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Wang Y, Jiang C, Xing YQ, Zou L, Song M, Qu X, Jia Z, Zhao L, Han X, Zong J, Wang S. Establishing a clinical prediction model for diabetic foot ulcers in type 2 diabetic patients with lower extremity arteriosclerotic occlusion using machine learning. Sci Rep 2025; 15:11737. [PMID: 40188298 PMCID: PMC11972369 DOI: 10.1038/s41598-025-96502-9] [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: 08/19/2024] [Accepted: 03/28/2025] [Indexed: 04/07/2025] Open
Abstract
The burden of diabetic foot ulcers (DFU) is exacerbated in diabetic patients with concomitant arteriosclerotic occlusion disease (ASO) in the lower extremities, who experience more severe symptoms and poorer prognoses. The study aims to develop a predictive model grounded in machine learning (ML) algorithms, specifically tailored to forecast the occurrence of DFU in diabetic patients with lower extremity ASO. The study involves the data from diabetic patients diagnosed with lower extremity ASO from January 1, 2011 to August 31, 2023. We conducted quality control on the data. Subsequently, the dataset was divided into a training set comprising patients before 2020 and a validation set comprising patients in 2020 and onwards. Patients were stratified into the DFU group or the non-DFU group based on the occurrence of DFU. Intergroup comparisons were conducted to analyze the differences between these two groups. Logistic regression analyses, 3 kinds of machine learning algorithms, a predictive model and nomogram was formulated to estimate the risk of DFU occurrence among diabetic patients with lower extremity ASO. Internal validation of the model was undertaken using the bootstrap method, combing with external temporal validation, with the results visually presented through the Receiver Operating Characteristic (ROC) curve and the Calibration curve. To evaluate the clinical practicality of the model, Decision Curve Analysis (DCA) and Clinical Impact Curve (CIC) were employed. Body Mass Index (BMI), hypertension, coronary heart disease, diabetic nephropathy, the number of lower leg artery occlusions, controlling glucose by insulin injection, age, number of cigarettes smoked per day, diastolic blood pressure, and C-reactive protein (CRP) were utilized to construct a clinical prediction model. This model exhibited a high predictive performance (AUC = 0.962), and the results from both internal validation and external temporal validation further confirmed its high accuracy and reproducibility (AUC = 0.968 and AUC = 0.977, respectively). Additionally, DCA and CIC demonstrated the high clinical practicality of this model. The clinical prediction model exhibited excellent accuracy and reproducibility, along with broad clinical practicality. It provides a good reference for the diagnosis and treatment of DFU.
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Affiliation(s)
- Yubo Wang
- Department of Orthopaedic Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Chunyu Jiang
- Department of Trauma Surgery, The Second Affiliated Hospital of Harbin Medical University, Dalian, China
| | - Yi Qi Xing
- Department of Orthopaedic Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Linxuan Zou
- Department of Orthopaedic Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Mingzhi Song
- Department of Orthopaedic Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Xueling Qu
- Pelvic Floor Repair Center, Dalian Women and Children Medical Center (Group), Dalian, China
| | - Zhuqiang Jia
- Naqu People's Hospital, Tibet, China
- The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Lin Zhao
- Department of Quality Management, Dalian Municipal Central Hospital, Dalian, China
| | - Xin Han
- Naqu People's Hospital, Tibet, China.
- Department of Orthopaedic Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, China.
| | - Junwei Zong
- Department of Orthopaedic Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China.
| | - Shouyu Wang
- Department of Orthopaedic Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China.
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He SQ, Huang B, Xu F, Yang JJ, Li C, Liu FR, Yuan LQ, Lin X, Liu J. Functions and application of circRNAs in vascular aging and aging-related vascular diseases. J Nanobiotechnology 2025; 23:216. [PMID: 40098005 PMCID: PMC11917153 DOI: 10.1186/s12951-025-03199-z] [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: 11/18/2024] [Accepted: 02/03/2025] [Indexed: 03/19/2025] Open
Abstract
Circular RNAs (circRNAs), constituting a novel class of endogenous non-coding RNAs generated through the reverse splicing of mRNA precursors, possess the capacity to regulate gene transcription and translation. Recently, the pivotal role of circRNAs in controlling vascular aging, as well as the pathogenesis and progression of aging-related vascular diseases, has garnered substantial attention. Vascular aging plays a crucial role in the increased morbidity and mortality of the elderly. Endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) are crucial components of the intima and media layers of the vascular wall, respectively, and are closely involved in the mechanisms underlying vascular aging and aging-related vascular diseases. The review aims to provide a comprehensive exploration of the connection between circRNAs and vascular aging, as well as aging-related vascular diseases. Besides, circRNAs, as potential diagnostic markers or therapeutic targets for vascular aging and aging-related vascular diseases, will be discussed thoroughly, along with the challenges and limitations of their clinical application. Investigating the role and molecular mechanisms of circRNAs in vascular aging and aging-related vascular diseases will provide a novel insight into early diagnosis and therapy, and even effective prognosis assessment of these conditions.
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Affiliation(s)
- Sha-Qi He
- Department of Radiology, the Second Xiangya Hospital of Central South University, Changsha, 410011, China
| | - Bei Huang
- Department of Radiology, the Second Xiangya Hospital of Central South University, Changsha, 410011, China
| | - Feng Xu
- National Clinical Research Center for Metabolic Diseases, Department of Metabolism and Endocrinology, the Second Xiangya Hospital of Central South University, Changsha, 410011, China
| | - Jun-Jie Yang
- Department of Radiology, the Second Affiliated Hospital of Xinjiang Medical University, Ürümqi, 830054, China
| | - Cong Li
- Department of Radiology, the Second Xiangya Hospital of Central South University, Changsha, 410011, China
| | - Feng-Rong Liu
- Department of Anesthesiology, the Second Xiangya Hospital of Central South University, Changsha, 410011, China
| | - Ling-Qing Yuan
- National Clinical Research Center for Metabolic Diseases, Department of Metabolism and Endocrinology, the Second Xiangya Hospital of Central South University, Changsha, 410011, China
| | - Xiao Lin
- Department of Radiology, the Second Xiangya Hospital of Central South University, Changsha, 410011, China.
| | - Jun Liu
- Department of Radiology, the Second Xiangya Hospital of Central South University, Changsha, 410011, China.
- Clinical Research Center for Medical Imaging in Hunan Province, Quality Control Center in Hunan Province, Changsha, 410011, China.
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Meloni M, Vas PRJ. Peripheral Arterial Disease in Diabetic Foot: One Disease with Multiple Patterns. J Clin Med 2025; 14:1987. [PMID: 40142794 PMCID: PMC11942964 DOI: 10.3390/jcm14061987] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2025] [Revised: 03/03/2025] [Accepted: 03/12/2025] [Indexed: 03/28/2025] Open
Abstract
Peripheral arterial disease (PAD) is a major complication in individuals with diabetes and is increasingly prevalent in those with diabetic foot ulcers (DFUs). Despite this, the characterisation of PAD in diabetic patients remains insufficiently refined, leading to suboptimal management and outcomes. This review underscores the necessity for a more nuanced understanding of PAD's anatomical and biological aspects in diabetic patients. The distribution of atherosclerotic plaques varies significantly among individuals, influencing prognosis and treatment efficacy. We describe three key patterns of PAD in diabetes: pattern 1 PAD-below-the-knee (BTK) disease (with infrageniculate disease where present); pattern 2-below-the-ankle (BTA) disease; and pattern 3-small artery disease (SAD), each presenting unique challenges and require tailored therapeutic approaches. BTK PAD, characterised by occlusions in the anterior tibial, posterior tibial, and peroneal arteries, necessitates targeted revascularisation to improve foot perfusion. BTA PAD, involving the pedal and plantar arteries, is associated with higher risks of amputation and requires advanced revascularisation techniques. SAD, affecting the small arteries of the foot, remains an enigma and is challenging to treat with the current mechanical methods, highlighting the potential of autologous cell therapy as a promising alternative. A refined characterisation of PAD in diabetes is crucial for developing effective, individualised treatment strategies, ultimately improving patient outcomes, and reducing the burden of diabetic foot complications. In light of these complexities, it is incredulous that we often use a single term, "peripheral arterial disease", to describe such a diverse array of disease patterns. This oversimplification can be perilous, as it may lead to inadequate therapeutic approaches and suboptimal patient care.
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Affiliation(s)
- Marco Meloni
- Division of Endocrinology and Diabetology, Department of Medical Sciences, Fondazione Policlinico “Tor Vergata”, 00133 Rome, Italy
- Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy
| | - Prashanth R. J. Vas
- Diabetes and Diabetic Foot, King’s College NHS Foundation Trust, London SE5 9RS, UK;
- Diabetes and Endocrinology, Guys and St Thomas’ NHS Foundation Trust, London SE1 9RT, UK
- School of Life Sciences, King’s College, London SE1 7EH, UK
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Rohrich RN, Li KR, Episalla NC, Atkinson K, Lin RP, Ferdousian S, Youn RC, Evans KK, Akbari CM, Attinger CE. Understanding the Prevalence of Medial Arterial Calcification Among Complex Reconstructive Patients: Insights from a Decade of Experience at a Tertiary Limb Salvage Center. J Clin Med 2025; 14:596. [PMID: 39860602 PMCID: PMC11765606 DOI: 10.3390/jcm14020596] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2024] [Revised: 01/08/2025] [Accepted: 01/16/2025] [Indexed: 01/27/2025] Open
Abstract
Background: Medial arterial calcification (MAC), a distinct form of vascular pathology frequently coexisting with peripheral arterial disease (PAD), poses unique challenges in limb salvage among patients with diabetes, chronic kidney disease, and end-stage renal disease. This study examines the incidence of MAC and its impact on limb salvage outcomes over a decade of experience at a tertiary limb salvage center. Methods: A retrospective review of all complex lower extremity (LE) reconstructions using local flap (LF) or free tissue transfer (FTT), performed from July 2011 to September 2022, was conducted. Patients were classified into MAC and No MAC groups based on pedal radiography evaluations using the Ferraresi MAC scoring system. The primary outcomes were major lower extremity amputation (MLEA), the need for postoperative vascular intervention, major adverse limb events (MALE; defined as the composite of any unplanned reoperation, MLEA, or postoperative revascularization attempt), and mortality. Results: During the study period, a total of 430 LE reconstructions were performed with LF or FTT. A total of 323 cases (75.1%) demonstrated no MAC while the remaining 107 (24.9%) demonstrated MAC. The MAC group exhibited significantly higher rates of diabetes, PAD, and renal disease. With a follow-up duration of 17.0 (IQR: 33.9) months, the MAC group demonstrated a significantly higher rate of MLEA (24.3% vs. 13.0%, p = 0.006), postoperative vascular intervention (23.4% vs. 8.7%, p < 0.001), MALE (57.0% vs. 25.7%, p < 0.001), and mortality (28.0% vs. 9.9%, p < 0.001). Multivariate analysis identified MAC as independently predictive of MALE (OR: 1.8, CI: 1.1-3.0, p = 0.033). Conclusion: MAC is prevalent among surgical candidates for limb salvage. Patients with MAC represent a significant medical and reconstructive challenge. Radiographic screening for MAC should be considered in all limb salvage candidates with LE wounds, especially in those with diabetes and kidney disease. Assessing MAC is important for better evaluating risk factors and surgical options so as to optimize outcomes in this challenging population.
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Affiliation(s)
- Rachel N. Rohrich
- Department of Plastic and Reconstructive Surgery, MedStar Georgetown University Hospital, 3800 Reservoir Road, NW, Washington, DC 20007, USA; (R.N.R.); (S.F.)
| | - Karen R. Li
- Department of Plastic and Reconstructive Surgery, MedStar Georgetown University Hospital, 3800 Reservoir Road, NW, Washington, DC 20007, USA; (R.N.R.); (S.F.)
- Georgetown University School of Medicine, Washington, DC 20007, USA
| | - Nicole C. Episalla
- Department of Plastic and Reconstructive Surgery, MedStar Georgetown University Hospital, 3800 Reservoir Road, NW, Washington, DC 20007, USA; (R.N.R.); (S.F.)
| | - Khaleel Atkinson
- Georgetown University School of Medicine, Washington, DC 20007, USA
| | - Ryan P. Lin
- Department of Plastic and Reconstructive Surgery, MedStar Georgetown University Hospital, 3800 Reservoir Road, NW, Washington, DC 20007, USA; (R.N.R.); (S.F.)
| | - Sami Ferdousian
- Department of Plastic and Reconstructive Surgery, MedStar Georgetown University Hospital, 3800 Reservoir Road, NW, Washington, DC 20007, USA; (R.N.R.); (S.F.)
- Georgetown University School of Medicine, Washington, DC 20007, USA
| | - Richard C. Youn
- Department of Plastic and Reconstructive Surgery, MedStar Georgetown University Hospital, 3800 Reservoir Road, NW, Washington, DC 20007, USA; (R.N.R.); (S.F.)
| | - Karen K. Evans
- Department of Plastic and Reconstructive Surgery, MedStar Georgetown University Hospital, 3800 Reservoir Road, NW, Washington, DC 20007, USA; (R.N.R.); (S.F.)
| | - Cameron M. Akbari
- Department of Vascular Surgery, MedStar Georgetown University Hospital, Washington, DC 20007, USA
| | - Christopher E. Attinger
- Department of Plastic and Reconstructive Surgery, MedStar Georgetown University Hospital, 3800 Reservoir Road, NW, Washington, DC 20007, USA; (R.N.R.); (S.F.)
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Leiva K, Gonzalez I, Murillo J, Espinosa A, Kirsner RS, Godavarty A. Breath-Holding as a Stimulus to Assess Peripheral Oxygenation Flow Using Near-Infrared Spectroscopic Imaging. Bioengineering (Basel) 2024; 11:1221. [PMID: 39768039 PMCID: PMC11673871 DOI: 10.3390/bioengineering11121221] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2024] [Revised: 11/27/2024] [Accepted: 11/28/2024] [Indexed: 01/11/2025] Open
Abstract
A mammalian breath-hold (BH) mechanism can induce vasoconstriction in the limbs, altering blood flow and oxygenation flow changes in a wound site. Our objective was to utilize a BH paradigm as a stimulus to induce peripheral tissue oxygenation changes via studies on control and diabetic foot ulcer (DFU) subjects. Subjects were imaged under a breath-hold paradigm (including 20 s BH) using a non-contact spatio-temporal-based NIRS device. Oxygenated flow changes were similar between darker and lighter skin colors but differed between wound site and normal background tissues. Thus, the ability of peripheral vasculature to response to oxygenation demand can be assessed in DFUs.
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Affiliation(s)
- Kevin Leiva
- Optical Imaging Laboratory, Department of Biomedical Engineering, Florida International University, Miami, FL 33174, USA; (K.L.); (I.G.); (J.M.)
| | - Isabella Gonzalez
- Optical Imaging Laboratory, Department of Biomedical Engineering, Florida International University, Miami, FL 33174, USA; (K.L.); (I.G.); (J.M.)
| | - Juan Murillo
- Optical Imaging Laboratory, Department of Biomedical Engineering, Florida International University, Miami, FL 33174, USA; (K.L.); (I.G.); (J.M.)
| | - Aliette Espinosa
- Phillip Frost Department of Dermatology & Cutaneous Surgery, UM Wound Care Center, University of Miami, Miami, FL 33136, USA; (A.E.); (R.S.K.)
| | - Robert S. Kirsner
- Phillip Frost Department of Dermatology & Cutaneous Surgery, UM Wound Care Center, University of Miami, Miami, FL 33136, USA; (A.E.); (R.S.K.)
| | - Anuradha Godavarty
- Optical Imaging Laboratory, Department of Biomedical Engineering, Florida International University, Miami, FL 33174, USA; (K.L.); (I.G.); (J.M.)
