Evidence map›Paper›PMID 37263302›Full record

ArticleGastroenterology2023

Amphipathic Liponecrosis Impairs Bacterial Clearance and Causes Infection During Sterile Inflammation.

Sergiy Kostenko, Biswajit Khatua, Shubham Trivedi, Anoop Narayana Pillai, Bryce McFayden, Mahmoud Morsy, Prasad Rajalingamgari, Vijeta Sharma, Pawan Noel, Krutika Patel and 9 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 6 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed, 1 pooled it
3.1field-weighted citation impact, top 8% 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

6 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.

  1. NSAIDs do not reduce severity among post-ERCP pancreatitis patients.Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] · 2024
    Pooled it
  2. Article
  3. Article
  4. Observational
  5. Review
  6. 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

19 authors at 5 institutions in 1 country.

Sergiy KostenkoDepartment of Medicine, Mayo Clinic, Rochester, Minnesota.
Biswajit KhatuaDepartment of Medicine, Mayo Clinic, Rochester, Minnesota.
Shubham TrivediDepartment of Medicine, Mayo Clinic, Rochester, Minnesota.
Anoop Narayana PillaiDepartment of Medicine, Mayo Clinic, Rochester, Minnesota.
Bryce McFaydenDepartment of Medicine, Mayo Clinic, Rochester, Minnesota.
Mahmoud MorsyDepartment of Medicine, Mayo Clinic, Rochester, Minnesota.
Prasad RajalingamgariDepartment of Medicine, Mayo Clinic, Rochester, Minnesota.
Vijeta SharmaDepartment of Medicine, Mayo Clinic, Rochester, Minnesota.
Pawan NoelDepartment of Medicine, Mayo Clinic, Rochester, Minnesota.
Krutika PatelDepartment of Medicine, Mayo Clinic, Rochester, Minnesota.
Bara El-KurdiDepartment of Medicine, Mayo Clinic, Rochester, Minnesota.
Henrique Borges da SilvaDepartment of Immunology, Mayo Clinic, Rochester, Minnesota.
Xianfeng ChenDepartment of Research Services, Mayo Clinic, Rochester, Minnesota.
Vishal ChandanDepartment of Pathology, School of Medicine, University of California, Irvine, California.
Sarah NavinaClin-Path Associates, Tempe, Arizona.
Stacie VelaGastroenterology Section, Carl T. Hayden Veterans' Administration Medical Center, Phoenix, Arizona.
Rodrigo Cartin-CebaDepartment of Pulmonary and Critical Care Medicine, Mayo Clinic, Scottsdale, Arizona.
Christine SnozekDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Scottsdale, Arizona.
Vijay P SinghDepartment of Medicine, Mayo Clinic, Rochester, Minnesota; Department of Biochemistry and Molecular Biology, Mayo Clinic, Scottsdale, Arizona. Electronic address: singh.vijay@mayo.edu.
Mayo Clinic · USMayo Clinic in Arizona · USCarl T. Hayden Veterans Affairs Medical Center · USCritical Path Institute · USUniversity of California, Irvine · US

Funding

Obesity related pancreatic fat worsens local injury via unsaturated fatty acidsR01DK092460 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SINGH, VIJAY PREM · 2011 to 2024
$5.5M
Pathogenesis of infection in pancreatitis: from sterile inflammation to sepsisR01DK119646 · NIDDK · MAYO CLINIC ARIZONA · PI SINGH, VIJAY PREM · 2019 to 2022
$1.9M
NIDDK NIH HHS R01 DK092460NIDDK NIH HHS R01 DK119646
6 · The paper itself

Abstract

BACKGROUND &

aimsAlthough transient bacteremia is common during dental and endoscopic procedures, infections developing during sterile diseases like acute pancreatitis (AP) can have grave consequences. We examined how impaired bacterial clearance may cause this transition.

methodsBlood samples from patients with AP, normal controls, and rodents with pancreatitis or those administered different nonesterified fatty acids (NEFAs) were analyzed for albumin-unbound NEFAs, microbiome, and inflammatory cell injury. Macrophage uptake of unbound NEFAs using a novel coumarin tracer were done and the downstream effects-NEFA-membrane phospholipid (phosphatidylcholine) interactions-were studied on isothermal titration calorimetry.

resultsPatients with infected AP had higher circulating unsaturated NEFAs; unbound NEFAs, including linoleic acid (LA) and oleic acid (OA); higher bacterial 16S DNA; mitochondrial DNA; altered β-diversity; enrichment in Pseudomonadales; and increased annexin V-positive myeloid (CD14) and CD3-positive T cells on admission. These, and increased circulating dead inflammatory cells, were also noted in rodents with unbound, unsaturated NEFAs. Isothermal titration calorimetry showed progressively stronger unbound LA interactions with aqueous media, phosphatidylcholine, cardiolipin, and albumin. Unbound NEFAs were taken into protein-free membranes, cells, and mitochondria, inducing voltage-dependent anion channel oligomerization, reducing ATP, and impairing phagocytosis. These were reversed by albumin. In vivo, unbound LA and OA increased bacterial loads and impaired phagocytosis, causing infection. LA and OA were more potent for these amphipathic interactions than the hydrophobic palmitic acid.

conclusionsRelease of stored LA and OA can increase their circulating unbound levels and cause amphipathic liponecrosis of immune cells via uptake by membrane phospholipids. This impairs bacterial clearance and causes infection during sterile inflammation.

Indexed as

PancreatitisAcute DiseaseAlbuminsFatty Acids, NonesterifiedHumansInflammationOleic AcidPhosphatidylcholinesAlbuminsFatty Acids, NonesterifiedOleic AcidPhosphatidylcholinesFatty AcidImmune ParalysisInfectionLipotoxicityVDAC

Identifiers

PMID37263302
PMCPMC10703425
OpenAlexW4379094251

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.