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Chen JQ, Chen ZH, Zheng WB, Shen XQ. Correlation of anxiety and depression with pain in patients with diabetic foot ulcers and analysis of risk factors. World J Psychiatry 2025; 15:105334. [DOI: 10.5498/wjp.v15.i6.105334] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2025] [Revised: 03/24/2025] [Accepted: 04/27/2025] [Indexed: 05/29/2025] Open
Abstract
BACKGROUND Pain often predisposes patients with diabetic foot ulcers (DFUs) to negative emotional states, such as anxiety and depression, which can significantly impair treatment outcomes and recovery. However, very few studies have explored the relationship between anxiety, depression, and pain in DFUs, as well as the associated risk factors.
AIM To analyze the correlation between anxiety, depression, and pain in patients with DFUs and to identify the associated risk factors.
METHODS This study included 106 patients diagnosed with DFUs who were admitted to Tiantai County People’s Hospital between March 2022 and March 2024. The patients’ anxiety levels were evaluated using Zung’s self-rating anxiety scale (SAS), depression status was assessed using Zung’s self-rating depression scale (SDS), and pain intensity was assessed using the visual analog scale (VAS). Subsequently, correlations between SAS, SDS, and VAS scores were analyzed. Univariate and multivariate analyses were conducted to explore the risk factors that contributed to anxiety and depression in patients with DFUs.
RESULTS Among the 106 patients, 39.62% exhibited anxiety and 43.40% presented with depression. Most patients experiencing anxiety or depression exhibited mild symptoms, with no severe cases observed. Compared with asymptomatic patients, those with anxiety or depression had significantly higher VAS scores. Correlation analysis indicated a significant positive relationship between both SAS and SDS scores and the VAS score. Univariate analysis identified sex, age, Wagner’s grade, presence of other complications, and smoking history as factors significantly associated with anxiety and depression. Multivariate analysis further confirmed that younger age, higher Wagner’s grade, and higher VAS scores were independent predictors of anxiety and depression.
CONCLUSION This study reveals a significant positive correlation between anxiety, depression, and pain in patients with DFUs. This finding suggests that timely and effective pain intervention may be beneficial in alleviating negative emotions such as anxiety and depression. In addition, younger age (< 50 years), higher Wagner’s grade, and higher VAS scores increase the risk of developing anxiety and depression in this patient population.
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Affiliation(s)
- Jiang-Qiang Chen
- Department of Plastic Surgery, Tiantai County People’s Hospital, Taizhou 317200, Zhejiang Province, China
| | - Zu-Hui Chen
- Department of Plastic Surgery, Tiantai County People’s Hospital, Taizhou 317200, Zhejiang Province, China
| | - Wei-Bin Zheng
- Department of Plastic Surgery, Tiantai County People’s Hospital, Taizhou 317200, Zhejiang Province, China
| | - Xiang-Qian Shen
- Department of Plastic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
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Mei XH, Zhang T, Yang Y, Sun L, Han RM, Wu N, Tian Y, Li BC, Ge M, Wang DF. Efficacy of Mesenchymal Stem Cells in the Treatment of Diabetic Foot Ulcers: A Meta-Analysis of Randomized Controlled Trials. INT J LOW EXTR WOUND 2025:15347346251348797. [PMID: 40530428 DOI: 10.1177/15347346251348797] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/20/2025]
Abstract
BackgroundDiabetic foot ulcers (DFUs), a severe chronic complication of diabetes, are characterized by refractory wounds and high risks of amputation/mortality, posing substantial public health challenges. Mesenchymal stem cells (MSCs) demonstrate therapeutic potential through synergistic mechanisms including paracrine signaling, immunomodulation, neovascularization, and tissue regeneration. This study conducts a systematic review and meta-analysis of randomized controlled trials (RCTs) to comprehensively evaluate the clinical efficacy of MSC-based therapy for DFUs, aiming to optimize treatment strategies with evidence-based insights.MethodWe systematically searched PubMed, Embase, Cochrane Library, and Web of Science for RCTs investigating MSC therapy in DFUs. Following PRISMA guidelines, studies were selected with pre-defined criteria. Meta-analyses employed random-/fixed-effects models based on I2 statistics. Primary endpoints encompassed complete healing rate (100% epithelialization), amputation incidence, serious adverse events (SAEs) risk, and recurrence rate. Furthermore, sensitivity analyses were conducted to evaluate the robustness of the findings. A comprehensive assessment of potential publication bias in the current meta-analysis was performed using Egger's linear regression test, Begg's rank correlation test, and funnel plot visualization.ResultsSix RCTs were included. MSC therapy significantly improved overall complete healing rates (RR = 1.63, 95% CI: 1.23-2.16; P = .0007), particularly in small ulcers (<5 cm2; RR = 1.71, 1.11-2.63, P = .02), but showed no efficacy for large ulcers (≥5 cm2; RR = 1.18, 0.75-1.86, P = .46). No significant differences emerged in amputation risk (P = .16), serious adverse events (P = .38), and recurrence (P = .33). Low heterogeneity and no publication bias were observed.ConclusionThis meta-analysis demonstrates MSCs therapy significantly enhances wound closure in diabetic foot ulcers, particularly achieving in small ulcers. However, no stable therapeutic benefits were observed for large ulcers, amputation prevention, recurrence reduction, and SAEs. Future multicenter phase III trials with standardized protocols are warranted to establish ulcer stage/size-specific treatments.
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Affiliation(s)
- Xiang-Hui Mei
- Clinical Medical College, Hebei University of Engineering, Handan, Hebei, China
| | - Tong Zhang
- Huahu Community Health Service Center, Huangshi, Hubei, China
| | - Yan Yang
- Clinical Medical College, Hebei University of Engineering, Handan, Hebei, China
| | - Li Sun
- Clinical Medical College, Hebei University of Engineering, Handan, Hebei, China
| | - Rui-Min Han
- Clinical Medical College, Hebei University of Engineering, Handan, Hebei, China
| | - Na Wu
- Clinical Medical College, Hebei University of Engineering, Handan, Hebei, China
| | - Ye Tian
- Clinical Medical College, Hebei University of Engineering, Handan, Hebei, China
| | - Bai-Chao Li
- Clinical Medical College, Hebei University of Engineering, Handan, Hebei, China
| | - Min Ge
- Clinical Medical College, Hebei University of Engineering, Handan, Hebei, China
| | - De-Feng Wang
- Endocrinology Department, Affiliated Hospital of Hebei University of Engineering, Handan, Hebei, China
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Sun HJ, Si SW, Ma YM, Liu XK, Geng HF, Liang J. Role of nuclear factor erythroid 2-related factor 2 in negative pressure wound therapy for diabetic foot ulcers. World J Diabetes 2025; 16:104350. [DOI: 10.4239/wjd.v16.i5.104350] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2024] [Revised: 01/27/2025] [Accepted: 03/03/2025] [Indexed: 04/25/2025] Open
Abstract
BACKGROUND Negative pressure wound therapy (NPWT) is a potential treatment for diabetic foot ulcers (DFUs), although the mechanisms underlying its effectiveness remain unclear. This study posits that NPWT may improve wound healing by promoting angiogenesis and activating the nuclear factor erythroid 2-related factor 2 (Nrf2)/Kelch-like epichlorohydrin-associated protein 1 (Keap1) signaling pathway, which is crucial for the body’s defense against oxidative stress. The hypothesis indicates that enhancing antioxidant defenses through NPWT may positively affect the healing process. There are still limited data on the roles of Nrf2, its downstream signaling molecules, and angiogenesis markers in patients undergoing NPWT.
AIM To study the mechanism of NPWT in DFUs.
METHODS This study included a total of 40 hospitalized patients with DFUs from Xuzhou Central Hospital, who were divided into Control group (n = 21) and NPWT group (n = 19). The levels of Nrf2 and Keap1 were analyzed in the granulation tissue 7 days after treatment. The wound condition, erythrocyte sedimentation rate (ESR), procalcitonin (PCT), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (b-FGF), cluster of differentiation 31 (CD31), and levels of oxidative stress [malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and total antioxidant capacity (T-AOC)] were analyzed before and 7 days after treatment by the Mann-Whitney U test.
RESULTS The NPWT group demonstrated significant improvements in wound healing compared to the control group after 7 days of treatment. The levels of ESR, PCT, IL-6, and TNF-α were significantly reduced in the NPWT group compared to the control group (P < 0.05), while the levels of CD31, VEGF, and b-FGF showed significant increases (P < 0.05). The NPWT group exhibited notable elevations in the levels of Nrf2 and its downstream targets (SOD, CAT, and T-AOC), accompanied by decreases in the levels of Keap1 and MDA (P < 0.05).
CONCLUSION NPWT may contribute to the healing of DFUs by potentially reducing levels of oxidative stress. Its effects could possibly be enhanced through the action of Nrf2.
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Affiliation(s)
- Hao-Jie Sun
- Department of Endocrinology, Xuzhou Central Hospital, Xuzhou 221009, Jiangsu Province, China
| | - Shan-Wen Si
- Department of Scientific Research, Fuyang Hospital of Anhui Medical University, Fuyang 236112, Anhui Province, China
| | - Ya-Mei Ma
- Electrocardiogram Room, Fuyang Hospital of Anhui Medical University, Fuyang 236112, Anhui Province, China
| | - Xue-Kui Liu
- Department of Endocrinology, Xuzhou Central Hospital, Xuzhou 221009, Jiangsu Province, China
| | - Hou-Fa Geng
- Department of Endocrinology, Xuzhou Central Hospital, Xuzhou 221009, Jiangsu Province, China
| | - Jun Liang
- Department of Endocrinology, Xuzhou Central Hospital, Xuzhou 221009, Jiangsu Province, China
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Lan NSR, Hiew J, Ferreira I, Ritter JC, Manning L, Fegan PG, Dwivedi G, Hamilton EJ. Achievement of low-density lipoprotein cholesterol goals in patients with diabetes-related foot ulceration. J Diabetes Complications 2025; 39:109069. [PMID: 40378501 DOI: 10.1016/j.jdiacomp.2025.109069] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2024] [Revised: 05/07/2025] [Accepted: 05/10/2025] [Indexed: 05/19/2025]
Abstract
Despite their elevated risk for cardiovascular complications, two-thirds of patients with diabetes-related foot ulceration in this contemporary real-world study were not achieving guideline-recommended goals for low-density lipoprotein cholesterol. Implementation research is needed to identify the barriers and facilitators to optimal lipid management in this high priority population.
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Affiliation(s)
- Nick S R Lan
- Centre of Excellence for Cardiometabolic Health, Fiona Stanley Hospital, Perth, Australia; Department of Cardiology, Fiona Stanley Hospital, Perth, Australia; Harry Perkins Institute of Medical Research, Perth, Australia; Medical School, The University of Western Australia, Perth, Australia
| | - Jonathan Hiew
- Centre of Excellence Multidisciplinary Diabetes Foot Ulcer Service, Fiona Stanley and Fremantle Hospitals Group, Perth, Australia; Department of Podiatry, Fiona Stanley Hospital, Perth, Australia
| | - Ivana Ferreira
- Centre of Excellence Multidisciplinary Diabetes Foot Ulcer Service, Fiona Stanley and Fremantle Hospitals Group, Perth, Australia; Department of Podiatry, Fiona Stanley Hospital, Perth, Australia
| | - J Carsten Ritter
- Centre of Excellence Multidisciplinary Diabetes Foot Ulcer Service, Fiona Stanley and Fremantle Hospitals Group, Perth, Australia; Department of Vascular Surgery, Fiona Stanley Hospital, Perth, Australia; Medical School, Curtin University, Perth, Australia
| | - Laurens Manning
- Medical School, The University of Western Australia, Perth, Australia; Centre of Excellence Multidisciplinary Diabetes Foot Ulcer Service, Fiona Stanley and Fremantle Hospitals Group, Perth, Australia; Department of Infectious Diseases, Fiona Stanley Hospital, Perth, Australia
| | - P Gerry Fegan
- Medical School, Curtin University, Perth, Australia; Department of Endocrinology and Diabetes, Fiona Stanley Hospital, Perth, Australia
| | - Girish Dwivedi
- Centre of Excellence for Cardiometabolic Health, Fiona Stanley Hospital, Perth, Australia; Department of Cardiology, Fiona Stanley Hospital, Perth, Australia; Harry Perkins Institute of Medical Research, Perth, Australia; Medical School, The University of Western Australia, Perth, Australia
| | - Emma J Hamilton
- Medical School, The University of Western Australia, Perth, Australia; Centre of Excellence Multidisciplinary Diabetes Foot Ulcer Service, Fiona Stanley and Fremantle Hospitals Group, Perth, Australia; Department of Endocrinology and Diabetes, Fiona Stanley Hospital, Perth, Australia.
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Ghadeer A, Yan T, Claire M, Ellen K, Caroline M, McIlwaine A. Diabetic foot ulcer related pain and its impact on health-related quality of life. J Tissue Viability 2025; 34:100856. [PMID: 39842137 DOI: 10.1016/j.jtv.2025.100856] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2024] [Revised: 11/19/2024] [Accepted: 01/03/2025] [Indexed: 01/24/2025]
Abstract
BACKGROUND Diabetic foot ulcers (DFUs) are a prevalent complication of diabetes. Individuals with DFUs can experience wound-related pain, which could be nociceptive and/or neuropathic in origin, which adversely affects health-related quality of life (HRQoL). AIM To determine the prevalence and characteristics of DFU-related pain and its impact on HRQoL in community-dwelling individuals with active DFUs. METHODS A cross-sectional quantitative study was conducted, employing the Short-form McGill Pain Questionnaire (SF-MPQ) and the Cardiff Wound Impact Schedule (CWIS), involving patients with DFU at a Podiatry Clinic in the West of Ireland. RESULTS This study evaluated 30 patients with DFUs, of whom 70.0 % (n = 21) were male. Among the participants, 70.0 % (n = 21) reported at least one sensory pain descriptor from the SF-MPQ, and 40.0 % (n = 12) chose descriptors indicative of neuropathic pain. "Tender" emerged as the most frequently selected sensory pain descriptor (n = 11, 36.7 %). The mean Visual Analogue Scale (VAS) score was 23.3 (±30.9) mm. For present pain intensity (PPI), 43.3 % (n = 13) reported pain ranging from mild to horrible pain. Spearman's correlation analysis revealed a significant negative correlation between SF-MPQ, VAS, PPI, and HRQoL, with moderate to strong associations. Patients with multiple DFU locations or neuropathic pain presented poorer HRQoL evaluation. Sensory pain (β = -3.582, P = 0.026) and PPI (β = -2.682, P = 0.020) were identified as independent predictors of HRQoL based on multiple linear regression analysis. CONCLUSION DFU-related pain is prevalent and significantly impacts patients' HRQoL. It is important to prioritise comprehensive and regular assessment of DFU-related pain during patient consultations. A patient-centred and holistic approach should be adopted, guided by the outcomes of pain assessments.
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Affiliation(s)
- Alfarhan Ghadeer
- Discipline of Podiatric Medicine, School of Health Sciences, University of Galway, Galway, H91 TK33, Ireland
| | - Tao Yan
- Discipline of Podiatric Medicine, School of Health Sciences, University of Galway, Galway, H91 TK33, Ireland
| | - MacGilchrist Claire
- Discipline of Podiatric Medicine, School of Health Sciences, University of Galway, Galway, H91 TK33, Ireland; Alliance for Research and Innovation in Wounds, College of Medicine, Nursing & Health Sciences, University of Galway, Galway, H91 TK3, Ireland
| | - Kirwan Ellen
- Discipline of Podiatric Medicine, School of Health Sciences, University of Galway, Galway, H91 TK33, Ireland.
| | - McIntosh Caroline
- Discipline of Podiatric Medicine, School of Health Sciences, University of Galway, Galway, H91 TK33, Ireland; Alliance for Research and Innovation in Wounds, College of Medicine, Nursing & Health Sciences, University of Galway, Galway, H91 TK3, Ireland
| | - A McIlwaine
- Discipline of Podiatric Medicine, School of Health Sciences, University of Galway, Galway, H91 TK33, Ireland
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Li N, Wang H, Ye Y, Dai W, Zhou Q. Patients' perceptions with high-risk diabetic foot on early access to medical care: A qualitative study. J Tissue Viability 2025; 34:100863. [PMID: 39908960 DOI: 10.1016/j.jtv.2025.100863] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2024] [Revised: 01/12/2025] [Accepted: 01/24/2025] [Indexed: 02/07/2025]
Abstract
AIMS To explore the perception of patients with high-risk diabetic foot on early access to medical care. DESIGN Qualitative interview study. METHODS We conducted a qualitative exploratory and descriptive study involving 11 community-based patients with high-risk diabetic foot residing in Hunan, China. Interviews were systematically coded and categorized into thematic groups using Colaizzi's method. RESULTS There were five main themes and nine subthemes, namely, (1) Attitude toward healthcare-seeking, (2) Lack of disease knowledge: (a) low symptom alertness, (b) necessity of health education, (3) Hospital visits: (a) doctor-patient relationship, (b) level of medical institutions, (c) obstacles in seeking healthcare, (4) Financial consideration: (a) apprehension about adding to family burden, (b) medical insurance to ease financial stress, (5)Environmental impact: (a) family and social supports, (b) communication between patients. CONCLUSIONS Patients with high-risk diabetic foot have barriers to early intention to seek medical care, and it is the result of a combination of many factors. Healthcare providers should provide relevant interventions for patients, and health insurance systems should be improved to increase coverage to facilitate timely access.
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Affiliation(s)
- Na Li
- Teaching and Research Section of Clinical Nursing, Xiangya Hospital of Central South University, Changsha, Hunan, China; Xiangya School of Nursing, Central South University, Changsha, Hunan, China
| | - Honglin Wang
- Teaching and Research Section of Clinical Nursing, Xiangya Hospital of Central South University, Changsha, Hunan, China; Xiangya School of Nursing, Central South University, Changsha, Hunan, China
| | - Ying Ye
- Department of Nursing, The First People's Hospital of Yunnan Province, Kunming, Yunnan, China
| | - Weiwei Dai
- Teaching and Research Section of Clinical Nursing, Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Qiuhong Zhou
- Teaching and Research Section of Clinical Nursing, Xiangya Hospital of Central South University, Changsha, Hunan, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital of Central South University, Changsha, Hunan, China.