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Duan W, Jin X, Zhao Y, Martin-Saldaña S, Li S, Qiao L, Shao L, Zhu B, Hu S, Li F, Feng L, Ma Y, Du B, Zhang L, Bu Y. Engineering injectable hyaluronic acid-based adhesive hydrogels with anchored PRP to pattern the micro-environment to accelerate diabetic wound healing. Carbohydr Polym 2024; 337:122146. [PMID: 38710570 DOI: 10.1016/j.carbpol.2024.122146] [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: 12/10/2023] [Revised: 03/16/2024] [Accepted: 04/08/2024] [Indexed: 05/08/2024]
Abstract
Diabetic wounds remain a global challenge due to disordered wound healing led by inflammation, infection, oxidative stress, and delayed proliferation. Therefore, an ideal wound dressing for diabetic wounds not only needs tissue adhesiveness, injectability, and self-healing properties but also needs a full regulation of the microenvironment. In this work, adhesive wound dressings (HA-DA/PRP) with injectability were fabricated by combining platelet rich plasma (PRP) and dopamine-modified-hyaluronic acid (HA-DA). The engineered wound dressings exhibited tissue adhesiveness, rapid self-healing, and shape adaptability, thereby enhancing stability and adaptability to irregular wounds. The in vitro experiments demonstrated that HA-DA/PRP adhesives significantly promoted fibroblast proliferation and migration, attributed to the loaded PRP. The adhesives showed antibacterial properties against both gram-positive and negative bacteria. Moreover, in vitro experiments confirmed that HA-DA/PRP adhesives effectively mitigated oxidative stress and inflammation. Finally, HA-DA/PRP accelerated the healing of diabetic wounds by inhibiting bacterial growth, promoting granulation tissue regeneration, accelerating neovascularization, facilitating collagen deposition, and modulating inflammation through inducing M1 to M2 polarization, in an in vivo model of infected diabetic wounds. Overall, HA-DA/PRP adhesives with the ability to comprehensively regulate the microenvironment in diabetic wounds may provide a novel approach to expedite the diabetic wounds healing in clinic.
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Affiliation(s)
- Wanglin Duan
- Institute of Medical Engineering, Department of Biophysics, School of Basic Medical Sciences, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China
| | - Xianzhen Jin
- Department of General Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, 710061 Xi'an, Shaanxi, China
| | - Yiyang Zhao
- Department of Rehabilitation Medicine, the First Medical Center, Chinese PLA General Hospital, No.28 Fuxing Road, Haidian District, Beijing 100853, China
| | - Sergio Martin-Saldaña
- POLYMAT, Applied Chemistry Department, Faculty of Chemistry, University of the Basque Country UPV/EHU, Paseo Manuel de Lardizabal 3, 20018 Donostia-San Sebastián, Spain
| | - Shuaijun Li
- Institute of Medical Engineering, Department of Biophysics, School of Basic Medical Sciences, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China
| | - Lina Qiao
- Department of General Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, 710061 Xi'an, Shaanxi, China
| | - Liang Shao
- Institute of Medical Engineering, Department of Biophysics, School of Basic Medical Sciences, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China
| | - Bin Zhu
- Institute of Medical Engineering, Department of Biophysics, School of Basic Medical Sciences, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China
| | - Shibo Hu
- Department of General Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, 710061 Xi'an, Shaanxi, China
| | - Furong Li
- Department of Dermatology, the Second Affiliated Hospital of Xi'an Jiaotong University, 710061 Xi'an, Shaanxi, China
| | - Luyao Feng
- Institute of Medical Engineering, Department of Biophysics, School of Basic Medical Sciences, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China
| | - Yao Ma
- Institute of Medical Engineering, Department of Biophysics, School of Basic Medical Sciences, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China
| | - Baoji Du
- Institute of Medical Engineering, Department of Biophysics, School of Basic Medical Sciences, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China.
| | - Lining Zhang
- Department of Rehabilitation Medicine, the First Medical Center, Chinese PLA General Hospital, No.28 Fuxing Road, Haidian District, Beijing 100853, China.
| | - Yazhong Bu
- Institute of Medical Engineering, Department of Biophysics, School of Basic Medical Sciences, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China; Department of Burns, Plastic and Wound Repair Surgery, the Second Affiliated Hospital of Xi'an Jiaotong University, 710061 Xi'an, Shaanxi, China.
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Yang L, Li D, Yan Y, Yang Q, Li L, Zha Y. Microvascular permeability and texture analysis of bone marrow in diabetic rabbits with critical limb ischemia based on dynamic contrast-enhanced magnetic resonance imaging. J Diabetes Investig 2024; 15:584-593. [PMID: 38240456 PMCID: PMC11060156 DOI: 10.1111/jdi.14145] [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: 05/11/2023] [Revised: 12/16/2023] [Accepted: 12/21/2023] [Indexed: 05/01/2024] Open
Abstract
BACKGROUND Early on in the development of diabetes, skeletal muscles can exhibit microarchitectural changes that can be detected using texture analysis (TA) based on volume transfer constant (Ktrans) maps. Nevertheless, there have been few studies and thus we evaluated microvascular permeability and the TA of the bone marrow in diabetics with critical limb ischemia (CLI). METHODS Eighteen male rabbits were randomly assigned equally into an operation group with hindlimb ischemia and diabetes, a sham-operated group with diabetes only, and a control group. Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) was performed on all rabbits at predetermined intervals (1, 5, 10, 15, 20, and 25 days post-surgery). The pharmacokinetic model was used to generate the permeability parameters, while the textural parameters were derived from the Ktrans map. Data analysis methods included the independent sample t-test, Mann-Whitney U test, repeated-measures analysis of variance, and Pearson correlation tests. RESULTS The Ktrans values reached a minimum on day 1 after ischemia induction, then gradually recovered, but remained lower than those of the sham-operated group. The volume fraction only showed a significant difference between the operation group and the sham-operated group on day 5 post-surgery, but not in the extravascular extracellular space volume fraction at all time points. A significantly reduced Ktrans on day 1, a decreased number of bone trabeculae (Tb.N), and the area of bone trabeculae (Tb.Ar), and an increased microvessel density on day 25 in the operation group compared with the sham-operated group were observed. At each time point, there was a discernible difference between the two groups in the mean value, mean of positive pixels, and sumAverage. CONCLUSIONS The early stages of diabetic bone marrow with CLI can be evaluated by DCE-MRI for microvascular permeability. Texture analysis based on DCE-MRI could act as an imaging discriminator and new radiological analysis tool for critical limb ischemia in diabetes mellitus.
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Affiliation(s)
- Liu Yang
- Department of RadiologyRenmin Hospital of Wuhan UniversityNo. 238 Jiefang RoadWuhan430060Wuchang DistrictChina
- Department of RadiologyUnion Hospital, Tongji Medical College, Huazhong University of Science and Technology1277 Jiefang AvenueWuhan430022China
| | - Donghang Li
- Department of Thoracic SurgeryRenmin Hospital of Wuhan UniversityNo.238 Jiefang RoadWuhan430060Wuchang DistrictChina
| | - Yuchen Yan
- Department of RadiologyRenmin Hospital of Wuhan UniversityNo. 238 Jiefang RoadWuhan430060Wuchang DistrictChina
| | - Qi Yang
- Department of RadiologyRenmin Hospital of Wuhan UniversityNo. 238 Jiefang RoadWuhan430060Wuchang DistrictChina
| | - Liang Li
- Department of RadiologyRenmin Hospital of Wuhan UniversityNo. 238 Jiefang RoadWuhan430060Wuchang DistrictChina
| | - Yunfei Zha
- Department of RadiologyRenmin Hospital of Wuhan UniversityNo. 238 Jiefang RoadWuhan430060Wuchang DistrictChina
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Guan H, Wang Y, Niu P, Zhang Y, Zhang Y, Miao R, Fang X, Yin R, Zhao S, Liu J, Tian J. The role of machine learning in advancing diabetic foot: a review. Front Endocrinol (Lausanne) 2024; 15:1325434. [PMID: 38742201 PMCID: PMC11089132 DOI: 10.3389/fendo.2024.1325434] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2023] [Accepted: 04/09/2024] [Indexed: 05/16/2024] Open
Abstract
Background Diabetic foot complications impose a significant strain on healthcare systems worldwide, acting as a principal cause of morbidity and mortality in individuals with diabetes mellitus. While traditional methods in diagnosing and treating these conditions have faced limitations, the emergence of Machine Learning (ML) technologies heralds a new era, offering the promise of revolutionizing diabetic foot care through enhanced precision and tailored treatment strategies. Objective This review aims to explore the transformative impact of ML on managing diabetic foot complications, highlighting its potential to advance diagnostic accuracy and therapeutic approaches by leveraging developments in medical imaging, biomarker detection, and clinical biomechanics. Methods A meticulous literature search was executed across PubMed, Scopus, and Google Scholar databases to identify pertinent articles published up to March 2024. The search strategy was carefully crafted, employing a combination of keywords such as "Machine Learning," "Diabetic Foot," "Diabetic Foot Ulcers," "Diabetic Foot Care," "Artificial Intelligence," and "Predictive Modeling." This review offers an in-depth analysis of the foundational principles and algorithms that constitute ML, placing a special emphasis on their relevance to the medical sciences, particularly within the specialized domain of diabetic foot pathology. Through the incorporation of illustrative case studies and schematic diagrams, the review endeavors to elucidate the intricate computational methodologies involved. Results ML has proven to be invaluable in deriving critical insights from complex datasets, enhancing both the diagnostic precision and therapeutic planning for diabetic foot management. This review highlights the efficacy of ML in clinical decision-making, underscored by comparative analyses of ML algorithms in prognostic assessments and diagnostic applications within diabetic foot care. Conclusion The review culminates in a prospective assessment of the trajectory of ML applications in the realm of diabetic foot care. We believe that despite challenges such as computational limitations and ethical considerations, ML remains at the forefront of revolutionizing treatment paradigms for the management of diabetic foot complications that are globally applicable and precision-oriented. This technological evolution heralds unprecedented possibilities for treatment and opportunities for enhancing patient care.
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Affiliation(s)
- Huifang Guan
- College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, China
| | - Ying Wang
- College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, China
| | - Ping Niu
- Department of Encephalopathy, The Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, Jilin, China
| | - Yuxin Zhang
- Institute of Metabolic Diseases, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Yanjiao Zhang
- Institute of Metabolic Diseases, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Runyu Miao
- Institute of Metabolic Diseases, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Xinyi Fang
- Institute of Metabolic Diseases, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Ruiyang Yin
- Institute of Metabolic Diseases, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Shuang Zhao
- College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, China
| | - Jun Liu
- Department of Hand Surgery, Second Hospital of Jilin University, Changchun, China
| | - Jiaxing Tian
- Institute of Metabolic Diseases, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
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Coşkun B, Ayhan M, Ulusoy S. Relationship between Prognostic Nutritional Index and Amputation in Patients with Diabetic Foot Ulcer. Diagnostics (Basel) 2024; 14:738. [PMID: 38611651 PMCID: PMC11011454 DOI: 10.3390/diagnostics14070738] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2024] [Revised: 03/25/2024] [Accepted: 03/28/2024] [Indexed: 04/14/2024] Open
Abstract
The prognostic nutritional index (PNI) is a new marker used to assess a patient's nutritional and immune status. It is calculated using serum albumin levels and total lymphocyte count. The aim of this study was to investigate the relationship between PNI and amputation in patients with diabetic foot ulcer (DFU). Patients with DFU were enrolled in this retrospective study. In our study, a total of 386 patient data, of 110 (28.5%) amputated and 276 (71.5%) non-amputated patients, were statistically analyzed. PNI values were significantly lower in the amputated patient group than in the non-amputee patient group (p < 0.001). According to the ROC analysis results, PNI was significant in the prediction of amputation at an excellent level (AUC = 0.937 (0.911-0.963), p < 0.001). The optimal cut-off point for PNI was found to be 39,005. There was classification success for this cut-off point: sensitivity was calculated as 82.7% (74.1-89) and specificity as 93.1% (89.3-95.7). In the multivariate model, the odds ratio (OR) (95% CI) was calculated as 81.8 (38.5-173.7) for PNI. The PNI was associated with an increase in amputation rate in patients with DFU. By using PNI, patients can be directed to advanced centers and have access to early and appropriate interventions.
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Affiliation(s)
- Belgin Coşkun
- Infectious Diseases and Clinical Microbiology, Ankara Bilkent City Hospital, 06800 Çankaya, Turkey;
| | - Müge Ayhan
- Infectious Diseases and Clinical Microbiology, Ankara Bilkent City Hospital, 06800 Çankaya, Turkey;
| | - Serap Ulusoy
- General Surgery, Ankara Bilkent City Hospital, 06800 Çankaya, Turkey;
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10
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Liang J, Gong X, Hu X, You C, Zhou J, Gao Y, Zong J, Liu Y. Integrated genetic analysis of diabetic complications: Bioinformatics insights into foot ulcers, neuropathy and peripheral artery disease. Int Wound J 2024; 21:e14748. [PMID: 38358067 PMCID: PMC10867868 DOI: 10.1111/iwj.14748] [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: 12/24/2023] [Accepted: 01/23/2024] [Indexed: 02/16/2024] Open
Abstract
Diabetic foot ulcers (DFU), diabetic peripheral neuropathy (DPN) and peripheral arterial disease (PAD) are common complications of diabetes mellitus, while diabetic peripheral neuropathy and peripheral arterial disease contribute to the pathogenesis of diabetic foot ulcers, and the pathogenic mechanisms between these three diseases still need further investigation. The keywords 'diabetic foot ulcer', 'diabetic peripheral neuropathy' and 'atherosclerosis' were used to search for related gene sets in the GEO database. Differentially expressed genes (DEGs) were screened and analysed for GO, KEGG and enrichR functional enrichment. Potential three disease biomarkers were identified by SVM-SVM-RFE and LASSO regression analysis. The results were also validated using external datasets and discriminability was measured by area under the ROC curve (AUC). Finally, biomarkers and co-upregulated genes were analysed through the GSEA and Attie Laboratories diabetes databases. A total of 11 shared genes (KRT16, CD24, SAMD9L, SRGAP2, FGL2, GPR34, DDIT4, NFE2L3, FBLN5, ANXA3 and CPA3), two biomarkers (SAMD9L and FGL2) and one co-upregulated gene (CD24) were screened. GO and KEGG pathway analysis of DEGs, enrichr enrichment analysis of shared differential genes and GSEA analysis of biomarkers showed that these significant genes were mainly focused on vasoregulatory, inflammatory-oxidative stress and immunomodulatory pathways. In this study, we used bioinformatics to investigate the intrinsic relationship and potential mechanisms of three common lower extremity complications of diabetes and identified two pivotal genes using the LASSO model and the SVM-RFE algorithm, which will further help clinicians to understand the relationship between diabetic complications, improve the diagnosis and treatment of diabetic foot problems and help doctors to identify the potential risk factors of diabetic foot.
