Lihong Chen MD1 | Shiyi Sun MD1 | Yunyi Gao MD2 | Xingwu Ran MD1

1 Innovation Center for Wound Repair, Diabetic Foot Care Center, Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, China

2 Department of Medical Affairs, West China Hospital, Sichuan University, Chengdu, China

Correspondence

Xingwu Ran, MD, Innovation Center for Wound Repair, Diabetic Foot Care Center, Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, 37 Guo Xue Lane, Chengdu 610041, China.

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Funding information

This study was partially supported by the Science and Technology Bureau of Sichuan Province (grant no. 2021JDKP004), West China Nursing Discipline Development Special Fund Project, Sichuan University (grant no. HXHL20005) and the 1.3.5 Project for disciplines of excellence, West China Hospital, Sichuan University (grant no. ZYGD18025).

Abstract

Aim: To estimate the long-term mortality and risk factors in patients with diabetic foot ulcer (DFU).

Methods: We systematically searched Medline (PubMed), Embase, Scopus, Web of Science, Cochrane Library, China Science and Technology Journal Database (CQVIP), China National Knowledge Infrastructure, the Chinese Biomedical Literature Database (SinoMed) and Wanfang Data from 1 January 2011 to 31 July 2022. All observational studies that reported long-term mortality of patients with DFU were included. Random effect models were used to pool the reconstructed participant data from Kaplan–Meier curves. The primary outcome was the long-term survival of patients with DFU. An aggregate data meta-analysis was also performed.

Results: We identified 34 studies, with 124 376 participants representing 16 countries, among whom there were 51 386 deaths. Of these, 27 studies with 21 171 patients were included in the Kaplan–Meier-based meta-analysis. The estimated Kaplan–Meier-based survival rates were 86.9% (95% confidence interval [CI] 82.6%- 91.5%) at 1 year, 66.9% (95% CI 59.3%-75.6%) at 3 years, 50.9% (95% CI 42.0%- 61.7%) at 5 years and 23.1% (95% CI 15.2%-34.9%) at 10 years. The results of the aggregate data-based meta-analysis were similar. Cardiovascular disease and infection were the most common causes of death, accounting for 46.6% (95% CI 33.5%-59.7%) and 24.8% (95% CI 16.0%-33.5%), respectively. Patients with older age (per1 year, hazard ratio [HR] 1.054, 95% CI 1.045-1.063), peripheral artery disease (HR 1.882, 95% CI 1.592-2.225), chronic kidney disease (HR 1.535, 95% CI 1.227-1.919), end-stage renal disease (HR 3.586, 95% CI 1.333-9.643), amputation (HR 2.415, 95% CI 1.323-4.408) and history of cardiovascular disease (HR 1.449, 95% CI 1.276-1.645) had higher mortality risk.

Conclusions: This meta-analysis found that the overall mortality of DFU was high, with nearly 50% mortality within 5 years. Cardiovascular disease and infection were the two leading causes of death.

KEYWORDS

cardiovascular disease, diabetic foot, mortality

Mandy Li Ling Tan, Jiah Shin Chin, Leigh Madden & David L. Becker

To cite this article: Mandy Li Ling Tan, Jiah Shin Chin, Leigh Madden & David L. Becker (2022): Challenges faced in developing an ideal chronic wound model, Expert Opinion on Drug Discovery,

DOI: 10.1080/17460441.2023.2158809

To link to this article: https://doi.org/10.1080/17460441.2023.2158809

© 2022 The Author(s). Published by Informa

UK Limited, trading as Taylor & Francis

Published online: 26 Dec 2022.

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Mandy Li Ling Tana,b# , Jiah Shin Chinb# , Leigh Maddenb and David L. Beckerb,c,d a Nanyang Institute of Health Technologies, Interdisciplinary Graduate School, Nanyang Technological University, 639798, Singapore; b Lee Kong Chian School of Medicine, Nanyang Technological University, 308232, Singapore; c Skin Research Institute Singapore, Clinical Sciences Building, 11 Mandalay Road, 308232, Singapore; d National Skin Centre, Mandalay Road, Singapore

ABSTRACT

Introduction: Chronic wounds are a major drain on healthcare resources and can lead to substantial reductions in quality of life for those affected. Moreover, they often precede serious events such as limb amputations and premature death. In the long run, this burden is likely to escalate with an ageing population and lifestyle diseases such as obesity. Thus far, the identification of beneficial therapeutics against chronic wounds have been hindered by the lack of an ideal chronic wound animal model. Although animal models of delayed healing have been developed, none of these models fully recapitulate the complexity of the human chronic wound condition. Furthermore, most animals do not develop chronic wounds. Only the thoroughbred racehorse develops chronic ulcers.

Areas covered: In this review, the different characteristics of chronic wounds that highlight its complexity are described. In addition, currently available models reflecting different aspects of chronic wound pathology and their relevance to human chronic wounds are discussed. This article concludes by listing relevant features representative of an ideal chronic wound model. Additionally, alternative approaches for the development of chronic wound models are discussed.

Expert opinion: Delayed models of healing, including the streptozotocin diabetic model, skin flap model and magnet-induced IR models have emerged. While these models have been widely adopted for preclinical therapeutic testing, their relevance towards human chronic wounds remains debatable. In particular, current delayed healing models often fail to fully incorporate the key characteristics of chronic ulcers. Ultimately, more representative models are required to expedite the advancement of novel therapeutics to the clinic.

ARTICLE HISTORY

Received 5 October 2021 Accepted 12 December 2022

KEYWORDS

Animal models; biofilm infection; chronic wounds; delayed healing models; delayed wound closure; excessive extracellular matrix degradation; hyper thickened epidermis; increased senescent cells population; persistent inflammation