versus 28.7 months (HR 1.14, 95% CI (0.63-2.08), p = 0.652) and mPFS: 16.9 versus 13.5 months (HR 0.99, 95% CI (0.57-1.74), p = 0.997) between patients who used steroids and those who did not. ICIs efficacy is higher in patients who developed irAEs. In our analyses, the grade of irAEs or the number of irAEs occurring in the individual had no effect on mOS and mPFS. In our patient group, steroid use was mostly related with irAEs, and we did not detect any negative effects of corticosteroid use on PFS and OS.

PMID:39984593 | DOI:10.1038/s41598-025-91102-z

Pharmacol Res Perspect. 2025 Apr;13(2):e70063. doi: 10.1002/prp2.70063.

ABSTRACT

Interstitial lung disease (ILD) is a clinically relevant adverse event associated with biologic agent use. However, the current incidence of ILD remains unclear as large-scale risk assessments of biologic agents have not been conducted. The aim of this study was to clarify the association between biologic agent use and ILD development in clinical practice by detecting adverse event signals using a spontaneous adverse drug reaction database. The VigiBase database is used for spontaneous adverse event reporting. The analysis focused on nine biologics used to treat psoriasis, rheumatoid arthritis, and Crohn's disease. The safety of each biologic agent was evaluated using the information component signal detection method. There were 32,520,983 reports in VigiBase, of which 68,489 (0.21%) were for ILD. Signals were mainly detected for tumor necrosis factor-α inhibitors when the information component for ILD caused by biologic agents was calculated. Comorbidity analysis in patients who developed ILD and analysis of the time from the start of treatment with each drug to ILD onset showed differences for each biologic agent. ILD is a serious adverse effect of biologic agents, and there are several cases in which a causal relationship with ILD development cannot be ruled out. The occurrence of interstitial ILD should be noted when using biologics, particularly TNF-α inhibitors.

PMID:39984304 | DOI:10.1002/prp2.70063

Cancer Metastasis Rev. 2025 Feb 21;44(1):35. doi: 10.1007/s10555-025-10246-6.

ABSTRACT

The efficacy and off-target effects of immune checkpoint inhibitors (ICI) in cancer treatment vary among patients. Monocytes likely contribute to this heterogeneous response due to their crucial role in immune homeostasis. We conducted a systematic review and meta-analysis to evaluate the impact of monocytes on ICI efficacy and immune-related adverse events (irAEs) in patients with cancer. We systematically searched PubMed, Web of Science, and Embase for clinical studies from January 2000 to December 2023. Articles were included if they mentioned cancer, ICI, monocytes, or any monocyte-related terminology. Animal studies and studies where ICIs were combined with other biologics were excluded, except for studies where two ICIs were used. This systematic review was registered with PROSPERO (CRD42023396297) prior to data extraction and analysis. Monocyte-related markers, such as absolute monocyte count (AMC), monocyte/lymphocyte ratio (MLR), specific monocyte subpopulations, and m-MDSCs were assessed in relation to ICI efficacy and safety. Bayesian meta-analysis was conducted for AMC and MLR. The risk of bias assessment was done using the Cochrane-ROBINS-I tool. Out of 5787 studies identified in our search, 155 eligible studies report peripheral blood monocyte-related markers as predictors of response to ICI, and 32 of these studies describe irAEs. Overall, based on 63 studies, a high MLR was a prognostic biomarker for short progression-free survival (PFS) and overall survival (OS) hazard ratio (HR): 1.5 (95% CI: 1.21-1.88) and 1.52 (95% CI:1.13-2.08), respectively. The increased percentage of classical monocytes was an unfavorable predictor of survival, while low baseline rates of monocytic myeloid-derived suppressor cells (m-MDSCs) were favorable. Elevated intermediate monocyte frequencies were associated but not significantly correlated with the development of irAEs. Baseline monocyte phenotyping may serve as a composite biomarker of response to ICI; however, more data is needed regarding irAEs. Monocyte-related variables may aid in risk assessment and treatment decision strategies for patients receiving ICI in terms of both efficacy and safety.