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Affiliation(s)
- Jiaru Liang
- Department of Rehabilitation MedicineThe First Affiliated Hospital of Dalian Medical UniversityDalianChina
- Institute (College) of Integrative MedicineDalian Medical UniversityDalianChina
| | - Xiaoyang Gong
- Department of Rehabilitation MedicineThe First Affiliated Hospital of Dalian Medical UniversityDalianChina
| | - Xuyang Hu
- Institute (College) of Integrative MedicineDalian Medical UniversityDalianChina
| | - Chong You
- Institute (College) of Integrative MedicineDalian Medical UniversityDalianChina
| | - Jiaqi Zhou
- Department of Rehabilitation MedicineThe First Affiliated Hospital of Dalian Medical UniversityDalianChina
| | - Yuling Gao
- Department of Rehabilitation MedicineThe First Affiliated Hospital of Dalian Medical UniversityDalianChina
| | - Junwei Zong
- Department of Orthopaedic SurgeryThe First Affiliated Hospital of Dalian Medical UniversityDalianChina
| | - Yong Liu
- Department of Rehabilitation MedicineThe First Affiliated Hospital of Dalian Medical UniversityDalianChina
- Institute (College) of Integrative MedicineDalian Medical UniversityDalianChina
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11
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Panda D, Nayak S. Stem Cell-Based Tissue Engineering Approaches for Diabetic Foot Ulcer: a Review from Mechanism to Clinical Trial. Stem Cell Rev Rep 2024; 20:88-123. [PMID: 37867186 DOI: 10.1007/s12015-023-10640-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/05/2023] [Indexed: 10/24/2023]
Abstract
Diabetic foot ulcer (DFU) is a complication from incomplete or prolonged wound healing, at times requires amputation, putting substantial health and socioeconomic burden. Wound healing is a dynamic overlapping process that can be regulated by arrays of molecular factors showing redundancy in function. However, dysregulation in the mechanism of angiogenesis, extra cellular matrix (ECM) formation and immune modulation are the major causes for impair wound healing in hyperglycaemic patients. Despite development of wound care research, there is a lack of well-accepted targeted therapy with multidisciplinary approach for DFU treatment. Stem cell therapy holds a promising outcome both in preclinical and clinical trials because of its ability to promote healing via regeneration and specialized tissue differentiation. Among different types of stem cells, regenerative potential of mesenchymal stem cell (MSC) is well demonstrated in both experimental and clinical trial. Still there is a huge knowledge gap among medical practitioners for deciding the best stem cell source, administration route, and safety. This review strengthens the fact that why stem cell therapy is a promising candidate to treat DFU and cited multiple tissue engineering and biomaterial-based approaches for delivering stem cells and their aftermath paracrine events. Based on the pre-clinical and clinical studies, the review tried to come up with optimum stem cell source and delivery route for the treatment of DFU. At last, the review glances on possible direction to enhance therapeutics strategy for the same, including different approaches like: phytocompounds, exosomes, scaffold geometry, cell preconditioning and licensing etc.
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Affiliation(s)
- Debarchan Panda
- Department of Integrative Biology, School of Bio Sciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, 632014, India
| | - Sunita Nayak
- Department of Integrative Biology, School of Bio Sciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, 632014, India.
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12
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Leiva K, Trinidad A, Gonzalez I, Espinosa A, Zwick T, Levine JE, Rodriguez MA, Lev-Tov H, Wu W, Kirsner RS, Godavarty A. Development of a Tissue Oxygenation Flow-Based Index Toward Discerning the Healing Status in Diabetic Foot Ulcers. Adv Wound Care (New Rochelle) 2024; 13:22-33. [PMID: 37060195 PMCID: PMC10654646 DOI: 10.1089/wound.2022.0170] [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: 12/12/2022] [Accepted: 04/09/2023] [Indexed: 04/16/2023] Open
Abstract
Objective: The objective of this study is to characterize breath-hold (BH)-induced oxygenation changes in diabetic foot ulcers (DFUs) and develop an oxygenation flow index (OFI) to discern nonhealing from healing DFUs. Approach: The imaging approach utilizes an innovative BH stimulus that induces vasoconstriction and measures for altering oxygenation flow in and around the tissues of DFUs and controls. The modified Beer-Lambert law was utilized to calculate hemoglobin-based spatiotemporal oxygenation maps in terms of oxygen saturation. Results: We found controls had synchronous BH-induced oxygenation changes across the dorsal (OFI: 29.0%) and plantar (OFI: 57.6%) aspects of the foot. Nonhealing DFUs, however, had less synchronous BH-induced oxygenation changes (OFI <28%). In addition, two complicated healing DFU cases, or cases with underlying issues or poor long-term healing outcomes, were observed to have OFIs <28%. Innovation: An OFI was developed to differentiate nonhealing DFUs from healing DFUs using a single, noncontact, near-infrared optical scanner for spatiotemporal oxygenation monitoring. The OFI has potential to provide immediate feedback on the microcirculation in DFUs, through hemoglobin-based oxygenation parameters. Conclusion: A preliminary threshold (OFI <28%) could differentiate nonhealing and complicated DFUs from healing DFUs. The overall oxygenation flow pattern was less synchronous (or the OFI value reduced) in the nonwound areas of the feet that were nonhealing. In other words, the reduced OFI value (<28%) in the entire foot, excluding the wound region is a possible indicator that the wound may not heal.
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Affiliation(s)
- Kevin Leiva
- Optical Imaging Laboratory, Department of Biomedical Engineering, Florida International University, Miami, Florida, USA
| | - Alexander Trinidad
- Optical Imaging Laboratory, Department of Biomedical Engineering, Florida International University, Miami, Florida, USA
| | - Isabella Gonzalez
- Optical Imaging Laboratory, Department of Biomedical Engineering, Florida International University, Miami, Florida, USA
| | - Aliette Espinosa
- Dr. Phillip Frost Department of Dermatology, UM Wound Care Center, University of Miami, Miami, Florida, USA
| | - Thomas Zwick
- Dr. Phillip Frost Department of Dermatology, UM Wound Care Center, University of Miami, Miami, Florida, USA
| | - Jason Edward Levine
- Dr. Phillip Frost Department of Dermatology, UM Wound Care Center, University of Miami, Miami, Florida, USA
| | - Magaly Adelaida Rodriguez
- Dr. Phillip Frost Department of Dermatology, UM Wound Care Center, University of Miami, Miami, Florida, USA
| | - Hadar Lev-Tov
- Dr. Phillip Frost Department of Dermatology, UM Wound Care Center, University of Miami, Miami, Florida, USA
| | - Wensong Wu
- Department of Mathematics and Statistics, Florida International University, Miami, Florida, USA
| | - Robert S. Kirsner
- Dr. Phillip Frost Department of Dermatology, UM Wound Care Center, University of Miami, Miami, Florida, USA
| | - Anuradha Godavarty
- Optical Imaging Laboratory, Department of Biomedical Engineering, Florida International University, Miami, Florida, USA
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Azhar A, Basheer M, Abdelgawad MS, Roshdi H, Kamel MF. Prevalence of Peripheral Arterial Disease in Diabetic Foot Ulcer Patients and its Impact in Limb Salvage. INT J LOW EXTR WOUND 2023; 22:518-523. [PMID: 34142882 DOI: 10.1177/15347346211027063] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Diabetic foot ulcer syndrome is a common complication of diabetes mellitus. Three main factors contribute to it: neuropathy, vasculopathy, and infection. This study was conducted to evaluate the prevalence of peripheral arterial disease (PAD) in diabetic foot ulcer patients and its impact on limb salvage as an outcome. This prospective cross-sectional study included 392 cases, who were divided according to the presence of PAD into 2 groups; patients with PAD were labeled as PAD +ve (172 cases) and those without PAD were labeled as PAD -ve (22 cases). All cases were clinically assessed, and routine laboratory examinations were ordered. Moreover, duplex ultrasound was done for suspected cases of having PAD by examination. Computed tomography angiography was ordered for patients who are in need of a revascularization procedure. Cases were managed by debridement and/or revascularization. After that, these cases were assessed clinically and radiologically for vascularity and infection and the possibility for amputation was evaluated. Infection was classified using Wagner Classification System, and revascularization was decided according to the TASC II system. The incidence of PAD in cases with diabetic foot ulcer syndrome was 43.87%. No difference was detected between the 2 groups regarding age and gender (P > .05). The prevalence of smoking, hemodialysis, ischemic heart disease (IHD), and hypertension was more significantly higher in cases with PAD (P < .05). Revascularization procedures were only performed in cases that had documented severe PAD or chronic limb-threatening ischemia in addition to foot ulcer and/or infection. With regard to limb salvage, it was more significantly performed in cases without PAD (82.3% vs 48.3% in PAD cases; P < .001). Male gender, smoking, ankle-brachial pressure index, hemodialysis, IHD, neuropathy, HbA1C, PAD, and high Wagner classification were predictors of limb amputation (P < .05). PAD is associated with worse outcomes in diabetic foot ulcer patients. Not only does it constitute a great number among diabetic foot ulcer patients, but it also has a negative impact on limb salvage.
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14
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Schönborn M, Gregorczyk-Maga I, Batko K, Maga M, Bogucka K, Gawlik K, Pawlica-Gosiewska D, Maga P. Angiogenic and Microvascular Status Alterations after Endovascular Revascularization of Lower Limb Arteries among Patients with Diabetic Foot Syndrome: A Prospective 12-Month Follow-Up Study. J Clin Med 2023; 12:5581. [PMID: 37685648 PMCID: PMC10488381 DOI: 10.3390/jcm12175581] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2023] [Revised: 07/31/2023] [Accepted: 08/25/2023] [Indexed: 09/10/2023] Open
Abstract
Peripheral arterial disease (PAD)-induced ischemia is an important component of diabetic foot syndrome (DFS). The results of revascularization of the lower extremity arteries (including percutaneous transluminal angioplasty [PTA]) do not always give satisfactory long-term results, which is due to many factors. The aim of the study was to investigate the alterations in selected circulating angiogenic factors and microcirculation parameters in 41 patients with DFS following PTA and analyze their relationships with clinical outcomes during 1-year follow-up. Our study revealed a general decrease in pro-angiogenic factor levels after PTA and their subsequent stabilization during subsequent observation. The results indicated a significant association between plasma circulating FGF-2 level and poor outcomes (including the incidence of restenosis/reocclusion of treated arteries) during 12 months of observation. The perioperative changes in FGF-2 showed a significant association with LDF alterations after PTA. Follow-up 1-3 months post-intervention showed a tendency towards elevated TcpO2, VEGF-A, and VEGF-R2 levels in patients free from adverse events. These results may provide a basis for further research on the potential use of selected circulating angiogenic factors for monitoring the treatment of patients with DFS following PTA.
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Affiliation(s)
- Martyna Schönborn
- Department of Angiology, Faculty of Medicine, Jagiellonian University Medical College, 31-008 Krakow, Poland; (M.M.); (P.M.)
- Doctoral School of Medical and Health Sciences, Jagiellonian University, 31-007 Krakow, Poland
- Clinical Department of Angiology, University Hospital in Krakow, 30-688 Kraków, Poland;
| | - Iwona Gregorczyk-Maga
- Faculty of Medicine, Institute of Dentistry, Jagiellonian University Medical College, 31-008 Kraków, Poland;
| | - Krzysztof Batko
- Department of Research and Development, Medicine Economy Law Society (MELS) Foundation, 30-040 Krakow, Poland;
| | - Mikołaj Maga
- Department of Angiology, Faculty of Medicine, Jagiellonian University Medical College, 31-008 Krakow, Poland; (M.M.); (P.M.)
- Clinical Department of Angiology, University Hospital in Krakow, 30-688 Kraków, Poland;
| | - Katarzyna Bogucka
- Clinical Department of Angiology, University Hospital in Krakow, 30-688 Kraków, Poland;
| | - Katarzyna Gawlik
- Department of Clinical Biochemistry, Jagiellonian University Medical College, 31-008 Krakow, Poland; (K.G.); (D.P.-G.)
| | - Dorota Pawlica-Gosiewska
- Department of Clinical Biochemistry, Jagiellonian University Medical College, 31-008 Krakow, Poland; (K.G.); (D.P.-G.)
| | - Paweł Maga
- Department of Angiology, Faculty of Medicine, Jagiellonian University Medical College, 31-008 Krakow, Poland; (M.M.); (P.M.)
- Clinical Department of Angiology, University Hospital in Krakow, 30-688 Kraków, Poland;
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15
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Alahakoon C, Singh TP, Morris D, Charles J, Fernando M, Lazzarini P, Moxon JV, Golledge J. Cohort Study Examining the Presentation, Distribution, and Outcomes of Peripheral Artery Disease in Aboriginal, Torres Strait Islander, and Non-Indigenous Australians. Eur J Vasc Endovasc Surg 2023; 66:237-244. [PMID: 37209994 DOI: 10.1016/j.ejvs.2023.05.027] [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: 12/08/2022] [Revised: 05/01/2023] [Accepted: 05/12/2023] [Indexed: 05/22/2023]
Abstract
OBJECTIVE This retrospective cohort study investigated the anatomical distribution, severity, and outcome of peripheral artery disease (PAD) in Aboriginal and Torres Strait Islanders compared with non-indigenous Australians. METHODS The distribution, severity, and outcome of PAD were assessed using a validated angiographic scoring system and review of medical records in a cohort of Aboriginal and Torres Strait Islander and non-indigenous Australians. The relationship between ethnicity and PAD severity, distribution, and outcome were examined using non-parametric statistical tests, Kaplan-Meier and Cox proportional hazard analyses. RESULTS Seventy-three Aboriginal and Torres Strait Islanders and 242 non-indigenous Australians were included and followed for a median of 6.7 [IQR 2.7, 9.3] years. Aboriginal and Torres Strait Islander patients were more likely to present with symptoms of chronic limb threatening ischaemia (81% vs. 25%; p < .001), had greater median [IQR] angiographic scores for the symptomatic limb (7 [5, 10] vs. 4 [2, 7]) and tibial arteries (5 [2, 6] vs. 2 [0, 4]) and had higher risk of major amputation (HR 6.1, 95% CI 3.6 - 10.5; p < .001) and major adverse cardiovascular events (HR 1.5, 95% CI 1.0 - 2.3; p = .036) but not for revascularisation (HR 0.8, 95% CI 0.5 - 1.3; p = .37) compared with non-indigenous Australians. The associations with major amputation and major adverse cardiovascular events were no longer statistically significant when adjusted for limb angiographic score. CONCLUSION Compared with non-indigenous patients, Aboriginal and Torres Strait Islander Australians had more severe tibial artery disease and a higher risk of major amputation and major adverse cardiovascular events.
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Affiliation(s)
- Chanika Alahakoon
- Queensland Research Centre for Peripheral Vascular Disease, College of Medicine and Dentistry, James Cook University, Townsville, Australia; Faculty of Medicine, University of Peradeniya, Peradeniya, Sri Lanka
| | - Tejas P Singh
- Queensland Research Centre for Peripheral Vascular Disease, College of Medicine and Dentistry, James Cook University, Townsville, Australia; The Department of Vascular and Endovascular Surgery, Townsville University Hospital, Townsville, Australia
| | - Dylan Morris
- Queensland Research Centre for Peripheral Vascular Disease, College of Medicine and Dentistry, James Cook University, Townsville, Australia; The Department of Vascular and Endovascular Surgery, Townsville University Hospital, Townsville, Australia
| | - James Charles
- First Peoples Health Unit, Griffith University, Queensland, Australia
| | - Malindu Fernando
- Queensland Research Centre for Peripheral Vascular Disease, College of Medicine and Dentistry, James Cook University, Townsville, Australia; Faculty of Health and Medicine, School of Health Sciences, University of Newcastle, Australia; The Australian Institute of Tropical Health and Medicine, James Cook University, Townsville, Australia
| | - Peter Lazzarini
- School of Public Health and Social Work, Queensland University of Technology, Brisbane, Australia; Allied Health Research Collaborative, Metro North Hospital and Health Service, Brisbane, Australia
| | - Joseph V Moxon
- Queensland Research Centre for Peripheral Vascular Disease, College of Medicine and Dentistry, James Cook University, Townsville, Australia; The Australian Institute of Tropical Health and Medicine, James Cook University, Townsville, Australia
| | - Jonathan Golledge
- Queensland Research Centre for Peripheral Vascular Disease, College of Medicine and Dentistry, James Cook University, Townsville, Australia; The Department of Vascular and Endovascular Surgery, Townsville University Hospital, Townsville, Australia; The Australian Institute of Tropical Health and Medicine, James Cook University, Townsville, Australia.
