Frontiers in toxicology最新文献

{"title":"Mapping safety in space: the emerging role of spatial transcriptomics in safe drug development.","authors":"Athena Golfinos-Owens, Terry Van Vleet, Rebecca Kohnken, Prathap Kumar Mahalingaiah, Stacey Fossey, Wayne Buck, Wei Liang, Shuaib Ali Khan Mayana, Anik Tuladhar, Panuwat Trairatphisan, Andy Vo","doi":"10.3389/ftox.2026.1817521","DOIUrl":"10.3389/ftox.2026.1817521","url":null,"abstract":"<p><p>Bulk tissue transcriptional profiling has played a key role in drug discovery and preclinical safety assessment by revealing mechanisms of toxicity. However, analyzing gene expression from whole tissues is challenging when toxicities are restricted to specific cell types or regions. Newer sequencing methods, including single-cell RNA sequencing and spatial transcriptomics, enable researchers to study cellular and spatial responses at higher resolution. These techniques provide unique insights into localized gene expression changes linked to drug toxicity. Despite their promise, spatial methods are not always the most practical option, as they present challenges related to cost, data complexity, and the need for specialized analytical expertise. Selection of an appropriate platform may depend on study objectives, tissue and species context, and the distribution of affected regions. Thoroughly assessing each platform's analytical strengths, resolution, and practical limitations is crucial for effectively applying spatial transcriptomics in preclinical safety research. In this review, we evaluate spatial transcriptomic approaches to inform omics platform selection for preclinical safety studies, highlighting platform-specific strengths and considerations specific to drug development.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"8 ","pages":"1817521"},"PeriodicalIF":5.1,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13357943/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148439210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Case Report: High-dose pregabalin ingestion in an adolescent: clinical course and serial plasma concentrations.","authors":"Raffaele Simeoli, Enrico Armiento, Sara Cairoli, Mara Pisani, Paola Silvestri, Marco Marano","doi":"10.3389/ftox.2026.1822851","DOIUrl":"10.3389/ftox.2026.1822851","url":null,"abstract":"<p><strong>Background: </strong>Pregabalin (PGB) is widely used for neuropathic pain, generalized anxiety disorder, and seizure management; however, recent epidemiological data highlight a progressive increase in its misuse and involvement in intoxications, particularly among adolescents and individuals with psychiatric comorbidities. Although dose-toxicity relationships have been explored in adult populations, substantial interindividual variability persists, and data in pediatric or adolescent patients remain limited. Establishing clearer associations between ingested dose, serum concentrations, and clinical severity is essential to guide management strategies and identify cases requiring advanced interventions such as extracorporeal removal.</p><p><strong>Case presentation: </strong>We describe the case of a 16-year-old girl who intentionally ingested 2,700 mg (54 mg/kg, based on the patient's body weight of 51 kg) of immediate-release pregabalin. She presented at the Emergency Care Unit 10 h after ingestion with marked somnolence, psychomotor slowing, and bilateral horizontal nystagmus, while vital signs, renal and hepatic function tests remained normal. Electrocardiography revealed only mild PR interval prolongation. Serial plasma concentrations of Pregabalin demonstrated a decline from 16.5 mg/L at 12 h to 8.4 mg/L at 18 h and 0.69 mg/L at 34 h, consistent with expected pharmacokinetics. No gastrointestinal decontamination was performed due to delayed presentation, and no extracorporeal treatments were deemed necessary. Patient was subjected to a clinical conservative management, and progressively recovered without neurological sequelae.</p><p><strong>Conclusion: </strong>Despite ingestion of a dose commonly associated with moderate to severe toxicity, the patient exhibited a mild and self-limited clinical course, emphasizing the variability of pregabalin toxicity in adolescents. Clinical assessment remains the primary guide, while serum concentrations provide supportive information when available.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"8 ","pages":"1822851"},"PeriodicalIF":5.1,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13345593/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148413932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Shaking culture improves physiological maintenance of primary rat kidney tissue slices.","authors":"Moeno Kadoguchi, Kohei Matsushita, Jun Takahashi, Katsuhiro Esashika, Jingjing Yang, Masahiro Sugimoto, Ikumi Tamai, Hiroshi Arakawa","doi":"10.3389/ftox.2026.1838970","DOIUrl":"10.3389/ftox.2026.1838970","url":null,"abstract":"<p><strong>Introduction: </strong>Maintaining viability and physiological function in kidney tissue slice cultures remains a major challenge for <i>ex vivo</i> renal models, primarily due to limited oxygen diffusion into the tissue interior. In this study, we investigated whether shaking culture could improve the maintenance of primary rat kidney tissue slices.