PMID:39982537 | DOI:10.1007/s10555-025-10246-6

Rev Panam Salud Publica. 2025 Feb 20;49:e18. doi: 10.26633/RPSP.2025.18. eCollection 2025.

ABSTRACT

The Manual for Surveillance of Events Supposedly Attributable to Vaccination or Immunization in the Region of the Americas represented one of the first steps toward building the regional system for surveillance of events supposedly attributable to vaccination or immunization (ESAVIs) and adverse events of special interest (AESIs). This manual establishes that, after notification and investigation of an event, a national committee of experts should classify the event in accordance with the World Health Organization (WHO) causality classification. The Pan American Committee for Safe Vaccination (COPAVASE) was created in response to the introduction of the new COVID-19 vaccines to support causality analysis of complex regional ESAVI cases and to advise the Pan American Health Organization (PAHO) on strategies for developing safety information and implementing risk mitigation measures. As part of this work, two strategic planning exercises were carried out, one with Committee members and PAHO staff and another that included national authorities and committee members, who contributed ideas on how to strengthen the work both at the regional level and in countries' surveillance systems.Suggested areas of work included definition of clear guidelines, development of model terms of reference and case presentation guidelines, training, and strategies to ensure committee sustainability.With the strategies identified, PAHO expects to be able to continue strengthening national safe vaccination committees as key institutions for maintaining public trust.

PMID:39980595 | PMC:PMC11836906 | DOI:10.26633/RPSP.2025.18

Drug Saf. 2025 Feb 20. doi: 10.1007/s40264-025-01520-1. Online ahead of print.

ABSTRACT

BACKGROUND: Drug adverse events (AEs) represent a significant public health concern. US Food and Drug Administration (FDA) drug labeling documents are an essential resource for studying drug safety such as assessing a drug's likelihood to cause certain organ toxicities; however, the manual extraction of AEs is labor-intensive, requires specialized expertise, and is challenging to maintain, due to frequent updates of the labeling documents.

OBJECTIVE: To automate the extraction of AE data from FDA drug labeling documents, we developed a workflow based on AskFDALabel, a large language model (LLM)-powered framework, and its demonstration in drug safety studies.

METHODS: This framework incorporates a retrieval-augmented generation (RAG) component based on FDALabel to enhance standard LLM inference. Key steps include (1) selection of a task-specific template, (2) FDALabel database querying, and (3) content preparation for LLM processing. We evaluated the performance of the framework in three benchmark experiments, including drug-induced liver injury (DILI) classification, drug-induced cardiotoxicity (DICT) classification, and AE term recognition.

RESULTS: AskFDALabel achieved F1-scores of 0.978 for DILI, 0.931 for DICT, and 0.911 for AE annotation, outperforming other traditional methods. It also provided cited labeling content and detailed explanations, facilitating manual verification.

CONCLUSION: AskFDALabel exhibited high consistency with human AE annotation, particularly in classifying and profiling DILI and DICT. Thus, it can significantly enhance the efficiency and accuracy of AE annotation, with promising potential for advanced AE surveillance and drug safety research.

PMID:39979771 | DOI:10.1007/s40264-025-01520-1

Lancet Oncol. 2025 Feb 17:S1470-2045(24)00737-X. doi: 10.1016/S1470-2045(24)00737-X. Online ahead of print.

ABSTRACT

BACKGROUND: We proposed in 2005 that androgens replace oestrogens as the driver steroids in a subgroup of triple-negative breast cancer (TNBC) with androgen receptor (AR) expression called molecular apocrine (MA) or luminal androgen receptor (LAR). Here, we report the analysis of a clinical trial evaluating the antitumour activity of the anti-androgen darolutamide in MA breast cancer. Our aim was to assess the clinical benefit in patients with AR-positive TNBCs defined by immunohistochemistry and by RNA profiling.