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16
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Zhang Y, Li M, Wang Y, Han F, Shen K, Luo L, Li Y, Jia Y, Zhang J, Cai W, Wang K, Zhao M, Wang J, Gao X, Tian C, Guo B, Hu D. Exosome/metformin-loaded self-healing conductive hydrogel rescues microvascular dysfunction and promotes chronic diabetic wound healing by inhibiting mitochondrial fission. Bioact Mater 2023; 26:323-336. [PMID: 36950152 PMCID: PMC10027478 DOI: 10.1016/j.bioactmat.2023.01.020] [Citation(s) in RCA: 57] [Impact Index Per Article: 28.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2022] [Revised: 01/08/2023] [Accepted: 01/27/2023] [Indexed: 03/17/2023] Open
Abstract
Chronic diabetic wounds remain a globally recognized clinical challenge. They occur due to high concentrations of reactive oxygen species and vascular function disorders. A promising strategy for diabetic wound healing is the delivery of exosomes, comprising bioactive dressings. Metformin activates the vascular endothelial growth factor pathway, thereby improving angiogenesis in hyperglycemic states. However, multifunctional hydrogels loaded with drugs and bioactive substances synergistically promote wound repair has been rarely reported, and the mechanism of their combinatorial effect of exosome and metformin in wound healing remains unclear. Here, we engineered dual-loaded hydrogels possessing tissue adhesive, antioxidant, self-healing and electrical conductivity properties, wherein 4-armed SH-PEG cross-links with Ag+, which minimizes damage to the loaded goods and investigated their mechanism of promotion effect for wound repair. Multiwalled carbon nanotubes exhibiting good conductivity were also incorporated into the hydrogels to generate hydrogen bonds with the thiol group, creating a stable three-dimensional structure for exosome and metformin loading. The diabetic wound model of the present study suggests that the PEG/Ag/CNT-M + E hydrogel promotes wound healing by triggering cell proliferation and angiogenesis and relieving peritraumatic inflammation and vascular injury. The mechanism of the dual-loaded hydrogel involves reducing the level of reactive oxygen species by interfering with mitochondrial fission, thereby protecting F-actin homeostasis and alleviating microvascular dysfunction. Hence, we propose a drug-bioactive substance combination therapy and provide a potential mechanism for developing vascular function-associated strategies for treating chronic diabetic wounds.
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Affiliation(s)
- Yue Zhang
- Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, 127 Changle West Road, Xi'an, Shaanxi, 710032, China
| | - Meng Li
- State Key Laboratory for Mechanical Behavior of Materials, And Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, 710049, China
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, 710049, China
| | - Yunchuan Wang
- Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, 127 Changle West Road, Xi'an, Shaanxi, 710032, China
| | - Fei Han
- Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, 127 Changle West Road, Xi'an, Shaanxi, 710032, China
| | - Kuo Shen
- Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, 127 Changle West Road, Xi'an, Shaanxi, 710032, China
| | - Liang Luo
- Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, 127 Changle West Road, Xi'an, Shaanxi, 710032, China
| | - Yan Li
- Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, 127 Changle West Road, Xi'an, Shaanxi, 710032, China
| | - Yanhui Jia
- Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, 127 Changle West Road, Xi'an, Shaanxi, 710032, China
| | - Jian Zhang
- Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, 127 Changle West Road, Xi'an, Shaanxi, 710032, China
| | - Weixia Cai
- Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, 127 Changle West Road, Xi'an, Shaanxi, 710032, China
| | - Kejia Wang
- Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, 127 Changle West Road, Xi'an, Shaanxi, 710032, China
| | - Ming Zhao
- Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, 127 Changle West Road, Xi'an, Shaanxi, 710032, China
| | - Jing Wang
- Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, 127 Changle West Road, Xi'an, Shaanxi, 710032, China
| | - Xiaowen Gao
- Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, 127 Changle West Road, Xi'an, Shaanxi, 710032, China
| | - Chenyang Tian
- Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, 127 Changle West Road, Xi'an, Shaanxi, 710032, China
| | - Baolin Guo
- State Key Laboratory for Mechanical Behavior of Materials, And Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, 710049, China
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, 710049, China
- Corresponding author. State Key Laboratory for Mechanical Behavior of Materials, and Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, 710049, China.
| | - Dahai Hu
- Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, 127 Changle West Road, Xi'an, Shaanxi, 710032, China
- Corresponding author.
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17
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Schönborn M, Gregorczyk-Maga I, Batko K, Bogucka K, Maga M, Płotek A, Pasieka P, Słowińska-Solnica K, Maga P. Circulating Angiogenic Factors and Ischemic Diabetic Foot Syndrome Advancement-A Pilot Study. Biomedicines 2023; 11:1559. [PMID: 37371653 DOI: 10.3390/biomedicines11061559] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2023] [Revised: 05/21/2023] [Accepted: 05/22/2023] [Indexed: 06/29/2023] Open
Abstract
Despite clear evidence of inadequate angiogenesis in ischemic diabetic foot syndrome (DFS) pathogenesis, angiogenic factor level changes in patients with ischemic DFS remain inconsistent. This study aimed to assess circulating angiogenic factors concerning ischemic DFS advancement and describe their relationships with patients' clinical characteristics, microvascular parameters, and diabetic control. The study included 41 patients with ischemic DFS (67.3 (8.84) years; 82.9% males). Angiogenic processes were assessed by identifying circulating concentrations of five pro- and two anti-angiogenic factors. We found that penetrating ulcers were related to a significantly higher FGF-2 level (8.86 (5.29) vs. 5.23 (4.17) pg/mL, p = 0.02). Moreover, plasma FGF-2 showed a significant correlation with the SINBAD score (r = 0.32, p = 0.04), platelet count (r = 0.43, p < 0.01), white cell count (r = 0.42, p < 0.01), and age (r = -0.35, p = 0.03). We did not observe any significant linear relationship between the studied biomarkers and microcirculatory parameters, nor for glycemic control. In a univariate analysis using logistic regression, an increase in plasma FGF-2 was tied to greater odds of high-grade ulcers (OR 1.16; 95% CI 1.02-1.38, p = 0.043). This suggests that circulating FGF-2 may serve as a potential biomarker for predicting DFU advancement and progression. It is necessary to conduct further studies with follow-up observations to confirm this hypothesis.
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Affiliation(s)
- Martyna Schönborn
- Department of Angiology, Faculty of Medicine, Jagiellonian University Medical College, 30-663 Krakow, Poland
- Doctoral School of Medical and Health Sciences, Jagiellonian University, 31-007 Krakow, Poland
- Clinical Department of Angiology, University Hospital in Krakow, 30-688 Krakow, Poland
| | - Iwona Gregorczyk-Maga
- Faculty of Medicine, Institute of Dentistry, Jagiellonian University Medical College, 30-663 Krakow, Poland
| | - Krzysztof Batko
- Department of Research and Development, Medicine Economy Law Society (MELS) Foundation, 30-040 Krakow, Poland
| | - Katarzyna Bogucka
- Clinical Department of Angiology, University Hospital in Krakow, 30-688 Krakow, Poland
| | - Mikołaj Maga
- Clinical Department of Angiology, University Hospital in Krakow, 30-688 Krakow, Poland
- Department of Rehabilitation in Internal Medicine, Faculty of Health Sciences, Jagiellonian University Medical College, 31-008 Krakow, Poland
| | - Anna Płotek
- Clinical Department of Angiology, University Hospital in Krakow, 30-688 Krakow, Poland
| | - Patrycja Pasieka
- Department of Dermatology, Faculty of Medicine, Jagiellonian University Medical College, 31-008 Krakow, Poland
| | | | - Paweł Maga
- Department of Angiology, Faculty of Medicine, Jagiellonian University Medical College, 30-663 Krakow, Poland
- Clinical Department of Angiology, University Hospital in Krakow, 30-688 Krakow, Poland
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Zheng SY, Wan XX, Kambey PA, Luo Y, Hu XM, Liu YF, Shan JQ, Chen YW, Xiong K. Therapeutic role of growth factors in treating diabetic wound. World J Diabetes 2023; 14:364-395. [PMID: 37122434 PMCID: PMC10130901 DOI: 10.4239/wjd.v14.i4.364] [Citation(s) in RCA: 33] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Revised: 01/16/2023] [Accepted: 03/21/2023] [Indexed: 04/12/2023] Open
Abstract
Wounds in diabetic patients, especially diabetic foot ulcers, are more difficult to heal compared with normal wounds and can easily deteriorate, leading to amputation. Common treatments cannot heal diabetic wounds or control their many complications. Growth factors are found to play important roles in regulating complex diabetic wound healing. Different growth factors such as transforming growth factor beta 1, insulin-like growth factor, and vascular endothelial growth factor play different roles in diabetic wound healing. This implies that a therapeutic modality modulating different growth factors to suit wound healing can significantly improve the treatment of diabetic wounds. Further, some current treatments have been shown to promote the healing of diabetic wounds by modulating specific growth factors. The purpose of this study was to discuss the role played by each growth factor in therapeutic approaches so as to stimulate further therapeutic thinking.
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Affiliation(s)
- Shen-Yuan Zheng
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
- Department of Anatomy and Neurobiology, School of Basic Medical Science, Central South University, Changsha 410013, Hunan Province, China
| | - Xin-Xing Wan
- Department of Endocrinology, Third Xiangya Hospital, Central South University, Changsha 410013, Hunan Province, China
| | - Piniel Alphayo Kambey
- Department of Neurobiology and Anatomy, Xuzhou Medical University, Xuzhou 221004, Jiangsu Province, China
| | - Yan Luo
- Clinical Medicine Eight-Year Program, Xiangya School of Medicine, Central South University, Changsha 410013, Hunan Province, China
| | - Xi-Min Hu
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
- Department of Anatomy and Neurobiology, School of Basic Medical Science, Central South University, Changsha 410013, Hunan Province, China
| | - Yi-Fan Liu
- Clinical Medicine Eight-Year Program, Xiangya School of Medicine, Central South University, Changsha 410013, Hunan Province, China
| | - Jia-Qi Shan
- Clinical Medicine Eight-Year Program, Xiangya School of Medicine, Central South University, Changsha 410013, Hunan Province, China
| | - Yu-Wei Chen
- Clinical Medicine Eight-Year Program, Xiangya School of Medicine, Central South University, Changsha 410013, Hunan Province, China
| | - Kun Xiong
- Department of Anatomy and Neurobiology, School of Basic Medical Science, Central South University, Changsha 410013, Hunan Province, China
- Key Laboratory of Emergency and Trauma, College of Emergency and Trauma, Hainan Medical University, Haikou 571199, Hainan Province, China
- Hunan Key Laboratory of Ophthalmology, Central South University, Changsha 410013, Hunan Province, China
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Using T1 mapping indices to evaluate muscle function and predict conservative treatment outcomes in diabetic patients with peripheral arterial disease. Eur Radiol 2023:10.1007/s00330-023-09392-8. [PMID: 36651955 DOI: 10.1007/s00330-023-09392-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Revised: 12/10/2022] [Accepted: 12/23/2022] [Indexed: 01/19/2023]
Abstract
OBJECTIVES To investigate interstitial muscle fibrosis via T1 mapping indices and its relationships with muscle function and conservative treatment outcomes. METHODS A total of 49 DM patients with PAD were prospectively recruited from 2016 to 2017. All PAD patients underwent pre-treatment MRI with conservative treatment via a rehabilitation program and antiplatelet therapy. The need to require percutaneous transluminal angioplasty intervention was recorded as intolerance to conservative treatment outcomes. We quantified calf interstitial muscle fibrosis using T1 mapping indices (native T1, post-contrast T1, and the extracellular volume fraction [ECV]). Muscle function was evaluated using a 6-min walking test (6MWT) and a 3-min stepping test (3MST). PAD patients were divided into two groups according to their tolerance or intolerance of the conservative treatment. Pearson's correlation, reproducibility, and multivariable Cox hazard analyses were performed with p < 0.05 indicating statistical significance. RESULTS Among the T1 mapping indices in the posterior compartment of the calf in PAD patients, the native T1 value was significantly correlated with 6MWT (r = -0.422, p = 0.010) and 3MST (r = -0.427, p = 0.009). All T1 mapping indices showed excellent intra-observer and inter-observer correlations. ECV was an independent predictor of conservative treatment intolerance (average ECV, hazard ratio: 1.045, 95% confidence interval: 1.011-1.079, p = 0.009). CONCLUSIONS T1 mapping measurements are reproducible with excellent intra-observer and inter-observer correlations. T1 mapping indices may be predictive of treatment and functional outcomes and carry promise in patient evaluation. TRIAL REGISTRATION Clinical Trials Identifier: NCT02850432 . KEY POINTS • T1 mapping measurements of the calf muscles are reproducible with excellent intra-observer and inter-observer correlations (0.98 and 0.95 for anterior and posterior compartment muscle extracellular volume matrix [ECV] measurements, respectively). • ECV is shown to independently predict conservative treatment intolerance. • T1 mapping indices may be predictive of treatment and functional outcomes and carry promise in patient evaluation.
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Dong B, Wang X, Wang W, Hong B, Wang J, Wang H, Gu Y. Effect of Percutaneous Endovascular Angioplasty Combined with Negative Pressure Drainage on the "One-Stop" Treatment of Ischemic Diabetic Foot Ulcer. Ann Vasc Surg 2022; 92:272-284. [PMID: 36586666 DOI: 10.1016/j.avsg.2022.12.066] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Revised: 11/20/2022] [Accepted: 12/04/2022] [Indexed: 12/29/2022]
Abstract
BACKGROUND To explore the therapeutic effect, safety, and economic benefit of a "one-stop" diagnosis and treatment mode of vascular surgery for ischemic diabetic foot (DF) ulcer and to analyze the associated and independent factors that affect ulcer healing. METHODS In a prospective, single-center study, patients with ischemic DF ulcers from January 2017 to July 2021 were treated with either percutaneous endovascular angioplasty combined with negative pressure closed drainage (PTA-VSD) or percutaneous endovascular angioplasty combined with depuration (PTA-UD). The effectiveness and economic benefits of the 2 measures were compared, and independent factors affecting ulcer healing were explored via univariate and logistic regression analyses. RESULTS Fifty patients with ischemic DF ulcer (25 patients in the PTA-VSD group and 25 patients in the PTA-UD group; 40 males and 10 females) were included, with an average age of 67.74 ± 10.71 years. No difference was observed in the demographic data. The findings showed that the ulcer healing time in the PTA-VSD group was significantly shorter than that in the PTA-UD group (154.79 vs. 238.31 days), and the ulcer healing rate at 180 days post surgery was significantly greater in the PTA-VSD group (52% vs. 12%) (P = 0.002, < 0.05). The ulcer score in the PTA-VSD group decreased significantly at 3, 6, and 12 months post surgery. The duration of hospitalization in the PTA-VSD group was greater (P = 0.002, <0.05), but no significant difference in hospitalization frequency and cost was observed between the 2 groups. During follow-up, there was 1 death and 1 amputation in the PTA-UD group, but no death or amputation in the PTA-VSD group. Arterial occlusion was primarily located in the femoral-popliteal artery and the inferior knee artery in the 2 groups, and PTA intervention effectively opened the outflow tract of the affected limb. Two to three outflow tracts were opened in 41 patients. The ankle-brachial index (ABI) after surgery was significantly higher in both groups than before. Univariate and multivariate logistic regression analyses revealed that the Wagner grade and number of outflow channels and therapies (PTA-VSD) could be independent factors affecting ulcer healing. CONCLUSIONS The severity of DF ulcers is an important factor affecting the quality of life of patients. A multidisciplinary "one-stop" treatment strategy based on percutaneous endovascular angioplasty combined with negative pressure-sealing drainage can rapidly and effectively restore the blood flow to the affected limb and promote ulcer healing without increasing medical costs.
