AME Case Rep. 2025 Apr 17;9:65. doi: 10.21037/acr-24-114. eCollection 2025.

ABSTRACT

BACKGROUND: Omalizumab is a monoclonal humanized antibody used as a third-line treatment for chronic spontaneous urticaria (CSU). While it has shown significant efficacy in controlling urticaria symptoms, it is also associated with various adverse effects. Cutaneous side effects of omalizumab have been reported, but the mechanisms underlying these reactions are not fully understood. This case report describes a patient who developed a maculopapular rash after receiving the 8th dose of omalizumab, which has not been previously reported.

CASE DESCRIPTION: The patient in this case was a 46-year-old male with CSU who had been receiving omalizumab injections every four weeks. After the 8th dose, he developed a generalized itchy erythematous skin eruption six days after the injection. The rash progressively worsened over a two-week period. Interestingly, the patient had experienced a milder skin reaction after the 6th dose, which resolved on its own. A skin biopsy showed mild interstitial edema in the dermis with a mild perivascular infiltrate of lymphocytes and eosinophils, consistent with a drug-induced eruption. The patient was advised to hold the next dose of omalizumab and was managed with topical steroids. Significant improvement and resolution of the lesions were observed, and no recurrence or relapse was reported after the patient resumed omalizumab.

CONCLUSIONS: This case adds to the existing literature by reporting a pityriasis rosea-like eruption as an adverse reaction to omalizumab, which has not been extensively documented. The delayed onset and progressive nature of the rash after the 8th dose, as well as the milder previous reaction after the 6th dose, highlight the importance of considering omalizumab as a potential cause of various cutaneous reactions. Physicians should be vigilant in monitoring patients receiving omalizumab for any signs of skin eruptions or other adverse effects. Further research is needed to understand the mechanisms underlying cutaneous reactions to omalizumab and to establish guidelines for their management. This case emphasizes the need for ongoing attention to potential side effects or reactions in patients receiving omalizumab.

PMID:40330944 | PMC:PMC12053656 | DOI:10.21037/acr-24-114

Cureus. 2025 Apr 3;17(4):e81663. doi: 10.7759/cureus.81663. eCollection 2025 Apr.

ABSTRACT

We report the case of a 30-year-old male patient who presented with a pruritic, irregular, 4x3 cm scaly purple-red plaque with surrounding papules on his lateral face, scalp, and chin after the introduction of semaglutide (Ozempic). Discoid lupus erythematosus (DLE) was suspected. A punch biopsy of a scalp lesion showed interface changes with loss of pilosebaceous units and follicular plugging, findings consistent with DLE. A complete blood count, antinuclear antibody (ANA), anti-double stranded DNA (dsDNA), and extractable nuclear antigen (ENA) panel was quantified along with erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), complement levels, creatinine, and glomerular filtration rate, ruling out systemic lupus erythematosus (SLE). The patient's condition improved with drug discontinuation as well as topical treatment, including tacrolimus 0.1% ointment and clobetasol lotion. Hydroxychloroquine 200 mg daily was trialed but discontinued due to the patient's concerns about ocular side effects. Follow-up after four months showed improvement, with less scale and erythema. Although semaglutide has been widely used for glycemic control and weight loss, cutaneous adverse effects are seldom reported. This case highlights the potential for drug-induced cutaneous lupus erythematosus (DICLE) associated with immune-modulating medications such as semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA).

PMID:40330408 | PMC:PMC12051072 | DOI:10.7759/cureus.81663

Orphanet J Rare Dis. 2025 May 6;20(1):215. doi: 10.1186/s13023-025-03715-2.

ABSTRACT

BACKGROUND: Onasemnogene abeparvovec (OA) is an adeno-associated virus vector-based gene therapy indicated for the treatment of paediatric patients with spinal muscular atrophy(SMA) with biallelic mutations in the survival motor neuron 1 (SMN1) gene. This study focused on analysis of the postmarketing adverse events(AEs) of onasemnogene abeparvovec (OA) reported in the US Food and Drug Administration public data open project (openFDA) database to assess the safety of OA in the real world and to provide a reference for the rational use of this drug in the clinic.

