Evidence map›Paper›PMID 39656818›Full record

Trial reportRheumatology (Oxford, England)2025

Dermal cellular senescence and EndMT in patients with systemic sclerosis undergoing cyclophosphamide or aHSCT treatment.

Yu-Hsiang Chiu, Marijke van Dijk, Roel Goldschmeding, Jacob M van Laar, Jeska K de Vries-Bouwstra, Julia Spierings

Abstract readRandomized Controlled Trial
In one paragraph

Trial report in Rheumatology (Oxford, England), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
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

6 authors.

Yu-Hsiang ChiuDepartment of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.ORCID 0000-0001-7925-895X
Marijke van DijkDepartment of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
Roel GoldschmedingDepartment of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
Jacob M van LaarDepartment of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.ORCID 0000-0001-5544-5785
Jeska K de Vries-BouwstraThe Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
Julia SpieringsDepartment of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.ORCID 0000-0002-2546-312X

Funding

Government of TaiwanStichting Het Sclerodermie Fonds
6 · The paper itself

Abstract

objectivesCellular senescence and endothelial-to-mesenchymal transition (EndMT) are profibrotic cellular processes involved in systemic sclerosis (SSc), but how they respond to treatment is largely unknown.

methodsSkin biopsies from diffuse cutaneous SSc (dcSSc) patients who underwent either autologous haematopoietic stem cell transplantation (aHSCT) or cyclophosphamide pulse (iv CYC) treatment were collected before and 6 months after randomization in the Autologous Stem Cell Transplantation International Scleroderma trial. The extent of fibrosis, inflammation, senescence, EndMT and tissue remodelling were examined in histopathology.

resultsFourteen pairs of skin biopsies were analysed. Decrease in modified Rodnan skin score was more pronounced in aHSCT-treated patients compared with iv CYC at 6 months (median change -14 [IQR -16 to -9] vs -6 [IQR -9 to -4], respectively, P = 0.028). Histologically, expression of urokinase-type plasminogen activator receptor (uPAR) on fibroblasts, P21 on vessels and EndMT decreased after treatment in both groups, yet the reduction was more pronounced in the aHSCT group. Poor skin response was associated with high baseline connective tissue growth factor (CTGF) on fibroblasts and low baseline P21 on vessels, with an odds ratio (OR) of 1.43 and 0.41, respectively. Furthermore, poor response was also seen in patients with a rise in CTGF on fibroblasts (OR 1.29) and P21 on vessels (OR 3.02) after treatment, P < 0.001.

conclusionBoth aHSCT and iv CYC in dcSSc reduced skin thickening clinically and attenuated EndMT, but affected cellular senescence not significantly different. EndMT and uPAR were associated with fibro-remodelling activity, whereas senescence, CTGF, uPAR and vascularity were associated with treatment response.

Indexed as

Cellular SenescenceCyclophosphamideHematopoietic Stem Cell TransplantationImmunosuppressive AgentsScleroderma, DiffuseScleroderma, SystemicSkinAdultBiopsyConnective Tissue Growth FactorEndothelial-Mesenchymal TransitionFemaleFibroblastsFibrosisHumansMaleConnective Tissue Growth FactorCyclophosphamideImmunosuppressive AgentsReceptors, Urokinase Plasminogen Activatorautologous haematopoietic stem cell transplantationfibrosispathologysclerodermasenescencesystemic sclerosis

Identifiers

PMID39656818
PMCPMC12107053

What Socratic holds

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Registered trials

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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 Socratic graph.