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Affiliation(s)
- Bo Dong
- Department of Vascular Surgery, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xixu Wang
- Department of Vascular Surgery, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Wei Wang
- Department of Vascular Surgery, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Biao Hong
- Department of Vascular Surgery, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
| | - Jue Wang
- Department of Vascular Surgery, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Heng Wang
- Department of Vascular Surgery, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yun Gu
- Department of Vascular Surgery, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Kumari A, Raina N, Wahi A, Goh KW, Sharma P, Nagpal R, Jain A, Ming LC, Gupta M. Wound-Healing Effects of Curcumin and Its Nanoformulations: A Comprehensive Review. Pharmaceutics 2022; 14:2288. [PMID: 36365107 PMCID: PMC9698633 DOI: 10.3390/pharmaceutics14112288] [Citation(s) in RCA: 70] [Impact Index Per Article: 23.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2022] [Revised: 09/28/2022] [Accepted: 10/10/2022] [Indexed: 08/13/2023] Open
Abstract
Wound healing is an intricate process of tissue repair or remodeling that occurs in response to injury. Plants and plant-derived bioactive constituents are well explored in the treatment of various types of wounds. Curcumin is a natural polyphenolic substance that has been used since ancient times in Ayurveda for its healing properties, as it reduces inflammation and acts on several healing stages. Several research studies for curcumin delivery at the wound site reported the effectiveness of curcumin in eradicating reactive oxygen species and its ability to enhance the deposition of collagen, granulation tissue formation, and finally, expedite wound contraction. Curcumin has been widely investigated for its wound healing potential but its lower solubility and rapid metabolism, in addition to its shorter plasma half-life, have limited its applications in wound healing. As nanotechnology has proven to be an effective technique to accelerate wound healing by stimulating appropriate mobility through various healing phases, curcumin-loaded nanocarriers are used for targeted delivery at the wound sites. This review highlights the potential of curcumin and its nanoformulations, such as liposomes, nanoparticles, and nano-emulsions, etc. in wound healing. This paper emphasizes the numerous biomedical applications of curcumin which collectively prepare a base for its antibiofilm and wound-healing action.
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Affiliation(s)
- Amrita Kumari
- School of Pharmaceutical Sciences, Delhi Pharmaceutical Sciences and Research University (DPSRU), New Delhi 110017, India
| | - Neha Raina
- School of Pharmaceutical Sciences, Delhi Pharmaceutical Sciences and Research University (DPSRU), New Delhi 110017, India
| | - Abhishek Wahi
- School of Pharmaceutical Sciences, Delhi Pharmaceutical Sciences and Research University (DPSRU), New Delhi 110017, India
| | - Khang Wen Goh
- Faculty of Data Science and Information Technology, INTI International University, Nilai 71800, Malaysia
| | - Pratibha Sharma
- University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India
| | - Riya Nagpal
- School of Pharmaceutical Sciences, Delhi Pharmaceutical Sciences and Research University (DPSRU), New Delhi 110017, India
| | - Atul Jain
- Department of Pharmaceutics, Delhi Institute of Pharmaceutical Sciences and Research, Delhi Pharmaceutical Sciences and Research University (DPSRU), New Delhi 110017, India
| | - Long Chiau Ming
- PAPRSB Institute of Health Sciences, Universiti Brunei Darussalam, Gadong BE1410, Brunei
| | - Madhu Gupta
- School of Pharmaceutical Sciences, Delhi Pharmaceutical Sciences and Research University (DPSRU), New Delhi 110017, India
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The Neuro-Ischaemic Charcot Foot: Prevalence, Characteristics and Severity of Peripheral Arterial Disease in Acute Charcot Neuro-Arthropathy. J Clin Med 2022; 11:jcm11216230. [PMID: 36362457 PMCID: PMC9656917 DOI: 10.3390/jcm11216230] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2022] [Revised: 10/12/2022] [Accepted: 10/17/2022] [Indexed: 01/25/2023] Open
Abstract
The study aimed to evaluate the prevalence, characteristics and outcomes of patients affected by Charcot neuro-arthropathy (CN) and peripheral arterial disease (PAD) compared to CN without PAD. Consecutive patients presenting with an acute CN were included. The sample size was calculated by the power analysis by adopting the two-tailed tests of the null hypothesis with alfa = 0.05 and a value of beta = 0.10 as the second type error and, therefore, a test power equal to 90%. Seventy-six patients were identified. Twenty-four patients (31.6%) had neuro-ischaemic CN; they were older (66 vs. 57yrs), p = 0.03, had a longer diabetes duration (19 vs. 14yrs), p < 0.001, and more cases of end-stage-renal-disease (12.5 vs. 0%), p = 0.04 and ischaemic heart disease (58.3 vs. 15.4%), p < 0.0001 than neuropathic CN. Fifty patients (65.8%) had concomitant foot ulcers, 62.5% and 67.3% (p = 0.3), respectively, in CN with and without PAD. Neuro-ischaemic CN show arterial lesions of 2.9 vessels, and PAD was located predominantly below-the-knee (75%) but not below-the-ankle (16.7%). The outcomes for neuro-ischaemic and neuropathic CN patients were, respectively: wound healing (86.7 vs. 94.3%), p = 0.08; minor amputation (25 vs. 7.7%), p = 0.003; major amputation (8.3 vs. 1.9%), p = 0.001; hospitalization (75 vs. 23%), p = 0.0001. The study showed a frequent association between CN and PAD, leading to a neuro-ischaemic Charcot foot type. Neuro-ischaemic CN leaded to an increased risk of minor and major amputation and hospitalization, compared to neuropathic CN.
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Gorden LYT, Ariel YF, Pei H, Meng L, Yi Zhen NG, Graves N. Decision-making for early major amputation in selected diabetic foot ulcer patients with peripheral vascular disease. HEALTH CARE SCIENCE 2022; 1:58-68. [PMID: 38938892 PMCID: PMC11080880 DOI: 10.1002/hcs2.17] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Revised: 07/25/2022] [Accepted: 08/17/2022] [Indexed: 06/29/2024]
Abstract
Objective To estimate the costs from delaying major amputation in patients with concurrent diabetic foot ulcer and peripheral vascular disease. We seek to model economic benefits from saved costs from promoting timely major amputations among these patients. Methods Retrospective modeling using data from National University Hospital, Singapore. We identified patients who might have delayed major amputations by applying a hierarchical clustering algorithm. We then modeled the transitions of all patients over time with a Markov process using a number of relevant health states to enable estimation of cost outcomes. We next summarized the expected changes to the bed days used and cost outcomes arising from reassigning some patients who may have had a delayed amputation to timely amputation. The findings from the sample were scaled to reflect national incidence rates for this disease for the years 2014-2019 in Singapore. Results and Conclusions Nine of the 137 patients (6.57%) would be suitable for a major amputation at 3 months, yet in reality, their amputation was delayed. Based on this, and assuming a timely amputation is done for the entire population of patients in Singapore we expect annual savings of 264,791 bed days and $211 million in costs. These findings are preliminary and uncertain. The value of this paper is to show a method for estimating outcomes, report the findings from a small sample, and stimulate future research. New cohort studies might be designed to capture a wider range of outcomes and recruit a larger sample of individuals.
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Affiliation(s)
- Lim York Tee Gorden
- Wound Care Innovation for the Tropics Programme, Skin Research Institute of SingaporeA*STARSingaporeSingapore
| | - Ying Fangting Ariel
- Health Services and Systems ResearchDuke‐NUS Medical SchoolSingaporeSingapore
| | - Ho Pei
- Department of Surgery, Yong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore
| | - Lingyan Meng
- Department of Surgery, Yong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore
| | - N. G. Yi Zhen
- Wound Care Innovation for the Tropics Programme, Skin Research Institute of SingaporeA*STARSingaporeSingapore
| | - Nicholas Graves
- Health Services and Systems ResearchDuke‐NUS Medical SchoolSingaporeSingapore
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24
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Tong KP, Intine R, Wu S. Vitamin C and the management of diabetic foot ulcers: a literature review. J Wound Care 2022; 31:S33-S44. [PMID: 36113854 DOI: 10.12968/jowc.2022.31.sup9.s33] [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: 01/07/2023]
Abstract
OBJECTIVE The lifetime risk of developing a diabetic foot ulcer (DFU) in people with diabetes is as high as 25%. A trio of factors constitute the diabetic foot syndrome that characterises DFUs, including neuropathy, vascular disease and infections. Vitamin C has important functions in the nervous, cardiovascular, and immune systems that are implicated in DFU development. Furthermore, vitamin C deficiency has been observed in individuals with DFUs, suggesting an important function of vitamin C in DFU management and treatment. Therefore, this literature review evaluates the role of vitamin C in the nervous, cardiovascular and immune systems in relation to wound healing and DFUs, as well as discussing vitamin C's lesser known role in depression, a condition that affects many individuals with a DFU. METHOD A literature search was done using PubMed, Cochrane Library, Embase, Ovid, Computer Retrieval of Information on Scientific Projects, and NIH Clinical Center. Search terms included 'diabetic foot ulcer,' 'diabetic foot,' 'vitamin C,' and 'ascorbic acid.' RESULTS Of the 71 studies initially identified, seven studies met the inclusion criteria, and only three were human clinical trials. Overall, the literature on this subject is limited, with mainly observational and animal studies, and few human clinical trials. CONCLUSION There is a need for additional human clinical trials on vitamin C supplementation in individuals with a DFU to fill the knowledge gap and guide clinical practice.
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Affiliation(s)
- Khanh Phuong Tong
- Dr William M Scholl College of Podiatric Medicine, Rosalind Franklin University of Medicine and Science, Illinois, US
| | - Robert Intine
- School of Graduate and Postdoctoral Studies, College of Health Professions, Rosalind Franklin University of Medicine and Science, Illinois, US
| | - Stephanie Wu
- Dr William M Scholl College of Podiatric Medicine, Rosalind Franklin University of Medicine and Science, Illinois, US
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Mascarenhas-Melo F, Gonçalves MBS, Peixoto D, Pawar KD, Bell V, Chavda VP, Zafar H, Raza F, Paiva-Santos AC, Paiva-Santos AC. Application of nanotechnology in management and treatment of diabetic wounds. J Drug Target 2022; 30:1034-1054. [PMID: 35735061 DOI: 10.1080/1061186x.2022.2092624] [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: 10/17/2022]
Abstract
Diabetic wounds are one of the most common health problems worldwide, enhancing the demand for new management strategies. Nanotechnology, as a developing subject in diabetic wound healing, is proving to be a promising and effective tool in treatment and care. It is, therefore, necessary to ascertain the available and distinct nanosystems and evaluate their performance when topically applied to the injury site, especially in diabetic wound healing. Several active ingredients, including bioactive ingredients, growth factors, mesenchymal stem cells, nucleic acids, and drugs, benefit from improved properties when loaded into nanosystems. Given the risk of problems associated with systemic administration, the topical application should be considered, provided stability and efficacy are assured. After nanoencapsulation, active ingredients-loaded nanosystems have been showing remarkable features of biocompatibility, healing process hastening, angiogenesis, and extracellular matrix compounds synthesis stimulation, contributing to a decrease in wound inflammation. Despite limitations, nanotechnology has attracted widespread attention in the scientific community and seems to be a valuable technological ally in the treatment and dressing of diabetic wounds. The use of nanotechnology in topical applications enables efficient delivery of the active ingredients to the specific skin site, increasing their bioavailability, stability, and half-life time, without compromising their safety.
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Affiliation(s)
- Filipa Mascarenhas-Melo
- Drug Development and Technology Laboratory, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, Coimbra, Portugal.,REQUIMTE/LAQV, Group of Pharmaceutical Technology, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, Coimbra, Portugal
| | - Maria Beatriz S Gonçalves
- Drug Development and Technology Laboratory, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, Coimbra, Portugal
| | - Diana Peixoto
- Drug Development and Technology Laboratory, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, Coimbra, Portugal
| | - Kiran D Pawar
- School of Nanoscience and Biotechnology, Shivaji University, Vidyanagar, Kolhapur, Maharashtra, India
| | - Victoria Bell
- Laboratory of Social Pharmacy and Public Health, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, Coimbra, Portugal
| | - Vivek P Chavda
- Department of Pharmaceutics and Pharmaceutical Technology, L M College of Pharmacy, Ahmedabad, Gujarat, India
| | - Hajra Zafar
- School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China
| | - Faisal Raza
- School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China
| | - Ana Cláudia Paiva-Santos
- Drug Development and Technology Laboratory, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, Coimbra, Portugal.,REQUIMTE/LAQV, Group of Pharmaceutical Technology, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, Coimbra, Portugal
| | - Ana Cláudia Paiva-Santos
- Drug Development and Technology Laboratory, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, Coimbra, Portugal.,REQUIMTE/LAQV, Group of Pharmaceutical Technology, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, Coimbra, Portugal
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Wang LP, Geng J, Liu C, Wang Y, Zhang Z, Yang GY. Diabetes Mellitus-Related Neurobehavioral Deficits in Mice Are Associated With Oligodendrocyte Precursor Cell Dysfunction. Front Aging Neurosci 2022; 14:846739. [PMID: 35693337 PMCID: PMC9177201 DOI: 10.3389/fnagi.2022.846739] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2021] [Accepted: 04/19/2022] [Indexed: 11/13/2022] Open
Abstract
Recent clinical studies demonstrated an increase of the incidence of neurobehavioral disorders in patients with diabetes mellitus. Studies also found an association between severity of diabetes mellitus and the progression of white matter hyperintensity on magnetic resonance imaging, which conferred risk for developing cognitive impairment. Since oligodendrocyte precursor cells participated in the white matter repair and remodeling after ischemic brain injury, we explored whether hyperglycemia induced neurobehavioral deficits were associated with dysfunction of oligodendrocyte precursor cells. Adult male C57BL/6 mice (n = 40) were randomly divided into 4-week diabetes, 8-week diabetes, and control groups. Experimental diabetic mice were induced by streptozotocin injection. Learning and cognitive function, exploratory, anxiety and depression behaviors were assessed by Morris water maze, open field test, elevated plus maze, and tail suspension test, respectively. Immunofluorescence staining of neuron-glial antigen 2 and myelin basic protein were performed. Oligodendrocyte precursor cells were cultured in different glucose level to explore possible mechanism in vitro. The learning and cognitive function of 4-week and 8-week diabetic mice were attenuated compared to the control group (p < 0.05). The diabetic mice had less exploratory behavior compared to the control (p < 0.05). However, the diabetic mice were more likely to show anxiety (p < 0.05) and depression (p < 0.01) compared to the control. Further study demonstrated the number of oligodendrocyte precursor cells and the level of myelin basic protein expression were decreased in diabetic mice and the migration and survival ability were suppressed in the hyperglycemic environment in vitro (p < 0.05). Our results demonstrated that diabetes mellitus induced neurological deficits were associated with the decreased number and dysfunction of oligodendrocyte precursor cells.