RESULTS: In total, 1,959 AEs were reported with "onasemnogene abeparvovec" as the primary suspected drug. The top 5 most frequent AEs were pyrexia (461 cases), vomiting (434 cases), aspartate aminotransferase increase (284 cases), alanine aminotransferase increase (260 cases), and hepatic enzyme increase (237 cases). A total of 77 alert signals were generated, 60 of which were not included in the drug label. The top 5 signals included troponin I increase ( ROR of 895.21, 95% CI: 734.43-1091.18), troponin T increase ( ROR of 313.30, 95% CI:220.85-444.44), rhinovirus infection ( ROR of 175.80, 95% CI:130.86-236.17), troponin increase ( ROR of 143.49, 95% CI:114.96-179.10), and increased bronchial secretion ( ROR of 142.71, 95% CI:96.63-210.77). Further analysis of AEs associated with gender and age differences identified 14 high-risk signals related to gender and 10 high-risk signals related to age. Female patients should be vigilant for vomiting, thrombotic microangiopathy, increased troponin T, proteinuria, haematuria, haemolytic anaemia, urinary tract infection, generalised oedema, and atypical haemolytic uraemic syndrome. Male patients should be alert to increased hepatic enzyme, increased bronchial secretion, respiratory tract infection, pallor, and increased blood creatine phosphokinase MB. Patients under 2 years of age should be vigilant for lethargy, increased monocyte count, decreased blood creatinine, and decreased neutrophil count. Patients over 2 years of age should be alert to hypertension, haematuria, rhinovirus infection, increased blood creatine phosphokinase, headache, and malaise.

CONCLUSIONS: Mining of OA alert signals using the openFDA database provides supplementary information on AEs not included in the drug label. Clinical attention should be focused on common, strong-signal, and label-unmentioned AEs to optimise medication regimens and control risks in clinical use.

PMID:40329332 | DOI:10.1186/s13023-025-03715-2

Sci Rep. 2025 May 6;15(1):15760. doi: 10.1038/s41598-025-00231-y.

ABSTRACT

This study employs a comprehensive approach to systematically identify drugs associated with Drug-Induced Erectile Dysfunction (DIED) risk and constructs a DIED risk assessment platform. Utilizing the FAERS database, we identified "Erectile Dysfunction," "Organic Erectile Dysfunction," and "Psychogenic Erectile Dysfunction" as relevant Preferred Terms (PTs) for DIED. After excluding patients diagnosed with Erectile Dysfunction (ED), drugs suspected as primary suspects (PS) in ≥ 10 DIP events were selected as target drugs. Through disproportionality analysis, we identified positive signals for these drugs using ROR, PRR, BCPNN, and EBGM. We further assessed the independent effects of positive drugs by adjusting for confounding factors such as age using multivariate logistic regression. Subsequently, we obtained the median onset time and outcome events of DIED for target drugs and compared them by age. The DIED platform is accessible for free at http://116.196.73.86:3838/ADR-DATABASE/DIED/. A total of 67 target drugs were identified as PS in DIED events with 10 or more cases. Based on disproportionality analysis, we further identified 28 drugs with DIED risk signals. Multivariate logistic regression revealed that 23 of these drugs were independent risk factors for DIED (OR > 1 and P < 0.05). Analysis of outcome events showed a significant difference in the median onset time of DIED between different age groups. This study identified 28 drugs associated with DIED risk. We also found some previously unreported DIP risk drugs, including omeprazole, antihypertensive drugs, etc., which should be of clinical concern.

PMID:40328828 | DOI:10.1038/s41598-025-00231-y

J Chem Inf Model. 2025 May 6. doi: 10.1021/acs.jcim.5c00136. Online ahead of print.