METHODS: In this multicentre, non-comparative, randomised, phase 2 trial, women aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0-1 and with advanced TNBC that was previously treated with a maximum of one line of chemotherapy were recruited from 45 hospitals in France. After central confirmation of TNBC status and AR positivity (≥10%; SP107 antibody), participants were randomly assigned (2:1) to receive darolutamide 600 mg orally twice daily or capecitabine minimum 1000 mg/m2 twice daily for 2 weeks on and 1 week off, until disease progression, unacceptable toxicity, lost to follow-up, or withdrawal of consent. Randomisation was done centrally using the minimisation procedure and was stratified according to the number of previous lines of chemotherapy. Transcriptomic analysis was used to classify tumours into groups with high and low AR activity (MAhigh and MAlow). The primary clinical endpoint was clinical benefit rate at 16 weeks (confirmed complete response, partial response, or stable disease). The primary translational endpoint was clinical benefit rate in the darolutamide group in MAhigh tumours versus all other tumours. Analyses were done per protocol. This trial is registered with ClinicalTrials.gov (NCT03383679), and is closed to recruitment.

FINDINGS: Between April 9, 2018, and July 20, 2021, 254 women were screened and 94 were randomly assigned to darolutamide (n=61) or capecitabine (n=33), of whom 90 were evaluable for efficacy analyses. Median follow-up at the data cutoff on July 20, 2022, was 22·5 months (IQR 16·5-30·5). The clinical benefit rate was 29% (17 of 58; 90% CI 19-39) with darolutamide and 59% (19 of 32; 90% CI 45-74) with capecitabine. In patients treated with darolutamide, the clinical benefit rate was 57% (12 of 21; 95% CI 36-78) in MAhigh tumours, and 16% (five of 31; 95% CI 3-29; p=0·0020) in other tumours. The most common grade 3 adverse events were palmar-plantar erythrodysaesthesia syndrome (none of 60 in the darolutamide group vs two [6%] of 33 in the capecitabine group), and headache (three [5%] vs none). No grade 4 or 5 adverse events were observed. Drug-related serious adverse events occurred in three (5%) patients in the darolutamide group and three (9%) in the capecitabine group, which were toxicoderma (n=1) and headache (n=2) in the darolutamide group, and diarrhoea, general physical deterioration, and hepatic cytolysis in the capecitabine group (n=1 each).

INTERPRETATION: This study did not reach its prespecified endpoint for darolutamide activity in patients with triple-negative breast cancer selected on the basis of immunohistochemistry for AR. Further studies selecting patients based on RNA profiling might allow better identification of tumours sensitive to anti-androgens.

FUNDING: Bayer and Fondation Bergonié.

PMID:39978376 | DOI:10.1016/S1470-2045(24)00737-X

J Infect Dev Ctries. 2025 Jan 31;19(1):58-66. doi: 10.3855/jidc.19554.

ABSTRACT

INTRODUCTION: A prescribing cascade occurs when new medications are prescribed to address an adverse drug reaction (ADR) associated with the preceding use of a medication, which may be mistaken as the onset of a novel disease or condition. The aim of this study was to evaluate the perceptions of hospital pharmacists regarding roles in preventing and minimizing prescribing cascades.

METHODOLOGY: A qualitative, semi-structured interview, followed by a quantitative, questionnaire-based study, was carried out at the Shifa International Hospital (SIH; Islamabad, Pakistan). Discharge summaries of patients aged ≥ 60 years were collected to assess the prevalence of polypharmacy at SIH.

RESULTS: Discharge summaries of n = 350 patients were collected; 60.2% (n = 211) had comorbid conditions, and the co-occurrence of diabetes and hypertension were the most common. 37.8% (n = 132) were taking 8 or more medications. Eight (n = 8) hospital pharmacists participated in the qualitative study, and 4 major themes were identified in their perceptions regarding prescribing cascades. Fifty-two (n = 52) pharmacists were recruited in the quantitative phase. 86.5% (n = 45) of the participants reported long standing illness/chronic conditions; 67.3% (n = 35) noted the presence of comorbidities as a high risk, while 90.3% (n = 47) noted multiple prescribers, and 75.0% (n = 39) identified the ageing population as important risks factors for polypharmacy.

CONCLUSIONS: The current research may inform the role and responsibilities of hospital pharmacists in outpatient and inpatient departments, and in interprofessional care teams, in preventing and minimizing prescribing cascades.

PMID:39977468 | DOI:10.3855/jidc.19554

Expert Opin Drug Saf. 2025 Feb 20:1-9. doi: 10.1080/14740338.2025.2468861. Online ahead of print.

