Evidence map›Paper›PMID 34893315›Full record

ArticleBritish journal of anaesthesia2022

Reduction of NETosis by targeting CXCR1/2 reduces thrombosis, lung injury, and mortality in experimental human and murine sepsis.

Mohmad Alsabani, Simon T Abrams, Zhenxing Cheng, Ben Morton, Steven Lane, Samar Alosaimi, Weiping Yu, Guozheng Wang, Cheng-Hock Toh

Open access · greenAbstract read
In one paragraph

Article in British journal of anaesthesia, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
74citing papers in PubMed, 1 pooled it
4.3field-weighted citation impact, top 4% 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

74 citing papers in PubMed, 1 synthesis or guideline pooled it, 94 citations in OpenAlex.

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14 more citing papers are in PubMed but not listed here.

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

9 authors at 4 institutions in 4 countries.

Mohmad AlsabaniDepartment of Clinical Infection, Microbiology and Immunology, University of Liverpool, Liverpool, UK; College of Applied Medical Sciences, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.
Simon T AbramsDepartment of Clinical Infection, Microbiology and Immunology, University of Liverpool, Liverpool, UK; Coagulation, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK.
Zhenxing ChengThe Medical School, Southeast University, Nanjing, China; Department of Gastroenterology, The First Affiliated Hospital, Anhui Medical University, Hefei, China.
Ben MortonDepartment of Clinical Science, Liverpool School of Tropical Medicine, Liverpool, UK; Malawi-Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi.
Steven LaneMedical Statistics, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
Samar AlosaimiDepartment of Clinical Infection, Microbiology and Immunology, University of Liverpool, Liverpool, UK.
Weiping YuThe Medical School, Southeast University, Nanjing, China.
Guozheng WangDepartment of Clinical Infection, Microbiology and Immunology, University of Liverpool, Liverpool, UK; Coagulation, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK. Electronic address: wangg@liverpool.ac.uk.
Cheng-Hock TohDepartment of Clinical Infection, Microbiology and Immunology, University of Liverpool, Liverpool, UK; Roald Dahl Haemostasis & Thrombosis Centre, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK. Electronic address: toh@liverpool.ac.uk.
University of Liverpool · GBSoutheast University · CNAintree University Hospitals NHS Foundation Trust · GBMalawi-Liverpool-Wellcome Trust Clinical Research Programme · MW

Funding

British Heart Foundation PG/14/19/30751British Heart Foundation PG/16/65/32313
6 · The paper itself

Abstract

backgroundNeutrophil extracellular traps (NETs) facilitate bacterial clearance but also promote thrombosis and organ injury in sepsis. We quantified ex vivo NET induction in septic humans and murine models of sepsis to identify signalling pathways that may be modulated to improve outcome in human sepsis.

methodsNET formation in human donor neutrophils was quantified after incubation with plasma obtained from patients with sepsis or systemic inflammation (double-blinded assessment of extracellular DNA using immunofluorescence microscopy). NET formation (% neutrophils forming NETs) was correlated with plasma cytokine levels (MultiPlex assay). Experimental sepsis (caecal ligation and puncture or intraperitoneal injection of Escherichia coli) was assessed in C57/BL6 male mice. The effect of pharmacological inhibition of CXCR1/2 signalling (reparixin) on NET formation, organ injury (hepatic, renal, and cardiac biomarkers), and survival in septic mice was examined.

resultsNET formation was higher after incubation with plasma from septic patients (median NETs=25% [10.5-46.5%]), compared with plasma obtained from patients with systemic inflammation (14% [4.0-23.3%]; P=0.02). Similar results were observed after incubation of plasma from mice with neutrophils from septic non-septic mice. Circulating CXCR1/2 ligands correlated with NETosis in patients (interleukin-8; r=0.643) and mice (macrophage inflammatory protein-2; r=0.902). In experimental sepsis, NETs were primarily observed in the lungs, correlating with fibrin deposition (r=0.702) and lung injury (r=0.692). Inhibition of CXCR1/2 using reparixin in septic mice reduced NET formation, multi-organ injury, and mortality, without impairing bacterial clearance.

conclusionCXCR1/2 signalling-induced NET formation is a therapeutic target in sepsis, which may be guided by ex vivo NET assays.

Indexed as

AnimalsCytokinesDisease Models, AnimalExtracellular TrapsHumansInflammationLung InjuryMaleMiceMice, Inbred C57BLNeutrophilsReceptors, Interleukin-8AReceptors, Interleukin-8BRetrospective StudiesSepsisSulfonamidesCXCR2 protein, humanCytokinesReceptors, Interleukin-8AReceptors, Interleukin-8BreparixinSulfonamidesCXCR1/2interleukin-8neutrophil depletionneutrophil extracellular trapsorgan injuryreparixinsepsis

Identifiers

PMID34893315
PMCPMC8792833
OpenAlexW4200518401

What OpenQuestion holds

Textmetadata
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.