ABSTRACT

Computational prediction of potential drug side effects plays a crucial role in reducing health risks for clinical patients and accelerating drug development. Recent methods have constructed heterogeneous graphs that represent drugs and their side effects, utilizing graph learning strategies such as graph convolutional networks to predict associations between them. However, existing approaches fail to fully exploit the diverse topologies and semantics present in multiple knowledge graphs. We propose MVDSA, a novel multi-view drug-side effect association prediction model. Our approach integrates multiple relationship semantics, local topologies of knowledge graphs, and multi-view features of drug-side effect entity pairs. First, we constructed two knowledge graphs based on drug functional and structural similarity, side effect similarity, and drug-side effect associations. These knowledge graphs capture the topological and semantic connections between drug and side effect entities from diverse perspectives. Second, considering the diverse similarities and associations between entities, we designed a space-sensitive learning strategy where a relation-gated semantic encoder is constructed for each type of relationship. This encoder adaptively adjusts the contribution of each entity feature to the relational semantic representation, facilitating the learning of entity-specific semantic features within each relational space. Third, for the two knowledge graphs, given the multiple types of connections between head and tail entities, we propose a connection-sensitive tail entity attention mechanism to integrate these diverse semantic relationships. To capture the contribution of different knowledge graphs to entity feature learning, we designed a knowledge graph-level attention mechanism to adaptively fuse the enhanced features from multiple knowledge graphs. Finally, we propose a multi-view enhanced multi-layer perceptron (MLP) strategy to encode the features of drug-side effect pairs from three perspectives and capture the potential associations between entities. Extensive experiments demonstrate that MVDSA outperforms 10 state-of-the-art methods in predicting drug-side effect associations. Ablation studies validate the contributions of the proposed innovations to improved prediction performance. Additionally, case studies on candidate side effects for five drugs highlight MVDSA's capability to discover potential drug-side effect associations.

PMID:40326886 | DOI:10.1021/acs.jcim.5c00136

Medicine (Baltimore). 2025 May 2;104(18):e42171. doi: 10.1097/MD.0000000000042171.

ABSTRACT

Previous studies have identified a relationship between fatty acid-binding proteins (FABPs) and immune diseases. This study aimed to investigate whether a causal relationship exists between FABPs and anaphylactic shock resulting from adverse drug reactions. Single nucleotide polymorphisms associated with FABPs were utilized as instrumental variables, sourced from the National Human Genome Research Institute-European Bioinformatics Institute Catalog of human genome-wide association studies. Data on anaphylactic shock due to adverse effects of correctly administered drugs were obtained from the FinnGen database, which includes genomic and health data from 500,000 Finnish biobank donors. A two-sample Mendelian randomization analysis was conducted to explore the causality between FABPs and anaphylactic shock due to adverse drug reactions. The analysis revealed a negative causal relationship between FABP5 (odds ratio [OR] = 0.40; 95% confidence interval [CI] = 0.17-0.92; P = .032) and FABP12 (OR = 0.77; 95% CI = 0.63-0.94; P = .009) and anaphylactic shock due to adverse drug reactions. These findings were corroborated by Mendelian randomization-Egger, weighted median, and weighted mode methods. This study provides robust evidence supporting a protective relationship between FABP5 and FABP12 and anaphylactic shock due to adverse drug reactions. Further experimental studies are warranted to elucidate the causal mechanisms and associations between FABP5, FABP12, and anaphylactic shock in the context of adverse drug reactions.

PMID:40324257 | DOI:10.1097/MD.0000000000042171

Anesthesiology. 2025 May 5. doi: 10.1097/ALN.0000000000005535. Online ahead of print.

ABSTRACT

BACKGROUND: Sugammadex is well-tolerated and effective for reversing neuromuscular blockade (NMB) in adults and children ≥2 years old. There is little information on its use in younger children. The aim of this study was to evaluate the efficacy and tolerability of sugammadex in children under 2 years of age.

METHODS: Phase IV, randomized, parallel-group, multicenter, clinical trial of sugammadex in participants aged birth to <2 years. Part A was open-label and included pharmacokinetic assessments to determine whether sugammadex dose-adjustment for Part B was necessary based on age. Part B was double-blind and evaluated sugammadex 2 mg/kg and 4 mg/kg. Participants were randomized to: 1) moderate NMB and reversal with 2 mg/kg sugammadex, or 2) moderate NMB and reversal with neostigmine + glycopyrrolate or atropine (hereafter, called neostigmine), or 3) deep NMB and reversal with 4 mg/kg sugammadex. The primary efficacy endpoint was time to neuromuscular recovery (TTNMR). The primary efficacy hypothesis was that sugammadex 2mg/kg would be superior to neostigmine for the reversal of moderate NMB as measured by TTNMR in Part B.

