{
  "abstract": "Background: Serial ferritin measurements have been examined in disease-specific cohorts with heterogeneous results, but the temporal pattern of ferritin in a large, clinically diverse population of hyperferritinaemic inpatients remains undefined.\n\nMethods: Retrospective single-centre cohort of adult inpatients with at least one serum ferritin ≥500 ng/mL (IRCCS Humanitas Research Hospital, October 2013–November 2024; N = 9,746). Thirty-day all-cause in-hospital mortality was analysed in 8,439 patients (668 deaths) by Kaplan–Meier and Cox regression adjusted for age, sex, Charlson Comorbidity Index and principal diagnosis (complete-case n = 6,549; 218 deaths). In a serial-sampling subgroup (n = 388; 387 with evaluable outcome, 45 deaths), parsimonious Cox models tested three scalar dynamic indices and mixed-effects models described log₁₀-ferritin trajectories across 0–3, 4–7 and >7 days; day-7 landmark analyses, restricted cubic splines, multiple imputation and Fine–Gray regression with live discharge as the competing event served as sensitivity analyses.\n\nResults: Thirty-day mortality rose across baseline ferritin strata (13.1%, 20.2% and 32.9%; log-rank p < 0.001); adjusted hazard ratios versus 500–999 ng/mL were 1.97 (95% CI 1.50–2.60) for 1,000–4,999 ng/mL and 5.46 (2.89–10.31) for ≥5,000 ng/mL. In age- and sex-adjusted longitudinal models, peak ferritin (HR 3.91 per log₁₀ unit, 95% CI 2.10–7.30; p < 0.001) and delta ferritin (HR 4.83, 1.60–14.57; p = 0.005), but not time-to-peak (p = 0.531), were associated with mortality. Beyond day 7, survivors' ferritin was 16.7% lower than during days 0–3 (p < 0.001), whereas the within-group change among patients who subsequently died was not significant; the relative difference was 15.5% (p = 0.020). Among 380 patients alive and hospitalised at day 7, the latest ferritin by the landmark predicted subsequent mortality (adjusted HR 2.86, 1.24–6.61; p = 0.014), whereas pre-landmark change, slope and any increase did not; thereafter ferritin fell by 2.30% per day in survivors but was stable in subsequent deaths (relative divergence 2.78% per day; p < 0.001). Spline modelling confirmed a non-linear time-by-outcome interaction (p = 0.036); Fine–Gray estimates were concordant.\n\nConclusions: Ferritin level and trajectory after the first week may identify a subgroup with persistent inflammatory activity and increased subsequent mortality. Day 7 should be regarded as a candidate temporal landmark for prospective validation, not as an established clinical decision threshold. These retrospective associations do not demonstrate that ferritin-guided interventions improve outcomes.",
  "abstract_shown": true,
  "affiliations": [
    "Rheumatology and Clinical Immunology, IRCCS Humanitas Research Hospital, Milan, Italy",
    "Department of Biomedical Sciences, Humanitas University, Milan, Italy",
    "Humanitas University, Milan, Italy"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Enrico Brunetta"
    },
    {
      "affs": [
        1
      ],
      "name": "Lorenzo Del Moro"
    },
    {
      "affs": [
        2
      ],
      "name": "Vahagn Menon"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Carlo F. Selmi"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/dyxy9wckv4pw3.bib",
  "cited_by": 0,
  "doi": "10.3389/fmed.2026.1952601",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13731380/",
  "id": "dyxy9wckv4pw3",
  "issns": [
    "2296-858X"
  ],
  "landing_url": "https://doi.org/10.3389/fmed.2026.1952601",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Research"
    ],
    [
      "openalex",
      "2720|Iron Metabolism and Disorders"
    ]
  ],
  "openalex": "W7223085794",
  "pdf_url": "https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2026.1952601/pdf",
  "pmcid": "PMC13731380",
  "pmid": "42984909",
  "published": "2026-10-21",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/dyxy9wckv4pw3.ris",
  "sources": [
    {
      "first_seen": "2026-11-08T12:21:35Z",
      "native_id": "PMC13731380",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fmed.2026.1952601"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2720|Iron Metabolism and Disorders",
      "subfield": "general"
    }
  ],
  "title": "The day-7 prognostic divergence: ferritin trajectories separate survivors from non-survivors in a decade-long cohort of 9,746 hospitalised adults",
  "title_text": "The day-7 prognostic divergence: ferritin trajectories separate survivors from non-survivors in a decade-long cohort of 9,746 hospitalised adults",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T12:21:35Z",
  "url": "https://research.draconitic.com/paper/dyxy9wckv4pw3",
  "venue": "Frontiers in Medicine",
  "versions": []
}