ABSTRACT

BACKGROUND: Drug-induced hypokalemia is often associated with adverse clinical outcomes, and unfortunately, the inability to fully understand the drugs that cause hypokalemia puts us in a passive position. This study applies pharmacovigilance data to present a panorama of suspected medications associated with hyperkalemia.

RESEARCH DESIGN AND METHODS: This study used disproportionality analysis to mine adverse events in OpenFDA, identified all suspected drugs that caused hypokalemia, and coded and classified the suspected drugs according to the Anatomical Therapeutic Chemical (ATC) classification system.

RESULTS: There are 19755 reports related to drug-induced hypokalemia. The majority of individuals with hypokalemia are females, with a concentrated age range of 65 to 84 years old. After the occurrence of hypokalemia, 8.02% died due to hypokalemia. This study identified 1141 suspected drugs, and among the top 50 drugs, 32 drugs did not include hypokalemia in their instructions. All suspected drugs can be categorized into 73 subgroups according to the ATC classification system.

CONCLUSIONS: By mining the OpenFDA database, we have identified all suspected drugs that cause hypokalemia and conducted a comprehensive evaluation. The instructions for most of the suspected drugs do not focus on hypokalemia. When the treatment regimen includes other drugs that can directly/indirectly cause a decrease in blood potassium, we recommend actively monitoring blood potassium when using suspected drugs.

PMID:39977281 | DOI:10.1080/14740338.2025.2468861

Neurol Ther. 2025 Feb 20. doi: 10.1007/s40120-024-00697-4. Online ahead of print.

ABSTRACT

INTRODUCTION: Efficacy/tolerability of adjunctive brivaracetam (BRV) for focal-onset seizures (FOS) in patients aged ≥ 16 years was established in randomized controlled trials. This study aimed to evaluate the effectiveness of adjunctive BRV in patients (≥ 16 years) with FOS with/without focal to bilateral tonic-clonic seizures in daily clinical practice.

METHODS: A 12-month, prospective, real-world, noninterventional study in nine European countries (EP0077/NCT02687711). BRV was prescribed per clinical practice and European Summary of Product Characteristics. Eligible patients had never received BRV before inclusion. Treating physicians made the decision to prescribe BRV, independently of study participation. Primary effectiveness outcome: BRV retention rate at 12 months; secondary effectiveness outcomes: 50% responder rate, seizure freedom.

RESULTS: A total of 544 patients received ≥ 1 BRV dose (mean age: 43.6 years; 52.8% female; mean time since diagnosis: 22.7 years). Patients had a mean of 7.3 lifetime antiseizure medications (ASMs) and median of 3.7 FOS/28 days during 3-month retrospective baseline. Median total ASM drug load (including BRV) was 3.0 at BRV initiation (n = 539) and 3.3 at study end (n = 314). At 12 months, 57.7% of 541 patients remained on BRV, 60.4% of 230 were responders (≥ 50% seizure reduction since baseline), and 13.8% of 269 were seizure-free since BRV initiation. Historical levetiracetam use appeared not to impact retention rate (56.6% of 320 and 59.3% of 221 patients with and without historical levetiracetam use, respectively). 36.0% of 544 patients had drug-related treatment-emergent adverse events (TEAEs), mostly (≥ 5% of patients) drug ineffective (11.4%) and seizure (6.3%). The three most common drug-related TEAEs leading to permanent BRV discontinuation (of 544 patients) were drug ineffective (10.1%), seizure (5.1%), and behavior disorder (3.3%).

CONCLUSIONS: Adjunctive BRV was effective in clinical practice in patients with predominantly difficult-to-treat FOS, as shown by BRV retention rate of 57.7% at 12 months, which is in line with real-world retention rates for other new-generation ASMs.

PMID:39976891 | DOI:10.1007/s40120-024-00697-4

bioRxiv [Preprint]. 2025 Jan 27:2025.01.24.634771. doi: 10.1101/2025.01.24.634771.