RESULTS: 138 participants aged 1 to 720 days were treated in Parts A+B (sugammadex 2mg/kg n=44, sugammadex 4 mg/kg n=63, neostigmine n=31). Based on pharmacokinetic assessments in Part A, no dose-adjustments for age were needed. In Part B, TTNMR for reversal of moderate NMB was faster with sugammadex 2 mg/kg than neostigmine (median of 1.4 minutes vs 4.4 minutes, hazard ratio = 2.40, 95% CI: 1.37, 4.18; p=0.0002). Sugammadex 4 mg/kg achieved rapid TTNMR for reversal of deep NMB with a median of 1.1 minutes (Parts A+B). The percentage of participants with ≥1 adverse event (Parts A+B) was similar for sugammadex and neostigmine. No deaths, drug-related serious adverse events, or hypersensitivity or anaphylaxis events were reported.

CONCLUSIONS: In children <2 years old, sugammadex 2 mg/kg reversed moderate NMB faster than neostigmine, and sugammadex 4 mg/kg rapidly reversed deep NMB. Sugammadex 2 mg/kg and 4 mg/kg were well-tolerated.

PMID:40324166 | DOI:10.1097/ALN.0000000000005535

J Ocul Pharmacol Ther. 2025 May 5. doi: 10.1089/jop.2024.0178. Online ahead of print.

ABSTRACT

Purpose: The aim of this study was to identify and quantify the occurrence of corneal deposits caused by medications, utilizing data from the Food and Drug Administration Adverse Event Reporting System (FAERS). Methods: We conducted a retrospective analysis of the national FAERS database, focusing on instances of drug-induced corneal deposits reported between 2004 and the third quarter of 2023. Our methodology included applying the proportional reporting ratio, reporting odds ratio, empirical Bayes geometric mean, and information component in our disproportionality analysis. A signal was considered present if all four of these disproportionality metrics showed positive results. Results: Over the span of 20 years, our research identified 383 adverse event reports linked to corneal deposits associated with 349 different medications. The most common age-group of these reports involved patients over 65 years of age (32.4%), with equal distribution between male (40.0%) and female (42.8%) patients. Thirty-one medications showed a positive signal. Notably, drugs such as amiodarone (68 reports), prednisolone (60 reports), and timolol (54 reports) were most frequently mentioned. Cyclopentolate and chloramphenicol demonstrated robust statistical relevance in association with corneal deposits. Conclusions: Positive signals for drug-induced corneal deposits included both well-known medications such as amiodarone and lesser-studied medications such as prednisolone and timolol. Clinician awareness of these findings alongside further investigation is needed.

PMID:40322910 | DOI:10.1089/jop.2024.0178

Cureus. 2025 Apr 3;17(4):e81664. doi: 10.7759/cureus.81664. eCollection 2025 Apr.

ABSTRACT

Hydroxychloroquine (HCQ) is a medication that is commonly used as an antimalarial or disease-modifying anti-rheumatic drug (DMARD). Adverse side effects typically include retinal damage, cardiomyopathy, and neuromyopathy. However, there has been relatively little documentation on the effects of HCQ toxicity on the liver. We describe a case of HCQ-induced hepatic failure in a 31-year-old female patient on HCQ for systemic lupus erythematous who presented with three days of fever, diarrhea, and non-bilious, non-bloody vomiting. Labs showed massively elevated liver function tests (LFTs) and negative viral serology. The abdominal ultrasound and magnetic resonance cholangiopancreatography were unremarkable. A liver biopsy showed portal tracts with mild to moderate expansion by mixed inflammatory infiltrates, including scattered eosinophils and rare plasma cells with occasional mild interface activity focally close to bridging inflammation. These findings are consistent with drug-induced liver injury (DILI). HCQ was subsequently held, and the patient was admitted to the ICU for conservative management. Repeat LFTs showed down-trending over the course of the patient's four days of admission after discontinuation of HCQ and returned to baseline within a two-month timeframe.

PMID:40322400 | PMC:PMC12049183 | DOI:10.7759/cureus.81664

Expert Opin Drug Saf. 2025 May 5. doi: 10.1080/14740338.2025.2500716. Online ahead of print.