</p><p><strong>Methods: </strong>Rat kidney tissue slices (200 µm) were cultured under static or shaking conditions for up to 7 days. Tissue viability, histological features, renal transporter activity, nephrotoxic responses, and metabolomic profiles were evaluated.</p><p><strong>Results: </strong>Shaking culture markedly improved tissue viability, as evidenced by sustained ATP levels over 7 days compared with static conditions. Histological analysis revealed partial preservation of epithelial polarity, indicated by the maintained apical localization of aquaporin 1. Transporter studies demonstrated that uptake activities of Oat1/3 and Oct2 substrates were better preserved under shaking conditions. Furthermore, shaking-cultured slices enabled the evaluation of nephron segment-specific injury, with cisplatin inducing tubular damage and puromycin or dasatinib affecting glomerular structures. Metabolomic analysis revealed distinct alterations in central carbon metabolism, including increased levels of tricarboxylic acid cycle intermediates, suggesting improved mitochondrial function.</p><p><strong>Conclusion: </strong>These findings demonstrate that shaking culture provides a simple and effective approach to improve the culture microenvironment, thereby improving the maintenance of viability and physiological function in kidney tissue slices. This system may serve as a useful platform for investigating renal pharmacokinetics and drug-induced kidney injury.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"8 ","pages":"1838970"},"PeriodicalIF":5.1,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13347121/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148426907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A comprehensive safety evaluation of approved 2'-fucosyllactose for human nutritional applications in China.","authors":"Jiangge Zheng, Huali Wang, Wenfeng Liu, Zhongzhou Chen, Jiyue Zhang, Jianbo Zhang","doi":"10.3389/ftox.2026.1836564","DOIUrl":"10.3389/ftox.2026.1836564","url":null,"abstract":"<p><strong>Background: </strong>2'-Fucosyllactose (2'-FL), as a significant human milk oligosaccharide, plays a crucial role in infant formula products. This study aims to provide a scientific basis for the safe application of 2'-FL by systematically evaluating its physicochemical properties, production strain safety, toxicological data, and population exposure levels.</p><p><strong>Methods: </strong>This study characterizes the physicochemical properties of 2'-FL, evaluates the safety of its production strain, and conducts a series of toxicological assessments, including an acute oral toxicity test, genotoxicity tests, a 90-day subchronic toxicity test, and a teratogenicity test. Additionally, an exposure assessment of 2'-FL was conducted by integrating usage level data with food consumption data.</p><p><strong>Result: </strong>The production strain for 2'-FL is recognized as safe, and all the results of toxicological experiments show negative or no observed adverse effects. Exposure assessment data further confirm that infant and young child populations exposed to 2'-FL remain within established safety limits under the specified usage levels. Consequently, the use of 2'-FL as a food ingredient is considered safe.</p><p><strong>Discussion: </strong>The safety and technological necessity of 2'-FL constitute the scientific basis for its approval as a novel nutritional additive authorized for use in infant formula products.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"8 ","pages":"1836564"},"PeriodicalIF":5.1,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13336670/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148439280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toxic epidermal necrolysis and acute kidney injury following co-trimoxazole rechallenge and voriconazole accumulation as an exacerbating cofactor: a case report.","authors":"Yu-Dong Zhao, San-Lan Wu, Tao Zhou, Chen Shi, Wei-Jing Gong","doi":"10.3389/ftox.2026.1797771","DOIUrl":"10.3389/ftox.2026.1797771","url":null,"abstract":"<p><strong>Background: </strong>Toxic epidermal necrolysis (TEN) is a life-threatening severe cutaneous adverse drug reaction with high mortality. Acute kidney injury (AKI) is a common complication of TEN, significantly increasing mortality risk. Immunocompromised patients frequently require combination therapy with voriconazole and co-trimoxazole for concurrent infections, which may lead to complex toxicities.