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Chen Y, Zhao J, Sun Y, Yang Z, Yang C, Zhu D. Association of the triglyceride glucose index with sudden cardiac death in the patients with diabetic foot ulcer. Diabetes Res Clin Pract 2025; 223:112143. [PMID: 40158857 DOI: 10.1016/j.diabres.2025.112143] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2025] [Accepted: 03/25/2025] [Indexed: 04/02/2025]
Abstract
BACKGROUND This study examines the relationship between the TyG index and the risk of sudden cardiac death (SCD) in the patients with diabetic foot ulcer (DFU). METHODS 688 type 2 diabetes mellitus (T2DM) inpatients with DFU between January 2010 and December 2023 was included in this retrospective study. The 1:1 propensity score matching (PSM) method was applied. The relationship between TyG index and SCD risk was analyzed using the Kaplan-Meier (K-M) survival curve analysis, multivariate Cox proportional hazard regression model, Restricted cubic spline (RCS) model analysis and subgroup analyses. RESULTS Over a median follow-up period of 61 months, 38 cases of SCD were recorded. After PSM, 71 pairs of score-matched patients according to TyG index were generated. K-M survival curves revealed higher SCD rates in patients with TyG index ≥9.65. The Cox proportional hazard model, independently associated with the risk of SCD (HR: 75.98; 95 % CI: 9.16 ∼ 630.40; P < 0.001). RCS model showed that SCD risk was non-linearly correlated with gradual increases in TyG index levels. Stratified analyses indicated a consistent relationship between increasing TyG index and SCD risk across all subgroups. CONCLUSIONS Elevated TyG index independently confers an increased risk for SCD in individuals with DFU.
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Affiliation(s)
- Yi Chen
- Department of Endocrinology, Air Force Medical Center, Beijing 100142, China; Graduate School of China Medical University, Shenyang 110122, China
| | - Junyan Zhao
- Department of Endocrinology, Air Force Medical Center, Beijing 100142, China
| | - Yuchen Sun
- Department of Endocrinology, Air Force Medical Center, Beijing 100142, China
| | - Zhongjing Yang
- Department of Endocrinology, Air Force Medical Center, Beijing 100142, China
| | - Caizhe Yang
- Department of Endocrinology, Air Force Medical Center, Beijing 100142, China.
| | - Di Zhu
- Department of Endocrinology, Air Force Medical Center, Beijing 100142, China.
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Tang G, Wang Y, Deng P, Wu J, Lu Z, Zhu R, Guo H, Zhang Y, Mo X, Chen Z. Mechanism of dracorhodin in accelerating diabetic foot ulcer healing via the Nrf2 pathway, a network pharmacology, molecular docking and experimental validation. Sci Rep 2025; 15:12492. [PMID: 40216975 PMCID: PMC11992152 DOI: 10.1038/s41598-025-97831-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2024] [Accepted: 04/07/2025] [Indexed: 04/14/2025] Open
Abstract
Delayed wound healing in diabetic foot ulcer (DFU) is a major cause of amputations, with ferroptosis impeding recovery. Dracorhodin (DP), a flavonoid from Dragon's Blood, has shown anti-inflammatory and wound-healing properties, though its molecular mechanisms is unclear. This study investigates DP's role in DFU treatment through bioinformatics and experimental approaches. A rat model of DFU was created with a high-fat/high-glucose diet and streptozotocin (STZ) induction, and wound healing was monitored after applying varying DP doses. Histopathological analysis and ELISA assessed tissue changes, inflammatory markers, and growth factors. Network pharmacology and molecular docking were used to identify core targets and pathways, while human umbilical vein endothelial cells (HUVECs) were used for in vitro testing. The results demonstrated that DP accelerated wound healing in DFU rats in a dose-dependent manner by enhancing collagen synthesis, angiogenesis, and growth factor levels, while simultaneously reducing inflammation and ROS levels. Network pharmacology and molecular docking analyses identified the Nrf2-mediated ferroptosis pathway as a potential key mechanism underlying DP's therapeutic effects in DFU. In vitro experiments further revealed that DP improved cell viability and migration, while decreasing ROS and lipid peroxidation levels, effects attributed to Nrf2 pathway activation. These outcomes were significantly attenuated by the Nrf2 inhibitor ML385. In conclusion, DP promotes DFU healing via activation of the Nrf2 pathway and inhibition of ferroptosis.
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Affiliation(s)
- Guangjun Tang
- Beijing University of Chinese Medicine, Beijing, China
- Beijing University of Chinese Medicine Third Affiliated Hospital, Beijing, China
| | - Ying Wang
- Beijing University of Chinese Medicine, Beijing, China
- Beijing University of Chinese Medicine Third Affiliated Hospital, Beijing, China
| | - Pin Deng
- Institute of Basic Theory of Traditional Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing, China
| | - Junde Wu
- Beijing University of Chinese Medicine, Beijing, China
- Beijing University of Chinese Medicine Third Affiliated Hospital, Beijing, China
| | - Zhongwen Lu
- Beijing University of Chinese Medicine, Beijing, China
- Beijing University of Chinese Medicine Third Affiliated Hospital, Beijing, China
| | - Ruizheng Zhu
- Beijing University of Chinese Medicine, Beijing, China
- Beijing University of Chinese Medicine Third Affiliated Hospital, Beijing, China
| | - Hui Guo
- Beijing University of Chinese Medicine, Beijing, China
- Beijing University of Chinese Medicine Third Affiliated Hospital, Beijing, China
| | - Yunhui Zhang
- Beijing University of Chinese Medicine, Beijing, China
- Beijing University of Chinese Medicine Third Affiliated Hospital, Beijing, China
| | - Xingjie Mo
- Beijing University of Chinese Medicine, Beijing, China
- Beijing University of Chinese Medicine Third Affiliated Hospital, Beijing, China
| | - Zhaojun Chen
- Beijing University of Chinese Medicine, Beijing, China.
- Beijing University of Chinese Medicine Third Affiliated Hospital, Beijing, China.
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Lim QH, Loy LCW, Abdul Hadi H, Faheem NAN, Shaharuddin IS, Sri La Ponnampalavanar S, Lim LL. Diabetic foot ulcer in the Western Pacific Region: Current data on ulceration rates and microbial profiles, gaps and charting strategies. Prim Care Diabetes 2025; 19:133-142. [PMID: 39824708 DOI: 10.1016/j.pcd.2024.12.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2024] [Revised: 12/26/2024] [Accepted: 12/31/2024] [Indexed: 01/20/2025]
Abstract
The Western Pacific Region hosts the largest proportion of people with diabetes. Despite being a key diabetes-related complication, diabetic foot ulcer has been neglected in both prevention and treatment efforts. This narrative review highlights available data on the burden (either prevalence or incidence), as well as microbial profiles of diabetic foot ulcers in the Western Pacific Region, identifies data gaps, and discusses strategies to address these gaps. There are substantial gaps in epidemiological data and microbial profiles for many countries in the Western Pacific Region. Addressing these gaps require developing and strengthening data collection systems for effective surveillance and benchmarking of diabetes care.
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Affiliation(s)
- Quan-Hziung Lim
- Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia.
| | - Lawrence Chun-Wei Loy
- Faculty of Medicine, National Heart and Lung Institute, Imperial College London, London SW7 2AZ, United Kingdom
| | - Haireen Abdul Hadi
- Department of Primary Care Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia
| | - Nik Aizah Nabilla Faheem
- Department of Orthopaedic Surgery (NOCERAL), Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia
| | | | | | - Lee-Ling Lim
- Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR; Asia Diabetes Foundation, Hong Kong SAR.
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Wernecke J, Wernecke M, Ebenau O, Spruth B, Krämer M, Vogelmann T, Zöllner Y. Epidemiology and the Medical Burden of Diabetic Foot Ulcers Especially in Patients With Infection-A Population-Based Analysis From Germany. Int Wound J 2025; 22:e70157. [PMID: 40129108 PMCID: PMC11932955 DOI: 10.1111/iwj.70157] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2024] [Revised: 11/25/2024] [Accepted: 11/25/2024] [Indexed: 03/26/2025] Open
Abstract
Due to limited data on the epidemiology of diabetic foot ulcers (DFU) in Germany, especially for those infected, the study determined the prevalence and incidence of DFU and the associated medical burden. Anonymised claims data of 3.3 million insured lives were sourced from a statutory health insurance fund. Patients with DFU between 04/01/2016 and 12/31/2019 were selected (n = 7764) and divided into patients with/without infection/with prophylactic use of antibiotics. Outcome variables were described categorically. Two-sided t-tests and chi-squared tests (p < 0.05) were performed. The prevalence and incidence in patients with DFU was 4.6% and 2.1%, respectively. The mean Charlson Comorbidity Index was 7.9, significantly higher in those infected than in those uninfected (8.1% vs. 7.2%, p < 0.0001). Amputations occurred significantly more often in DFU patients with infection than in those without (minor 25.4% vs. 3.0%, p < 0.0001; major 6.7% vs. 1.2%, p < 0.0001). The 5-year mortality rate was significantly higher in patients with infection than in those without (64.0% vs. 51.3%, p < 0.0001). The occurrence of comorbidities and complications associated with DFU, in particular the high overall medical burden and mortality rate-especially in DFU patients with infections-underscores the importance of prevention and early, appropriate treatment.
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Affiliation(s)
- Jürgen Wernecke
- Clinic for DiabetesAgaplesion Diakonieklinikum HamburgHamburgGermany
| | - Marie Wernecke
- Clinic for DiabetesAgaplesion Diakonieklinikum HamburgHamburgGermany
| | - Olaf Ebenau
- BSN medical GmbH (Essity Group)HamburgGermany
| | | | | | | | - York Zöllner
- Department of Health SciencesHamburg University of Applied SciencesHamburgGermany
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Allemailem KS, Almousa S, Alissa M, Alrumaihi F, Alharbi HO, Almansour NM, Aldaiji LA, Abouzied AS, Alsugoor MH, Alasmari O, Albakawi MJ, Stride J. Innovations in quantitative rapid testing: Early prediction of health risks. Curr Probl Cardiol 2025; 50:103000. [PMID: 39900212 DOI: 10.1016/j.cpcardiol.2025.103000] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2025] [Accepted: 01/28/2025] [Indexed: 02/05/2025]
Abstract
As health monitoring becomes increasingly intricate, the demand for innovative solutions to predict and assess health status is more pressing than ever. This review focuses on the transformative potential of multi-sensor technologies in health monitoring, emphasizing their role in early health status prediction. By integrating diverse sensor types ranging from wearable fitness trackers to implantable devices and environmental monitors healthcare professionals can gain a richer, more nuanced understanding of an individual's physiological state. We analyze various configurations of multi-sensor networks and their efficacy in identifying early indicators of health issues, such as cardiovascular diseases, diabetes, and respiratory ailments. For example, the combination of biometric sensors that track vital signs with environmental data on pollutants can yield invaluable insights into a patient's overall health. This integrated approach not only improves the accuracy of health assessments but also facilitates timely interventions. Furthermore, we address the challenges inherent in multi-sensor systems, including data integration, device interoperability, and the need for advanced algorithms capable of processing complex datasets. Recent advancements in machine learning and artificial intelligence are underscored as pivotal in enhancing the capabilities of these technologies for predictive health analytics. Ultimately, this review highlights how multi-sensor systems can redefine early health status prediction, paving the way for proactive healthcare strategies that significantly improve patient outcomes and optimize healthcare delivery.
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Affiliation(s)
- Khaled S Allemailem
- Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah 51452, Saudi Arabia
| | - Saad Almousa
- Department of Medical Laboratory, Al Kharj Military Industries Corporation Hospital, Al Kharj, Saudi Arabia
| | - Mohammed Alissa
- Department of Medical Laboratory, College of Applied Medical Sciences, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia
| | - Faris Alrumaihi
- Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah 51452, Saudi Arabia
| | - Hajed Obaid Alharbi
- Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah 51452, Saudi Arabia
| | - Nahlah Makki Almansour
- Department of Biology, College of Science, University of Hafr Al Batin, Hafr Al Batin 31991, Saudi Arabia
| | - Leen A Aldaiji
- Department of Laboratories & Blood Bank, Dr. Sulaiman Al Habib Medical Group, Qassim 51431, Saudi Arabia
| | - Amr S Abouzied
- Department of Pharmaceutical Chemistry, College of Pharmacy, University of Hail, Hail 81442, Saudi Arabia
| | - Mahdi H Alsugoor
- Department of Medical Laboratory, Al Kharj Military Industries Corporation Hospital, Al Kharj, Saudi Arabia
| | - Omer Alasmari
- Department of Medical Laboratory, Al Kharj Military Industries Corporation Hospital, Al Kharj, Saudi Arabia
| | - Marwh Jamal Albakawi
- Department of Laboratory and Blood Bank, King Fahad Specialist Hospital, Tabuk 47717, Saudi Arabia
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12
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Geng XQ, Chen SF, Wang FY, Yang HJ, Zhao YL, Xu ZR, Yang Y. Correlation between key indicators of continuous glucose monitoring and the risk of diabetic foot. World J Diabetes 2025; 16:99277. [PMID: 40093283 PMCID: PMC11885981 DOI: 10.4239/wjd.v16.i3.99277] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2024] [Revised: 11/09/2024] [Accepted: 12/23/2024] [Indexed: 01/21/2025] Open
Abstract
BACKGROUND Continuous glucose monitoring (CGM) metrics, such as time in range (TIR) and glycemic risk index (GRI), have been linked to various diabetes-related complications, including diabetic foot (DF). AIM To investigate the association between CGM-derived indicators and the risk of DF in individuals with type 2 diabetes mellitus (T2DM). METHODS A total of 591 individuals with T2DM (297 with DF and 294 without DF) were enrolled. Relevant clinical data, complications, comorbidities, hematological parameters, and 72-hour CGM data were collected. Logistic regression analysis was employed to examine the relationship between these measurements and the risk of DF. RESULTS Individuals with DF exhibited higher mean blood glucose (MBG) levels and increased proportions of time above range (TAR), TAR level 1, and TAR level 2, but lower TIR (all P < 0.001). Patients with DF had significantly lower rates of achieving target ranges for TIR, TAR, and TAR level 2 than those without DF (all P < 0.05). Logistic regression analysis revealed that GRI, MBG, and TAR level 1 were positively associated with DF risk, while TIR was inversely correlated (all P < 0.05). Achieving TIR and TAR was inversely correlated with white blood cell count and glycated hemoglobin A1c levels (P < 0.05). Additionally, achieving TAR was influenced by fasting plasma glucose, body mass index, diabetes duration, and antidiabetic medication use. CONCLUSION CGM metrics, particularly TIR and GRI, are significantly associated with the risk of DF in T2DM, emphasizing the importance of improved glucose control.
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Affiliation(s)
- Xin-Qian Geng
- Department of Endocrinology, Affiliated Hospital of Yunnan University, Second People’s Hospital of Yunnan Province, Kunming 650021, Yunnan Province, China
| | - Shun-Fang Chen
- Department of Endocrinology, Affiliated Hospital of Yunnan University, Second People’s Hospital of Yunnan Province, Kunming 650021, Yunnan Province, China
| | - Fei-Ying Wang
- Department of Endocrinology, Affiliated Hospital of Yunnan University, Second People’s Hospital of Yunnan Province, Kunming 650021, Yunnan Province, China
| | - Hui-Jun Yang
- Department of Endocrinology, Affiliated Hospital of Yunnan University, Second People’s Hospital of Yunnan Province, Kunming 650021, Yunnan Province, China
| | - Yun-Li Zhao
- Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education and Yunnan Province, Yunnan University, Kunming 650500, Yunnan Province, China
| | - Zhang-Rong Xu
- The Diabetic Center of PLA, The Ninth Medical Center of PLA General Hospital (306th Hosp PLA), Beijing 100101, China
| | - Ying Yang
- Department of Endocrinology and Metabolism, Affiliated Hospital of Yunnan University, Second People’s Hospital of Yunnan Province, Kunming 650021, Yunnan Province, China
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13
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Liang J, An H, Hu X, Gao Y, Zhou J, Gong X, Zong J, Liu Y. Correlation between chronic kidney disease and all-cause mortality in diabetic foot ulcers: evidence from the 1999-2004 national health and nutrition examination survey (NHANES). Front Endocrinol (Lausanne) 2025; 16:1533087. [PMID: 40162314 PMCID: PMC11949790 DOI: 10.3389/fendo.2025.1533087] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2024] [Accepted: 02/21/2025] [Indexed: 04/02/2025] Open
Abstract
Background The poor prognosis of diabetic foot ulcers (DFUs) often leads to amputation and high mortality rates, becoming a heavy economic burden on the healthcare system. Several clinical studies have been conducted to investigate the risk factors for DFU mortality and to provide clinical guidance for better prevention and control of DFU mortality. Methods We used R to organize the mortality data of patients with DFU, collected from the NHANES database during the 1994-2004 period, along with three kidney function indicators including Albumin-to-Creatinine Ratio (ACR), estimated Glomerular Filtration Rate (eGFR) and cystatin C, used to assess chronic kidney disease (CKD). We explored the relationship between CKD and the risk of death in DFU patients through multiple kidney function indicators. Baseline characteristics of the surviving group and the mortality group of patients with DFU were analyzed using the 'svyby' function in the 'survey' package. We used Kaplan-Meier curves, multivariable logistic regression models, Cox proportional risk regression models, and time-dependent ROC curves to analyze the relationship between CKD and the risk of death in patients with DFU. Results This study included a total of 112 patients with DFU. The overall sample had an average age of 65 years, with 43 females (38.39%) and 69 males (61.61%). During the follow-up time, 29 survived and 89 died. All-cause mortality in DFU patients was analyzed based on clinical classifications of ACR, eGFR, and cystatin C, with Kaplan-Meier curves illustrating survival variability. Multivariable logistic regression analysis showed no significant correlation between the risk of death in patients with DFU and CKD. However, analysis of Cox proportional risk regression model that accounted for time effects found a significant association between all-cause mortality and cystatin C levels in patients with DFU. Time-dependent ROC curve analysis demonstrated that cystatin C had superior diagnostic accuracy and stability for predicting all-cause mortality in DFU patients. Conclusions In this study, we found that cystatin C demonstrated greater stability and accuracy in assessing the risk of death and predicting mortality in patients with DFU.