ABSTRACT

BACKGROUND: Non-infectious pneumonitis (NIP) is a severe adverse drug reaction. To better understand drug-induced NIP, improve patient safety, and inform clinical decision-making, this study aims to utilize the FDA Adverse Event Reporting System (FAERS) database to evaluate the association between medications and NIP, identify potential risk factors, and offer clinical alerts.

RESEARCH DESIGN AND METHODS: We reviewed the FAERS database from the 2004 through the second quarter of 2024. Using 'NIP' as the search term, we sorted, counted, and analyzed cases by generic drug name and trends of reports related to NIP submitted to FAERS database. We employed four statistical methods to identify drugs associated with the NIP.

RESULTS: From 21,433,114 reported drug adverse events (AEs), 9,224 cases were classified as NIP. Our analysis identified 20 drugs associated with NIP, with the main categories being antineoplastic agents, antibiotics and immunosuppressants. Daptomycin, methotrexate, and tacrolimus had the highest NIP-related deaths. Trends in AEs reporting indicate that the drugs showing the fastest increase in NIP reports are daptomycin, methotrexate, sertraline, and amiodarone.

CONCLUSION: These findings could assist clinicians in the early identification of drug-related NIP and provide valuable insights for future research into the mechanisms underlying drug-related NIP.

PMID:40321104 | DOI:10.1080/14740338.2025.2500716

Cancer Immunol Immunother. 2025 May 3;74(6):190. doi: 10.1007/s00262-025-04033-z.

ABSTRACT

Immune checkpoint inhibitors (ICI) targeting CTLA-4 and PD-1 have shown remarkable antitumor efficacy, but can also cause immune-related adverse events, including checkpoint inhibitor-induced liver injury (ChILI). This multi-omic study aimed to investigate changes in blood samples from treated cancer patients who developed ChILI. PBMCs were sequenced for by transcriptomic and T cell receptor repertoire (bulk and single-cell immune profiling), and extracellular vesicle (EV) enrichment from plasma was analyzed by mass spectroscopy proteomics. Data were analyzed by comparing the ChILI patient group to the control group who did not develop ChILI and by comparing the onset of ChILI to pre-ICI treatment baseline. We identified significant changes in T cell clonality, gene expression, and proteins in peripheral blood mononuclear cells (PBMCs) and plasma in response to liver injury. Onset of ChILI was accompanied by an increase in T cell clonality. Pathway analysis highlighted the involvement of innate and cellular immune responses, mitosis, pyroptosis, and oxidative stress. Single-cell RNA sequencing revealed that these changes were primarily found in select T cell subtypes (including CD8 + effector memory cells), while CD16 + monocytes exhibited enrichment in metabolic pathways. Proteomic analysis of plasma extracellular vesicles showed enrichment in liver-associated proteins among differentially expressed proteins. Interestingly, an increase in PBMC PD-L1 gene expression and plasma PD-L1 protein was also found to be associated with ChILI onset. These findings provide valuable insights into the immune and molecular mechanisms underlying ChILI as well as potential biomarkers of ChILI.Trial registration number NCT04476563.

PMID:40317333 | DOI:10.1007/s00262-025-04033-z

BMC Immunol. 2025 May 2;26(1):35. doi: 10.1186/s12865-025-00714-7.

ABSTRACT

BACKGROUND: This study utilizes the FDA Adverse Event Reporting System (FAERS) database to compare the adverse reaction signals of cyclosporine and tacrolimus, two widely used immunosuppressants, in relation to drug-induced kidney injury. The findings aim to inform clinical decision-making.

METHODS: The study retrospectively analyzed data from January 2004 to September 2024, employing both frequency analysis and Bayesian methods. We assessed and compared the mortality rates, hospitalization rates, and the association of cyclosporine and tacrolimus with kidney injury to elucidate the renal toxicity of these two drugs.