</p><p><strong>Case presentation: </strong>A 60-year-old male with nephrotic syndrome on long-term corticosteroids was diagnosed with <i>Aspergillus</i> and <i>Pneumocystis jirovecii</i> co-infection. He was initiated on voriconazole and co-trimoxazole on Day 6 and discharged on Day 9. Following a 20-day interruption of co-trimoxazole, he resumed the drug on Day 37 and developed widespread mucocutaneous erythema within hours. He presented on Day 40 with stage 2 AKI (eGFR 39 mL/min/1.73 m²) and severe systemic inflammation. Upon admission on Day 42, TEN was diagnosed with skin detachment >30% body surface area. Trough voriconazole level was 9.81 mg/L (therapeutic upper limit 5.5 mg/L). Pharmacogenetic testing revealed CYP2C19 *1/*2 genotype (intermediate metabolizer). ALDEN score was 9 for co-trimoxazole (\"highly probable\") and 4 for voriconazole (\"probable\"). Renal replacement therapy was initiated on Day 49. Despite comprehensive treatment and transient improvement of skin lesions, the patient ultimately died on Day 63, 17 days after the initiation of hemodialysis. The precise cause of death could not be determined.</p><p><strong>Conclusion: </strong>Co-trimoxazole rechallenge strongly supports a causal link to TEN. AKI pathogenesis was multifactorial: primarily driven by TEN-associated systemic inflammation, with voriconazole accumulation due to CYP2C19 intermediate metabolism and drug interaction serving as a likely exacerbating co-factor. This case underscores the importance of therapeutic drug monitoring, pharmacogenetic testing, and integrated cross-organ surveillance when using high-risk antimicrobial combinations.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"8 ","pages":"1797771"},"PeriodicalIF":5.1,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13333233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148392645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypoxia-induced metabolic shifting and AHR/BCRP axis impairment drive placental dysfunction in early-onset preeclampsia and FGR.","authors":"Jingjing Shi, Wenxuan Zhu, Haixia Liu, Ping Yang, Yongzhong Gu, Wen Peng, Jinlai Meng","doi":"10.3389/ftox.2026.1782187","DOIUrl":"10.3389/ftox.2026.1782187","url":null,"abstract":"<p><strong>Background: </strong>Placental hypoxia and vascular dysfunction are hallmarks of preeclampsia (PE). The Breast Cancer Resistance Protein (BCRP) is critical for maintaining the placental barrier against oxidative stress. We investigated whether the hypoxic microenvironment drives BCRP dysregulation and how this correlates with fetal growth restriction (FGR) in severe preeclampsia.</p><p><strong>Methods: </strong>This case-control study enrolled 59 normotensive and 72 preeclamptic pregnancies to compare clinical phenotypes and placental BCRP expression across distinct gestational age subgroups. Mechanistic investigations were conducted using human BeWo trophoblasts under pathological hypoxia (1%O₂​). We integrated metabolic profiling (glycolytic shift and JC-1 mitochondrial assays) with rigorous molecular techniques-including Co-immunoprecipitation (Co-IP) and subcellular fractionation-to elucidate the competitive crosstalk between HIF-1α and AHR, further validating barrier impairment via Hoechst 33342 functional efflux assays.</p><p><strong>Results: </strong>Clinically, patients with early-onset preeclampsia (28-33⁺⁶ weeks) exhibited a markedly higher incidence of FGR compared to late-onset or control groups. In these compromised placentas, BCRP expression was significantly suppressed and inversely correlated with the hypoxia marker GLUT1. <i>In vitro</i> assays delineated a \"dual-hit\" pathological cascade triggered by chronic hypoxia. First, trophoblasts underwent severe metabolic reprogramming characterized by massive glycolytic upregulation and mitochondrial dysfunction. Second, stabilized HIF-1α competitively sequestered the obligate co-receptor ARNT, systematically dismantling the AHR/ARNT transcriptional complex. This specific molecular \"competitive binding\" impaired AHR-mediated protective signaling, resulting in a critical loss of functional BCRP efflux capacity.</p><p><strong>Conclusion: </strong>Our study defines a distinct \"dual-hit\" molecular phenotype in early-onset preeclampsia. Chronic hypoxia not only drives an acute metabolic crisis but also actively dismantles the protective AHR/BCRP placental barrier via HIF-1α-mediated ARNT sequestering. This synergistic failure compromises placental xenobiotic detoxification, exacerbates fetal toxicological vulnerability, and fundamentally contributes to the profound severity of FGR.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"8 ","pages":"1782187"},"PeriodicalIF":5.1,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13333173/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148392659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Refining drug screening with automated home cage monitoring: a crossover study in socially housed rats.","authors":"David A Connor, Brady Nifong, Jason D Payseur, XueJun Wu, Eric I Rossman, Ajeesh Koshy Cherian","doi":"10.3389/ftox.2026.1818599","DOIUrl":"10.3389/ftox.2026.1818599","url":null,"abstract":"<p><p>Attrition in drug development due to central nervous system (CNS)-related adverse events is costly and can pose risks to volunteer safety during clinical development, underscoring the need to refine preclinical CNS screening strategies. The