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Affiliation(s)
- Li-Ping Wang
- Department of Neurology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China
| | - Jieli Geng
- Department of Neurology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- *Correspondence: Jieli Geng,
| | - Chang Liu
- Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China
| | - Yuyang Wang
- Department of Rehabilitation Medicine, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China
| | - Zhijun Zhang
- Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China
| | - Guo-Yuan Yang
- Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China
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Sun S, Mao W, Tao S, Wan L, Zou X, Zhang G, Chen M. Association Between Preoperative Blood Glucose Level and Hospital Length of Stay in Patients With Kidney Stones Undergoing Percutaneous Nephrolithotomy. Front Surg 2022; 8:820018. [PMID: 35127809 PMCID: PMC8811039 DOI: 10.3389/fsurg.2021.820018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2021] [Accepted: 12/27/2021] [Indexed: 11/13/2022] Open
Abstract
AimTo assess the effect of preoperative blood glucose (POBG) levels on the length of stay (LOS) in patients with kidney stones undergoing percutaneous nephrolithotomy (PCNL).MethodsWe conducted a retrospective study of patients who underwent PCNL at the Zhongda Hospital of Southeast University from 2013 to 2019. The relationship between POBG level and LOS was investigated by dose-response analysis curves of restricted cubic spline function.ResultsWe included 310 patients and divided them into three groups (<5.04, 5.04 to <6.88, ≥6.88 mmol/L) according to the POBG levels. Patients with POBG levels ≥6.88 mmol/L (adjusted odds risk [aOR] 1.67; 95% CI 0.83–3.33) had a 67% higher risk of LOS > 2 weeks than patients with POBG levels <5.04 mmol/L. A positive dose-response analysis curve was observed between POBG and the adjusted risk of LOS >2 weeks. Similar results were observed in the subgroups analysis.ConclusionWe demonstrated that higher POBG levels were significantly associated with longer LOS in patients with kidney stones undergoing PCNL.
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Affiliation(s)
- Si Sun
- Department of Urology, Zhongda Hospital, Southeast University, Nanjing, China
| | - Weipu Mao
- Department of Urology, Zhongda Hospital, Southeast University, Nanjing, China
- Surgical Research Center, Institute of Urology, Southeast University Medical School, Nanjing, China
- Department of Urology, Nanjing Lishui District People's Hospital, Zhongda Hospital Lishui Branch, Southeast University, Nanjing, China
| | - Shuchun Tao
- Department of Urology, Zhongda Hospital, Southeast University, Nanjing, China
| | - Lilin Wan
- Department of Urology, Zhongda Hospital, Southeast University, Nanjing, China
| | - Xiangyu Zou
- School of Basic Medical Sciences, Weifang Medical University, Weifang, China
| | - Guangyuan Zhang
- Department of Urology, Zhongda Hospital, Southeast University, Nanjing, China
- Surgical Research Center, Institute of Urology, Southeast University Medical School, Nanjing, China
- Guangyuan Zhang
| | - Ming Chen
- Department of Urology, Zhongda Hospital, Southeast University, Nanjing, China
- Surgical Research Center, Institute of Urology, Southeast University Medical School, Nanjing, China
- Department of Urology, Nanjing Lishui District People's Hospital, Zhongda Hospital Lishui Branch, Southeast University, Nanjing, China
- *Correspondence: Ming Chen
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van de Vyver M, Idensohn PJ, Niesler CU. A regenerative approach to the pharmacological management of hard-to-heal wounds. Biochimie 2022; 194:67-78. [PMID: 34982983 DOI: 10.1016/j.biochi.2021.12.016] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Revised: 11/27/2021] [Accepted: 12/29/2021] [Indexed: 12/12/2022]
Abstract
A wound is considered hard-to-heal when, despite the appropriate clinical analysis and intervention, the wound area reduces by less than a third at four weeks and complete healing fails to occur within 12 weeks. The most prevalent hard-to-heal wounds are associated with underlying metabolic diseases or vascular insufficiency and include arterial, venous, pressure and diabetic foot ulcers. Their common features include an abnormal immune response and extended inflammatory phase, a subdued proliferation phase due to cellular insufficiencies and finally an almost non-existent remodeling phase. Advances in wound care technology, tested in both pre-clinical models and clinical trials, have paved the way for improved treatment options, focused on regeneration. These interventions have been shown to limit the extent of ongoing inflammatory damage, decrease bacterial load, promote angiogenesis and deposition of granulation tissue, and stimulate keratinocyte migration thereby promoting re-epithelialization in these wounds. The current review discusses these hard-to-heal wounds in the context of their underlying pathology and potential of advanced treatment options, which if applied promptly as a standard of care, could reduce morbidity, promote quality of life, and alleviate the burden on a strained health system.
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Affiliation(s)
- M van de Vyver
- Division of Clinical Pharmacology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, South Africa.
| | - P J Idensohn
- CliniCare Medical Centre, Ballito, KwaZulu-Natal, South Africa; School of Nursing, Faculty of Health Sciences, University of the Free State, Bloemfontein, South Africa
| | - C U Niesler
- Discipline of Biochemistry, School of Life Sciences, University of KwaZulu Natal, Scottsville, South Africa
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30
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Leutner M, Kaleta M, Bellach L, Kautzky A, Thurner S, Klimek P, Kautzky-Willer A. Insulin as Monotherapy and in Combination with Other Glucose-Lowering Drugs Is Related to Increased Risk of Diagnosis of Pneumonia: A Longitudinal Assessment over Two Years. J Pers Med 2021; 11:jpm11100984. [PMID: 34683125 PMCID: PMC8537451 DOI: 10.3390/jpm11100984] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2021] [Revised: 09/21/2021] [Accepted: 09/24/2021] [Indexed: 01/22/2023] Open
Abstract
Objective: Patients with type 2 diabetes mellitus (T2DM) are at an increased risk of developing infectious diseases such as pneumonia. Hitherto, there has been uncertainty as to whether there is a relationship between different antidiabetic drug combinations and development of pneumonia in this specific cohort. Research Design and Methods: In this longitudinal retrospective study we used multiple logistic regression analysis to assess the odds ratios (ORs) of pneumonia during an observational period of 2 years in 31,397 patients with T2DM under previously prescribed stable antidiabetic drug combinations over a duration of 4 years in comparison to 6568 T2DM patients without drug therapy over 4 years adjusted for age, sex and hospitalization duration. Results: Of the 37,965 patients with T2DM, 3720 patients underwent stable monotherapy treatment with insulin (mean age: 66.57 ± 9.72 years), 2939 individuals (mean age: 70.62 ± 8.95 y) received stable statin and insulin therapy, and 1596 patients were treated with a stable combination therapy of metformin, insulin and statins (mean age: 68.27 ± 8.86 y). In comparison to the control group without antidiabetic drugs (mean age: 72.83 ± 9.96 y), individuals undergoing insulin monotherapy (OR: 2.07, CI: 1.54–2.79, p < 0.001); insulin and statin combination therapy (OR: 2.24, CI: 1.68–3.00, p < 0.001); metformin, insulin and statin combination therapy (OR: 2.27, CI: 1.55–3.31, p < 0.001); statin, insulin and dipeptidyl peptidase-4 inhibitor (DPP-IV inhibitor) combination therapy (OR: 4.31, CI: 1.80–10.33, p = 0.001); as well as individuals treated with metformin and sulfonylureas (OR: 1.70, CI: 1.08–2.69, p = 0.02) were at increased risk of receiving a diagnosis of pneumonia. Conclusions: Stable monotherapy with insulin, but also in combination with other antidiabetic drugs, is related to an increased risk of being diagnosed with pneumonia during hospital stays in patients with type 2 diabetes mellitus compared to untreated controls.
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Affiliation(s)
- Michael Leutner
- Department of Internal Medicine III, Clinical Division of Endocrinology and Metabolism, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria; (M.L.); (L.B.)
| | - Michaela Kaleta
- Section for Science of Complex Systems, CeMSIIS, Medical University of Vienna, Spitalgasse 23, A-1090 Vienna, Austria; (M.K.); (S.T.); (P.K.)
- Complexity Science Hub Vienna, Josefstaedter Strasse 39, A-1080 Vienna, Austria
| | - Luise Bellach
- Department of Internal Medicine III, Clinical Division of Endocrinology and Metabolism, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria; (M.L.); (L.B.)
| | - Alexander Kautzky
- Department of Psychiatry and Psychotherapy, Medical University of Vienna, A-1090 Vienna, Austria;
| | - Stefan Thurner
- Section for Science of Complex Systems, CeMSIIS, Medical University of Vienna, Spitalgasse 23, A-1090 Vienna, Austria; (M.K.); (S.T.); (P.K.)
- Complexity Science Hub Vienna, Josefstaedter Strasse 39, A-1080 Vienna, Austria
- Santa Fe Institute, 1399 Hyde Park Road, Santa Fe, NM 85701, USA
| | - Peter Klimek
- Section for Science of Complex Systems, CeMSIIS, Medical University of Vienna, Spitalgasse 23, A-1090 Vienna, Austria; (M.K.); (S.T.); (P.K.)
- Complexity Science Hub Vienna, Josefstaedter Strasse 39, A-1080 Vienna, Austria
| | - Alexandra Kautzky-Willer
- Department of Internal Medicine III, Clinical Division of Endocrinology and Metabolism, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria; (M.L.); (L.B.)
- Gender Institute, A-3571 Gars am Kamp, Austria
- Correspondence:
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31
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Schönborn M, Łączak P, Pasieka P, Borys S, Płotek A, Maga P. Pro- and Anti-Angiogenic Factors: Their Relevance in Diabetic Foot Syndrome-A Review. Angiology 2021; 73:299-311. [PMID: 34541892 DOI: 10.1177/00033197211042684] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Peripheral arterial disease can involve tissue loss in up to 50% of patients with diabetic foot syndrome (DFS). Consequently, revascularization of narrowed or occluded arteries is one of the most common forms of comprehensive treatment. However, technically successful angioplasty does not always result in the healing of ulcers. The pathomechanism of this phenomenon is still not fully understood, but inadequate angiogenesis in tissue repair may play an essential role. Changes in pro- and anti-angiogenic factors among patients with DFS are not always clear and conclusive. In particular, some studies underline the role of decreased concentration of pro-angiogenic factors and higher levels of anti-angiogenic mediators. Nevertheless, there are still controversial issues, including the paradox of impaired wound healing despite high concentrations of some pro-angiogenic factors, dynamics of their expression during the healing process, and their mutual relationships. Exploring this process among diabetic patients may provide new insight into well-known methods of treatment and show their real benefits and chances for improving outcomes.
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Affiliation(s)
- Martyna Schönborn
- Department of Angiology, Faculty of Medicine, 162261Jagiellonian University Medical College, Krakow, Poland.,Doctoral School of Medical and Health Sciences, 162261Jagiellonian University, Krakow, Poland
| | - Patrycja Łączak
- Department of Angiology, Faculty of Medicine, 162261Jagiellonian University Medical College, Krakow, Poland
| | - Paweł Pasieka
- Department of Angiology, Faculty of Medicine, 162261Jagiellonian University Medical College, Krakow, Poland
| | - Sebastian Borys
- Department of Metabolic Diseases, Faculty of Medicine, 162261Jagiellonian University Medical College, Krakow, Poland
| | - Anna Płotek
- Department of Angiology, Faculty of Medicine, 162261Jagiellonian University Medical College, Krakow, Poland
| | - Paweł Maga
- Department of Angiology, Faculty of Medicine, 162261Jagiellonian University Medical College, Krakow, Poland
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32
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Li Y, Zhao S, der Merwe LV, Dai W, Lin C. Efficacy of curcumin for wound repair in diabetic rats/mice: a systematic review and meta-analysis of preclinical studies. Curr Pharm Des 2021; 28:187-197. [PMID: 34139977 DOI: 10.2174/1381612827666210617122026] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2020] [Accepted: 04/08/2021] [Indexed: 12/09/2022]
Abstract
BACKGROUND Curcumin possesses multiple bioactivities that have beneficial effects on diabetic foot ulcers. Herein, we aimed to conduct a systematic preclinical review of 9 studies including a total of 262 animals, to assess the possible mechanisms of curcumin for wound healing in diabetic animals. METHODS Five databases were searched from inception to May 12, 2020; Rev-Man 5.3 software was applied for data analyses. Cochrane Collaboration's tool 10-item checklist was used to evaluate the methodological quality, and data revealed scores of risk of bias ranging from 2 to 5. RESULTS Meta-analysis indicated that curcumin had significant effects on wound healing rate and blood vessel density when compared with control (P < 0.05). The wound regeneration properties of curcumin for diabetic wounds are thought to mainly work through the possible mechanisms of antioxidation, enhanced cell proliferation, increased collagen formation, and angiogenesis. However, the anti-inflammatory effect on wounds in diabetic animals remains controversial. CONCLUSIONS The findings indicate that more randomized controlled trials should be pursued to obtain more reliable results regarding inflammatory response. Overall, curcumin might be a probable candidate for diabetic foot ulcers and may contribute to future clinical trials.
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Affiliation(s)
- Yuan Li
- Department of Burn, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
| | - Sheng Zhao
- Department of Burn, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
| | - Leanne Van der Merwe
- School of International Studies, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China
| | - Wentong Dai
- Department of Burn, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
| | - Cai Lin
- Department of Burn, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
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33
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Foussard N, Saulnier PJ, Potier L, Ragot S, Schneider F, Gand E, Monlun M, Baillet-Blanco L, Velho G, Marre M, Roussel R, Rigalleau V, Mohammedi K, Hadjadj S. Relationship Between Diabetic Retinopathy Stages and Risk of Major Lower-Extremity Arterial Disease in Patients With Type 2 Diabetes. Diabetes Care 2020; 43:2751-2759. [PMID: 33055101 DOI: 10.2337/dc20-1085] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2020] [Accepted: 08/05/2020] [Indexed: 02/03/2023]
Abstract
OBJECTIVE We evaluated the association between diabetic retinopathy stages and lower-extremity arterial disease (LEAD), its prognostic value, and the influence of potential contributors to this relationship in a prospective cohort of patients with type 2 diabetes. RESEARCH DESIGN AND METHODS Diabetic retinopathy was staged at baseline as absent, nonproliferative, or proliferative. A Cox regression model was fitted in order to compute the hazard ratio (HR) (95% CI) for major LEAD (lower-limb amputation or revascularization) during follow-up by baseline retinopathy stages. The retinopathy-LEAD association was assessed in subgroups by age, sex, diabetes duration, HbA1c, systolic blood pressure, diabetic kidney disease, smoking, and macrovascular disease at baseline. The performance of retinopathy in stratifying LEAD risk was assessed by using the C statistic, integrated discrimination improvement (IDI), and net reclassification improvement (NRI). RESULTS Among 1,320 participants without a history of LEAD at baseline, 94 (7.1%) developed a major LEAD during a 7.1-year median follow-up (incidence rate 9.6 per 1,000 person-years [95% CI 7.8-11.7]). The LEAD incidence rate (per 1,000 person-years) increased as retinopathy worsened: it was 5.5 (95% CI 3.9-7.8) in participants in whom retinopathy was absent, 14.6 (11.1-19.3) in those with nonproliferative retinopathy, and 20.1 (11.1-36.3) in those with proliferative retinopathy. Nonproliferative retinopathy (adjusted HR 2.31 [95% CI 1.43-3.81], P = 0.0006) and proliferative retinopathy (3.14 [1.40-6.15], P = 0.007) remained associated with major LEAD. No heterogeneity was observed across subgroups. Retinopathy enhanced the C statistic (+0.023 [95% CI 0.003-0.044], P = 0.02), IDI (0.209 [0.130-0.321], P < 0.001), and NRI (0.562 [0.382-0.799], P < 0.001) values for risk of LEAD, beyond traditional risk factors. CONCLUSIONS An independent dose-response relationship was identified between diabetic retinopathy stages and major LEAD. Retinopathy yielded incremental prognostic information for stratifying risk of LEAD, suggesting its usefulness as a predictor of LEAD.