RESULTS: After data processing, we identified a total of 3,449 cyclosporine-related kidney injury reports and 5,538 tacrolimus-related kidney injury reports. The results revealed a stronger association between tacrolimus and kidney injury. Additionally, kidney injuries associated with both cyclosporine and tacrolimus predominantly affected males. Furthermore, the hospitalization rate for cyclosporine-related kidney injury was 34.40%, compared to 44.50% for tacrolimus. The mortality rate associated with cyclosporine-induced kidney injury was higher than that of tacrolimus.

CONCLUSION: This study utilized the FDA Adverse Event Reporting System (FAERS) database from January 2004 to September 2024 to perform a comprehensive analysis of adverse drug-related kidney injury reactions to cyclosporine and tacrolimus. The results suggest that both cyclosporine and tacrolimus are associated with renal injury, but tacrolimus appears to reduce mortality while increasing hospitalization rates. This serves as a critical warning for planning future treatment regimens, drug monitoring, and reducing adverse effects.

PMID:40316906 | DOI:10.1186/s12865-025-00714-7

BMC Geriatr. 2025 May 1;25(1):300. doi: 10.1186/s12877-025-05965-y.

ABSTRACT

BACKGROUND: Drug-drug interactions (DDIs) are significant causes of adverse drug reactions among patients with cancer. We aimed to identify the prevalence, severity, and predictors of potential DDIs among geriatric oncology patients.

METHODS: A cross-sectional, retrospective study was conducted at two tertiary medical centers. Geriatric patients (≥ 65 years) who were diagnosed with solid tumors and received outpatient prescriptions with a minimum of two drugs between January 2018 and December 2022 were included in the study. Patients' medications were screened for DDIs using Lexi-Interact. Univariate and multivariable logistic regression models were used to explore factors associated with DDIs.

RESULTS: The study included 247 geriatric patients with a mean age of 74.0 ± 7.3 years, and 48.6% of the patients were female. The most common type of cancer was gastrointestinal cancer (35.6%), followed by genitourinary cancer (20.6%), and 50.6% of the patients had metastasized tumors. Approximately one-half of the patients (49.0%) received anticancer therapy, and hormonal therapy (21.9%) or chemotherapy (16.6%) was the most common therapy. The mean number of medications used per patient was 6.9 ± 3.5. The majority of patients (79.4%) had at least one DDI, with a mean of 5.6 ± 5.3 DDIs per patient. Most of the interactions were classified as moderate (58.9%), and only 19.3% were classified as major. Multiple logistic regression revealed that females were more vulnerable to DDIs than their male counterparts were (adjusted odds ratio (AOR) = 37.4; 95% CI 4.13-338.3). The number of medications used was significantly associated with the risk of DDIs (AOR = 4.07; 95% CI 2.53-6.54). Compared with patients with gastrointestinal cancers, patients with breast or gynecologic cancers had lower odds of experiencing DDI (AOR = 0.02; 95% CI < 0.01-0.24 and AOR = 0.04; 95% CI < 0.01-0.29, respectively).

CONCLUSION: This study revealed a high prevalence of DDIs among geriatric oncology patients, with most interactions classified as moderate. Female patients and patients taking multiple medications had a greater risk of experiencing DDIs. Routine screening for potential DDIs is essential for this vulnerable population, and the factors identified in this study should be carefully considered.

PMID:40312689 | DOI:10.1186/s12877-025-05965-y

Trials. 2025 May 1;26(1):145. doi: 10.1186/s13063-024-08671-z.

ABSTRACT

BACKGROUND: We define clinical study reports (CSRs) as standardized full reports of the protocols, results, and other pertinent details of clinical studies that are typically submitted by pharmaceutical companies to regulatory authorities when they apply for marketing authorization.

METHODS: In this systematic review we searched various databases (Clarivate Web of Science, EMBASE and Ovid Medline, Google Scholar, and PubMed) for publications containing the term "clinical study report/s", without restrictions.

THEMATIC SYNTHESIS: In the first part of this review we discussed the history of CSRs, their contents and structure, definitions, and relevant terminology. In this second part we discuss the uses of CSRs, concentrating on the individual benefits and harms of pharmacological interventions, and thus the benefit to harm balance. We also discuss adherence to interventions, prepublication of protocols of clinical trials, and how CSRs are written, factors that can all affect estimation of the benefit-harm balance.