primary preclinical method to assess CNS risk is the Functional Observation Battery (FOB)/Irwin; however, these tests are limited by subjective assessment and restricted temporal resolution. Automated neurobehavioral assessment, such as the Home Cage Analyzer (HCA), may provide a solution to these challenges. Moreover, home cage assessments are in alignment with the 3Rs principles of refinement and reduction of animal use. Here, we detail our efforts to validate the HCA as part of GSK's CNS safety assessment strategy. To this end, we evaluated the HCA using tool compounds-amphetamine, diazepam, and chlorpromazine-each with differing pharmacology and pharmacokinetics. Additionally, we employed a 4 × 4 Latin-square crossover study design allowing each animal to serve as its own control. Our results demonstrate that the HCA captured the expected pharmacological effects of stimulant and sedative compounds across differing light phases. Notably, at the highest amphetamine dose, we observed a distinct shift in behavior: horizontal locomotor activity decreased, vertical rearing activity markedly increased, a nuanced effect that could be missed by traditional observational methods and highlights the value of multimodal assessment. Together, these data strongly support the use of the HCA as a first-line tool in preclinical CNS safety assessment.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"8 ","pages":"1818599"},"PeriodicalIF":5.1,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13322677/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148371341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Animal-free matrix alternative for three-dimensional <i>in vitro</i> angiogenesis models.","authors":"Elle Koivunotko, Chris S Pridgeon, Lauri Paasonen, Riina Harjumäki","doi":"10.3389/ftox.2026.1768268","DOIUrl":"10.3389/ftox.2026.1768268","url":null,"abstract":"<p><p>All metabolically active tissues have a dense vascular network to supply oxygen and nutrients. Angiogenesis, the formation of new blood vessels from existing ones, can be activated by the lack of oxygen in cells, disease, trauma, or tumor growth. Due to its essential role in cell survival, angiogenesis has been extensively studied, and therapeutic control of this process is of growing interest. Simultaneously, research aims to find and standardize non-animal testing methods for future use. However, the establishment of reproducible and physiologically relevant vascular networks <i>in vitro</i> is challenging, particularly due to the widespread use of heterogeneous animal-derived matrices which are not in keeping with the principles of the 3Rs (Replacement, Reduction, Refinement) in science and research. To address these limitations and support the development of ethical and sustainable <i>in vitro</i> methods, we present a novel animal-free, three-dimensional angiogenesis model based on medical grade plant-derived nanofibrillated cellulose hydrogel (NFCh). The model uses human umbilical vein endothelial cells (HUVECs) and human adipose-derived stromal cells (hASCs) cultured in medium supplemented with human serum and NFCh matrix. First, HUVECs were stimulated with stem cell-conditioned medium and cultured in varying NFCh concentrations (0.125%-2.4%) tuned to identify the optimal matrix stiffness for capillary-like structure formation. HUVECs were then cocultured with hASCs in the best-performing hydrogel concentration, followed by imaging and proteomics analysis. We observed formation of capillary-like structures, comparable to the most commonly used animal-derived extracellular matrix (ECM) control. Interestingly cells in lower NFCh concentration (0.125%) had higher expression of wound healing and angiogenesis-related proteins while higher stiffnesses (1.5%) had higher ECM-related protein expression. Importantly, vascular network morphology and organization could be adjusted by modifying only NFCh concentration. These findings demonstrate the potential of NFCh as a reproducible, animal-free alternative to conventional angiogenesis matrices with relevance to regenerative therapies, toxicological testing, drug screening, and the development of a 3Rs-compliant <i>in vitro</i> system.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"8 ","pages":"1768268"},"PeriodicalIF":5.1,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13322768/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148371343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A human liver organoid platform for hepatotoxicity assessment: evaluation using reference compounds.","authors":"Min Jeong Kim, Seo Yoon Choi, Su Min Youn, Tae Sung Kim, Il Ung Oh, Sang Aeh Park, Jae Ho Oh, Myung Jin Son, Jin Hee Lee","doi":"10.3389/ftox.2026.1805474","DOIUrl":"10.3389/ftox.2026.1805474","url":null,"abstract":"<p><strong>Background: </strong>Recent advances in organoid technology have enabled the development of human-relevant models. However, their application in toxicity assessments remains limited. Our previous study employed a liver organoid platform to evaluate drug toxicity and subsequently suggested its utility as a model for toxicity assessment. Building on this, we aimed to assess the exploratory response of the liver organoid model using a panel of selected reference compounds, including substances classified according to the United Nations Globally Harmonized System acute toxicity criteria.