Evidence map›Paper›PMID 37263310›Full record

ArticleGastroenterology2023

A Medium-Chain Fatty Acid Analogue Prevents Intestinal Failure-Associated Liver Disease in Preterm Yorkshire Piglets.

Scott C Fligor, Savas T Tsikis, Thomas I Hirsch, Amy Pan, Kamila Moskowitzova, Lorena Rincon-Cruz, Ashlyn E Whitlock, Paul D Mitchell, Arthur P Nedder, Kathleen M Gura and 2 more

Open access · hybridAbstract read
In one paragraph

Article in Gastroenterology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.8field-weighted citation impact, top 17% 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

11 citing papers in PubMed, 11 citations in OpenAlex.

  1. Review
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  5. Review
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  8. Fat malabsorption in short bowel syndrome: A review of pathophysiology and management.Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition · 2024
    Review
  9. Article
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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

12 authors at 2 institutions in 1 country.

Scott C FligorVascular Biology Program, Department of Surgery, Boston Children's Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts.
Savas T TsikisVascular Biology Program, Department of Surgery, Boston Children's Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts.
Thomas I HirschVascular Biology Program, Department of Surgery, Boston Children's Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts.
Amy PanVascular Biology Program, Department of Surgery, Boston Children's Hospital, Boston, Massachusetts.
Kamila MoskowitzovaVascular Biology Program, Department of Surgery, Boston Children's Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts.
Lorena Rincon-CruzVascular Biology Program, Department of Surgery, Boston Children's Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts.
Ashlyn E WhitlockVascular Biology Program, Department of Surgery, Boston Children's Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts.
Paul D MitchellInstitutional Centers for Clinical and Translational Research, Boston Children's Hospital, Boston, Massachusetts.
Arthur P NedderAnimal Resources Children's Hospital, Boston Children's Hospital, Boston, Massachusetts.
Kathleen M GuraHarvard Medical School, Boston, Massachusetts; Department of Pharmacy and the Division of Gastroenterology, Hepatology, and Nutrition, Boston Children's Hospital, Boston, Massachusetts.
David A FraserNorthSea Therapeutics, Amsterdam, Netherlands.
Mark PuderVascular Biology Program, Department of Surgery, Boston Children's Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts. Electronic address: Mark.Puder@childrens.harvard.edu.
Harvard University · USBoston Children's Hospital · US

Funding

HARVARD-LONGWOOD RESEARCH TRAINING IN VASCULAR SURGERYT32HL007734 · NHLBI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI FERRAN, CHRISTIANE, LOGERFO, FRANK W · 1993 to 2023
$10.5M
RESEARCH TRAINING IN ALIMENTARY TRACT SURGERYT32DK007754 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI HODIN, RICHARD A. · 1997 to 2025
$6.5M
NHLBI NIH HHS T32 HL007734NIDDK NIH HHS T32 DK007754
6 · The paper itself

Abstract

BACKGROUND &

aimsAt least 20%-30% of patients with intestinal failure receiving long-term parenteral nutrition will develop intestinal failure-associated liver disease (IFALD), for which there are few therapeutic options. SEFA-6179 is a first-in-class structurally engineered medium-chain fatty acid analogue that acts through GPR84, PPARα, and PPARγ agonism. We hypothesized that SEFA-6179 would prevent biochemical and histologic liver injury in a preterm piglet model of IFALD.

methodsPreterm Yorkshire piglets were delivered by cesarean section, and parenteral nutrition was provided for 14 days via implanted central venous catheters. Animals were treated with either medium-chain triglyceride vehicle control or SEFA-6179.

resultsCompared to medium-chain triglyceride vehicle at day of life 15, SEFA-6179 prevented biochemical cholestasis (direct bilirubin: 1.9 vs <0.2 mg/dL, P = .01; total bilirubin: 2.7 vs 0.4 mg/dL, P = .02; gamma glutamyl transferase: 172 vs 30 U/L, P = .01). SEFA-6179 also prevented steatosis (45.6 vs 13.9 mg triglycerides/g liver tissue, P = .009), reduced bile duct proliferation (1.6% vs 0.5% area cytokeratin 7 positive, P = .009), and reduced fibrosis assessed by a masked pathologist (median Ishak score: 3 vs 1, P = 0.007). RNA sequencing of liver tissue demonstrated that SEFA-6179 broadly impacted inflammatory, metabolic, and fibrotic pathways, consistent with its in vitro receptor activity (GPR84/PPARα/PPARγ agonist).

conclusionsIn a preterm piglet model of IFALD, SEFA-6179 treatment prevented biochemical cholestasis and steatosis and reduced bile duct proliferation and fibrosis. SEFA-6179 is a promising first-in-class therapy for the prevention and treatment of IFALD that will be investigated in an upcoming phase II clinical trial.

Indexed as

CholestasisIntestinal DiseasesIntestinal FailureLiver DiseasesLiver FailureAnimalsBilirubinCesarean SectionFatty AcidsFemaleFibrosisLiverPPAR alphaPPAR gammaPregnancySwineBilirubinFatty AcidsPPAR alphaPPAR gammaTriglyceridesAnimalCholestasisIntestinal FailureLiver Diseases/Drug TherapyModelsParenteral Nutrition

Identifiers

PMID37263310
PMCPMC10527514
OpenAlexW4379094602

What OpenQuestion holds

Textmetadata
LicenceTDM
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.