Evidence mapPaperPMID 41789236Full record

ArticleAnnals of medicine and surgery (2012)2026

Inflammation-modulating agents in chronic limb-threatening ischemia: a narrative review of therapeutic potential and future directions.

Aditya Gaur, Precious Dike, Timilehin Mayowa, Favour C Mekowulu, Anas Abdulkader, Medha Sridhar Rao, Awogboro Shola, Promise Ajala, Oderinde Oluwatobi, Israel Charles Abraham and 3 more

Abstract read
In one paragraph

Article in Annals of medicine and surgery (2012), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

13 authors.

Aditya GaurDepartment of Medicine, Yeovil District Hospital, Somerset NHS Foundation Trust, Higher Kingston, Yeovil, United Kingdom.
Precious DikeDepartment of Medicine, Watford General Hospital, West Hertfordshire Teaching Hospitals Trust, Watford, United Kingdom.
Timilehin MayowaDepartment of Medicine, University College Hospital, Ibadan, Nigeria.
Favour C MekowuluDepartment of Medicine, Specialist Practice for Cardiology and Pulmonology Eggenfelden, Germany.
Anas AbdulkaderCollege of Medicine, AlMaarefa University, Riyadh, Saudi Arabia.
Medha Sridhar RaoSchool of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, United Kingdom.
Awogboro SholaDepartment of Medicine, Obafemi Awolowo University, Ife, Nigeria.
Promise AjalaDepartment of Medicine, University College Hospital, Ibadan, Nigeria.
Oderinde OluwatobiDepartment of Medicine, Obafemi Awolowo University, Ife, Nigeria.
Israel Charles AbrahamDepartment of Medicine and Surgery, University of Ilorin, Ilorin, Nigeria.
Emmanuel KokoriDepartment of Medicine and Surgery, University of Ilorin, Ilorin, Nigeria.
Gbolahan OlatunjiDepartment of Medicine and Surgery, University of Ilorin, Ilorin, Nigeria.
Nicholas AderintoDepartment of Medicine and Surgery, Ladoke Akintola University of Technology, Ogbomoso, Nigeria.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Chronic limb-threatening ischemia (CLTI) represents the most severe form of peripheral artery disease (PAD), driven by both advanced atherosclerosis and chronic inflammation. Despite advancements in revascularization and medical therapy, outcomes remain poor. Inflammation has emerged as a key therapeutic target, and several anti-inflammatory agents are under investigation for potential benefit in CLTI. A comprehensive literature review was conducted using PubMed, Scopus, Embase, Google Scholar, and Web of Science to identify studies published between 1990 and 2025. Keywords included "chronic limb-threatening ischemia," "peripheral artery disease," "colchicine," "canakinumab," "methotrexate," "NLRP3 inflammasome," and "anti-inflammatory therapy." Eligible studies included original research, clinical trials, systematic reviews, and relevant guidelines focused on inflammation-targeted interventions in atherosclerosis and limb ischemia. Colchicine has shown significant reductions in major adverse cardiovascular events in large trials and retrospective PAD studies, though no randomized controlled trials (RCTs) have specifically addressed CLTI. Canakinumab reduced inflammatory biomarkers and improved walking performance in PAD but had no effect on plaque progression. Methotrexate did not demonstrate cardiovascular benefit in the Cardiovascular Inflammation Reduction Trial. Preclinical agents targeting the NLRP3 inflammasome (e.g., MCC950) have shown anti-inflammatory effects but lack human data. Nutraceuticals, including omega-3 fatty acids and polyphenols, may offer adjunctive benefits, though evidence remains limited. Inflammation-modulating therapies hold promise as adjuncts in CLTI management, potentially improving outcomes by targeting the underlying immune mechanisms of disease progression. However, current evidence is insufficient for clinical adoption in CLTI. Large-scale, well-designed RCTs focusing on limb-specific outcomes are necessary to clarify the role of these therapies in high-risk vascular populations.

Indexed as

canakinumabchronic limb-threatening ischemiacolchicineinflammationNLRP3 inflammasome

Identifiers

PMID41789236
PMCPMC12959765

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.