Evidence map›Paper›PMID 39953524›Full record

Trial reportJournal of translational medicine2025

Infusion of young donor plasma components in older patients modifies the immune and inflammatory response to surgical tissue injury: a randomized clinical trial.

Brice Gaudilliere, Lei Xue, Amy S Tsai, Xiaoxiao Gao, Tiffany N McAllister, Martha Tingle, Gladys Porras, Igor Feinstein, Dorien Feyaerts, Franck Verdonk and 15 more

Registry-linked trialAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Journal of translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03981419 (A Randomized, Placebo-Controlled, Double-Blind Pilot Study to Evaluate the Effect of GRF6021 on Intracellular Signaling Cascades in Blood Leukocytes and Postoperative Recovery Following Primary Hip or Knee Arthroplasty), which is not on this map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03981419 phase2completednot on this map

A Randomized, Placebo-Controlled, Double-Blind Pilot Study to Evaluate the Effect of GRF6021 on Intracellular Signaling Cascades in Blood Leukocytes and Postoperative Recovery Following Primary Hip or Knee Arthroplasty

TypeinterventionalSponsorAlkahest, Inc.Ran2019 to 2021Enrolled38ConditionsPostoperative RecoveryArmsGRF6021, Placebo
3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Review
  2. Inflammatory Stewardship-A Perspective for Active Management of Acute Inflammation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Article
  3. Review
  4. Article
  5. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

25 authors.

Brice Gaudilliere *Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA, 94305, USA.
Lei Xue *Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA, 94305, USA.
Amy S Tsai *Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA, 94305, USA.
Xiaoxiao GaoDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA, 94305, USA.
Tiffany N McAllisterDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA, 94305, USA.
Martha TingleDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA, 94305, USA.
Gladys PorrasDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA, 94305, USA.
Igor FeinsteinDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA, 94305, USA.
Dorien FeyaertsDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA, 94305, USA.
Franck VerdonkDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA, 94305, USA.
Maximilian SabayevDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA, 94305, USA.
Julien HedouDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA, 94305, USA.
Edward A GanioDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA, 94305, USA.
Eloïse BersonDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA, 94305, USA.
Martin BeckerDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA, 94305, USA.
Camilo EspinosaDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA, 94305, USA.
Yeasul KimDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA, 94305, USA.
Benoit LehallierAlkahest Inc, San Carlos, CA, USA.
Esther RawnerAlkahest Inc, San Carlos, CA, USA.
Chunmiao FengAlkahest Inc, San Carlos, CA, USA.
Derek F AmanatullahDepartment of Orthopedic Surgery, Stanford University School of Medicine, Stanford, CA, USA.
James I HuddlestonDepartment of Orthopedic Surgery, Stanford University School of Medicine, Stanford, CA, USA.
Stuart B GoodmanDepartment of Orthopedic Surgery, Stanford University School of Medicine, Stanford, CA, USA.
Nima Aghaeepour *Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA, 94305, USA.
Martin S Angst *Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA, 94305, USA. ang@stanford.edu.ORCID 0000-0002-1550-8136

Funding

Alkahest Inc Alkahest Inc
6 · The paper itself

Abstract

backgroundPreclinical evidence suggests that young plasma has beneficial effects on multiple organ systems in aged mice. Whether young plasma exerts beneficial effects in an aging human population remains highly controversial. Despite lacking data, young donor plasma infusions have been promoted for age-related conditions. Given the preclinical evidence that young plasma exerts beneficial effects by attenuating inflammation, this study examined whether administering a young plasma protein fraction to an elderly population would exert anti-inflammatory and immune modulating effects in humans, using surgery as a tissue injury model.

methodsThis double-blind, placebo-controlled study enrolled and randomized 38 patients undergoing major joint replacement surgery. Patients received four separate infusions of a plasma protein fraction derived from young donors, or placebo one day before surgery, before and after surgery on the day of surgery, and one day after surgery. Blood specimens for proteomic and immunological analyses were collected before each infusion. Based on the high-content assessment of circulating plasma proteins with single-cell analyses of peripheral immune cells, proteomic signatures and cell-type-specific signaling responses that separated the treatment groups were derived with regression models.

resultsElastic net regression models revealed that administration a young plasma protein fraction significantly altered the proteomic (AUC = 0.796, p = 0.002) and the cellular immune response (AUC 0.904, p < 0.001) to surgical trauma resulting in signaling pathway- and cell type-specific anti-inflammatory immune modulation. Affected proteomic pathways regulating inflammation included JAK-STAT, NF-kappa B, and MAPK (p < 0.001). These findings were confirmed at the cellular level as the MAPK and JAK/STAT signaling responses were diminished and IkB, the negative regulator of NFkB, was elevated in adaptive immune cells.

conclusionReported findings provide a first proof of principle in humans that a young plasma protein fraction actively regulates inflammatory and immune responses in an elderly population. They provide a solid rationale for elucidating active principles in young plasma that may be of therapeutic benefits for a range of age-related pathologies.

trial registrationClinicalTrials.gov, NCT03981419.

Indexed as

Blood DonorsImmunityInflammationPlasmaTissue DonorsAdultAgedBlood ProteinsDouble-Blind MethodFemaleHumansMaleMiddle AgedProteomicsBlood ProteinsAgingElderly populationImmune cellsInflammagingInflammationProteomicsSurgeryTissue injuryYoung plasma

Identifiers

PMID39953524
PMCPMC11829456

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.