CONCLUSIONS: When clinical trial data from CSRs are compared with the data in published trial reports, the apparent benefits of pharmacological interventions are less impressive, and more information emerges about harms they can cause. Both of these effects change how the benefit-harm balance of a pharmacological intervention is estimated, generally making it less favourable than was otherwise thought. For more accurate assessment of the benefit-harm balance of an intervention, full, not abbreviated or synoptic, clinical study reports should continue to be made publicly available by regulatory authorities and manufacturers. Authorities that do not currently make them available should do so. CSRs should be introduced for assessment of surgical operations, therapeutic devices, and other non-pharmacological interventions in clinical trials.

PMID:40312342 | DOI:10.1186/s13063-024-08671-z

DEN Open. 2025 Apr 29;6(1):e70124. doi: 10.1002/deo2.70124. eCollection 2026 Apr.

ABSTRACT

A 74-year-old man with decreased appetite, weight, and heartburn was referred to our hospital. His medications included olmesartan. Esophagogastroduodenoscopy (EGD) revealed antral-dominant erosive gastritis and nodular mucosa. A gastric biopsy revealed inflammatory cell infiltration. The serum anti-Helicobacter pylori immunoglobulin G antibody test result was negative. Famotidine was ineffective in relieving his symptoms, and esomeprazole failed to prevent overt gastric bleeding, which required endoscopic hemostasis. The working diagnosis was drug-induced gastritis, particularly olmesartan-induced gastritis. His appetite loss started to improve within a week of olmesartan withdrawal. The erosions healed on EGD 2 months later. Over the next 10 months, he remained in his usual state until olmesartan was inadvertently administered. Subsequent EGD revealed a mild gastritis relapse. We diagnosed olmesartan-induced gastritis and discontinued olmesartan treatment. Mucosal healing was confirmed by EGD 1 year later. Olmesartan is known to cause angiotensin II receptor blocker-induced enteropathy. Although angiotensin II receptor blocker-induced enteropathy affects the stomach, angiotensin II receptor blocker-induced gastritis without lower gastrointestinal symptoms is rare. The characteristic endoscopic appearance may provide a clue to the correct diagnosis.

PMID:40309044 | PMC:PMC12038180 | DOI:10.1002/deo2.70124

Cureus. 2025 Mar 31;17(3):e81513. doi: 10.7759/cureus.81513. eCollection 2025 Mar.

ABSTRACT

Capivasertib, a protein kinase B (AKT) inhibitor manufactured by AstraZeneca pharmaceutical and used in the treatment of various malignancies, has been implicated in cases of drug-induced diabetic ketoacidosis (DKA). We present a case of capivasertib-induced DKA in a patient with no prior history of diabetes, highlighting the metabolic complications associated with this targeted therapy. The proposed mechanism involves AKT inhibition leading to impaired insulin signaling, reduced glucose uptake, and increased lipolysis, ultimately resulting in ketogenesis. This case underscores the need for vigilant glucose monitoring in patients receiving capivasertib, especially those with predisposing risk factors for insulin resistance or pancreatic dysfunction.

PMID:40308416 | PMC:PMC12043024 | DOI:10.7759/cureus.81513

Nat Commun. 2025 Apr 29;16(1):3997. doi: 10.1038/s41467-025-59431-9.

ABSTRACT

Adverse drug-drug interaction events (DDIEs) pose serious risks to patient safety, yet rare but severe interactions remain challenging to identify due to limited clinical data. Existing computational methods rely heavily on abundant samples, failing to identify rare DDIEs. Here we introduce RareDDIE, a metric-based meta-learning model that employs a dual-granular structure-driven pair variational representation to enhance rare DDIE prediction. To further address the challenge of zero-shot DDIE identification, we develop the Biological Semantic Transferring (BST) module, integrating large-scale sentence embeddings to form the ZetaDDIE variant. Our model outperforms existing methods in few-sample and zero-sample settings. Furthermore, we verify that knowledge transfer from DDIE can improve drug synergy predictions, surpassing existing models. Case studies on antiplatelet activity reduction and non-small cell lung cancer drug synergy further illustrate the practical value of RareDDIE. By analyzing the meta-knowledge construction process, we provide interpretability into the model's decision-making. This work establishes an effective computational framework for rare DDIE prediction, leveraging meta-learning and knowledge transfer to overcome key challenges in data-limited scenarios.

