{
  "abstract": "Introduction: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, but traditional pharmacovigilance lacks a translational computational framework capable of resolving target-specific nonlinear temporal risks of adverse events such as hypokalemia.\n\nMethods: We integrated 3,243 ICI-related hypokalemia reports from the FDA Adverse Event Reporting System (FAERS) and VigiBase (2014–2024). An ensemble signal-detection strategy cross-validated four disproportionality algorithms (Reporting Odds Ratio [ROR], Proportional Reporting Ratio [PRR], Empirical Bayesian Geometric Mean [EBGM], and Information Component [IC]). Flexible nonlinear survival analysis was performed using restricted cubic spline (RCS) Cox regression to model time-to-event dynamics.\n\nResults: Programmed Death-Ligand 1 (PD-L1) inhibitors triggered the strongest signal (ROR = 3.20, 95% CI: 2.95–3.48), with ultra-early onset (median 23 days) and the highest case fatality rate (23.7%). An asymmetric biphasic mortality pattern showed a nadir at 60 days: early-onset (≤30 days) hypokalemia peaked at a hazard ratio (HR) of ∼1.9, whereas late-onset (>90 days) risk gradually rose to HR ∼1.8 within 350 days. Programmed Death-1 (PD-1) inhibitors significantly increased severe hypokalemia risk (odds ratio [OR] = 28.32), with male predominance across PD-1 and CTLA-4 subgroups.\n\nDiscussion: This interpretable ensemble framework reveals target-specific temporal toxicity signatures from multi-source real-world data, providing a computationally grounded translational pharmacology foundation for precision electrolyte monitoring and mechanism-informed safety prediction.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Neurosurgery, The Third Hospital of Xiamen , , ,",
    "The Second Clinical College of China Medical University , ,",
    "Dalian Medical University , ,",
    "The First Clinical College of China Medical University , ,",
    "Department of Neurosurgery, Xiamen Xinglin Hospital , ,"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Shengwang Chen"
    },
    {
      "affs": [
        1
      ],
      "name": "Ziyi Dai"
    },
    {
      "affs": [
        2
      ],
      "name": "Zihan Guo"
    },
    {
      "affs": [
        1
      ],
      "name": "Ziyi Li"
    },
    {
      "affs": [
        3
      ],
      "name": "Ruiqi Liu"
    },
    {
      "affs": [
        4
      ],
      "name": "Xuewen Jiang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/edj5nm4007md2.bib",
  "cited_by": 0,
  "doi": "10.3389/fphar.2026.1960328",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13668552/?tool=EBI",
  "id": "edj5nm4007md2",
  "issns": [
    "1663-9812"
  ],
  "landing_url": "https://europepmc.org/article/PMC/PMC13668552",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "3005|Pharmacovigilance and Adverse Drug Reactions"
    ]
  ],
  "openalex": "W7215132434",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13668552/pdf/?tool=EBI",
  "pmcid": "PMC13668552",
  "pmid": null,
  "published": "2026-10-01",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/edj5nm4007md2.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:18Z",
      "native_id": "PMC:PMC13668552",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13668552"
    },
    {
      "first_seen": "2026-10-30T12:20:06Z",
      "native_id": "10.3389/fphar.2026.1960328",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1960328/full"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:3005|Pharmacovigilance and Adverse Drug Reactions",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "Ensemble signal detection reveals target-specific temporal risk of hypokalemia after immune checkpoint inhibition: a translational pharmacology framework",
  "title_text": "Ensemble signal detection reveals target-specific temporal risk of hypokalemia after immune checkpoint inhibition: a translational pharmacology framework",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:06Z",
  "url": "https://research.draconitic.com/paper/edj5nm4007md2",
  "venue": "Frontiers in pharmacology",
  "versions": []
}