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Affiliation(s)
- Jiaru Liang
- Department of Rehabilitation Medicine, First Affiliated Hospital, Dalian Medical University, Dalian, China
- College of Integrative Medicine, Dalian Medical University, Dalian, China
| | - Hang An
- College of Integrative Medicine, Dalian Medical University, Dalian, China
| | - Xuyang Hu
- College of Integrative Medicine, Dalian Medical University, Dalian, China
| | - Yuling Gao
- Department of Rehabilitation Medicine, First Affiliated Hospital, Dalian Medical University, Dalian, China
| | - Jiaqi Zhou
- Department of Rehabilitation Medicine, First Affiliated Hospital, Dalian Medical University, Dalian, China
| | - Xiaoyang Gong
- Department of Rehabilitation Medicine, First Affiliated Hospital, Dalian Medical University, Dalian, China
| | - Junwei Zong
- Department of Orthopaedic Surgery, First Affiliated Hospital, Dalian Medical University, Dalian, China
| | - Yong Liu
- Department of Rehabilitation Medicine, First Affiliated Hospital, Dalian Medical University, Dalian, China
- College of Integrative Medicine, Dalian Medical University, Dalian, China
- College of Health-Preservation and Wellness, Dalian Medical University, Dalian, China
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14
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Chen L, Chen D, Gong H, Wang C, Gao Y, Li Y, Tang W, Zha P, Ran X. Response to Commentary on "Pedal Medial Arterial Calcification in Diabetic Foot Ulcers: A Significant Risk Factor of Amputation and Mortality". J Diabetes 2025; 17:e70070. [PMID: 40038787 PMCID: PMC11879775 DOI: 10.1111/1753-0407.70070] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2025] [Accepted: 02/24/2025] [Indexed: 03/06/2025] Open
Affiliation(s)
- Lihong Chen
- Department of Endocrinology & Metabolism, West China HospitalSichuan UniversityChengduChina
- Innovation Center for Diabetic Foot, Diabetic Foot Care Center, West China HospitalSichuan UniversityChengduChina
| | - Dawei Chen
- Department of Endocrinology & Metabolism, West China HospitalSichuan UniversityChengduChina
| | - Hongping Gong
- International Medical Center Ward, Department of General Practice, West China HospitalSichuan UniversityChengduChina
| | - Chun Wang
- Department of Endocrinology & Metabolism, West China HospitalSichuan UniversityChengduChina
| | - Yun Gao
- Department of Endocrinology & Metabolism, West China HospitalSichuan UniversityChengduChina
| | - Yan Li
- Department of Clinical Research Management, West China HospitalSichuan UniversityChengduChina
| | - Weiwei Tang
- Department of Endocrinology & Metabolism, West China HospitalSichuan UniversityChengduChina
- Innovation Center for Diabetic Foot, Diabetic Foot Care Center, West China HospitalSichuan UniversityChengduChina
| | - Panpan Zha
- Department of Endocrinology & Metabolism, West China HospitalSichuan UniversityChengduChina
- Innovation Center for Diabetic Foot, Diabetic Foot Care Center, West China HospitalSichuan UniversityChengduChina
| | - Xingwu Ran
- Department of Endocrinology & Metabolism, West China HospitalSichuan UniversityChengduChina
- Innovation Center for Diabetic Foot, Diabetic Foot Care Center, West China HospitalSichuan UniversityChengduChina
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15
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Zhuang HR, Yu HP, Gu YJ, Li LJ, Yao JL. The Effect of Telemedicine Interventions on Patients with Diabetic Foot Ulcers: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Adv Wound Care (New Rochelle) 2025; 14:133-142. [PMID: 38618714 DOI: 10.1089/wound.2024.0030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/16/2024] Open
Abstract
Objective: The meta-analysis was performed to evaluate the effectiveness of telemedicine interventions on patients with diabetic foot ulcers (DFU). Approach: The authors conducted a comprehensive search across eight databases. The aim was to identify randomized controlled trials examining the effectiveness of telemedicine for patients with DFU. Methodological qualities of included studies were assessed using Cochrane Handbook for Systematic Reviews of Intervention. Subsequently, a meta-analysis was conducted using RevMan 5.3 to synthesize the findings. Results: Ten studies involving 1,678 patients with DFU were included in the meta-analysis. In comparison to the face-to-face intervention group, telemedicine interventions significantly reduced the amputation rate (risk ratio = 0.64, 95% confidence interval [CI] = 0.44-0.92, p = 0.02), decreased costs (mean difference [MD] = -4158.51, 95% CI = -7304.69 to -1012.34, p = 0.01), better controlled fasting blood glucose (MD = -0.89, 95% CI = -1.43 to -0.36, p = 0.001), and achieved superior glycated hemoglobin control (MD = -0.71, 95% CI = -1.01 to -0.41, p < 0.00001). No significant differences were observed between the telemedicine group and the face-to-face group in terms of healing rate, mortality, and healing time. Innovations: Our study suggests that telemedicine is a viable strategy for managing DFU. Conclusions: The meta-analysis indicates that telemedicine interventions have a positive effect on DFU. Nevertheless, more well-designed and high-quality studies are needed to reach a conclusion with greater confidence.
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Affiliation(s)
- Hui-Ren Zhuang
- Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Hai-Ping Yu
- Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Ying-Jie Gu
- Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Ling-Jun Li
- Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Jia-Li Yao
- Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
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16
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Sailer M, Wergeland H, Randsborg P. Implementation of a clinical pathway for diabetes-related foot ulcers reduced the number of amputations and shortened hospital stay. J Foot Ankle Res 2025; 18:e70024. [PMID: 39875339 PMCID: PMC11774619 DOI: 10.1002/jfa2.70024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2024] [Accepted: 11/29/2024] [Indexed: 01/30/2025] Open
Abstract
INTRODUCTION Diabetes-related foot ulcer (DFU) is the leading cause for lower extremity amputations (LEAs) in western countries, and may cause social isolation, depression, and death. However, people with DFU are not offered the same prioritized care as cancer patients, despite comparable mortality rates. We therefore decided to create a clinical pathway for patients with DFU. The purpose of this study is to evaluate the efficacy of implementing a new clinical pathway on rates of LEA, length of hospital stays, and cost reduction. METHODS On January 1, 2019, a new clinical pathway ensured that all patients with a DFU were evaluated in a designated clinic run by a foot and ankle orthopedic surgeon in collaboration with the vascular surgeons, supported by a specialized wound nurse and a certified prosthetist/orthotist (CPO). We designed an algorithm for the first consultation to identify patients in need for further investigation by other specialties such as endocrinology, infectious diseases, cardiology, or vascular surgery. All patients underwent a surgical wound debridement of DFU. Negative pressure wound therapy (NPWT) was not applied. After surgery, the dressings were changed daily on the ward, until the wound was deemed viable and clean. The patients were followed for two years and compared to a historic cohort of patients with DFU admitted to the institution in 2017. RESULTS The number of major amputations was reduced from 65% (13/20) to 7.4% (2/27) (p < 0.001) after the introduction of the clinical pathway. Both the mean number of surgical revisions (5.5 vs. 1.2) and the median length of stay (46 vs. 9 days) were statistically significantly reduced. The median cost per patient was reduced by 76% (from €538 000 to €129 000, p < 0.001). CONCLUSION The clinical pathway for managing DFUs resulted in a reduction in major amputations and shorter hospital stays. Discontinuing NPWT after surgical debridement did not adversely affect clinical outcomes. The new pathway also contributed to lower healthcare costs.
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Affiliation(s)
- Monica Sailer
- Department of Orthopaedic SurgeryAkershus University HospitalLørenskogNorway
- Institute of Clinical MedicineFaculty of MedicineUniversity of OsloOsloNorway
| | - Hilde Wergeland
- Department of Economics and FinanceAkershus University HospitalLørenskogNorway
| | - Per‐Henrik Randsborg
- Department of Orthopaedic SurgeryAkershus University HospitalLørenskogNorway
- Institute of Clinical MedicineFaculty of MedicineUniversity of OsloOsloNorway
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Wang Z, Feng C, Liu H, Xia Y, Shan M, Hao Y. Hypoxia-induced adipose derived stem cells-derived exosomes promote diabetic wound healing through circ-0001747/miR-199a-5p/HIF-1α axis. Arch Dermatol Res 2025; 317:456. [PMID: 39987303 DOI: 10.1007/s00403-025-03921-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2024] [Revised: 01/21/2025] [Accepted: 01/27/2025] [Indexed: 02/24/2025]
Abstract
Diabetic foot ulcers (DFU) are a serious complication of diabetes that lead to significant morbidity and mortality. The studies reported that promoting angiogenesis is a key step in wound healing. Hypoxia-induced adipose-derived mesenchymal stem cell-derived exosomes (ADSC-Exo) were observed to promote skin wound healing and alleviate DFU development. Howere, the detailed molecular mechanism of hypoxia-induced ADSC-Exo in wound healing of DFU remain undetermined. In this study, we identified aberrantly expressed circRNAs in normoxic-induced ADSC-Exo (Exo) versus hypoxia-induced ADSC-Exo (HExo) by high-throughput sequencing. The expression of circ-0001747 in Exo and HExo were detected by qRT-PCR. Subsequently, the overexpression of circ_0001747-HExo was constructed to observe the wound healing and therapeutic effect of DFU mice. Bioinformatics analysis, luciferase reporter gene assays, qRT-PCR, flow cytometry and angiogenesis assay, were used to study the regulatory mechanism of circ-0001747. The results showed that circ-0001747 was higher in HExo. Compared with the Exo group, overexpression of circ-0001747-HExo significantly restored wound healing, promoted vascular differentiation, and inhibited cell apoptosis and ROS production. Additionally, miR-199a-5p and HIF1α were identified as downstream targets of circ-0001747 and further verified by luciferase reporter gene analysis. Notably, overexpression of miR-199a-5p or inhibition of HIF1α reversed the protective effects of the circ-0001747-mediated microenvironment on endothelial cells. These results showed that overexpression of circ-0001747-HExo inhibited endothelial cell damage and promotes wound healing by targeting the miR-199a-5p/HIF1α axis.
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Affiliation(s)
- Zhi Wang
- Department of Plastic & Cosmetic Surgery, Peking Union Medical College Hospital (Xidan Campus), No.41 Damucang Hutong, Xicheng District, Beijing, 100032, China.
| | - Cheng Feng
- Department of Plastic & Cosmetic Surgery, Peking Union Medical College Hospital (Xidan Campus), No.41 Damucang Hutong, Xicheng District, Beijing, 100032, China
| | - Hao Liu
- Department of Plastic & Cosmetic Surgery, Peking Union Medical College Hospital (Xidan Campus), No.41 Damucang Hutong, Xicheng District, Beijing, 100032, China
| | - Yijun Xia
- Department of Plastic & Cosmetic Surgery, Peking Union Medical College Hospital (Xidan Campus), No.41 Damucang Hutong, Xicheng District, Beijing, 100032, China
| | - Mengjie Shan
- Department of Plastic & Cosmetic Surgery, Peking Union Medical College Hospital (Xidan Campus), No.41 Damucang Hutong, Xicheng District, Beijing, 100032, China
| | - Yan Hao
- Department of Plastic & Cosmetic Surgery, Peking Union Medical College Hospital (Xidan Campus), No.41 Damucang Hutong, Xicheng District, Beijing, 100032, China
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18
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Niu Z, Mao L, Han L, Niu J, Zhang X, Wei G. The effects of immune cell phenotypes and plasma metabolomes on diabetic foot ulcer: a Mendelian randomization study and mediation analysis. Arch Dermatol Res 2025; 317:460. [PMID: 39987406 DOI: 10.1007/s00403-025-03942-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2024] [Revised: 12/24/2024] [Accepted: 02/03/2025] [Indexed: 02/24/2025]
Abstract
This study investigates the causal relationships between plasma metabolites, immune cell phenotypes, and diabetic foot ulcer (DFU). A Mendelian randomization (MR) study was conducted, which included 731 immune cell phenotypes, 1400 metabolites, and DFU. The primary analytical approach was the inverse variance-weighted method. Sensitivity analyses were performed to assess heterogeneity and pleiotropy, and MR analyses in the reverse direction were conducted to examine the possibility of reverse causation. In addition, a mediation analysis was performed to reveal how metabolites mediate the impact of immune cells on DFU. Through MR, reverse MR and sensitivity analysis, the casualty was found in 17 immune cell phenotypes and 18 metabolites. A total of 15 mediating relationships were identified through mediation analysis, including 9 metabolites and 10 immune cell phenotypes. Among them, the highest mediation proportion was citrulline levels mediating CD24+ CD27+ AC (absolute count, B cell panel) to DFU, with a proportion of 11.60%. In conclusion, the study identified causal relationships between 10 immune cell phenotypes mediated by 9 metabolites. These discoveries offered fresh perspectives on the processes behind DFU and laid the groundwork for subsequent studies to create specific treatments for DFU.
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Affiliation(s)
- Zehao Niu
- Department of Burns and Plastic Surgery, The 83 Affiliated Hospital of Xinxiang Medical University, Xinxiang, China
- Department of Plastic Surgery, Southwest Hospital, Army Medical University, Chongqing, China
| | - Libin Mao
- Department of Outpatient, The 83 Affiliated Hospital of Xinxiang Medical University, Xinxiang, China
| | - Liu Han
- Department of Plastic Surgery, Southwest Hospital, Army Medical University, Chongqing, China
- Department of General Practice, 66284 Military Hospital, Beijing, China
| | - Jun Niu
- Department of Burns and Plastic Surgery, The 83 Affiliated Hospital of Xinxiang Medical University, Xinxiang, China
| | - Xuhui Zhang
- Department of Orthopedics, The 83 Affiliated Hospital of Xinxiang Medical University, Xinxiang, China.
| | - Guoxing Wei
- Department of Burns and Plastic Surgery, The 83 Affiliated Hospital of Xinxiang Medical University, Xinxiang, China.
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Miranda MB, Alves RF, da Rocha RB, Cardoso VS. Effects and parameterization of low-level laser therapy in diabetic ulcers: an umbrella review of systematic reviews and meta-umbrella. Lasers Med Sci 2025; 40:109. [PMID: 39982518 DOI: 10.1007/s10103-025-04366-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2024] [Accepted: 02/13/2025] [Indexed: 02/22/2025]
Abstract
This study aimed to systematically verify the available systematic reviews and meta-analyses of Low-level laser therapy (LLLT) in diabetic foot ulcer (DFUs) to identify the effects and optimal parameters of LLLT in the management of DFUs. This umbrella review was written according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) report items and registered in the International Prospective Register of Systematic Review (PROSPERO). The search for articles was performed in the Pubmed, Scopus, Web of Science and Embase databases. The following terms were used: Diabetic Foot, Diabetic Neuropathies, Peripheral Vascular Diseases, Peripheral Neuropathy, Diabetic Foot Ulcer, LASER Therapy, Low-Level Light Therapy, LLLT, LASER Biostimulation, Low Intensity LASER Irradiation, Low Power LASER Irradiation, Low Intensity LASER Therapy, Low Power LASER Therapy. A search was performed in the references section of the included studies. The systematic review (SR) included studies that compared LLLT with non-therapeutic doses (parameters considered low to modify healing), sham irradiation, and conventional DFU treatment. The interventions were performed using red and infrared wavelengths. Although two studies included in the SR used wavelengths below 600 nm, these were combined with diodes with infrared wavelengths within the same device. Another study performed a comparative analysis of LLLT at different wavelengths (632 nm and 904 nm), with area reduction rates of 63.7% and 56.8%, respectively, with no statistically significant difference. This is study indicated that, compared with standard treatment and non-irradiation treatments, the use of photobiomodulation (PBM) with different parameters was effective in promoting UPD healing. Further studies are warranted to determine the ideal parameters for improving patient outcomes. (International Prospective Register of Systematic Review Registration number: CRD42022362447).
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Affiliation(s)
- Mariana Bezerra Miranda
- Universidade Federal Do Delta Do Parnaíba, Parnaíba, Brazil
- Center of Medical Specialties, Parnaíba, Piauí, Brazil
| | - Rayana Fontenele Alves
- Universidade Federal Do Delta Do Parnaíba, Parnaíba, Brazil
- Center of Medical Specialties, Parnaíba, Piauí, Brazil
| | | | - Vinicius Saura Cardoso
- Universidade Federal Do Delta Do Parnaíba, Parnaíba, Brazil.
- Center of Medical Specialties, Parnaíba, Piauí, Brazil.
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da Silva AKA, Nunes GAMDA, Faria RM, Fleury Rosa MF, da Costa LBM, de Faria N, da Rocha AF, Tatmatsu-Rocha JC, Fleury Rosa SDSR. Development of Mathematical Model for Understanding Microcirculation in Diabetic Foot Ulcers Based on Ankle-Brachial Index. Bioengineering (Basel) 2025; 12:206. [PMID: 40001725 PMCID: PMC11851477 DOI: 10.3390/bioengineering12020206] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2024] [Revised: 02/05/2025] [Accepted: 02/11/2025] [Indexed: 02/27/2025] Open
Abstract
This study proposes an innovative mathematical model for assessing microcirculation in patients with diabetic ulcers, using the ankle-brachial index (ABI). The methodology combines Bond Graph (BG) modeling and Particle Swarm Optimization (PSO), enabling a detailed analysis of hemodynamic patterns in a pilot sample of three patients. The results revealed a correlation between ulcer size and reduced ABI values, suggesting that deficits in microcirculation directly impact the severity of lesions. Furthermore, despite variations in ABI values and arterial pressures, all patients exhibited high capillary resistance, indicating difficulties in microcirculatory blood flow. The PSO-optimized parameters for the capillary equivalent circuit were found to be R1=89.784Ω, R2=426.55Ω, L=27.506H, and C=0.00040675F, which confirms the presence of high vascular resistance and reduced compliance in the microvascular system of patients with diabetic foot ulcers. This quantitative analysis, made possible through mathematical modeling, is crucial for detecting subtle changes in microcirculatory dynamics, which may not be easily identified through conventional pressure measurements alone. The increased capillary resistance observed may serve as a key indicator of vascular impairment, potentially guiding early intervention strategies and optimizing diabetic ulcer treatment. We acknowledge that the sample size of three patients represents a limitation of the study, but this number was intentionally chosen to allow for a detailed and controlled analysis of the variables involved. Although the findings are promising, additional experimental validations are necessary to confirm the clinical applicability of the model in a larger patient sample, thus solidifying its relevance in clinical practice.