ABSTRACT

Synthetic prostaglandin analogues, such as latanoprost, are first-line treatments to reduce intraocular pressure (IOP) in the management of glaucoma, treating millions of patients daily. Glaucoma is a leading cause of blindness, characterized by progressive optic neuropathy, with elevated IOP being the sole modifiable risk factor. Despite this importance, the underlying latanoprost mechanism is still not well defined, being associated with both acute and long term activities, and ocular side effects. Prostaglandins are eicosanoid lipid mediators. Yet, there has not been a comprehensive assessment of small lipid mediators in glaucomatous eyes. Here we performed a lipidomic screen of aqueous humour sampled from glaucoma patients or healthy control eyes. The resulting signature was surprisingly focused on significantly elevated levels of arachidonic acid (AA) and the potent proresolving mediator, lipoxin A 4 (LXA 4 ) in glaucoma eyes. Subsequent experiments revealed that this response is due to latanoprost actions, rather than a consequence of elevated IOP. We demonstrated that increased LXA 4 inhibits pro-inflammatory cues and promotes TGF-β 3 mediated tissue remodeling in the anterior chamber. In concert, an autocrine prostaglandin circuit mediates rapid IOP-lowering. This work reveals parallel mechanisms underlying acute and long-term latanoprost activities during the treatment of glaucoma.

PMID:39975338 | PMC:PMC11838192 | DOI:10.1101/2025.01.24.634771

Front Neurol. 2025 Feb 5;16:1530438. doi: 10.3389/fneur.2025.1530438. eCollection 2025.

ABSTRACT

BACKGROUND: Widespread use of ocrelizumab, an anti-CD20 monoclonal antibody, for treating patients with multiple sclerosis (MS), has led to an increase in reported adverse events following real-world observation. Among these, drug-induced colitis is a rare, but severe side effect, prompting a recent FDA statement regarding this safety concern. Objectives: We analyzed a cohort of ocrelizumab treated patients in our MS center to evaluate the incidence of drug-induced colitis.

METHODS: We present a critical review of the available literature on diagnosis and management of anti-CD20 induced colitis and display a case series of 3 suspected patients in our cohort.

RESULTS: Two patients met the full criteria for ocrelizumab-induced colitis, while a third partially met the criteria. Following symptomatic treatment and discontinuation of ocrelizumab, the patients showed favorable outcomes.

CONCLUSION: Ocrelizumab-induced colitis is a rare, but severe adverse event. Its incidence may be higher than expected, reaching 1,95% in our cohort of MS patients. Further reporting of such cases is essential to broaden our understanding of this side effect.

PMID:39974366 | PMC:PMC11835689 | DOI:10.3389/fneur.2025.1530438

Int J Risk Saf Med. 2024 Nov;35(4):317-333. doi: 10.1177/09246479241292008. Epub 2024 Nov 6.

ABSTRACT

Background: Of many pharmaceutical products launched for the benefit of humanity, a significant number have had to be recalled from the marketplace due to adverse events. A systematic review found market recalls for 462 pharmaceutical products between 1953 and 2013. In our current and remarkable period of medical history, excess mortality figures are high in many countries. Yet these statistics receive limited attention, often ignored or dismissed by mainstream news outlets. This excess mortality may include adverse effects caused by novel pharmaceutical agents that use gene-code technology.Objective: To examine key pharmaceutical product withdrawals and derive lessons that inform the current use of gene-based COVID-19 vaccines.Methods: Selective narrative review of historical pharmaceutical recalls and comparative issues with recent COVID-19 vaccines.Results: Parallels with past drug withdrawals and gene-based vaccines include distortion of clinical trial data, with critical adverse event data absent from high-impact journal publications. Delayed regulatory action on pharmacovigilance data to trigger market withdrawal occurred with Vioxx (rofecoxib) and is apparent with the gene-based COVID-19 vaccines.Conclusion: Public health requires access to raw clinical trial data, improved transparency from corporations and heightened, active pharmacovigilance worldwide.

PMID:39973420 | DOI:10.1177/09246479241292008

J Acquir Immune Defic Syndr. 2025 Feb 20. doi: 10.1097/QAI.0000000000003648. Online ahead of print.

ABSTRACT

BACKGROUND: Leronlimab is a humanized κ-IgG4 monoclonal antibody that blocks C-C chemokine receptor type 5 (CCR5). We investigated leronlimab as a treatment option for people living with multidrug-resistant HIV-1.

