Evidence map›Paper›PMID 30528323›Full record

SynthesisTranslational research : the journal of laboratory and clinical medicine2019

Systematic review and meta-analysis of experimental studies evaluating the organ protective effects of histone deacetylase inhibitors.

Syabira I Yusoff, Marius Roman, Florence Y Lai, Bryony Eagle-Hemming, Gavin J Murphy, Tracy Kumar, Marcin Wozniak

Open access · hybridAbstract readMeta-AnalysisSystematic Review
In one paragraph

Synthesis in Translational research : the journal of laboratory and clinical medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed, 2 pooled it
0.6field-weighted citation impact, top 33% of its field
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

7 citing papers in PubMed, 2 syntheses or guidelines pooled it, 11 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Review
  4. Review
  5. Review
  6. Article
  7. 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

7 authors at 1 institution in 1 country.

Syabira I YusoffDepartment of Cardiovascular Sciences and NIHR Leicester Biomedical Research Unit in Cardiovascular Medicine, University of Leicester, Clinical Sciences Wing, Glenfield Hospital, Leicester, UK. Electronic address: ny70@le.ac.uk.
Marius RomanDepartment of Cardiovascular Sciences and NIHR Leicester Biomedical Research Unit in Cardiovascular Medicine, University of Leicester, Clinical Sciences Wing, Glenfield Hospital, Leicester, UK.
Florence Y LaiDepartment of Cardiovascular Sciences and NIHR Leicester Biomedical Research Unit in Cardiovascular Medicine, University of Leicester, Clinical Sciences Wing, Glenfield Hospital, Leicester, UK.
Bryony Eagle-HemmingDepartment of Cardiovascular Sciences and NIHR Leicester Biomedical Research Unit in Cardiovascular Medicine, University of Leicester, Clinical Sciences Wing, Glenfield Hospital, Leicester, UK.
Gavin J MurphyDepartment of Cardiovascular Sciences and NIHR Leicester Biomedical Research Unit in Cardiovascular Medicine, University of Leicester, Clinical Sciences Wing, Glenfield Hospital, Leicester, UK.
Tracy KumarDepartment of Cardiovascular Sciences and NIHR Leicester Biomedical Research Unit in Cardiovascular Medicine, University of Leicester, Clinical Sciences Wing, Glenfield Hospital, Leicester, UK.
Marcin WozniakDepartment of Cardiovascular Sciences and NIHR Leicester Biomedical Research Unit in Cardiovascular Medicine, University of Leicester, Clinical Sciences Wing, Glenfield Hospital, Leicester, UK.
University of Leicester · GB

Funding

British Heart Foundation CH/12/1/29419British Heart Foundation RG/13/6/29947British Heart Foundation RG/17/9/32812Department of Health
6 · The paper itself

Abstract

The clinical efficacy of organ protection interventions are limited by the redundancy of cellular activation mechanisms. Interventions that target epigenetic mechanisms overcome this by eliciting genome wide changes in transcription and signaling. We aimed to review preclinical studies evaluating the organ protection effects of histone deacetylase inhibitors (HDACi) with a view to informing the design of early phase clinical trials. A systematic literature search was performed. Methodological quality was assessed against prespecified criteria. The primary outcome was mortality, with secondary outcomes assessing mechanisms. Prespecified analyses evaluated the effects of likely moderators on heterogeneity. The analysis included 101 experimental studies in rodents (n = 92) and swine (n = 9), exposed to diverse injuries, including: ischemia (n = 72), infection (n = 7), and trauma (n = 22). There were a total of 448 comparisons due to the evaluation of multiple independent interventions within single studies. Sodium valproate (VPA) was the most commonly evaluated HDACi (50 studies, 203 comparisons). All of the studies were judged to have significant methodological limitations. HDACi reduced mortality in experimental models of organ injury (risk ratio = 0.52, 95% confidence interval 0.40-0.68, p < 0.001) without heterogeneity. HDACi administration resulted in myocardial, brain and kidney protection across diverse species and injuries that was attributable to increases in prosurvival cell signaling, and reductions in inflammation and programmed cell death. Heterogeneity in the analyses of secondary outcomes was explained by differences in species, type of injury, HDACi class (Class I better), drug (trichostatin better), and time of administration (at least 6 hours prior to injury better). These findings highlight a potential novel application for HDACi in clinical settings characterized by acute organ injury.

Indexed as

AnimalsHistone Deacetylase InhibitorsHumansOrgan PreservationTranslational Research, BiomedicalHistone Deacetylase Inhibitors

Identifiers

PMID30528323
PMCPMC6386580
OpenAlexW2901026132

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.