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Affiliation(s)
- Ana Karoline Almeida da Silva
- Postgraduate Programme in Mechatronic Systems, Mechanical Engineering Department, Campus Darcy Ribeiro, University of Brasilia, Brasilia 70910-900, DF, Brazil; (G.A.M.d.A.N.); (S.d.S.R.F.R.)
| | - Gustavo Adolfo Marcelino de Almeida Nunes
- Postgraduate Programme in Mechatronic Systems, Mechanical Engineering Department, Campus Darcy Ribeiro, University of Brasilia, Brasilia 70910-900, DF, Brazil; (G.A.M.d.A.N.); (S.d.S.R.F.R.)
| | - Rafael Mendes Faria
- Department of Electrical Engineering, Federal Institute of Education, Science and Technology of Triângulo Mineiro, Campus Paracatu, Paracatu 38603-402, MG, Brazil;
| | - Mário Fabrício Fleury Rosa
- Postgraduate Programme in Biomedical Engineering, Faculty of Science and Engineering Technologies (FCTE), University of Brasilia, Gama 72444-240, DF, Brazil; (M.F.F.R.); (L.B.M.d.C.); (A.F.d.R.)
| | - Lindemberg Barreto Mota da Costa
- Postgraduate Programme in Biomedical Engineering, Faculty of Science and Engineering Technologies (FCTE), University of Brasilia, Gama 72444-240, DF, Brazil; (M.F.F.R.); (L.B.M.d.C.); (A.F.d.R.)
| | - Newton de Faria
- Meinig School of Biomedical Engineering, Master of engineering (M.Eng.) Program, Cornell University, Ithaca, NY 14853, USA;
| | - Adson Ferreira da Rocha
- Postgraduate Programme in Biomedical Engineering, Faculty of Science and Engineering Technologies (FCTE), University of Brasilia, Gama 72444-240, DF, Brazil; (M.F.F.R.); (L.B.M.d.C.); (A.F.d.R.)
- Graduate Program on Electrical Engineering, Department of Electrical Engineering, University of Brasilia, Darcy Ribeiro 70910-900, DF, Brazil
| | - José Carlos Tatmatsu-Rocha
- Postgraduate Program in Physiotherapy in Functionality, Federal University of Ceará, Fortaleza 60430-275, CE, Brazil;
| | - Suelia de Siqueira Rodrigues Fleury Rosa
- Postgraduate Programme in Mechatronic Systems, Mechanical Engineering Department, Campus Darcy Ribeiro, University of Brasilia, Brasilia 70910-900, DF, Brazil; (G.A.M.d.A.N.); (S.d.S.R.F.R.)
- Postgraduate Programme in Biomedical Engineering, Faculty of Science and Engineering Technologies (FCTE), University of Brasilia, Gama 72444-240, DF, Brazil; (M.F.F.R.); (L.B.M.d.C.); (A.F.d.R.)
- Meinig School of Biomedical Engineering, Master of engineering (M.Eng.) Program, Cornell University, Ithaca, NY 14853, USA;
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21
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Lan NSR, Hiew J, Ferreira I, Ritter JC, Manning L, Fegan PG, Dwivedi G, Hamilton EJ. Increased risk of major adverse cardiovascular events in patients with deep and infected diabetes-related foot ulcers. Diabetologia 2025; 68:460-470. [PMID: 39508881 PMCID: PMC11732954 DOI: 10.1007/s00125-024-06316-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2024] [Accepted: 09/27/2024] [Indexed: 11/15/2024]
Abstract
AIMS/HYPOTHESIS Diabetes-related foot ulceration (DFU) is associated with increased cardiovascular risk, but the mechanisms remain unclear. Inflammation and infection are mediators of CVD, which may be important in DFU. METHODS Prospectively collected data from patients attending a multidisciplinary DFU service were analysed. A deep ulcer was defined as one that reached muscle, tendon or deeper structures. Patients were categorised into four DFU groups: not deep and no infection (D-/I-), not deep but infected (D-/I+), deep with no infection (D+/I-) or deep with infection (D+/I+). Incident major adverse cardiovascular events (MACE) were defined as hospitalisation for myocardial infarction, stroke or transient ischaemic attack, or heart failure. Survival analyses were performed using the logrank test and multivariate Cox regression. RESULTS Of 513 patients, 241 (47.0%) were in the D-/I- group, 110 (21.4%) were in the D-/I+ group, 35 (6.8%) were in the D+/I- group and 127 (24.8%) were in the D+/I+ group. MACE or all-cause mortality occurred in 75 patients (14.6%), and MACE alone occurred in 46 patients (9.0%) after median follow-up of 381 days (IQR 220-551) and 404 days (IQR 228-576), respectively. Infection was associated with significantly higher MACE or all-cause mortality (21.5% vs 8.7%; p<0.001) and MACE alone (13.5% vs 5.1%; p=0.003). MACE or all-cause mortality was significantly higher in the D+/I+ group (D-/I- 7.9%; D-/I+ 15.5%; D+/I- 14.3%; D+/I+ 26.8%; p<0.001), as was MACE alone (D-/I- 5.0%; D-/I+ 10.9%; D+/I- 5.7%; D+/I+ 15.7%; p=0.017). Infection and a deep ulcer were independent predictors of adverse outcomes. CONCLUSIONS/INTERPRETATION Deep and/or infected DFUs are associated with increased cardiovascular risk compared with DFUs that are not deep or infected. These findings provide a potential mechanistic explanation that requires investigation.
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Affiliation(s)
- Nick S R Lan
- Centre of Excellence for Cardiometabolic Health, Fiona Stanley Hospital, Perth, Australia
- Department of Cardiology, Fiona Stanley Hospital, Perth, Australia
- Medical School, The University of Western Australia, Perth, Australia
- Harry Perkins Institute of Medical Research, Perth, Australia
| | - Jonathan Hiew
- Centre of Excellence Multidisciplinary Diabetes Foot Ulcer Service, Fiona Stanley and Fremantle Hospitals Group, Perth, Australia
- Department of Podiatry, Fiona Stanley Hospital, Perth, Australia
| | - Ivana Ferreira
- Centre of Excellence Multidisciplinary Diabetes Foot Ulcer Service, Fiona Stanley and Fremantle Hospitals Group, Perth, Australia
- Department of Podiatry, Fiona Stanley Hospital, Perth, Australia
| | - J Carsten Ritter
- Centre of Excellence Multidisciplinary Diabetes Foot Ulcer Service, Fiona Stanley and Fremantle Hospitals Group, Perth, Australia
- Medical School, Curtin University, Perth, Australia
- Department of Vascular Surgery, Fiona Stanley Hospital, Perth, Australia
| | - Laurens Manning
- Medical School, The University of Western Australia, Perth, Australia
- Centre of Excellence Multidisciplinary Diabetes Foot Ulcer Service, Fiona Stanley and Fremantle Hospitals Group, Perth, Australia
- Department of Infectious Diseases, Fiona Stanley Hospital, Perth, Australia
| | - P Gerry Fegan
- Medical School, Curtin University, Perth, Australia
- Department of Endocrinology and Diabetes, Fiona Stanley Hospital, Perth, Australia
| | - Girish Dwivedi
- Centre of Excellence for Cardiometabolic Health, Fiona Stanley Hospital, Perth, Australia.
- Department of Cardiology, Fiona Stanley Hospital, Perth, Australia.
- Medical School, The University of Western Australia, Perth, Australia.
- Harry Perkins Institute of Medical Research, Perth, Australia.
| | - Emma J Hamilton
- Medical School, The University of Western Australia, Perth, Australia.
- Centre of Excellence Multidisciplinary Diabetes Foot Ulcer Service, Fiona Stanley and Fremantle Hospitals Group, Perth, Australia.
- Department of Endocrinology and Diabetes, Fiona Stanley Hospital, Perth, Australia.
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22
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Doss ER, Popejoy LL, Vogelsmeier AA, Lane KR, Canada KE. Family Impacts of Diabetic Extremity Wound Caregiving: A Qualitative Multiple Case Study Report. JOURNAL OF FAMILY NURSING 2025:10748407251314569. [PMID: 39878325 DOI: 10.1177/10748407251314569] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/31/2025]
Abstract
More than three million people in the United States are treated for diabetic extremity wounds every year, with numerous physical, financial, and psychosocial impacts not only to patients but also their families who care for them. This study examined the experiences of families who care for adult members with a diabetic extremity wound. A qualitative multiple case study was conducted with four family cases recruited from an urban academic medical center in the Southeastern United States, with data collection consisting of individual interviews, demographic survey instruments, and family caregiving genogram construction. Individual- and cross-case synthesis was completed using reflexive thematic analysis. Themes related to impacts on family functioning, the caregiving experience, and formal health care utilization were identified. These findings provide insight into the experiences of families living with diabetic extremity wounds, as well as clinical and research directions for the future.
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Affiliation(s)
- Elizabeth R Doss
- University of Alabama Health Services Foundation, Birmingham, USA
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23
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Savelieff MG, Elafros MA, Viswanathan V, Jensen TS, Bennett DL, Feldman EL. The global and regional burden of diabetic peripheral neuropathy. Nat Rev Neurol 2025; 21:17-31. [PMID: 39639140 DOI: 10.1038/s41582-024-01041-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/29/2024] [Indexed: 12/07/2024]
Abstract
Diabetic peripheral neuropathy (DPN) is length-dependent peripheral nerve damage arising as a complication of type 1 or type 2 diabetes in up to 50% of patients. DPN poses a substantial burden on patients, who can experience impaired gait and loss of balance, predisposing them to falls and fractures, and neuropathic pain, which is frequently difficult to treat and reduces quality of life. Advanced DPN can lead to diabetic foot ulcers and non-healing wounds that often necessitate lower-limb amputation. From a socioeconomic perspective, DPN increases both direct health-care costs and indirect costs from loss of productivity owing to neuropathy-related disability. In this Review, we highlight the importance of understanding country-specific and region-specific variations in DPN prevalence to inform public health policy and allocate resources appropriately. We also explore how identification of DPN risk factors can guide treatment and prevention strategies and aid the development of health-care infrastructure for populations at risk. We review evidence that metabolic factors beyond hyperglycaemia contribute to DPN development, necessitating a shift from pure glycaemic control to multi-targeted metabolic control, including weight loss and improvements in lipid profiles.
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Affiliation(s)
- Masha G Savelieff
- Department of Biomedical Sciences, University of North Dakota, Grand Forks, ND, USA
| | - Melissa A Elafros
- Department of Neurology, University of Michigan, Ann Arbor, MI, USA
- NeuroNetwork for Emerging Therapies, University of Michigan, Ann Arbor, MI, USA
| | - Vijay Viswanathan
- MV Hospital for Diabetes and Prof. M. Viswanathan Diabetes Research Centre, Royapuram, Chennai, India
| | - Troels S Jensen
- Department of Neurology, Aarhus University Hospital, Aarhus, Denmark
- Danish Pain Research Center, Aarhus University, Aarhus, Denmark
| | - David L Bennett
- Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford, UK
| | - Eva L Feldman
- Department of Neurology, University of Michigan, Ann Arbor, MI, USA.
- NeuroNetwork for Emerging Therapies, University of Michigan, Ann Arbor, MI, USA.
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24
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Peng L, Tian Y, Wu X, Liu F, Zhou M, Wu Z, Xia Y, Liu X, Cheng C. Suppression of TRIM72-mediated endoplasmic reticulum stress facilitates FOXM1 promotion of diabetic ulcer healing. Wound Repair Regen 2025; 33:e13247. [PMID: 39721954 PMCID: PMC11669624 DOI: 10.1111/wrr.13247] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2024] [Revised: 11/09/2024] [Accepted: 12/10/2024] [Indexed: 12/28/2024]
Abstract
Foot ulcers are amongst the most prevalent complications of diabetes, known for their delayed healing process. Recent research indicates that the transcription factor forkhead box M1 (FOXM1) plays a role in promoting diabetic ulcer repair. However, the precise mechanisms underlying FOXM1 functions in this context remain unclear. This study aimed to clarify the role of tripartite motif-containing protein 72 (TRIM72)-mediated endoplasmic reticulum stress in FOXM1 promotive effects. Immunohistochemistry revealed that FOXM1 expression was significantly reduced in the lesion tissues of diabetic foot ulcer patients. In vitro experiments revealed a decrease in FOXM1 expression in cultured dermal fibroblasts under high glucose conditions. Activating FOXM1 with a plasmid accelerated the proliferation, migration, and differentiation of dermal fibroblasts and mitigated endoplasmic reticulum stress under high glucose conditions. Additionally, ChIP and luciferase reporter gene assays confirmed that FOXM1 suppressed TRIM72 expression transcriptionally by binding to its promoter. Furthermore, high glucose induced ubiquitination of adenosine 5'-monophosphate-activated protein kinase alpha (AMPKα), whilst inactivation of AMPKα signalling reversed the aforementioned effects of FOXM1 on cells. Finally, the FOXM1-overexpressing plasmid was transfected in vivo, which promoted wound healing in a murine diabetic ulcer model. In conclusion, FOXM1 reduces endoplasmic reticulum stress by inhibiting TRIM72-mediated AMPKα ubiquitination, thereby accelerating the healing of diabetic ulcers.
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Affiliation(s)
- Lingling Peng
- Department of DermatologyThe Second Affiliated Hospital of Xi'an Jiaotong UniversityXi'anChina
| | - Yaning Tian
- Department of DermatologyThe Second Affiliated Hospital of Xi'an Jiaotong UniversityXi'anChina
| | - Xiangkai Wu
- Department of HorticultureXinjiang Agricultural UniversityUrumqiChina
| | - Fengqi Liu
- Department of DermatologyThe Second Affiliated Hospital of Xi'an Jiaotong UniversityXi'anChina
| | - Mingzhu Zhou
- Department of DermatologyThe Second Affiliated Hospital of Xi'an Jiaotong UniversityXi'anChina
| | - Zixi Wu
- Wuhan Britain‐China International SchoolWuhanChina
| | - Yumin Xia
- Department of DermatologyThe Second Affiliated Hospital of Xi'an Jiaotong UniversityXi'anChina
| | - Xiaoming Liu
- Department of DermatologySouthern University of Science and Technology HospitalShenzhenChina
| | - Chuantao Cheng
- Department of DermatologyThe Second Affiliated Hospital of Xi'an Jiaotong UniversityXi'anChina
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25
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Meng L, Bishnoi P, Lo ZJ, Yong E, Chong TT, Carmody D, Dharmaraj RB, Ng YZ, Harding K, Ho P. A Multi-Center Prospective Study on the Healing of Neuro-Ischemic Ulcers in Singapore: A Prospective Cohort Study. Health Sci Rep 2025; 8:e70332. [PMID: 39867718 PMCID: PMC11758156 DOI: 10.1002/hsr2.70332] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2024] [Revised: 11/02/2024] [Accepted: 12/18/2024] [Indexed: 01/28/2025] Open
Abstract
Background and Aims Neuro-ischemic ulcers (NIU) present a substantial clinical and economic burden on the healthcare systems. This study aims to evaluate their healing rate, associated healthcare resource utilization, and prognostic factors influencing healing. Methods Consecutive patients attended specialist clinics or admitted to wards in three tertiary hospitals for new or existing NIUs from November 2019 to November 2021 were eligible for this study. Each participant was followed up three times (1-month, 3-month and 6-month after enrollment), with ulcer healing as the primary outcome of interest. Cox regression analysis was performed to identify independent predictors of NIU healing. Results In total, 439 patients were recruited. Six months after they seek care in the tertiary healthcare setting, 36.0% of the participants had their ulcer fully healed. Male gender (adjusted HR: 0.71, 95% CI: 0.53-0.93), history of coronary intervention (adjusted HR: 0.62; 95% CI: 0.41-0.93), requirement of lower extremity revascularization (adjusted HR: 0.72; 95% CI: 0.54-0.98) and offloading (adjusted HR: 0.61; 95% CI: 0.46-0.81) were found to be associated with failure to heal. Ulcers located over the toes (adjusted HR: 1.64; 95% CI: 1.17-2.32) was associated with better healing. Dependent activity of daily living (adjusted HR: 0.74; 95% CI: 0.55-1.01) was also potentially a risk factor for slow healing with borderline significance.Nonhealed group of patients incurred higher requirement of revascularization (42.3% vs. 25.3%, p < 0.001), negative pressure wound therapy (40.6% vs. 29.7%, p = 0.03), off-loading (57.3% vs. 46.8%, p = 0.04) and antibiotic treatment (45.2% vs. 26.6%, p < 0.001), compared to those in the healed group. Conclusion NIU imposes a significant burden on both patients and the healthcare system in Singapore, with low healing rates even after 6 months of tertiary-level care. Early identification and risk stratification of high-risk patients may help improve outcomes.