SETTING: and Methods: In a phase 2b/3, multicenter, randomized, double-blind, placebo-controlled study conducted in 21 hospital centers in the United States, treatment-experienced people living with HIV (PLWH) with documented drug resistance were randomly assigned once weekly leronlimab (350 mg subcutaneously) or matching placebo for one week overlapping existing failing antiretroviral treatment (ART), followed by a 24-week single-arm extension with weekly leronlimab combined with a new optimized background treatment (OBT). The primary endpoint was achieving ≥0.5 log10 reduction in plasma HIV-1 RNA from baseline at the end of the one-week double-blinded treatment period.

RESULTS: 52 participants were enrolled (25 leronlimab and 27 placebo). After the one-week randomized phase, by the intent-to-treat analysis 64.0% (16/25) receiving leronlimab achieved ≥0.5 log10 reduction in plasma HIV-1 RNA versus 23.1% (6/26) receiving placebo (p=0.0032), while by per protocol analysis 72.7% (16/22) receiving leronlimab achieved ≥0.5 log10 reduction in plasma HIV-1 RNA versus 24.0% (6/25) receiving placebo (p=0.0008). Leronlimab was generally well tolerated with no drug-related SAEs reported. Overall, 175 adverse events were reported by 34/52 participants, with 120 (68.6%) adverse events categorized as mild.

CONCLUSIONS: Leronlimab resulted in significantly reduced plasma HIV-1 within one week after addition to failing ART. After 24 weeks combined with an OBT, most participants had plasma HIV-1 RNA levels <50 copies per mL plasma, suggesting utility of leronlimab as a component of salvage therapy.

PMID:39972543 | DOI:10.1097/QAI.0000000000003648

Sci Rep. 2025 Feb 19;15(1):6022. doi: 10.1038/s41598-025-90135-8.

ABSTRACT

Hepatitis B vaccines (HBVs) are widely used duo to their high clinical use and mild effects. However, as post-marketing data accumulate, several serious adverse events (SAEs) following HBV have been reported. Currently, quantitative studies based on real-world data are lacking, and information on their adverse events is limited. Adverse reaction signals of the HBV were mined and analyzed using the U.S. Vaccine Adverse Event Reporting System (VAERS) to provide a reference for the safe clinical use of this vaccine. Multiple statistical methods, including the reporting odds ratio (ROR) method, the Medicines and Healthcare Products Regulatory Agency (MHRA) method, and the Bayesian Confidence Propagation Neural Network (BCPNN) method, were utilized to identify signals of HBV-associated adverse reactions, and positive signals consistent with designated medical events (DMEs) were singled out for focused comparison and discussion. Analysis of 54,136 HBV-related adverse events (AEs) identified 254 positive signals across 22 System Organ Classifications (SOCs), with General disorders and administration site conditions being the most common. Three potential positive new signals consistent with Preferred Terms (PTs) were identified in DME: Aplastic anaemia, Dermatitis exfoliative, and Haemolytic anaemia. This study suggests that HBV has a potential risk in terms of causing Aplastic anaemia, Dermatitis exfoliative, and Haemolytic anaemia. Some subtypes of Aplastic anaemia, Dermatitis exfoliative, Haemolytic anaemia are autoimmune diseases, and immunization may stimulate potential autoimmune genetic predisposition, people with autoimmune diseases or a family history of hereditary immune diseases should be monitored after receiving HBV. Health professionals should be contacted to take measures to help if anaemia, palpitations, and high fever occur.

PMID:39972053 | DOI:10.1038/s41598-025-90135-8

Basic Clin Pharmacol Toxicol. 2025 Mar;136(3):e70009. doi: 10.1111/bcpt.70009.