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Affiliation(s)
- Ninon Foussard
- Hôpital Haut-Lévêque, Département d'Endocrinologie, Diabétologie, Nutrition, Pessac, Bordeaux, France
| | - Pierre-Jean Saulnier
- Université de Poitiers, UFR de Médecine et Pharmacie, Poitiers, France.,CHU de Poitiers, Centre d'Investigation Clinique, Poitiers, France.,INSERM, CIC 1402, Poitiers, France
| | - Louis Potier
- Assistance Publique-Hôpitaux de Paris, Bichat Hospital, Département de Diabétologie, Endocrinologie, Nutrition, Paris, France.,Université de Paris, Paris, France.,Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université de Paris, Paris, France
| | - Stéphanie Ragot
- Université de Poitiers, UFR de Médecine et Pharmacie, Poitiers, France.,CHU de Poitiers, Centre d'Investigation Clinique, Poitiers, France.,INSERM, CIC 1402, Poitiers, France
| | - Fabrice Schneider
- Université de Poitiers, UFR de Médecine et Pharmacie, Poitiers, France.,Département de Chirurgie Vasculaire, CHU de Poitiers, Poitiers, France
| | - Elise Gand
- CHU de Poitiers, Centre d'Investigation Clinique, Poitiers, France
| | - Marie Monlun
- Hôpital Haut-Lévêque, Département d'Endocrinologie, Diabétologie, Nutrition, Pessac, Bordeaux, France
| | - Laurence Baillet-Blanco
- Hôpital Haut-Lévêque, Département d'Endocrinologie, Diabétologie, Nutrition, Pessac, Bordeaux, France
| | - Gilberto Velho
- Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université de Paris, Paris, France
| | - Michel Marre
- Université de Paris, Paris, France.,Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université de Paris, Paris, France.,CMC Ambroise Paré, Neuilly-sur-Seine, France
| | - Ronan Roussel
- Assistance Publique-Hôpitaux de Paris, Bichat Hospital, Département de Diabétologie, Endocrinologie, Nutrition, Paris, France.,Université de Paris, Paris, France.,Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université de Paris, Paris, France
| | - Vincent Rigalleau
- Hôpital Haut-Lévêque, Département d'Endocrinologie, Diabétologie, Nutrition, Pessac, Bordeaux, France.,Université de Bordeaux, UFR de Médecine, Bordeaux, France.,INSERM U1219 "Bordeaux Population Health," Bordeaux, France
| | - Kamel Mohammedi
- Hôpital Haut-Lévêque, Département d'Endocrinologie, Diabétologie, Nutrition, Pessac, Bordeaux, France .,Université de Bordeaux, UFR de Médecine, Bordeaux, France.,INSERM U1034, Biologie des Maladies Cardiovasculaires, Bordeaux, France
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Kim J, Park IW, Kwon S. Factors predicting final visual outcome in quiescent proliferative diabetic retinopathy. Sci Rep 2020; 10:17233. [PMID: 33057083 PMCID: PMC7566633 DOI: 10.1038/s41598-020-74184-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2020] [Accepted: 09/22/2020] [Indexed: 12/04/2022] Open
Abstract
To investigate factors reflecting visual outcome and macular perfusion in quiescent proliferative diabetic retinopathy (PDR) patients after panretinal photocoagulation (PRP). We included 118 patients with quiescent PDR who had completed PRP. All participants had standardized interview to determine ocular history, smoking status, cardiovascular risk factors, and history of diabetic mellitus (DM). Foveal avascular zone (FAZ) area, retinal vessel density (VD) and vessel length density (VLD) were measured using optical coherence tomography angiography. VD was negatively correlated with hypertension, diabetic foot, HbA1c, and time after PRP (β = − 0.181, P = 0.046; β = − 0.231, P = 0.020; β = − 0.244, P = 0.010; β = − 0.278, P = 0.029). FAZ area of superficial capillary plexus and deep capillary plexus (DCP) was positively correlated with DM duration and diabetic foot (β = 0.178, P = 0.047; β = 0.293, P = 0.002; β = 0.252, P = 0.045; β = 0.304, P = 0.002). Macular perfusion state in patients with quiescent PDR was associated with diabetic foot, DM duration, HbA1c, and time after PRP. Of note, diabetic foot showed the strongest correlation with macular perfusion among various systemic factors. VLD, especially in DCP was associated with poor visual outcome.
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Affiliation(s)
- Jinsoo Kim
- Department of Ophthalmology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, 22, Gwanpyeong-ro 170beon-gil, Dongan-gu, Anyang, 14068, Republic of Korea
| | - In Won Park
- Department of Ophthalmology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, 22, Gwanpyeong-ro 170beon-gil, Dongan-gu, Anyang, 14068, Republic of Korea
| | - Soonil Kwon
- Department of Ophthalmology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, 22, Gwanpyeong-ro 170beon-gil, Dongan-gu, Anyang, 14068, Republic of Korea.
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Ranaldi GT, Villani ER, Franza L. Rationale for ozone-therapy as an adjuvant therapy in COVID-19: a narrative review. Med Gas Res 2020; 10:134-138. [PMID: 33004712 PMCID: PMC8086623 DOI: 10.4103/2045-9912.289462] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Coronavirus disease 2019 (COVID-19) is the respiratory disease caused by the novel severe acute respiratory syndrome-coronavirus-2 and is characterized by clinical manifestations ranging from mild, flu-like symptoms to severe respiratory insufficiency and multi-organ failure. Patients with more severe symptoms may require intensive care treatments and face a high mortality risk. Also, thrombotic complications such as pulmonary embolisms and disseminated intravascular coagulation are frequent in these patients. Indeed, COVID-19 is characterized by an abnormal inflammatory response resembling a cytokine storm, which is associated to endothelial dysfunction and microvascular complications. To date, no specific treatments are available for COVID-19 and its life-threatening complication. Immunomodulatory drugs, such as hydroxychloroquine and interleukin-6 inhibitors, as well as antithrombotic drugs such as heparin and low molecular weight heparin, are currently being administered with some benefit. Ozone therapy consists in the administration of a mixture of ozone and oxygen, called medical ozone, which has been used for over a century as an unconventional medicine practice for several diseases. Medical ozone rationale in COVID-19 is the possibility of contrasting endothelial dysfunction, modulating the immune response and acting as a virustatic agent. Thus, medical ozone could help to decrease lung inflammation, slow down viral growth, regulate lung circulation and oxygenation and prevent microvascular thrombosis. Ozone-therapy could be considered a feasible, cost-effective and easy to administer adjuvant therapy while waiting for the synthesis of a therapy or the development of the vaccine.
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Affiliation(s)
- Giovanni Tommaso Ranaldi
- Unità Operativa Semplice Dipartimentale Farmacologia Clinica e Sperimentazione Clinica, Azienda Sanitaria, Potenza, Italy
| | | | - Laura Franza
- Department of Emergency Medicine, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy
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36
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Normahani P, Agrawal R, Sounderajah V, Tsinaslanidis P, Musonda P, Mehar Z, Powezka K, Bravis V, Aslam M, Jaffer U. Arterial spectral waveform analysis in the prediction of diabetic foot ulcer healing. Perfusion 2020; 36:751-756. [PMID: 32957822 PMCID: PMC8446888 DOI: 10.1177/0267659120957849] [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] [Indexed: 11/23/2022]
Abstract
Objective: We assessed the association between (1) severity of vessel wall
calcification, (2) number of patent vessels at the ankle and (3) arterial
spectral waveform features, as assessed on a focused ankle Duplex ultrasound
(DUS), and healing at 12-months in a cohort of patients who had their
diabetic foot ulcers conservatively managed. Research design and methods: Scans performed on 50 limbs in 48 patients were included for analysis.
Patient health records were prospectively reviewed for 12-months to assess
for the outcome of ulcer healing. Results: We identified that the number of waveform components, peak systolic velocity,
systolic rise time and long forward flow as well as the number of vessels
patent at the ankle on DUS, may be useful independent predictors of healing,
as noted by the trend towards statistical significance. Conclusion: Arterial spectral waveform features may be useful in predicting the chance of
diabetic foot ulcer healing.
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Affiliation(s)
- Pasha Normahani
- Imperial Vascular Unit, Imperial College NHS Healthcare Trust, London, UK
| | - Rishi Agrawal
- Imperial Vascular Unit, Imperial College NHS Healthcare Trust, London, UK
| | | | | | - Patrick Musonda
- School of Medicine, Health Policy & Practice, University of East Anglia, London, UK
| | - Zaheer Mehar
- West Middlesex University Hospital Diabetic Foot Service, Chelsea and Westminster Hospital NHS Foundation Trust, Isleworth, London, UK
| | - Katarzyna Powezka
- Imperial Vascular Unit, Imperial College NHS Healthcare Trust, London, UK
| | - Vasiliki Bravis
- Department of Diabetes and Endocrinology, St Mary's Hospital, Imperial College NHS Healthcare Trust, London, UK
| | - Mohammed Aslam
- Imperial Vascular Unit, Imperial College NHS Healthcare Trust, London, UK
| | - Usman Jaffer
- Imperial Vascular Unit, Imperial College NHS Healthcare Trust, London, UK
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37
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Zografou I, Iliadis F, Sambanis C, Didangelos T. Validation of Neuropad in the Assessment of Peripheral Diabetic Neuropathy in Patients with Diabetes Mellitus Versus the Michigan Neuropathy Screening Instrument, 10g Monofilament Application and Biothesiometer Measurement. Curr Vasc Pharmacol 2020; 18:517-522. [DOI: 10.2174/1570161117666190723155324] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2019] [Revised: 06/30/2019] [Accepted: 07/05/2019] [Indexed: 12/24/2022]
Abstract
Objective:
Sudomotor dysfunction is a feature of Diabetic Peripheral Neuropathy (DPN). The
indicator plaster Neuropad can provide an easy and accurate way to diagnose DPN. The aim of the present
study was to evaluate Neuropad’s specificity, sensitivity and accuracy in detecting DPN in patients
with Diabetes Mellitus (DM).
Methods:
A total of 174 patients with DM (79 with type 1 DM, 88 women), mean age 49.8 ± 16.1 years
and mean DM duration 17.3 ± 7.7 years were included in the present study. The following methods
were used to diagnose DPN: the Michigan Neuropathy Screening Instrument Questionnaire and Examination
(MNSIQ and MNSIE, respectively), application of 10 g monofilament (MONO) and measurement
of vibration perception threshold with biothesiometer (BIO). Neuropad was applied to both feet in
all patients and according to the presence or absence of color change of the sticker, patients were divided
in two groups: group A (n = 82, complete change in color from blue to pink, depicting normal
perspiration) and group B (n = 92, incomplete or no change, depicting abnormal perspiration).
Results:
MNSIQ and MNSIE were positive for DPN in 111 and 119 patients, respectively. BIO was
abnormal in 109 and MONO in 59 patients. Sensitivity of Neuropad testing was 95% vs. MONO, 73%
vs. BIO, 73% vs. MNSIE and 75% vs. ΜNSIQ. Specificity was 69, 81, 90 and 92%, respectively and
accuracy of the test was 78, 76, 78 and 83%, respectively.
Conclusion:
Neuropad has a high sensitivity and specificity in detecting DPN vs. MNSIQ, MNSIE and
BIO. Neuropad has a high sensitivity but moderate specificity vs. MONO. The accuracy of the test was
high in all measurements.
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Affiliation(s)
- Ioanna Zografou
- Diabetes Center, 2nd Propedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, Hippocration Hospital, Thessaloniki, Greece
| | - Fotios Iliadis
- Diabetes Center, 1st Propedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, ''AHEPA'' Hospital, Thessaloniki, Greece
| | - Christos Sambanis
- Diabetes Center, 2nd Propedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, Hippocration Hospital, Thessaloniki, Greece
| | - Triantafyllos Didangelos
- Diabetes Center, 1st Propedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, ''AHEPA'' Hospital, Thessaloniki, Greece
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38
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Li Y, Guo M, Qian X, Lin W, Zheng Y, Yu K, Zeng B, Xu Z, Zheng C, Xu M. Single snapshot spatial frequency domain imaging for risk stratification of diabetes and diabetic foot. BIOMEDICAL OPTICS EXPRESS 2020; 11:4471-4483. [PMID: 32923057 PMCID: PMC7449725 DOI: 10.1364/boe.394929] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/13/2020] [Revised: 06/24/2020] [Accepted: 06/25/2020] [Indexed: 05/29/2023]
Abstract
Diabetic foot is one of the major complications of diabetes. In this work, a real-time Single Snapshot Multiple-frequency Demodulation (SSMD) - Spatial Frequency Domain Imaging (SFDI) system was used to image the forefoot of healthy volunteers, diabetes, and diabetic foot patients. A layered skin model was used to obtain the 2D maps of optical and physiological parameters, including cutaneous hemoglobin concentration, oxygen saturation, scattering properties, melanin content, and epidermal thickness, from every single snapshot. We observed a strong correlation between the measured optical and physiological parameters and the degree of diabetes. The cutaneous hemoglobin concentration, oxygen saturation, and epidermal thickness decrease, whereas the melanin content increases with the progress of diabetes. The melanin content further increases, and the reduced scattering coefficient and scattering power are lower for diabetic foot patients than those of both healthy and diabetic subjects. High accuracies (AUC) of 97.2% (distinguishing the diabetic foot patients among all subjects), 95.2% (separating healthy subjects from the diabetes patients), and 87.8% (classifying mild vs severe diabetes), respectively, are achieved in binary classifications in sequence using the SSMD-SFDI system, demonstrating its applicability to risk stratification of diabetes and diabetic foot. The prognostic value of the SSMD-SFDI system in the prediction of the occurrence of the diabetic foot and other applications in monitoring tissue microcirculation and peripheral vascular disease are also addressed.