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Affiliation(s)
- Lingyan Meng
- Department of Cardiac, Thoracic and Vascular SurgeryNational University Health SystemSingaporeSingapore
| | - Priya Bishnoi
- Wound Care Innovation for the Tropics Programme, Skin Research Institute of Singapore, A*STARSingaporeSingapore
- A*STAR Skin Research LabsSingaporeSingapore
| | - Zhiwen Joseph Lo
- Centre for Population Health Sciences, Lee Kong Chian School of MedicineNanyang Technological UniversitySingaporeSingapore
- Department of General SurgeryWoodlands HealthSingaporeSingapore
| | - Enming Yong
- Vascular Surgery Service, Department of General SurgeryTan Tock Seng HospitalSingaporeSingapore
| | - Tze Tec Chong
- Department of Vascular SurgerySingapore General HospitalSingaporeSingapore
| | - David Carmody
- Department of EndocrinologySingapore General HospitalSingaporeSingapore
| | - Rajesh Babu Dharmaraj
- Department of Cardiac, Thoracic and Vascular SurgeryNational University Health SystemSingaporeSingapore
| | - Yi Zhen Ng
- Wound Care Innovation for the Tropics Programme, Skin Research Institute of Singapore, A*STARSingaporeSingapore
- A*STAR Skin Research LabsSingaporeSingapore
| | - Keith Harding
- Wound Care Innovation for the Tropics Programme, Skin Research Institute of Singapore, A*STARSingaporeSingapore
| | - Pei Ho
- Department of Cardiac, Thoracic and Vascular SurgeryNational University Health SystemSingaporeSingapore
- Department of EndocrinologySingapore General HospitalSingaporeSingapore
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26
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Yao Y, Chen L, Qian Y. Age Characteristics of Patients With Type 2 Diabetic Foot Ulcers and Predictive Risk Factors for Lower Limb Amputation: A Population-Based Retrospective Study. J Diabetes Res 2024; 2024:2380337. [PMID: 39735416 PMCID: PMC11671627 DOI: 10.1155/jdr/2380337] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2024] [Accepted: 10/26/2024] [Indexed: 12/31/2024] Open
Abstract
Background: Limited data are available about the epidemiological characteristics and the risk factors for amputation, particularly in developing countries from Asia, especially in China. Objective: We aim to investigate the age features of patients with Type 2 diabetic foot ulcers (DFUs) and analyze the critical influencing factors predicting lower extremity amputation and major amputation. Methods: Data were retrieved from the electric medical record system to identify patients aged > 18 years with Type 2 DFU from January 1, 2017, to December 31, 2023. A logistic regression model was adopted to analyze the risk factors for amputation and major amputation. Results: Nine hundred eighteen patients with Type 2 DFU were eligible for our study, 68.2% of whom were male. In patients with Type 2 diabetes in the hospitals we studied, the prevalence of Type 2 DFU was 1.07%. A majority of patients with DFU were in the 70-79 age group in the winter season, and deaths also peaked in this age group. A total of 38.8% of patients aged 50-59 years underwent amputation. Vascular CTA, complications, history of amputation, and infection sites were the important contributing factors in patients with DFU lower extremity amputation. History of amputation and hemoglobin were the main influencing factors of patients with major amputation resulting from DFU. Conclusion: Most patients with DFU were in the age group of 50-59 years, but the majority of deaths occurred in the 70-79-year age group. Several factors influence the amputation, and those findings provide new insights into the relationship between the severity of narrowed blood vessels and the likelihood of amputation.
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Affiliation(s)
- Yuanying Yao
- Department of Medical Record Management, The First Affiliated Hospital of Wannan Medical College 241000, Wuhu, China
| | - Lei Chen
- Department of Burn and Plastic Surgery, The First Affiliated Hospital of Wannan Medical College 241000, Wuhu, China
| | - Yu Qian
- Department of Ultrasound Medicine, The First Affiliated Hospital of Wannan Medical College 241000, Wuhu, China
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27
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Lan NSR, Dwivedi G, Fegan PG, Game F, Hamilton EJ. Unravelling the cardio-renal-metabolic-foot connection in people with diabetes-related foot ulceration: a narrative review. Cardiovasc Diabetol 2024; 23:437. [PMID: 39696281 PMCID: PMC11657306 DOI: 10.1186/s12933-024-02527-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2024] [Accepted: 11/26/2024] [Indexed: 12/20/2024] Open
Abstract
Diabetes-related foot ulceration (DFU), a serious but preventable complication of diabetes, is a leading cause of hospitalisation, lower extremity amputation and disability worldwide. People with DFU have a greater burden of cardiovascular risk factors, heart failure and chronic kidney disease, resulting in over two-fold higher risk of cardiovascular death compared with people with diabetes without DFU. Here, we propose a "cardio-renal-metabolic-foot" connection in people with diabetes based on shared pathophysiological mechanisms linking DFU with cardiovascular and renal disease. Whilst these mechanistic links remain to be fully elucidated, systemic inflammation and infection in the context of DFU are postulated as key mediators in the development, and progression of, cardiovascular and renal disease. However, cardiovascular and renal disease are also implicated in the pathogenesis of DFU, highlighting the multi-directional interplay between conditions. The impact of screening, prevention, and early management of cardiovascular complications associated with DFU requires further research. Multi-modality cardiac imaging could play a role in unravelling disease mechanisms leading to novel therapeutic strategies, as well as facilitating personalised risk assessment and management. Recent clinical trials have transformed the therapeutic landscape for people with type 2 diabetes, by demonstrating that sodium glucose co-transporter 2 inhibitors, glucagon-like peptide-1 agonists and non-steroidal mineralocorticoid receptor antagonists improve cardiovascular and renal outcomes. Although dedicated research in people with DFU is warranted, these therapies could target multiple facets of the "cardio-renal-metabolic-foot" connection. The holistic, person-centred approach to managing DFU should incorporate new multidisciplinary models of care focusing on the prevention and management of cardiovascular and kidney disease.
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Affiliation(s)
- Nick S R Lan
- Centre of Excellence for Cardiometabolic Health, Fiona Stanley Hospital, Perth, Australia
- Department of Cardiology, Fiona Stanley Hospital, Perth, Australia
- Medical School, The University of Western Australia, Perth, Australia
- Harry Perkins Institute of Medical Research, Perth, Australia
| | - Girish Dwivedi
- Centre of Excellence for Cardiometabolic Health, Fiona Stanley Hospital, Perth, Australia
- Department of Cardiology, Fiona Stanley Hospital, Perth, Australia
- Medical School, The University of Western Australia, Perth, Australia
- Harry Perkins Institute of Medical Research, Perth, Australia
| | - P Gerry Fegan
- Centre of Excellence for Cardiometabolic Health, Fiona Stanley Hospital, Perth, Australia
- Medical School, Curtin University, Perth, Australia
- Department of Endocrinology and Diabetes, Fiona Stanley Hospital, Perth, Australia
| | - Fran Game
- Department of Diabetes and Endocrinology, University Hospitals of Derby and Burton NHS Foundation Trust, Derby, UK
| | - Emma J Hamilton
- Medical School, The University of Western Australia, Perth, Australia.
- Department of Endocrinology and Diabetes, Fiona Stanley Hospital, Perth, Australia.
- Centre of Excellence Multidisciplinary Diabetes Foot Ulcer Service, Fiona Stanley and Fremantle Hospitals Group, 11 Robin Warren Drive, Murdoch, Perth, Australia.
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28
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Madaan T, Doan K, Hartman A, Gherardini D, Ventrola A, Zhang Y, Kotagiri N. Advances in Microbiome-Based Therapeutics for Dermatological Disorders: Current Insights and Future Directions. Exp Dermatol 2024; 33:e70019. [PMID: 39641544 PMCID: PMC11663288 DOI: 10.1111/exd.70019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2024] [Revised: 10/30/2024] [Accepted: 11/19/2024] [Indexed: 12/07/2024]
Abstract
The human skin hosts an estimated 1000 bacterial species that are essential for maintaining skin health. Extensive clinical and preclinical studies have established the significant role of the skin microbiome in dermatological disorders such as atopic dermatitis, psoriasis, diabetic foot ulcers, hidradenitis suppurativa and skin cancers. In these conditions, the skin microbiome is not only altered but, in some cases, implicated in disease pathophysiology. Microbiome-based therapies (MBTs) represent an emerging category of live biotherapeutic products with tremendous potential as a novel intervention platform for skin diseases. Beyond using established wild-type strains native to the skin, these therapies can be enhanced to express targeted therapeutic molecules, offering more tailored treatment approaches. This review explores the role of the skin microbiome in various common skin disorders, with a particular focus on the development and therapeutic potential of MBTs for treating these conditions.
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Affiliation(s)
- Tushar Madaan
- James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, OH 45267
| | - Kyla Doan
- James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, OH 45267
| | - Alexandra Hartman
- James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, OH 45267
| | - Dominick Gherardini
- James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, OH 45267
| | - Alec Ventrola
- James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, OH 45267
| | - Yuhang Zhang
- James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, OH 45267
| | - Nalinikanth Kotagiri
- James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, OH 45267
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29
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Luo W, Zhou Q, Xu J, Tan Z, Li X, Ye Y, Wang H, Peng S. Development and validation of a brief diabetic foot risk screening scale for diabetic patients. INTERNATIONAL JOURNAL OF NURSING STUDIES ADVANCES 2024; 7:100230. [PMID: 39399391 PMCID: PMC11470238 DOI: 10.1016/j.ijnsa.2024.100230] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2024] [Revised: 07/23/2024] [Accepted: 08/01/2024] [Indexed: 10/15/2024] Open
Abstract
Objective To develop a concise screening tool for diabetic foot risk assessment in patients with diabetes, and rigorously evaluate its reliability and validity. Methods 390 adults diagnosed with diabetes were selected for a study in Changsha, China. The study was conducted in two phases. In the first phase, initial items were developed by amalgamating existing diabetic foot risk screening tools and group discussions. Additionally, diabetic foot experts established content validity during this phase. In the second phase, the validity and reliability of the developed items were evaluated through various methods such as item analysis, exploratory factor analysis, confirmatory factor analysis, Cronbach's alpha coefficient, retest reliability, inter-rater reliability, ROC curve and AUC. Results The Brief Diabetic Foot Risk Screening Scale consists of 6 dimensions and 19 items. An exploratory factor analysis was conducted on the scale, revealing six principal factors that accounted for 74.139 % of the total variance. The I-CVI was greater than 0.8, indicating good content validity, while the S-CVI was 0.737. Confirmatory factor analysis showed that the model fit well. The scale's Cronbach's α coefficient was 0.770, indicating good internal consistency, and its test-retest reliability was 0.958. The AUC suggests that the Brief Diabetic Foot Risk Screening Scale is an effective measure for identifying diabetic foot. Conclusion The Scale is a reliable and valid tool for assessing foot risk.
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Affiliation(s)
- Wenjing Luo
- Division of Abdominal Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, China
- Teaching and Research Section of Clinical Nursing, Xiangya Hospital of Central South University, Changsha, China
| | - Qiuhong Zhou
- Teaching and Research Section of Clinical Nursing, Xiangya Hospital of Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Jingcan Xu
- Teaching and Research Section of Clinical Nursing, Xiangya Hospital of Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Zheyu Tan
- Teaching and Research Section of Clinical Nursing, Xiangya Hospital of Central South University, Changsha, China
| | - Xinyi Li
- Teaching and Research Section of Clinical Nursing, Xiangya Hospital of Central South University, Changsha, China
| | - Ying Ye
- Teaching and Research Section of Clinical Nursing, Xiangya Hospital of Central South University, Changsha, China
- Xiangya School of Nursing, Central South University, Changsha, China
| | - Honglin Wang
- Teaching and Research Section of Clinical Nursing, Xiangya Hospital of Central South University, Changsha, China
- Xiangya School of Nursing, Central South University, Changsha, China
| | - Shuyi Peng
- Xiangya School of Nursing, Central South University, Changsha, China
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30
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Luo W, Li N, Liu J, Li D, Li Y, Ma Q, Lin C, Lu L, Lin S. Bulk and Single-Cell Transcriptome Analyses Unravel Gene Signatures of Mitochondria-Associated Programmed Cell Death in Diabetic Foot Ulcer. J Cell Mol Med 2024; 28:e70319. [PMID: 39730319 DOI: 10.1111/jcmm.70319] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Revised: 12/05/2024] [Accepted: 12/13/2024] [Indexed: 12/29/2024] Open
Abstract
Mitochondrial programmed cell death (PCD) plays a critical role in the pathogenesis of diabetic foot ulcers (DFU). In this study, we performed a comprehensive transcriptome analysis to identify potential hub genes and key cell types associated with PCD and mitochondria in DFU. Using intersection analysis of PCD- and mitochondria-related genes, we identified candidate hub genes through protein-protein interaction and random forest analysis. At the single-cell level, key cell types were further validated based on the expression of hub genes. Additionally, we explored the transcription factors (TFs) regulating hub gene expression and the cellular heterogeneity of DFU. Finally, the expression of key hub genes and TFs was validated in clinical specimens. Our results identified BCL2 and LIPT1 as significantly downregulated hub genes in DFU, with Keratinocytes, as the key cell type. Immunohistochemistry confirmed downregulation of BCL2 and LIPT1 in DFU samples (p < 0.05). Additionally, TFs CEBPD and IRF1 were significantly upregulated in DFU, as confirmed by real-time polymerase chain reaction analysis (p < 0.05).
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Affiliation(s)
- Wenqiang Luo
- Department of Orthopedics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, P. R. China
| | - Ning Li
- Department of Orthopedics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, P. R. China
| | - Jin Liu
- Department of Orthopedics, Shenshan Medical Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Shanwei, Guangdong, P. R. China
- Guangdong Provincial Key Laboratory of Cancer Pathogenesis and Precision Diagnosis and Treatment, Shanwei, Guangdong, P. R. China
| | - Duoyu Li
- Department of Orthopedics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, P. R. China
| | - Yongheng Li
- Department of Orthopedics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, P. R. China
| | - Qing Ma
- Department of Orthopedics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, P. R. China
| | - Chuangxin Lin
- Department of Orthopedic Surgery, Shantou Central Hospital, Shantou, P. R. China
| | - Liang Lu
- Department of Orthopedics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, P. R. China
| | - Sipeng Lin
- Department of Orthopedics, Shenshan Medical Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Shanwei, Guangdong, P. R. China
- Guangdong Provincial Key Laboratory of Cancer Pathogenesis and Precision Diagnosis and Treatment, Shanwei, Guangdong, P. R. China
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Cheng L, Zhuang Z, Yin M, Lu Y, Liu S, Zhan M, Zhao L, He Z, Meng F, Tian S, Luo L. A microenvironment-modulating dressing with proliferative degradants for the healing of diabetic wounds. Nat Commun 2024; 15:9786. [PMID: 39532879 PMCID: PMC11557877 DOI: 10.1038/s41467-024-54075-7] [Citation(s) in RCA: 15] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2024] [Accepted: 10/31/2024] [Indexed: 11/16/2024] Open
Abstract
Diabetic wounds are usually entangled in a disorganized and self-perpetuating microenvironment and accompanied by a prolonged delay in tissue repair. Sustained and coordinated microenvironment regulation and tissue regeneration are key to the healing process of diabetic wounds, yet they continue to pose a formidable challenge. Here we report a rational double-layered dressing design based on chitosan and a degradable conjugated polymer polydiacetylene, poly(deca-4,6-diynedioic acid) (PDDA), that can meet this intricate requirement. With an alternating ene-yne backbone, PDDA degrades when reacting with various types of reactive oxygen species (ROS), and more importantly, generates proliferative succinic acid as a major degradant. Inheriting from PDDA, the developed PDDA-chitosan double layer dressing (PCD) can eliminate ROS in the microenvironment of diabetic wounds, alleviate inflammation, and downregulate gene expression of innate immune receptors. PCD degradation also triggers simultaneous release of succinic acid in a sustainable manner, enabling long-term promotion on tissue regeneration. We have validated the biocompatibility and excellent performance of PCD in expediting the wound healing on both diabetic mouse and porcine models, which underscores the significant translational potential of this microenvironment-modulating, growth-promoting wound dressing in diabetic wounds care.
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Affiliation(s)
- Lianghui Cheng
- National Engineering Research Center for Nanomedicine and Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China
| | - Zhiyong Zhuang
- National Engineering Research Center for Nanomedicine and Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China
| | - Mingming Yin
- National Engineering Research Center for Nanomedicine and Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China
| | - Yuan Lu
- National Engineering Research Center for Nanomedicine and Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China
| | - Sujuan Liu
- National Engineering Research Center for Nanomedicine and Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China
| | - Minle Zhan
- National Engineering Research Center for Nanomedicine and Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China
| | - Liyuan Zhao
- National Engineering Research Center for Nanomedicine and Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China
| | - Zhenyan He
- National Engineering Research Center for Nanomedicine and Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China
| | - Fanling Meng
- National Engineering Research Center for Nanomedicine and Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
- Hubei Key Laboratory of Bioinformatics and Molecular Imaging, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
- Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, Wuhan, China.
| | - Sidan Tian
- National Engineering Research Center for Nanomedicine and Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
- Hubei Key Laboratory of Bioinformatics and Molecular Imaging, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
| | - Liang Luo
- National Engineering Research Center for Nanomedicine and Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
- Hubei Key Laboratory of Bioinformatics and Molecular Imaging, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
- Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, Wuhan, China.
