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Record W4403526311 · doi:10.1101/2024.10.17.24315679

Reduction of clonal hematopoiesis mutation burden in coronary patients treated with low-dose colchicine

2024· preprint· en· W4403526311 on OpenAlexafffund
Jean‐Claude Tardif, Lambert Busque, Steve Geoffroy, Johanna Sandoval, Louis‐Philippe Lemieux Perreault, Ian Mongrain, Diane Valois, Marie-Josée Gaulin-Marion, Manuel Buscarlet, Sylvie Provost, Aldo P. Maggioni, Simon Kouz, Fausto J. Pinto, José López-Sendón, David D. Waters, Rafael Díaz, Habib Gamra, Ghassan S. Kiwan, Colin Berry, Wolfgang Köenig, Jean‐Claude Grégoire, Philippe L. L’Allier, Mylène Provencher, Marie‐Claude Guertin, François Roubille, Essaïd Oussaïd, Amina Barhdadi, Marie‐Pierre Dubé

Bibliographic record

VenuemedRxiv · 2024
Typepreprint
Languageen
FieldMedicine
TopicMyeloproliferative Neoplasms: Diagnosis and Treatment
Canadian institutionsHôpital Maisonneuve-RosemontUniversité de MontréalCegep regional de LanaudiereHealth Care FoundationMontreal Heart Institute
FundersCanadian Institutes of Health ResearchInstitut de Cardiologie de MontréalFondation Institut de Cardiologie de MontréalAstraZenecaCanada Research ChairsSanofiSingulex
KeywordsColchicineReduction (mathematics)HaematopoiesisMutationMedicineInternal medicineGeneticsBiologyStem cellMathematics

Abstract

fetched live from OpenAlex

ABSTRACT Clonal hematopoiesis involves mutations in hematopoietic stem/progenitor cells, which increase the risk of cardiovascular disease, particularly under pro-inflammatory conditions. This study assessed the impact of the anti-inflammatory medication colchicine on clonal hematopoiesis in patients with recent myocardial infarction from the COLCOT trial. Participants were randomly assigned to low-dose colchicine (0.5 mg daily) or placebo, with 848 providing two DNA samples for longitudinal analysis. Targeted error-corrected sequencing was used, and 15,919 mutations were followed over a median period of 19.5 months. The results showed significantly lower variant allele fractions in the colchicine group compared to placebo (p interaction=0.03), with notable reductions in TET2 (10.3%, p=0.007; p interaction=0.001), TP53 (11.8%, p=0.001; p interaction=0.03), and SF3B1 mutations (19.9%, p=0.006; p interaction=0.005). Thus, colchicine reduced the proportion of clonal hematopoiesis mutations in patients with coronary disease, and longer-term studies with diverse populations are needed to confirm its potential benefits in mitigating related health risks.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.008

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.013
GPT teacher head0.267
Teacher spread0.254 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations3
Published2024
Admission routes2
Has abstractyes

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