ABSTRACT

Precision medicine has significantly advanced through the development of predictive biomarkers based on pharmacogenetic (PGx) testing. These tests identify interactions between drugs and genetic variants that influence patient responses to treatments. Understanding genetic variations in drug-metabolizing enzymes, receptors and transporters and their impact on pharmacokinetics and pharmacodynamics allows for the prediction of drug effects and side effects, enabling tailored treatments for different patient groups. This review focuses on drugs metabolized by cytochrome P450 (CYP450) enzymes, for example, citalopram and clopidogrel or transported by the solute carrier organic anion transporter family member 1B1 (SLCO1B1), for example, atorvastatin and simvastatin, with PGx dosing guidelines, in the context of consumption in Scandinavian countries. A major barrier to the widespread adoption of PGx tests in clinical practice has been healthcare professionals' uncertainty about their efficacy, complexity in result interpretation and questions regarding the evidence base. However, recent studies have demonstrated PGx testing has the potential to improve treatment outcomes, reduce adverse drug reactions and achieve cost savings. These findings underscore the potential of PGx testing as a valuable tool in clinical decision making, promoting its use in a pre-emptive manner to enhance patient care.

PMID:39971612 | DOI:10.1111/bcpt.70009

Drug Ther Bull. 2025 Feb 19:dtb-2025-000008. doi: 10.1136/dtb.2025.000008. Online ahead of print.

NO ABSTRACT

PMID:39971479 | DOI:10.1136/dtb.2025.000008

Reg Anesth Pain Med. 2025 Feb 19:rapm-2024-106152. doi: 10.1136/rapm-2024-106152. Online ahead of print.

NO ABSTRACT

PMID:39971388 | DOI:10.1136/rapm-2024-106152

Intern Med. 2025 Feb 18. doi: 10.2169/internalmedicine.4431-24. Online ahead of print.

ABSTRACT

The causes of hypercalcemia vary. There are high-calcium-containing preparations in Chinese herbal medicine, which may contribute to drug-induced hypercalcemia. We encountered a case of hypercalcemia following the simultaneous administration of an active vitamin D3 preparation and several Chinese herbal medicines. The patient had been treated at several medical institutions, with one institution administering eldecalcitol and another institution administering Keishikaryukotsuboreito, Borei powder, and Goreisan. The patient presented with drug-induced hypercalcemia due to an unexpected synergistic effect. Confirmation of prescriptions for patients with multiple medical visits and recognition of the components and side effects of Chinese herbal medicines is thus considered to be extremely important.

PMID:39971300 | DOI:10.2169/internalmedicine.4431-24

Case Rep Dent. 2025 Feb 11;2025:8318894. doi: 10.1155/crid/8318894. eCollection 2025.

ABSTRACT

Background: Pemphigus vulgaris (PV) is a chronic autoimmune disorder affecting mucous membranes and skin, with potential life-threatening risks. It is typically characterized by blisters within the oral cavity with or without subsequent skin involvement. Given the importance of timely intervention, dental professionals are responsible for diagnosing this condition, as prompt detection and intervention greatly influence the disease progression and prognosis. Case Description: A 44-year-old male patient presented with swollen and bleeding gums, accompanied by multiple chronic ulcers in the oral cavity. He was initially diagnosed with PV in 2018; his case posed significant challenges, including drug-influenced gingival enlargement and the psychological burden of managing a chronic, relapsing condition. Management and Prognosis: The patient received treatment with an immunosuppressive medication (cyclosporin) along with long-term systemic steroids (prednisolone). In November 2022, cyclosporin was replaced with a steroid-sparing medication (methotrexate) to control drug-influenced gingival enlargement. The periodontal condition improved after 3 months of changing the medication regimen, nonsurgical periodontal therapy, and reinforced oral hygiene practices. The patient undergoes regular medical evaluations every 6 months with the dermatology department. Clinical Implications: Effective management of PV necessitates long-term systemic steroid therapy, often supplemented with immunosuppressive agents, to control the disease and minimize relapse risks. Regular clinical assessments are essential for patients receiving steroid and immunosuppressive treatment to monitor potential side effects, including cyclosporin-induced gingival enlargement. If gingival enlargement is compounded by periodontal disease, it can further complicate the management of PV. Drug-induced gingival enlargement has a favorable prognosis and is reversible upon discontinuation or substitution of the causative medication. An interdisciplinary approach involving primary clinicians, dentists, and the healthcare team is crucial to addressing the patient's signs and symptoms effectively.

PMID:39968166 | PMC:PMC11835479 | DOI:10.1155/crid/8318894