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Metaoy S, Rusu I, Pillai A. Microbial profile of diabetic foot osteomyelitis from the northwest of England. Clin Diabetes Endocrinol 2024; 10:35. [PMID: 39516954 PMCID: PMC11549820 DOI: 10.1186/s40842-024-00193-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2024] [Accepted: 06/26/2024] [Indexed: 11/16/2024] Open
Abstract
BACKGROUND Osteomyelitis of the diabetic foot is a common and challenging complication affecting patients with diabetic foot ulcers and infections. The complexity of these infections lies in their polymicrobial nature, high rates of persistence and recurrence. This study examined the microbiological profile of diabetic foot osteomyelitis from a teaching hospital in Northwest England and their resistance patterns to understand its impact on infection persistence and to direct effective treatment. METHODS A retrospective review of 105 patients who underwent surgical management for diabetic foot osteomyelitis between 2019 and 2024. We analysed three consecutive culture samples for each patient to assess for the microbiological profile and resistance patterns of these infections and to monitor infection recurrence and persistence rates. RESULTS A total of 105 patients were identified. Infection eradication was noted in 42% of the cohort, infection persistence in 18%, and late infection recurrence in 40%. Polymicrobial growth was evident in 72% of our study sample. Gram-positive bacteria made up the majority of the bacterial isolates in all 3 culture samples, 74.81% in sample 1, 69.31% in sample 2, and 55.1% in sample 3. Staphylococcus aureus was the most prevalent gram-positive bacteria, at 52.38% in sample 1, 36.19% in sample 2, and 18.09% in sample 3, followed by Haemolytic Streptococcus, Enterococcus and Corynebacterium. The frequently identified gram-negative bacteria were Pseudomonas in sample 1 (7.61%), E. coli and Proteus in sample 2 (5,71%), Pseudomonas and Proteus in sample 3 (2.85%). Gram-positive bacteria were resistant to penicillin and macrolides with resistance of staphylococcus aureus to clarithromycin identified among all 3 culture samples. Gram-negative bacteria were most resistant to amoxicillin. Staphylococcus aureus was responsible for infection persistence in most of our cohort (12/19) 63.15%. Among those patients, Staphylococcus was resistant to clarithromycin in 6 of the cases. The 5-year mortality rate for our study sample was 32.38%. CONCLUSION This study highlights the prevalence of polymicrobial growth and multi-drug resistant pathogens in the scope of diabetic foot osteomyelitis. It highlights the predominance of Staphylococcus aureus and its resistant strains among patients affected by diabetic foot osteomyelitis in Greater Manchester.
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Affiliation(s)
- Sara Metaoy
- University of Manchester, Manchester, UK.
- Wythenshawe Hospital Manchester, Wythenshawe, UK.
| | - Iulia Rusu
- University of Manchester, Manchester, UK
| | - Anand Pillai
- University of Manchester, Manchester, UK
- Wythenshawe Hospital Manchester, Wythenshawe, UK
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Ge L, Ang YG, Molina J, Sun Y, Tan E, Liew H, Hoe J, Hui Xian Lin J, Koo HY, Low KQ, Choo J, Yap T, Bte Azmi NAS, Tan D, Loh YB, Zhu X, Yong E, Hong Q, Chew T, Chan DYS, Shi C, Law C, Hoi WH, Siow J, Lim JA, Abisheganaden JA, Chew D, Lo ZJ. Investigating Nonadherence in an Integrated Diabetic Limb Salvage Programme: Reasons, Associated Factors, and Impacts on Care Outcomes. INT J LOW EXTR WOUND 2024:15347346241294178. [PMID: 39497533 DOI: 10.1177/15347346241294178] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
Adherence to treatment plans is crucial for patients with diabetic foot ulcers (DFUs) to achieve positive outcomes. With limited understanding of nonadherence and its impacts on care outcomes, this study aimed to explore the reasons and factors associated with nonadherence in an integrated diabetic limb salvage (DLS) programme and evaluate its effects on care outcomes. This study included 2798 DFU patients who were enrolled in an integrated DLS programme across multiple institutions in central and northern Singapore from 2020 to 2021. Reasons for nonadherence were obtained via telephone interviews. Factors associated with nonadherence were identified using multiple logistic regression. Differences in one-year outcomes, including minor and major lower extremity amputation (LEA), mortality, LEA-free survival, and healthcare utilisation between adherent and nonadherent patients, were examined based on a significance level of P < .05. Nonadherence was observed in 40.2% of patients, with higher rates among younger patients, Malays and Indians, and those with higher HbA1c levels. Patient-related factors were the most commonly reported reasons for missed appointments (50.4%). Compared to adherent patients, nonadherent patients exhibited a relatively higher minor LEA rate (13.0% vs 10.2%, OR = 1.18, 95% CI: 0.93, 1.51), lower mortality rate (8.6% vs18.1%, OR = 0.50, 95% CI: 0.39, 0.65), higher overall LEA-free survival (76.4% vs 71.1%, OR = 1.27, 95% CI: 1.06, 1.53), and more hospitalisations (IRR = 1.22, 95% CI: 1.11, 1.33) and emergency visits (IRR = 1.27, 95% CI: 1.16, 1.39). While nonadherent patients showed relatively higher minor LEA rates and more healthcare utilisation, they also exhibited lower mortality and higher LEA-free survival. This suggests that nonadherence in this population may be associated with complex patient characteristics and behaviours that warrant further investigation to tailor interventions effectively.
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Affiliation(s)
- Lixia Ge
- Health Services and Outcomes Research, National Healthcare Group, Singapore, Singapore
| | - Yee Gary Ang
- Health Services and Outcomes Research, National Healthcare Group, Singapore, Singapore
| | - Joseph Molina
- Health Services and Outcomes Research, National Healthcare Group, Singapore, Singapore
| | - Yan Sun
- Health Services and Outcomes Research, National Healthcare Group, Singapore, Singapore
| | - Elaine Tan
- National Healthcare Group Polyclinics, Singapore, Singapore
| | - Huiling Liew
- Department of Endocrinology, Tan Tock Seng Hospital, Singapore, Singapore
| | - Jeremy Hoe
- Department of General Medicine, Khoo Teck Puat Hospital, Singapore
| | | | - Hui Yan Koo
- Group Integrated Care, National Healthcare Group, Singapore, Singapore
| | - Kai Qiang Low
- Group Integrated Care, National Healthcare Group, Singapore, Singapore
| | - Julia Choo
- Group Integrated Care, National Healthcare Group, Singapore, Singapore
| | - Theophilus Yap
- Group Integrated Care, National Healthcare Group, Singapore, Singapore
| | | | - Donna Tan
- National Healthcare Group Polyclinics, Singapore, Singapore
| | - Yi Bing Loh
- National Healthcare Group Polyclinics, Singapore, Singapore
| | - Xiaoli Zhu
- National Healthcare Group Polyclinics, Singapore, Singapore
| | - Enming Yong
- Department of General Surgery, Tan Tock Seng Hospital, Singapore, Singapore
| | - Qiantai Hong
- Department of General Surgery, Tan Tock Seng Hospital, Singapore, Singapore
| | - Tiffany Chew
- Department of Podiatry, Tan Tock Seng Hospital, Singapore, Singapore
| | - Dexter Yak Seng Chan
- Vascular Surgery Service, Department of General Surgery, Khoo Teck Puat Hospital, Singapore, Singapore
| | - Claris Shi
- Department of Orthopaedic Surgery, Khoo Teck Puat Hospital, Singapore, Singapore
| | - Chelsea Law
- Department of Podiatry, Khoo Teck Puat Hospital, Singapore, Singapore
| | - Wai Han Hoi
- Department of Endocrinology, Woodlands Health, Singapore, Singapore
| | - James Siow
- Department of Orthopaedic Surgery, Woodlands Health, Singapore, Singapore
| | - Jo Ann Lim
- Department of Podiatry, Woodlands Health, Singapore, Singapore
| | | | - Daniel Chew
- Department of Endocrinology, Tan Tock Seng Hospital, Singapore, Singapore
| | - Zhiwen Joseph Lo
- Vascular Surgery Service, Department of Surgery, Woodlands Health, Singapore, Singapore
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
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Reed AJM, Lim NTY, Yip SWL, Thurley N, Wormald JCR, Rodrigues JN, Shirley RA, Chan JKK. Outcomes of Flap Reconstruction for Diabetic Foot Ulcers: A Systematic Review and Meta-Analysis of Clinical Studies. Plast Reconstr Surg 2024; 154:1118-1130. [PMID: 38334716 DOI: 10.1097/prs.0000000000011231] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/10/2024]
Abstract
BACKGROUND People with diabetic foot ulcers (DFUs) are at risk of major amputation, which is associated with a high mortality rate (exceeding 50% at 5 years) and reduced quality of life. The authors hypothesized that flap reconstruction of DFUs improves patient outcomes in comparison with standard treatment modalities, including major amputation. METHODS MEDLINE, Embase, the Cochrane Library, and gray literature were searched on February 9, 2022. Comparative and single-arm studies reporting outcomes of DFUs treated with local, regional, or free flaps that included function, limb loss, mortality rates, and flap failure rates were included. Risk of bias was assessed, and meta-analysis of proportions was performed. RESULTS A total of 3878 records were retrieved, of which 45 met the inclusion criteria, including the records of 1681 patients who underwent flap reconstruction of DFUs. Free flaps were most commonly performed ( n = 1257 [72%]). Only one study used a verified functional outcome measure. At 12 months, the mortality rate was 6.35% (95% CI, 3.89% to 10.20%), the limb loss rate was 11.39% (95% CI, 7.02% to 17.96%), and the free flap failure rate was 9.95% (95% CI, 8.19% to 12.05%). All studies were at high risk of bias. A comparative meta-analysis of interventions was not performed because of study method and outcome heterogeneity. CONCLUSIONS There is short-term evidence that flap reconstruction (including microsurgical transfer) has low mortality, limb loss, and flap failure rates. However, there are limited high-quality comparative studies, and uncertainty remains regarding the outcome of DFU flap reconstruction in comparison to other treatments.
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Affiliation(s)
- Alistair J M Reed
- From the Department of Plastic and Reconstructive Surgery, Stoke Mandeville Hospital, Buckinghamshire Healthcare NHS Trust
| | - Nicole T Y Lim
- From the Department of Plastic and Reconstructive Surgery, Stoke Mandeville Hospital, Buckinghamshire Healthcare NHS Trust
| | | | | | - Justin C R Wormald
- Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences, University of Oxford
| | - Jeremy N Rodrigues
- From the Department of Plastic and Reconstructive Surgery, Stoke Mandeville Hospital, Buckinghamshire Healthcare NHS Trust
- Warwick Clinical Trials Unit, Warwick Medical School
| | - Rebecca Anna Shirley
- From the Department of Plastic and Reconstructive Surgery, Stoke Mandeville Hospital, Buckinghamshire Healthcare NHS Trust
| | - James K K Chan
- From the Department of Plastic and Reconstructive Surgery, Stoke Mandeville Hospital, Buckinghamshire Healthcare NHS Trust
- Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences, University of Oxford
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Wang L, Wang C, Huang C, Zhou Z, Yang R, Huang Y, Chen Z, Zhang Y, Wang S, Feng K. Role of microRNAs in diabetic foot ulcers: Mechanisms and possible interventions. Diabetes Res Clin Pract 2024; 217:111858. [PMID: 39284457 DOI: 10.1016/j.diabres.2024.111858] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2024] [Revised: 08/24/2024] [Accepted: 09/13/2024] [Indexed: 09/21/2024]
Abstract
Diabetic foot ulcer (DFU) is a common and serious complication among diabetic patients, and its incidence and difficulty in treatment have placed large burdens on patient health and quality of life. Diabetic foot tissue typically exhibits chronic wounds, ulcers, or necrosis that are difficult to heal, are prone to infection, and, in severe cases, may even lead to amputation. Recent studies have shown that microRNAs (miRNAs) play key roles in the development and healing of DFUs. miRNAs are a class of short noncoding RNA molecules that regulate gene expression to affect cellular functions and physiological processes. miRNAs may be involved in the development of DFUs by regulating cell growth, proliferation, differentiation and apoptosis. miRNAs can also participate in the healing and recovery of DFUs by regulating key steps, such as inflammation, angiogenesis, cell migration and proliferation, tissue repair and matrix remodeling. Therefore, altering the pathological processes of diabetic foot by modulating the expression of miRNAs could improve the recovery and treatment outcomes of patients. This review provides new insights and perspectives for the treatment of DFUs by summarizing the roles of miRNAs in the development and healing of DFUs and the mechanisms.
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Affiliation(s)
- Lin Wang
- Pingshan District People's Hospital of Shenzhen, Pingshan General Hospital of Southern Medical University, Shenzhen 518118, Guangdong, China
| | - Cong Wang
- Pingshan District People's Hospital of Shenzhen, Pingshan General Hospital of Southern Medical University, Shenzhen 518118, Guangdong, China
| | - Caiyan Huang
- Pingshan District People's Hospital of Shenzhen, Pingshan General Hospital of Southern Medical University, Shenzhen 518118, Guangdong, China
| | - Zhongyu Zhou
- Pingshan District People's Hospital of Shenzhen, Pingshan General Hospital of Southern Medical University, Shenzhen 518118, Guangdong, China
| | - Ruihong Yang
- Pingshan District People's Hospital of Shenzhen, Pingshan General Hospital of Southern Medical University, Shenzhen 518118, Guangdong, China
| | - Ying Huang
- Pingshan District People's Hospital of Shenzhen, Pingshan General Hospital of Southern Medical University, Shenzhen 518118, Guangdong, China
| | - Zhuangsen Chen
- Pingshan District People's Hospital of Shenzhen, Pingshan General Hospital of Southern Medical University, Shenzhen 518118, Guangdong, China
| | - Yanrong Zhang
- Pingshan District People's Hospital of Shenzhen, Pingshan General Hospital of Southern Medical University, Shenzhen 518118, Guangdong, China
| | - Shanshan Wang
- Pingshan District People's Hospital of Shenzhen, Pingshan General Hospital of Southern Medical University, Shenzhen 518118, Guangdong, China
| | - Kun Feng
- Pingshan District People's Hospital of Shenzhen, Pingshan General Hospital of Southern Medical University, Shenzhen 518118, Guangdong, China.
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Anbarasi LJ, Jawahar M, Jayakumari RB, Narendra M, Ravi V, Neeraja R. An overview of current developments and methods for identifying diabetic foot ulcers: A survey. WIRES DATA MINING AND KNOWLEDGE DISCOVERY 2024; 14. [DOI: 10.1002/widm.1562] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/14/2024] [Accepted: 09/04/2024] [Indexed: 01/06/2025]
Abstract
AbstractDiabetic foot ulcers (DFUs) present a substantial health risk across diverse age groups, creating challenges for healthcare professionals in the accurate classification and grading. DFU plays a crucial role in automated health monitoring and diagnosis systems, where the integration of medical imaging, computer vision, statistical analysis, and gait information is essential for comprehensive understanding and effective management. Diagnosing DFU is imperative, as it plays a major role in the processes of diagnosis, treatment planning, and neuropathy research within automated health monitoring and diagnosis systems. To address this, various machine learning and deep learning‐based methodologies have emerged in the literature to support healthcare practitioners in achieving improved diagnostic analyses for DFU. This survey paper investigates various diagnostic methodologies for DFU, spanning traditional statistical approaches to cutting‐edge deep learning techniques. It systematically reviews key stages involved in diabetic foot ulcer classification (DFUC) methods, including preprocessing, feature extraction, and classification, explaining their benefits and drawbacks. The investigation extends to exploring state‐of‐the‐art convolutional neural network models tailored for DFUC, involving extensive experiments with data augmentation and transfer learning methods. The overview also outlines datasets commonly employed for evaluating DFUC methodologies. Recognizing that neuropathy and reduced blood flow in the lower limbs might be caused by atherosclerotic blood vessels, this paper provides recommendations to researchers and practitioners involved in routine medical therapy to prevent substantial complications. Apart from reviewing prior literature, this survey aims to influence the future of DFU diagnostics by outlining prospective research directions, particularly in the domains of personalized and intelligent healthcare. Finally, this overview is to contribute to the continual evolution of DFU diagnosis in order to provide more effective and customized medical care.This article is categorized under:
Application Areas > Health Care
Technologies > Machine Learning
Technologies > Artificial Intelligence
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Affiliation(s)
- L. Jani Anbarasi
- School of Computer Science and Engineering Vellore Institute of Technology Chennai India
| | - Malathy Jawahar
- Leather Process Technology Division CSIR‐Central Leather Research Institute Chennai India
| | | | - Modigari Narendra
- School of Computer Science and Engineering Vellore Institute of Technology Chennai India
| | - Vinayakumar Ravi
- Center for Artificial Intelligence Prince Mohammad Bin Fahd University Khobar Saudi Arabia
| | - R. Neeraja
- School of Computer Science and Engineering Vellore Institute of Technology Chennai India
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Xiaoling W, Shengmei Z, BingQian W, Wen L, Shuyan G, Hanbei C, Chenjie Q, Yao D, Jutang L. Enhancing diabetic foot ulcer prediction with machine learning: A focus on Localized examinations. Heliyon 2024; 10:e37635. [PMID: 39386877 PMCID: PMC11462210 DOI: 10.1016/j.heliyon.2024.e37635] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2024] [Revised: 09/03/2024] [Accepted: 09/06/2024] [Indexed: 10/12/2024] Open
Abstract
Background diabetices foot ulcer (DFU) are serious complications. It is crucial to detect and diagnose DFU early in order to provide timely treatment, improve patient quality of life, and avoid the social and economic consequences. Machine learning techniques can help identify risk factors associated with DFU development. Objective The aim of this study was to establish correlations between clinical and biochemical risk factors of DFU through local foot examinations based on the construction of predictive models using automated machine learning techniques. Methods The input dataset consisted of 566 diabetes cases and 50 DFU risk factors, including 9 local foot examinations. 340 patients with Class 0 labeling (low-risk DFU), 226 patients with Class 1 labeling (high-risk DFU). To divide the training group (consisting of 453 cases) and the validation group (consisting of 113 cases), as well as preprocess the data and develop a prediction model, a Monte Carlo cross-validation approach was employed. Furthermore, potential high-risk factors were analyzed using various algorithms, including Bayesian BYS, Multi-Gaussian Weighted Classifier (MGWC), Support Vector Machine (SVM), and Random Forest Classifier (RF). A three-layer machine learning training was constructed, and model performance was estimated using a Confusion Matrix. The top 30 ranking feature variables were ultimately determined. To reinforce the robustness and generalizability of the predictive model, an independent dataset comprising 248 cases was employed for external validation. This validation process evaluated the model's applicability and reliability across diverse populations and clinical settings. Importantly, the external dataset required no additional tuning or adjustment of parameters, enabling an unbiased assessment of the model's generalizability and its capacity to predict the risk of DFU. Results The ensemble learning method outperformed individual classifiers in various performance evaluation metrics. Based on the ROC analysis, the AUC of the AutoML model for assessing diabetic foot risk was 88.48 % (74.44-97.83 %). Other results were found to be as follows: 87.23 % (63.33 %-100.00 %) for sensitivity, 87.43 % (70.00 %-100.00 %) for specificity, 87.33 % (76.66 %-95.00 %) for accuracy, 87.69 % (75.00 %-100.00 %) for positive predictive value, and 87.70 % (71.79 %-100.00 %) for negative predictive value. In addition to traditional DFU risk factors such as cardiovascular disorders, peripheral artery disease, and neurological damage, we identified new risk factors such as lower limb varicose veins, history of cerebral infarction, blood urea nitrogen, GFR (Glomerular Filtration Rate), and type of diabetes that may be related to the development of DFU. In the external validation set of 158 samples, originating from an initial 248 with exclusions due to missing labels or features, the model still exhibited strong predictive accuracy. The AUC score of 0.762 indicated a strong discriminatory capability of the model. Furthermore, the Sensitivity and Specificity values provided insights into the model's ability to correctly identify both DFU cases and non-cases, respectively. Conclusion The predictive model, developed through AutoML and grounded in local foot examinations, has proven to be a robust and practical instrument for the screening, prediction, and diagnosis of DFU risk. This model not only aids medical practitioners in the identification of potential DFU cases but also plays a pivotal role in mitigating the progression towards adverse outcomes. And the recent successful external validation of our DFU risk prediction model marks a crucial advancement, indicating its readiness for clinical application. This validation reinforces the model's efficacy as an accessible and reliable tool for early DFU risk assessment, thereby facilitating prompt intervention strategies and enhancing overall patient outcomes.