</p><p><strong>Methods: </strong>Human liver organoids derived from induced pluripotent stem cells were exposed to a panel of reference compounds, and toxicity responses were evaluated using multiple endpoints, including cell viability assays, functional biomarker measurements, imaging, and transcriptomic analysis.</p><p><strong>Results: </strong>Exposure to the reference compounds resulted in compound-specific changes across multiple endpoints, including cell viability, hepatic functional markers such as albumin secretion, and transcriptomic responses. Transcriptomic analysis further revealed compound-specific changes in gene expression associated with hepatotoxic responses, supporting the observed functional alterations. These findings suggest that liver organoids may capture compound-specific and multi-dimensional toxicity responses, supporting their potential as an <i>in vitro</i> platform for integrative toxicity assessment. However, this study was conducted using a limited set of reference compounds and did not include direct comparisons with established <i>in vitro</i> or <i>in vivo</i> models. In addition, functional metabolic capacity, including CYP activity, was not assessed.</p><p><strong>Conclusion: </strong>Therefore, the present results should be interpreted as an exploratory evaluation of platform performance rather than evidence of predictive capability. Future studies incorporating greater chemical diversity and functional validation are required to assess the broader applicability of this model.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"8 ","pages":"1805474"},"PeriodicalIF":5.1,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13310563/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148347548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predictors of in-hospital mortality in patients with multiple wasp stings in southwest China.","authors":"Yujie Tang, Qin Li, Zhifei Zhang, Yanxia Yi, Zhipeng Zhan","doi":"10.3389/ftox.2026.1856026","DOIUrl":"10.3389/ftox.2026.1856026","url":null,"abstract":"<p><strong>Background: </strong>Multiple wasp stings can cause severe systemic toxicity, multiple organ dysfunction, and death, but early identification of high-risk patients remains challenging. This study aimed to describe the epidemiological and clinical characteristics of hospitalized patients with multiple wasp stings and to identify independent predictors of in-hospital mortality for early risk stratification.</p><p><strong>Methods: </strong>In this single-center retrospective study, we analyzed 1,501 patients admitted for multiple wasp stings at Suining Central Hospital between 2011 and 2019. For descriptive analyses, all 1,501 patients were included. For comparative analyses and nomogram development, a subset of 714 adult patients with complete clinical and outcome data was included. Univariate and multivariable logistic regression analyses were performed to identify independent predictors of in-hospital mortality. A nomogram was subsequently constructed, and its discrimination was assessed using the area under the receiver operating characteristic curve (AUC).</p><p><strong>Results: </strong>In the overall cohort of 1,501 patients, the median age was 52.1 years, 60.2% were male, and the median time from envenomation to hospital admission was 3 days. Major complications included liver injury (16.3%), rhabdomyolysis (15.7%), acute kidney injury (10.3%), myocardial injury (10.2%), hemolysis (4.5%), and pneumonia/acute respiratory distress syndrome (3.1%). Overall, 27.5% of patients required rescue therapy and 7.0% underwent dialysis. Among the 714 adult patients in the analytical cohort, 68 (9.5%) died during hospitalization. Multivariable logistic regression identified serum potassium (OR 2.55, 95% CI 1.59-4.09; p < 0.001), indirect bilirubin (per 10-unit increase; OR 1.15, 95% CI 1.04-1.28; p = 0.005), and prothrombin time (OR 1.14, 95% CI 1.03-1.27; p = 0.015) as independent predictors of in-hospital mortality. The nomogram showed acceptable discrimination, with an AUC of 0.72 (95% CI, 0.65-0.79).</p><p><strong>Conclusion: </strong>In patients with multiple wasp stings, in-hospital mortality is closely associated with venom-induced multi-organ dysfunction. A nomogram incorporating serum potassium, indirect bilirubin, and prothrombin time may provide a practical and accessible tool for early risk stratification and help clinicians identify high-risk patients for timely intervention.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"8 ","pages":"1856026"},"PeriodicalIF":5.1,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13299090/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148347515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}