PMID:40301328 | DOI:10.1038/s41467-025-59431-9

Nat Commun. 2025 Apr 29;16(1):3851. doi: 10.1038/s41467-025-59132-3.

ABSTRACT

Genomic variation drives phenotypic diversity, including individual differences in drug response. While coding polymorphisms linked to drug efficacy and adverse reactions are well characterized, the contribution of noncoding regulatory elements remains underexplored. Using CAGE (Cap Analysis of Gene Expression), profiling transcription initiations of mRNAs and enhancer RNAs, we identify candidate cis-regulatory elements (CREs) and assessed their activities simultaneously in HepG2 cells expressing the drug-responsive transcription factor pregnane X receptor (PXR). Comparison with GWAS data reveals strong enrichment of the drug-induced CREs near variants associated with bilirubin and vitamin D levels. Among those bound by PXR in primary hepatocytes, we identify enhancers of UGT1A1, TSKU, and CYP24A1 and functional alleles that alter regulatory activities. We also find that TSKU influences expression of vitamin D-metabolizing enzymes. This study expands the landscape of PXR-mediated regulatory elements and uncovers noncoding variants impacting drug response, providing insights into the genomic basis of adverse drug reactions.

PMID:40301309 | DOI:10.1038/s41467-025-59132-3

Mol Cancer Ther. 2025 Apr 29. doi: 10.1158/1535-7163.MCT-24-0955. Online ahead of print.

ABSTRACT

The Warburg effect is a shift from oxidative phosphorylation to anaerobic glycolysis, accompanied by an enormous increase in glucose uptake into cancer cells. We have utilized this effect to design a new group of targeted 1,4-naphthoquinone-glucose derivatives conjugated with a novel thiomethylene linker, which are cytotoxic to prostate cancer cells. Compound PeS-9 revealed the highest efficacy and selectivity, which was conditioned by a GLUT-1-mediated uptake. PeS-9 induced androgen receptor degradation followed by downregulation of its signaling. In addition, it increased reactive oxygen species production and induced DNA double-strand breaks. Combinational therapy with PARP-inhibitor olaparib resulted in synergistic effects in homologous recombination deficient cells. The underlying mode of PeS-9's cytotoxic action involved mitochondrial targeting, leading to a loss of mitochondrial membrane potential, release of cytochrome C and AIF, activation of caspases-3 and -9, PARP cleavage, and apoptotic cell death. This process was stipulated by down-regulation of several antiapoptotic factors and induction of endoplasmic reticulum stress. Moreover, drug-induced activation of signaling pathway mediated by p38, JNK1/2, and ERK1/2 kinases was identified as an important factor of the cytotoxic activity. The anticancer activity of PeS-9 could be confirmed ex vivo using patients-derived tumoroids as well as in vivo in xenografts demonstrating suppression of tumor growth and decreased dissemination of prostate cancer cells to the lungs. No serious side effects were observed in animal models. This unique combination of anticancer properties makes PeS-9 an attractive candidate for targeted monotherapy against GLUT-1-overexpressing tumors and as a potential combination partner, especially with PARP inhibitors.

PMID:40299783 | DOI:10.1158/1535-7163.MCT-24-0955

Pac Symp Biocomput. 2025;30:360-376. doi: 10.1142/9789819807024_0026.

ABSTRACT

Patients experiencing adverse drug events (ADE) from polypharmaceutical regimens present a huge challenge to modern healthcare. While computational efforts may reduce the incidence of these ADEs, current strategies are typically non-generalizable for standard healthcare systems. To address this, we carried out a retrospective study aimed at developing a statistical approach to detect and quantify potential ADEs. The data foundation comprised of almost 2 million patients from two health regions in Denmark and their drug and laboratory data during the years 2011 to 2016. We developed a series of multistate Cox models to compute hazard ratios for changes in laboratory test results before and after drug exposure. By linking the results to data from a drug-drug interaction database, we found that the models showed potential for applications for medical safety agencies and improved efficiency for drug approval pipelines.

PMID:40299602 | DOI:10.1142/9789819807024_0026