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Affiliation(s)
- Wang Xiaoling
- Department of Endocrinology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
| | - Zhu Shengmei
- Department of Pediatric Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
| | - Wang BingQian
- Intensive Care Medicine Department, Suzhou Traditional Chinese Medicine Hospital, Suzhou, Jiangsu 215009, China
| | - Li Wen
- Department of Endocrinology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
| | - Gu Shuyan
- Center for Health Policy and Management Studies, School of Government, Nanjing University, Nanjing 210023, China
| | - Chen Hanbei
- Department of Endocrinology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
| | - Qin Chenjie
- Department of Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China
| | - Dai Yao
- Nursing Department of Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
| | - Li Jutang
- Hongqiao International Institute of Medicine,Tongren Hospital, Shanghai Jiao Tong University School of Medicine, 1111 XianXia Road, Shanghai 200336, China
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Jones PJ, Armstrong DG, Frykberg R, Davies M, Rowlands AV. Footwear fit as a causal factor in diabetes-related foot ulceration: A systematic review. Diabet Med 2024; 41:e15407. [PMID: 39012919 DOI: 10.1111/dme.15407] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2024] [Revised: 06/25/2024] [Accepted: 06/28/2024] [Indexed: 07/18/2024]
Abstract
AIMS Incorrectly fitting footwear (IFF) poses a risk of trauma to at-risk feet with diabetes. The aim of this systematic review was to summarise and assess the evidence that IFF is a statistically significant cause of ulceration. METHODS We searched PubMed, Scopus, Web of Science and Google Scholar for English-language peer-reviewed studies reporting the number or percentage of people with diabetes-related foot ulceration (DFU) attributed to wearing IFF and included a physical examination of the footwear worn. Two independent reviewers assessed the risk of bias using the Newcastle-Ottawa scale. RESULTS 4318 results were retrieved excluding duplicates with 45 studies shortlisted. Ten studies met the inclusion criteria with most rated as fair (n = 6) or good (n = 3). There is some evidence that DFU is significantly associated with IFF, but this is limited: only 3 of 10 included studies found a statistically significant percentage of those with DFU were wearing IFF or inappropriate footwear which included fastening, material, type or fit (15.0%-93.3%). Risk of bias in these three studies ranged from 'fair' to 'poor'. IFF definitions were often unreported or heterogeneous. Only one study reported IFF-related ulcer sites: 70% were at plantar hallux/toes and 10% at plantar metatarsal heads. CONCLUSIONS There is some evidence that IFF is a cause of DFU, but further research is needed, which defines IFF, and methodically records footwear assessment, ulcer location and physical activity. Researchers need to uncover why IFF is worn and if this is due to economic factors, a need for footwear education or other reasons.
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Affiliation(s)
- Petra J Jones
- Leicester Diabetes Centre, University Hospitals of Leicester, Leicester General Hospital, Leicester, UK
- Diabetes Research Centre, University of Leicester, Leicester General Hospital, Leicester, UK
| | - David G Armstrong
- Keck School of Medicine, University of Southern California, Los Angeles, California, USA
| | | | - Melanie Davies
- Leicester Diabetes Centre, University Hospitals of Leicester, Leicester General Hospital, Leicester, UK
- Diabetes Research Centre, University of Leicester, Leicester General Hospital, Leicester, UK
- NIHR Leicester Biomedical Research Centre, University of Leicester, Leicester, UK
| | - Alex V Rowlands
- Diabetes Research Centre, University of Leicester, Leicester General Hospital, Leicester, UK
- NIHR Leicester Biomedical Research Centre, University of Leicester, Leicester, UK
- Division of Health Sciences, Alliance for Research in Exercise, Nutrition and Activity (ARENA), UniSA Allied Health and Human Performance, University of South Australia, Adelaide, South Australia, Australia
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Sloan G, Dela Pena P, Andag-Silva A, Cunanan E, Jimeno C, Robles JJ, Tesfaye S. Sheffield One-Stop Service: A potential model to improve the screening uptake of diabetic peripheral neuropathy and other microvascular complications of diabetes. J Diabetes Investig 2024; 15:1355-1362. [PMID: 39037334 PMCID: PMC11442755 DOI: 10.1111/jdi.14268] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2024] [Revised: 06/28/2024] [Accepted: 07/03/2024] [Indexed: 07/23/2024] Open
Abstract
The world is experiencing an enormous rise in the prevalence of diabetes, which is associated with massive healthcare costs that threaten to overwhelm many healthcare systems. Most of the diabetes expenditure is attributed to the management of chronic diabetes complications, including diabetic peripheral neuropathy (DPN)/diabetic foot complications, chronic kidney disease, sight-threatening retinopathy and cardiovascular diseases. Of these complications, the most overlooked is DPN. Most consultations around the world do not even involve taking off shoes and socks to carry out a foot examination, and even when carried out, the peripheral neurological examination using the 10-g monofilament diagnoses DPN when it is already at an advanced stage. Thus, all too often diabetes complications are diagnosed late, resulting in devastating outcomes, particularly in low- to middle-income countries. There is, therefore, an urgent need to instigate new strategies to improve microvascular screening uptake using a holistic protocol for annual diabetes health checks outside the busy diabetes clinic. One such approach, the Sheffield One-Stop Microvascular Screening Service, which involves modern point of care devices to diagnose DPN, has been shown to be feasible and effective, resulting in high uptake and early management of diabetes complications. This article outlines the advantages of this One-Stop Microvascular Screening Service and a plan to trial an adapted version of this service to a resource-limited country, the Philippines. If successful, this model has the potential for implementation in other countries around the world.
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Affiliation(s)
- Gordon Sloan
- Division of Clinical Medicine, University of Sheffield, Sheffield, UK
- Diabetes Research Unit, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
| | - Pepito Dela Pena
- Section of Endocrinology, Diabetes and Metabolism, East Avenue Medical Center, Quezon City, Philippines
| | - Aimee Andag-Silva
- Section of Endocrinology and Diabetes, De La Salle University Medical Center, Cavite, Philippines
| | - Elaine Cunanan
- Section of Endocrinology, Diabetes and Metabolism, University of St. Tomas Hospital, Manila, Philippines
| | - Cecilia Jimeno
- Section of Endocrinology, Diabetes and Metabolism, University of the Philippines, Philippine General Hospital, Manila, Philippines
| | - Jeremy Jones Robles
- Section of Endocrinology, Diabetes and Metabolism, Chong Hua Hospital, Cebu, Philippines
| | - Solomon Tesfaye
- Diabetes Research Unit, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
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Liu JP, Yao XC, Xu ZY, Wu Y, Shi M, Li M, Du XR, Zhao H. From Novice to Mastery: Learning Curve and Efficacy Analysis of Short-Term Spinal Cord Stimulation for Diabetic Foot Ulcers. World Neurosurg 2024; 190:e851-e858. [PMID: 39128611 DOI: 10.1016/j.wneu.2024.08.023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Accepted: 08/04/2024] [Indexed: 08/13/2024]
Abstract
BACKGROUND To analyze the learning curve of novices in mastering short-term Spinal cord stimulation (st-SCS) for diabetic foot, evaluating the efficacy, safety, and difficulty of this technique. METHODS A retrospective review of diabetic foot patients treated with st-SCS at our hospital was conducted. All procedures were performed by the same physician and patients were sequentially numbered according to the order of surgery. Learning curves were plotted using segmented linear regression and cumulative sum curves based on surgery duration. Patients were divided into 2 groups according to the inflection points on the learning curve: the learning group and the mastery group. Pre- and postoperative efficacy indicators were recorded and compared, along with general patient data, perioperative parameters, and incidence of complications. RESULTS A total of 36 patients were included. Significant improvements were observed post-st-SCS in ulcer size (from 7.00 cm2 to 4.00 cm2), visual analog scale (from 7.00 to 3.00), foot temperature (from 30.06°C to 32.37°C), and Pittsburgh Sleep Quality Index (from 14.42 to 8.36) (P < 0.05). The physician could proficiently perform st-SCS after 9 cases. Surgery time was significantly shorter in the mastery group (1-9 cases) compared to the learning group (10-36 cases) (28.04 vs. 43.56 min, P < 0.05). There were no significant differences between the 2 groups in baseline data, improvement in efficacy indicators, or complications (P > 0.05). CONCLUSIONS St-SCS is beneficial for wound healing, pain relief, improving peripheral circulation, and improving sleep quality. Surgeons can master this simple and safe technique in about 9 cases.
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Affiliation(s)
- Jun-Peng Liu
- Department of Orthopedic Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Xing-Chen Yao
- Department of Orthopedic Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Zi-Yu Xu
- Department of Orthopedic Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Yue Wu
- Department of Orthopedic Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Ming Shi
- Department of Orthopedic Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Meng Li
- Department of Orthopedic Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Xin-Ru Du
- Department of Orthopedic Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Hui Zhao
- Department of Orthopedic Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
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Biondo M, Tomasello L, Giordano C, Arnaldi G, Pizzolanti G. The promising approach of 3D bioprinting for diabetic foot ulcer treatment: A concise review of recent developments. Heliyon 2024; 10:e36707. [PMID: 39281506 PMCID: PMC11395744 DOI: 10.1016/j.heliyon.2024.e36707] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2024] [Revised: 08/06/2024] [Accepted: 08/21/2024] [Indexed: 09/18/2024] Open
Abstract
Diabetic foot ulcer (DFU), one of the most significant complications of diabetes, is a condition that causes anatomical and functional alterations of the foot resulting in an important social and economic impact, related to disability and health care costs. Recently, three-dimensional bioprinting - which allows the fabrication of complex and biocompatible structures - has been identified as a promising approach in the field of regenerative medicine to promote the healing of chronic wounds, such as DFU. In this concise review we highlight the most relevant and recent attempts of using 3D bioprinted constructs in vivo - both on animals and people - in order to treat non-healing diabetic ulcers and prevent their worsening. Finally, we briefly focus on the future implications of bioprinting, suggesting its forthcoming importance not only for DFU treatment but also for other areas of clinical care.
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Affiliation(s)
- Mattia Biondo
- Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Viale delle Scienze (building 16), 90128, Palermo, Italy
| | - Laura Tomasello
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (ProMISE) "G. D'Alessandro", University of Palermo, Piazza delle Cliniche 2, 90127, Palermo, Italy
| | - Carla Giordano
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (ProMISE) "G. D'Alessandro", University of Palermo, Piazza delle Cliniche 2, 90127, Palermo, Italy
| | - Giorgio Arnaldi
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (ProMISE) "G. D'Alessandro", University of Palermo, Piazza delle Cliniche 2, 90127, Palermo, Italy
| | - Giuseppe Pizzolanti
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (ProMISE) "G. D'Alessandro", University of Palermo, Piazza delle Cliniche 2, 90127, Palermo, Italy
- ATeN (Advanced Technologies Network) Center, University of Palermo, Italy
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Wu PY, Yu YL, Zhao WR, Zhou B. Identifying and Validating Extracellular Matrix-Related Gene CTSH in Diabetic Foot Ulcer Using Bioinformatics and Machine Learning. J Inflamm Res 2024; 17:5871-5887. [PMID: 39228680 PMCID: PMC11370762 DOI: 10.2147/jir.s467507] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2024] [Accepted: 08/24/2024] [Indexed: 09/05/2024] Open
Abstract
Background Diabetic foot ulcer (DFU) is a serious clinical problem with high amputation and mortality rates, yet there is a lack of desirable therapy. While the extracellular matrix (ECM) contributes significantly to wound healing, ECM-related biomarker for DFU is still unknown. The study was designed to identify ECM-related biomarker in DFU using bioinformatics and machine learning and validate it in STZ-induced mice models. Methods GSE80178 and GSE134431 microarray datasets were fetched from the GEO database, and differentially expressed genes (DEGs) analysis was performed, respectively. By analyzing DEGs and ECM genes, we identified ECM-related DEGs, and functional enrichment analysis was conducted. Subsequently, three machine learning algorithms (LASSO, RF and SVM-RFE) were applied to filter ECM-related DEGs to identify key ECM-related biomarkers. Next, we conducted immune infiltration analysis, GSEA, and correlation analysis to explore the hub gene underlying mechanism. A lncRNA-miRNA-mRNA and drug regulatory network were constructed. Finally, we validated the key ECM-related biomarker in STZ-induced mice models. Results One hundred and forty-five common DEGs in adult DFU between the two datasets were identified. Taking the intersection of 145 common DEGs and 964 ECM genes, we identified 13 ECM-related DEGs. Thirteen ECM-related DEGs were mainly enriched in pathways associated with tissue remodeling, inflammation and defense against infectious agents. Ultimately, CTSH was identified as the key ECM-related biomarker. CTSH was associated with difference immune cells during the occurrence and development of DFU, and it influenced hedgehog, IL-17 and TNF signaling pathway. Additionally, CTSH expression is correlated with many ECM- and immune-related genes. A lncRNA-miRNA-mRNA and drug regulatory network were constructed with 10 lncRNAs, 2 miRNAs, CTSH and 1 drug. Finally, CTSH was validated as a key biomarker for DFU in animal models. Conclusion Our study found that CTSH can be used for both diagnostic and prognostic purposes and might be a potential therapeutic target.
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Affiliation(s)
- Pei-Yu Wu
- Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China
- Department of VIP, Chongqing General Hospital, Chongqing University, Chongqing, People’s Republic of China
| | - Yan-Lin Yu
- Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China
| | - Wen-Rui Zhao
- Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China
| | - Bo Zhou
- Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China
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Zhang S, Meng N, Liu S, Ruan J, Li H, Xu X, Ruan Q, Xie W. Targeting senescent HDF with the USP7 inhibitor P5091 to enhance DFU wound healing through the p53 pathway. Biochem Biophys Res Commun 2024; 722:150149. [PMID: 38788355 DOI: 10.1016/j.bbrc.2024.150149] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2024] [Accepted: 05/20/2024] [Indexed: 05/26/2024]
Abstract
OBJECTIVE The objective of this study was to examine the potential of USP7 as a target for senolytic therapy and to investigate the molecular mechanism by which its inhibitor selectively induced apoptosis in senescent HDF and enhanced DFU wound healing. METHODS Clinical samples of DFU were collected to detect the expression of USP7 and aging-related proteins using immunohistochemistry and Western blot. In addition, β-galactosidase staining, qPCR, flow cytometry, ROS and MMP kits, and Western blot were used to analyze the biological functions of P5091 on senescence, cycle, and apoptosis. RNAseq was employed to further analyze the molecular mechanism of P5091. Finally, the DFU rat model was established to evaluate the effect of P5091 on wound healing. RESULTS The expression of USP7 and p21 were increased in DFU clinical samples. After treatment with d-glucose (30 mM, 7 days), β-galactosidase staining was deepened, proliferation rate decreased. USP7 inhibitors (P5091) could reduce the release of SASP factors, activate the production of ROS, and reduce MMP. In addition, it induced apoptosis and selectively clears senescent cells through the p53 signaling pathway. Finally, P5091 can improve diabetic wound healing in rats. CONCLUSION This study clarified the molecular mechanism of USP7 inhibitor (P5091) selectively inducing apoptosis of high glucose senescent HDF cells. This provides a new senolytics target and experimental basis for promoting DFU wound healing.
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Affiliation(s)
- Siyu Zhang
- Institute of Burns, Wuhan Third Hospital (Tongren Hospital of WuHan University), Wuhan 430060, China.
| | - Na Meng
- School of Medicine, Jianghan University, Wuhan, 430056, China.
| | - Shuhua Liu
- Institute of Burns, Wuhan Third Hospital (Tongren Hospital of WuHan University), Wuhan 430060, China.
| | - Jingjing Ruan
- Institute of Burns, Wuhan Third Hospital (Tongren Hospital of WuHan University), Wuhan 430060, China.
| | - Hongju Li
- Marine Biomedical Research Institute of Qingdao, Key Laboratory of Marine Drugs Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao, 266003, China.
| | - Ximing Xu
- Marine Biomedical Research Institute of Qingdao, Key Laboratory of Marine Drugs Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao, 266003, China.
| | - Qiongfang Ruan
- Institute of Burns, Wuhan Third Hospital (Tongren Hospital of WuHan University), Wuhan 430060, China.
| | - Weiguo Xie
- Institute of Burns, Wuhan Third Hospital (Tongren Hospital of WuHan University), Wuhan 430060, China.
