{
  "abstract": "The diagnostic paradigm for fever of unknown origin (FUO) has shifted with the advent of functional imaging and genomic technologies. This study evaluated the clinical impact of targeted next-generation sequencing (NGS) and 18-FDG-PET/CT in a single-center FUO cohort, while examining clinical features associated with spontaneous resolution. Among 116 patients analyzed, definitive diagnoses were established in 75.9%. In a selected subgroup with strong clinical suspicion of autoinflammatory disease, targeted NGS identified candidate variants in 88.9%, supporting clinico-genomic diagnostic confirmation in integration with clinical criteria. In a descriptive series of 15 cases evaluated by FDG-PET/CT at attending physicians’ discretion, imaging contributed to direct diagnosis in 33.3%. Notably, 25 of 28 undiagnosed patients experienced spontaneous resolution. Higher hemoglobin, higher albumin, absence of renal dysfunction, and a preserved appetite were identified as exploratory clinical markers associated with spontaneous remission; however, the association for appetite was attenuated in multivariable models adjusted for baseline status. While advanced technologies are valuable diagnostic tools in selected high-pre-test probability settings, a substantial proportion of undiagnosed FUO cases resolve spontaneously. A preserved appetite, alongside systemic baseline stability, may serve as an exploratory clinical surrogate supporting a cautious “watchful waiting” strategy in selected patients.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences",
    "Department of General Medicine, Nagasaki University Graduate School of Biomedical Sciences",
    "Nagasaki Medical Education Center (N-MEC), Nagasaki University Hospital",
    "Leading Medical Research Core Unit, Nagasaki University Graduate School of Biomedical Science",
    "Department of Rheumatology, Saiseikai Nagasaki Hospital",
    "Acute and Critical Care Center, Nagasaki University Hospital",
    "Department of Clinical Medicine, Institute of Tropical Medicine, Nagasaki University"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 22,
  "authors": [
    {
      "affs": [
        0,
        1,
        2,
        3,
        4
      ],
      "name": "Masataka Umeda"
    },
    {
      "affs": [
        0
      ],
      "name": "Lamiaa Mohamed"
    },
    {
      "affs": [
        0
      ],
      "name": "Kazusato Hara"
    },
    {
      "affs": [
        0
      ],
      "name": "Mizuna Otsuka"
    },
    {
      "affs": [
        0
      ],
      "name": "Shota Kurushima"
    },
    {
      "affs": [
        0
      ],
      "name": "Tomohisa Uchida"
    },
    {
      "affs": [
        0
      ],
      "name": "Toru Michitsuji"
    },
    {
      "affs": [
        0
      ],
      "name": "Yoshika Tsuji"
    },
    {
      "affs": [
        0
      ],
      "name": "Yushiro Endo"
    },
    {
      "affs": [
        0
      ],
      "name": "Ayuko Takatani"
    },
    {
      "affs": [
        0
      ],
      "name": "Shoichi Fukui"
    },
    {
      "affs": [
        0
      ],
      "name": "Remi Sumiyoshi"
    },
    {
      "affs": [
        0,
        4
      ],
      "name": "Tomohiro Koga"
    },
    {
      "affs": [
        0
      ],
      "name": "Shin-ya Kawashiri"
    },
    {
      "affs": [
        0
      ],
      "name": "Naoki Iwamoto"
    },
    {
      "affs": [
        0
      ],
      "name": "Takashi Igawa"
    },
    {
      "affs": [
        0
      ],
      "name": "Mami Tamai"
    },
    {
      "affs": [
        0
      ],
      "name": "Tomoki Origuchi"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "Hiroo Izumino"
    },
    {
      "affs": [
        1,
        3
      ],
      "name": "Takahiro Maeda"
    },
    {
      "affs": [
        6
      ],
      "name": "Koya Ariyoshi"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Atsushi Kawakami"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8krs8rb26s0dd.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1899032",
  "fulltext_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1899032/full",
  "id": "8krs8rb26s0dd",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1899032/full",
  "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": [
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      "lcc",
      "RC581-607"
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    [
      "openalex",
      "2711|Hematological disorders and diagnostics"
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  "openalex": "W7223384052",
  "pdf_url": "https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1899032/pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-23",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/8krs8rb26s0dd.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:17Z",
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  "subjects": [
    {
      "field": "biology",
      "origin": "issn:1664-3224",
      "subfield": "immunology"
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    {
      "field": "medicine",
      "origin": "lcc:RC581-607",
      "subfield": "general"
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  ],
  "title": "Fever of unknown origin in adults: diagnostic spectrum, the contribution of FDG-PET/CT and targeted sequencing, and spontaneous resolution",
  "title_text": "Fever of unknown origin in adults: diagnostic spectrum, the contribution of FDG-PET/CT and targeted sequencing, and spontaneous resolution",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:43:48Z",
  "url": "https://research.draconitic.com/paper/8krs8rb26s0dd",
  "venue": "Frontiers in Immunology",
  "versions": []
}