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Norton P, Trus P, Wang F, Thornton MJ, Chang C. Understanding and treating diabetic foot ulcers: Insights into the role of cutaneous microbiota and innovative therapies. SKIN HEALTH AND DISEASE 2024; 4:e399. [PMID: 39104636 PMCID: PMC11297444 DOI: 10.1002/ski2.399] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/20/2023] [Revised: 04/22/2024] [Accepted: 05/18/2024] [Indexed: 08/07/2024]
Abstract
Background Notoriously known as the silent pandemic, chronic, non-healing diabetic foot ulcers (DFUs), pose a significant rate of incidence for amputation and are a major cause of morbidity. Alarmingly, the treatment and management strategies of chronic wounds represent a significant economic and health burden as well as a momentous drain on resources with billions per annum being spent in the US and UK alone. Defective wound healing is a major pathophysiological condition which propagates an acute wound to a chronic wound, further propelled by underlying conditions such as diabetes and vascular complications which are more prevalent amongst the elderly. Chronic wounds are prone to infection, which can exacerbate the condition, occasionally resulting in amputation for the patient, despite the intervention of modern therapies. However, amputation can only yield a 5-year survival rate for 50% of patients, highlighting the need for new treatments for chronic wounds. Findings The dynamic cutaneous microbiota is comprised of diverse microorganisms that often aid wound healing. Conversely, the chronic wound microbiome consists of a combination of common skin commensals such as Staphylococcus aureus and Staphylococcus epidermidis, as well as the opportunistic pathogen Pseudomonas aeruginosa. These bacteria have been identified as the most prevalent bacterial pathogens isolated from chronic wounds and contribute to prolific biofilm formation decreasing the efficiency of antimicrobials and further perpetuating a hyper-inflammatory state. Discussion and Conclusion Here, we review recent advances and provide a new perspective on alternative treatments including phage and microbiome transplant therapies and how the definitive role of the cutaneous microbiota impacts the aetiology of DFUs.
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Affiliation(s)
- Paul Norton
- School of Dental SciencesFaculty of Medical SciencesNewcastle UniversityNewcastle Upon TyneUK
- Biosciences InstituteFaculty of Medical SciencesNewcastle UniversityNewcastle Upon TyneUK
- Centre for Skin SciencesFaculty of Life SciencesUniversity of BradfordBradfordUK
| | - Pavlos Trus
- School of Dental SciencesFaculty of Medical SciencesNewcastle UniversityNewcastle Upon TyneUK
- Biosciences InstituteFaculty of Medical SciencesNewcastle UniversityNewcastle Upon TyneUK
| | - Fengyi Wang
- School of Dental SciencesFaculty of Medical SciencesNewcastle UniversityNewcastle Upon TyneUK
- Biosciences InstituteFaculty of Medical SciencesNewcastle UniversityNewcastle Upon TyneUK
| | - M. Julie Thornton
- Centre for Skin SciencesFaculty of Life SciencesUniversity of BradfordBradfordUK
| | - Chien‐Yi Chang
- School of Dental SciencesFaculty of Medical SciencesNewcastle UniversityNewcastle Upon TyneUK
- Biosciences InstituteFaculty of Medical SciencesNewcastle UniversityNewcastle Upon TyneUK
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Lin G, Liu X. Key extracellular proteins and TF-miRNA co-regulatory network in diabetic foot ulcer: Bioinformatics and experimental insights. PLoS One 2024; 19:e0307205. [PMID: 39037979 PMCID: PMC11262672 DOI: 10.1371/journal.pone.0307205] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2024] [Accepted: 07/02/2024] [Indexed: 07/24/2024] Open
Abstract
BACKGROUND Diabetic foot ulcers (DFUs), a serious complication of diabetes, are associated with abnormal extracellular protein (EP) metabolism. The identification of key EPs and their regulatory networks is crucial for the understanding of DFU formation and development of effective treatments. In this study, a large-scale bioinformatics analysis was conducted to identify potential therapeutic targets and experimental validation was performed to ensure the reliability and biological relevance of the findings. METHODS Due to the comprehensive profiling of DFU samples provided by the GSE80178 dataset, we initially selected it to derive differentially expressed genes (DEGs) associated with DFU. Subsequently, utilizing the UniProt database and annotated EP list from the Human Protein Atlas annotation database, we screened for extracellular protein-related differentially expressed genes (EP-DEGs) due to their crucial role in the pathogenesis and healing of DFU. We examined EP-DEG pathway enrichment and protein-protein interaction networks, analyzed paired full-thickness skin tissue samples from 24 patients with DFUs and healthy controls, and performed polymerase chain reaction (PCR) experiments to validate candidate genes. Ultimately, we constructed a transcription factor (TF)-microRNA (miRNA)-hub gene co-regulatory network to explore upstream and downstream regulatory connections based on validated DEGs. RESULTS Four crucial candidate genes (FMOD, LUM, VCAN, and S100A12) were identified and verified via PCR analysis. The TF-miRNA-hub EP-DEG regulatory network contained the pivotal TFs TRIM28 and STAT3 and the miRNAs hsa-mir-20a-5p, hsa-miR-21, and hsa-miR-203. CONCLUSION The findings of this study advance our understanding of the pathology of DFU by defining key roles of specific EPs and elucidating a comprehensive regulatory network. These insights pave the way for novel approaches to improve DFU treatment outcomes.
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Affiliation(s)
- Guanlin Lin
- Department of Orthopaedic Surgery, General Hospital of Central Theater Command, Wuhan, China
- College of Acupuncture and Orthopaedic, Hubei University of Chinese Medicine, Wuhan, China
- The First Affiliated Hospital of Xiamen University, Xiamen, China
| | - Ximing Liu
- Department of Orthopaedic Surgery, General Hospital of Central Theater Command, Wuhan, China
- College of Acupuncture and Orthopaedic, Hubei University of Chinese Medicine, Wuhan, China
- The First School of Clinical Medicine, Southern Medical University, Guangzhou, China
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Rukmini PG, Hegde RB, Basavarajappa BK, Bhat AK, Pujari AN, Gargiulo GD, Gunawardana U, Jan T, Naik GR. Recent Innovations in Footwear and the Role of Smart Footwear in Healthcare-A Survey. SENSORS (BASEL, SWITZERLAND) 2024; 24:4301. [PMID: 39001080 PMCID: PMC11243832 DOI: 10.3390/s24134301] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 05/20/2024] [Revised: 06/16/2024] [Accepted: 06/27/2024] [Indexed: 07/16/2024]
Abstract
Smart shoes have ushered in a new era of personalised health monitoring and assistive technologies. Smart shoes leverage technologies such as Bluetooth for data collection and wireless transmission, and incorporate features such as GPS tracking, obstacle detection, and fitness tracking. As the 2010s unfolded, the smart shoe landscape diversified and advanced rapidly, driven by sensor technology enhancements and smartphones' ubiquity. Shoes have begun incorporating accelerometers, gyroscopes, and pressure sensors, significantly improving the accuracy of data collection and enabling functionalities such as gait analysis. The healthcare sector has recognised the potential of smart shoes, leading to innovations such as shoes designed to monitor diabetic foot ulcers, track rehabilitation progress, and detect falls among older people, thus expanding their application beyond fitness into medical monitoring. This article provides an overview of the current state of smart shoe technology, highlighting the integration of advanced sensors for health monitoring, energy harvesting, assistive features for the visually impaired, and deep learning for data analysis. This study discusses the potential of smart footwear in medical applications, particularly for patients with diabetes, and the ongoing research in this field. Current footwear challenges are also discussed, including complex construction, poor fit, comfort, and high cost.
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Affiliation(s)
- Pradyumna G. Rukmini
- Department of Electronics & Communication Engineering, NMAM Institute Technology, NITTE (Deemed to be University), Nitte 574110, India; (P.G.R.); (R.B.H.); (B.K.B.); (A.K.B.)
| | - Roopa B. Hegde
- Department of Electronics & Communication Engineering, NMAM Institute Technology, NITTE (Deemed to be University), Nitte 574110, India; (P.G.R.); (R.B.H.); (B.K.B.); (A.K.B.)
| | - Bommegowda K. Basavarajappa
- Department of Electronics & Communication Engineering, NMAM Institute Technology, NITTE (Deemed to be University), Nitte 574110, India; (P.G.R.); (R.B.H.); (B.K.B.); (A.K.B.)
| | - Anil Kumar Bhat
- Department of Electronics & Communication Engineering, NMAM Institute Technology, NITTE (Deemed to be University), Nitte 574110, India; (P.G.R.); (R.B.H.); (B.K.B.); (A.K.B.)
| | - Amit N. Pujari
- School of Physics, Engineering and Computer Science, University of Hertfordshire, Hertfordshire AL10 9AB, UK;
- School of Engineering, University of Aberdeen, Aberdeen AB24 3FX, UK
| | - Gaetano D. Gargiulo
- School of Engineering, Design and Built Environment, Western Sydney University, Penrith, NSW 2751, Australia; (G.D.G.); (U.G.)
- The MARCS Institute for Brain, Behaviour, and Development, Western Sydney University, Penrith, NSW 2751, Australia
- Translational Health Research Institute, Western Sydney University, Penrith, NSW 2751, Australia
- The Ingham Institute for Applied Medical Research, Liverpool, NSW 2170, Australia
| | - Upul Gunawardana
- School of Engineering, Design and Built Environment, Western Sydney University, Penrith, NSW 2751, Australia; (G.D.G.); (U.G.)
| | - Tony Jan
- Centre for Artificial Intelligence Research and Optimization (AIRO), Design and Creative Technology Vertical, Torrens University, Ultimo, NSW 2007, Australia;
| | - Ganesh R. Naik
- Centre for Artificial Intelligence Research and Optimization (AIRO), Design and Creative Technology Vertical, Torrens University, Ultimo, NSW 2007, Australia;
- College of Medicine and Public Health, Flinders University, Adelaide, SA 5042, Australia
- Design and Creative Technology Vertical, Torrens University, Wakefield Street, Adelaide, SA 5000, Australia
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Heald A, Lu W, Robinson A, Schofield H, Rashid H, Dunn G, Whyte MB, Jude E, Gibson JM, Stedman M, Edmonds M. Mortality in people with a diabetes foot ulcer: An update from the Salford podiatry clinic follow-up study. Diabet Med 2024; 41:e15328. [PMID: 38594820 DOI: 10.1111/dme.15328] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2024] [Accepted: 03/25/2024] [Indexed: 04/11/2024]
Affiliation(s)
- Adrian Heald
- Department of Diabetes and Endocrinology, Salford Royal Hospital, Salford, UK
- Division of Diabetes, Endocrinology and Gastroenterology, University of Manchester, Manchester, UK
| | - Wenqi Lu
- Faculty of Science and Engineering, Manchester Metropolitan University, Manchester, UK
| | - Adam Robinson
- Department of Diabetes and Endocrinology, Salford Royal Hospital, Salford, UK
| | | | - Hamid Rashid
- Department of Diabetes and Endocrinology, Salford Royal Hospital, Salford, UK
| | - George Dunn
- Department of Podiatry, East Cheshire Trust, Macclesfield, UK
| | - Martin B Whyte
- Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK
| | - Edward Jude
- Department of Diabetes, Tameside General Hospital and Glossop Integrated Care NHS Foundation Trust, Ashton under Lyne, UK
| | - J Martin Gibson
- Department of Diabetes and Endocrinology, Salford Royal Hospital, Salford, UK
- Division of Diabetes, Endocrinology and Gastroenterology, University of Manchester, Manchester, UK
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Vikraman PP, Amin K, Mohandas S, Umapathy D, Kesavan R, Ramkumar KM. Dysregulation of miR-146a is associated with exacerbated inflammation, oxidative and endoplasmic reticulum stress in the progression of diabetic foot ulcer. Wound Repair Regen 2024; 32:464-474. [PMID: 38656652 DOI: 10.1111/wrr.13186] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2024] [Revised: 03/20/2024] [Accepted: 04/09/2024] [Indexed: 04/26/2024]
Abstract
Recent evidence has implicated the role of microRNA-146a (miR-146a) in regulating inflammatory responses. In the present study, we investigated the role of miRNA-146a in the progression of diabetic foot ulcer (DFU) in type 2 diabetes mellitus patients (T2DM) and studied its correlation with stress mediators such as Endoplasmic Reticulum (ER) and oxidative stress. Ninety subjects were enrolled and evenly distributed among three groups: Controls (n = 30), T2DM without complications (n = 30) and T2DM with foot ulcers (n = 30). Subsequently, each group was further subdivided based on the University of Texas classification. Peripheral blood was collected from all the study subjects, while tissue biopsies were taken only from DFU patients. Total RNA from both PBMCs and wound tissues were isolated using miRNA isolation kit and qPCR was performed to check the expression of miR-146a, ER stress and oxidative stress markers. Our findings revealed a significant decrease in miR-146a expression among T2DM patients with Grade 2 and Grade 3 DFUs compared with those with Grade 0 and Grade 1 DFUs. Notably, inflammatory genes regulated by miR-146a, including TRAF6, IRAK-1 and ADAM, were all upregulated in T2DM patients with Grade 2 and Grade 3 DFUs. Moreover, reduced miR-146a levels were correlated with increased markers of ER stress and oxidative stress in Grade 2 and Grade 3 DFU patients. Furthermore, our in vitro experiment using mouse 3T3 fibroblasts demonstrated a downregulation of miR-146a following induction of hyperglycaemia, ER stress and oxidative stress in these cells. These findings suggest a potential link between diminished miR-146a expression and heightened oxidative and ER stress in T2DM patients with more severe grades of DFUs. Our results imply that targeting miR-146a may hold therapeutic promise for managing disease progression in DFU patients, as it could help alleviate oxidative and ER stress associated with diabetic complications.
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Affiliation(s)
- Pooja Prathyushaa Vikraman
- Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu, India
| | - Karan Amin
- Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu, India
| | - Sundhar Mohandas
- Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu, India
| | - Dhamodharan Umapathy
- Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu, India
| | - Rajesh Kesavan
- Department of Podiatry, Hycare Super Speciality Hospital, Chennai, Tamilnadu, India
| | - Kunka Mohanram Ramkumar
- Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu, India
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Tiwari B, Germano P, Hemler SL, Koechli C, Pataky Z, Civet Y, Perriard Y. Prototyping and Experimental Analysis of Active Offloading Footwear for Patients With Diabetes Using an Array of Magnetorheological Fluid-Based Modules. J Diabetes Sci Technol 2024:19322968241260037. [PMID: 38887019 PMCID: PMC11571706 DOI: 10.1177/19322968241260037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 06/20/2024]
Abstract
BACKGROUND Diabetic foot ulceration is a serious challenge worldwide which imposes an immense risk of lower extremity amputation and in many cases may lead to the death. The presented work focuses on the offloading requirements using an active approach and considers the use of magnetorheological fluid-based modules to redistribute high plantar pressures (PPs). METHODS & RESULTS Experimentation validated a single module with a threshold peak pressure of 450 kPa, whereas an offloading test with a three-module array and complete footwear validated a maximum pressure reduction of 42.5% and 34.6%, respectively. CONCLUSION To our knowledge, no such active and electrically controllable offloading footwear has been reported yet that has experimentally demonstrated PP reduction of more than 30% over the offloading site.
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Affiliation(s)
- Bhawnath Tiwari
- Integrated Actuators Laboratory, Ecole Polytechnique Fédérale de Lausanne, Neuchâtel, Switzerland
| | - Paolo Germano
- Integrated Actuators Laboratory, Ecole Polytechnique Fédérale de Lausanne, Neuchâtel, Switzerland
| | - Sarah L. Hemler
- Unit of Therapeutic Patient Education, World Health Organization Collaborating Centre, University Hospitals of Geneva and University of Geneva, Geneva, Switzerland
| | - Christian Koechli
- Integrated Actuators Laboratory, Ecole Polytechnique Fédérale de Lausanne, Neuchâtel, Switzerland
| | - Zoltan Pataky
- Unit of Therapeutic Patient Education, World Health Organization Collaborating Centre, University Hospitals of Geneva and University of Geneva, Geneva, Switzerland
| | - Yoan Civet
- Integrated Actuators Laboratory, Ecole Polytechnique Fédérale de Lausanne, Neuchâtel, Switzerland
| | - Yves Perriard
- Integrated Actuators Laboratory, Ecole Polytechnique Fédérale de Lausanne, Neuchâtel, Switzerland
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Yunir E, Adesta FEA, Rizka A, Tarigan TJE. Correlation between initial serum 25-hydroxyvitamin D and granulation growth in diabetic foot ulcers. J Wound Care 2024; 33:clii-clix. [PMID: 38850545 DOI: 10.12968/jowc.2021.0243] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/10/2024]
Abstract
OBJECTIVE To determine the correlation between initial serum 25-hydroxyvitamin D (25(OH)D) levels with granulation growth in diabetic foot ulcers (DFUs) after 21 days of treatment. METHOD This cohort study involved patients with type 2 diabetes who had a DFU treated at hospital. Blood samples were taken from patients on admission. The chemiluminescent immunoassay technique was used to measure 25(OH)D levels. Granulation tissue growth was analysed by comparing the photographs from the initial treatment to day 21 of treatment. RESULTS The median value of 25(OH)D levels at initial treatment was 8 ng/ml. The result showed no correlation between 25(OH)D levels and the granulation growth in DFUs (p=0.86). CONCLUSION The initial serum 25(OH)D level was not correlated with the growth of granulation tissue in DFUs.
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Affiliation(s)
- Em Yunir
- Division of Endocrinology, Metabolism, and Diabetes, Department of Internal Medicine, Dr. Cipto Mangunkusumo National General Hospital, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia
| | - Fajar Englando Alan Adesta
- Department of Internal Medicine, Dr. Cipto Mangunkusumo National General Hospital, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia
| | - Aulia Rizka
- Division of Geriatric, Department of Internal Medicine, Dr. Cipto Mangunkusumo National General Hospital, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia
| | - Tri Juli Edi Tarigan
- Division of Endocrinology, Metabolism, and Diabetes, Department of Internal Medicine, Dr. Cipto Mangunkusumo National General Hospital, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia
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