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Affiliation(s)
- Ying Li
- Institute of Lasers and Biomedical Photonics, Biomedical Engineering College, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China
| | - Mingrou Guo
- Institute of Lasers and Biomedical Photonics, Biomedical Engineering College, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China
| | - Xiafei Qian
- Institute of Lasers and Biomedical Photonics, Biomedical Engineering College, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China
| | - Weihao Lin
- Institute of Lasers and Biomedical Photonics, Biomedical Engineering College, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China
| | - Yang Zheng
- Institute of Lasers and Biomedical Photonics, Biomedical Engineering College, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China
| | - Kangyuan Yu
- Institute of Lasers and Biomedical Photonics, Biomedical Engineering College, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China
| | - Bixin Zeng
- Institute of Lasers and Biomedical Photonics, Biomedical Engineering College, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China
| | - Zhang Xu
- The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China
| | - Chao Zheng
- The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China
| | - M. Xu
- Institute of Lasers and Biomedical Photonics, Biomedical Engineering College, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China
- Dept. of Physics and Astronomy, Hunter College and the Graduate Center, The City University of New York, 695 Park Avenue, New York, NY 10065, USA
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Lewis JE, Morris K, Powell T, Thomas RL, Owens DR. Combining diabetic foot and retinopathy screening: A step in the right direction? - a feasibility study. SAGE Open Med 2020; 8:2050312120946244. [PMID: 32782799 PMCID: PMC7388135 DOI: 10.1177/2050312120946244] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2020] [Accepted: 07/09/2020] [Indexed: 12/26/2022] Open
Abstract
Objectives Peripheral artery disease is a major cardiovascular disease affecting more than 200 million people globally and up to 4 times more frequent in the diabetic population. It can lead to lower extremity amputations or revascularisation and is associated with an increased risk of myocardial infarction, stroke and early mortality. This novel cross-sectional study aimed to explore the feasibility and acceptability of incorporating diabetic foot screening at routine diabetic retinopathy screening appointments. Methods Participants underwent foot screening during the interval between pupil dilatation and retinal photography as part of the eye screening procedure. Lower limb arterial assessment included ankle brachial index, pulse volume waveform and protective light touch sensation. Results Of 364 participants invited, 88% (n = 321) met the inclusion criteria. About 26.4% (n = 86) had asymptomatic peripheral artery disease and 3% (n = 10) had peripheral sensory neuropathy. Binary logistical regression analysis identified age (p < 0.005), existing coronary heart disease (p < 0.005) and gender (p = 0.03) as predictors of peripheral artery disease. Conclusion Incorporating foot examination during eye screening appointments is feasible and was well received by participants and staff alike. Undiagnosed early peripheral artery disease was evident in a third of the study population emphasising the benefit of introducing foot surveillance into eye screening appointments for the early identification of lower limb arterial disease and peripheral sensory neuropathy.
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Affiliation(s)
| | | | - Thomas Powell
- Cwm Taf Morgannwg University Health Board, Abercynon, UK
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Saeed K, Esposito S, Akram A, Ascione T, Bal AM, Bassetti M, Carnelutti A, Chan M, Davis J, Dryden M, Farhan MFM, Fernando S, Gottlieb T, Gould I, Yildiz M, Lye DC, Pagliano P, Poole S, Pottinger PS, Spera AM, Unal S, Yalcin AN. Hot topics in diabetic foot infection. Int J Antimicrob Agents 2020; 55:105942. [PMID: 32194153 DOI: 10.1016/j.ijantimicag.2020.105942] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2019] [Revised: 03/05/2020] [Accepted: 03/06/2020] [Indexed: 01/12/2023]
Affiliation(s)
- Kordo Saeed
- Southampton University Hospitals NHS Foundation Trust, Microbiology Innovation and Research Unit (MIRU), Microbiology Department, Southampton, UK; University of Southampton, School of Medicine, Southampton, UK.
| | | | - Ayesha Akram
- John Hunter Hospital, University of Newcastle, Australia
| | | | - Abhijit M Bal
- Department of Microbiology, University Hospital Cross House, NHS, Ayrshire & Arran, UK; Faculty of Medicine, University of Glasgow, Glasgow, UK (Honorary Associate Professor)
| | - Matteo Bassetti
- Infectious Diseases Clinic, Department of Health Sciences and Ospedale Policlinico San Martino, Genoa, Italy
| | - Alessia Carnelutti
- Infectious Diseases Clinic, Department of Medicine University of Udine and Azienda Sanitaria Universitaria Integrata di Udine, Udine, Italy
| | - Monica Chan
- Department of Infectious Diseases, Tan Tock Seng Hospital, National Centre for Infectious Diseases, Singapore
| | - Joshua Davis
- Menzies School of Health Research, John Hunter Hospital, University of Newcastle, Australia
| | - Matthew Dryden
- Hampshire Hospitals NHS Foundation trust, Winchester and Basingstoke, UK; Public Health England, Rare and Imported Fever Services, Porton Down, UK
| | | | - Shelanah Fernando
- Department of Microbiology & Infectious Diseases, Concord Repatriation General Hospital, Hospital Road, Concord, NSW, Australia; Department of Medicine, University of Sydney, Sydney, Australia
| | - Thomas Gottlieb
- Department of Microbiology & Infectious Diseases, Concord Repatriation General Hospital, Hospital Road, Concord, NSW, Australia; Department of Medicine, University of Sydney, Sydney, Australia
| | - Ian Gould
- Department of Medical Microbiology, Aberdeen Royal Infirmary, Aberdeen, UK
| | - Merve Yildiz
- Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Akdeniz University, Antalya, Turkey
| | - David Chien Lye
- National Centre for Infectious Diseases; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Tan Tock Seng Hospital, Singapore
| | | | - Stephen Poole
- Southampton University Hospitals NHS Foundation Trust, Microbiology Innovation and Research Unit (MIRU), Microbiology Department, Southampton, UK
| | - Paul S Pottinger
- Department of Medicine, Division of Allergy & Infectious Diseases, University of Washington, Seattle Washington, USA
| | | | - Serhat Unal
- Department of Infectious Diseases, Faculty of Medicine, Hacettepe University, Ankara, Turkey
| | - Ata Nevzat Yalcin
- Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Akdeniz University, Antalya, Turkey
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Kokkinidis DG, Giannopoulos S, Haider M, Jordan T, Sarkar A, Singh GD, Secemsky EA, Giri J, Beckman JA, Armstrong EJ. Active smoking is associated with higher rates of incomplete wound healing after endovascular treatment of critical limb ischemia. Vasc Med 2020; 25:427-435. [PMID: 32460647 DOI: 10.1177/1358863x20916526] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
The association between active smoking and wound healing in critical limb ischemia (CLI) is unknown. Our objective was to examine in a retrospective cohort study whether active smoking is associated with higher incomplete wound healing rates in patients with CLI undergoing endovascular interventions. Smoking status was assessed at the time of the intervention, comparing active to no active smoking, and also during follow-up visits at 6 and 9 months. Cox regression analysis was conducted to compare the incomplete wound healing rates of the two groups during follow-up. A total of 264 patients (active smokers: n = 41) were included. Active smoking was associated with higher rates of incomplete wound healing in the 6-month univariate Cox regression analysis (hazard ratio (HR) for incomplete wound healing: 4.54; 95% CI: 1.41-14.28; p = 0.012). The 6-month Kaplan-Meier (KM) estimates for incomplete wound healing were 91.1% for the active smoking group versus 66% for the non-current smoking group. Active smoking was also associated with higher rates of incomplete wound healing in the 9-month univariable (HR for incomplete wound healing: 2.32; 95% CI: 1.11-4.76; p = 0.026) and multivariable analysis (HR for incomplete wound healing: 9.09; 95% CI: 1.06-100.0; p = 0.044). The 9-month KM estimates for incomplete wound healing were 75% in the active smoking group versus 54% in the non-active smoking group. In conclusion, active smoking status at the time of intervention in patients with CLI is associated with higher rates of incomplete wound healing during both 6- and 9-month follow-up.
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Affiliation(s)
- Damianos G Kokkinidis
- Division of Cardiology, Rocky Mountain Regional VA Medical Center, University of Colorado, Denver, CO, USA
| | - Stefanos Giannopoulos
- Division of Cardiology, Rocky Mountain Regional VA Medical Center, University of Colorado, Denver, CO, USA
| | - Moosa Haider
- Vascular Center and Division of Cardiovascular Medicine, University of California, Davis, Sacramento, CA, USA
| | - Timothy Jordan
- Vascular Center and Division of Cardiovascular Medicine, University of California, Davis, Sacramento, CA, USA
| | - Anita Sarkar
- Vascular Center and Division of Cardiovascular Medicine, University of California, Davis, Sacramento, CA, USA
| | - Gagan D Singh
- Vascular Center and Division of Cardiovascular Medicine, University of California, Davis, Sacramento, CA, USA
| | - Eric A Secemsky
- Department of Medicine, Smith Center for Outcomes Research in Cardiology, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Jay Giri
- Penn Cardiovascular Outcomes, Quality and Evaluative Research Center, Leonard Davis Institute of Health Economics, University of Pennsylvania, Philadelphia, PA, USA.,Cardiovascular Medicine Division, University of Pennsylvania, Philadelphia, PA, USA
| | - Joshua A Beckman
- Department of Medicine-Cardiology, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Ehrin J Armstrong
- Division of Cardiology, Rocky Mountain Regional VA Medical Center, University of Colorado, Denver, CO, USA
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Long G, Liu D, He X, Shen Y, Zhao Y, Hou X, Chen B, OuYang W, Dai J, Li X. A dual functional collagen scaffold coordinates angiogenesis and inflammation for diabetic wound healing. Biomater Sci 2020; 8:6337-6349. [PMID: 33025970 DOI: 10.1039/d0bm00999g] [Citation(s) in RCA: 45] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Chronic diabetic wounds, which are associated with persistent inflammation and impaired angiogenesis, occur frequently in diabetic patients.
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Ku EJ, Won GW, Lee YH, Lee DH, Jeon HJ, Oh TK. Genetic variation in TCF7L2 rs7903146 correlating with peripheral arterial disease in long-standing type 2 diabetes. Diab Vasc Dis Res 2020; 17:1479164119888475. [PMID: 31775533 PMCID: PMC7510358 DOI: 10.1177/1479164119888475] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
AIM The aim of this study was to investigate the association between the transcription factor 7-like 2 gene (TCF7L2) rs7903146 polymorphism and peripheral arterial disease in type 2 diabetes. METHODS In total, 1818 Korean type 2 diabetes patients were enrolled from January 2013 to December 2017. Subjects were categorized into two groups according to their duration of type 2 diabetes: long (⩾10 years, n = 771) and short (<10 years, n = 1047) durations. A multivariate logistic regression model was used for assuming an additive effect on peripheral arterial disease for the presence of a variant allele in TCF7L2 rs7903146. RESULTS The frequency of the minor T-allele was 7.6% (n = 139), and this allele was significantly associated with a 2.6-fold higher risk of peripheral arterial disease (odds ratio = 2.595, 95% confidence interval = 1.177-5.722, p = 0.018) in patients exhibiting a long duration of type 2 diabetes (⩾10 years). This result was significant after adjusting for age, sex, body mass index, familial history of diabetes, smoking, duration of diabetes and laboratory measurements, which included glycated haemoglobin, fasting plasma glucose and lipid profiles. In patients with diabetes < 10 years, there was no significant association between TCF7L2 rs7903146 and peripheral arterial disease (odds ratio = 1.233, 95% confidence interval = 0.492-3.093, p = 0.655). CONCLUSION Our results provide evidence that genetic variation in TCF7L2 rs7903146 could increase risk for peripheral arterial disease in patients exhibiting long-standing type 2 diabetes.
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Affiliation(s)
- Eu Jeong Ku
- Department of Internal Medicine, Chungbuk
National University Hospital, Cheongju, Republic of Korea
- Department of Internal Medicine, College of
Medicine, Chungbuk National University, Cheongju, Republic of Korea
| | - Gun Woo Won
- Department of Biochemistry, College of
Medicine, Chungbuk National University, Cheongju, Republic of Korea
| | - Yong Hee Lee
- Department of Biochemistry, College of
Medicine, Chungbuk National University, Cheongju, Republic of Korea
| | - Dong-Hwa Lee
- Department of Internal Medicine, Chungbuk
National University Hospital, Cheongju, Republic of Korea
- Department of Internal Medicine, College of
Medicine, Chungbuk National University, Cheongju, Republic of Korea
| | - Hyun Jeong Jeon
- Department of Internal Medicine, Chungbuk
National University Hospital, Cheongju, Republic of Korea
- Department of Internal Medicine, College of
Medicine, Chungbuk National University, Cheongju, Republic of Korea
| | - Tae Keun Oh
- Department of Internal Medicine, Chungbuk
National University Hospital, Cheongju, Republic of Korea
- Department of Internal Medicine, College of
Medicine, Chungbuk National University, Cheongju, Republic of Korea
- Tae Keun Oh, Department of Internal Medicine,
College of Medicine, Chungbuk National University, Cheongju 28644, Republic of Korea.
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Current Therapeutic Strategies in Diabetic Foot Ulcers. Medicina (B Aires) 2019; 55:medicina55110714. [PMID: 31731539 PMCID: PMC6915664 DOI: 10.3390/medicina55110714] [Citation(s) in RCA: 109] [Impact Index Per Article: 18.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2019] [Revised: 10/16/2019] [Accepted: 10/21/2019] [Indexed: 01/07/2023] Open
Abstract
Diabetic foot ulcers (DFUs) are the fastest growing chronic complication of diabetes mellitus, with more than 400 million people diagnosed globally, and the condition is responsible for lower extremity amputation in 85% of people affected, leading to high-cost hospital care and increased mortality risk. Neuropathy and peripheral arterial disease trigger deformities or trauma, and aggravating factors such as infection and edema are the etiological factors for the development of DFUs. DFUs require identifying the etiology and assessing the co-morbidities to provide the correct therapeutic approach, essential to reducing lower-extremity amputation risk. This review focuses on the current treatment strategies for DFUs with a special emphasis on tissue engineering techniques and regenerative medicine that collectively target all components of chronic wound pathology.
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Wang M, Wang C, Chen M, Xi Y, Cheng W, Mao C, Xu T, Zhang X, Lin C, Gao W, Guo Y, Lei B. Efficient Angiogenesis-Based Diabetic Wound Healing/Skin Reconstruction through Bioactive Antibacterial Adhesive Ultraviolet Shielding Nanodressing with Exosome Release. ACS NANO 2019; 13:10279-10293. [PMID: 31483606 DOI: 10.1021/acsnano.9b03656] [Citation(s) in RCA: 359] [Impact Index Per Article: 59.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/15/2023]
Abstract
Diabetic wound healing and angiogenesis remain a worldwide challenge for both clinic and research. The use of adipose stromal cell derived exosomes delivered by bioactive dressing provides a potential strategy for repairing diabetic wounds with less scar formation and fast healing. In this study, we fabricated an injectable adhesive thermosensitive multifunctional polysaccharide-based dressing (FEP) with sustained pH-responsive exosome release for promoting angiogenesis and diabetic wound healing. The FEP dressing possessed multifunctional properties including efficient antibacterial activity/multidrug-resistant bacteria, fast hemostatic ability, self-healing behavior, and tissue-adhesive and good UV-shielding performance. FEP@exosomes (FEP@exo) can significantly enhance the proliferation, migration, and tube formation of endothelial cells in vitro. In vivo results from a diabetic full-thickness cutaneous wound model showed that FEP@exo dressing accelerated the wound healing by stimulating the angiogenesis process of the wound tissue. The enhanced cell proliferation, granulation tissue formation, collagen deposition, remodeling, and re-epithelialization probably lead to the fast healing with less scar tissue formation and skin appendage regeneration. This study showed that combining bioactive molecules into multifunctional dressing should have great potential in achieving satisfactory healing in diabetic and other vascular-impaired related wounds.
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Affiliation(s)
- Min Wang
- Frontier Institute of Science and Technology, Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology , Xi'an Jiaotong University , Xi'an 710000 , China
| | - Chenggui Wang
- Key Laboratory of Orthopedics of Zhejiang Province , Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University , Wenzhou 325027 , China
- Department of Orthopedics Surgery , Second Affiliated Hospital, School of Medicine, Zhejiang University , Hangzhou 310009 , China
| | - Mi Chen
- Frontier Institute of Science and Technology, Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology , Xi'an Jiaotong University , Xi'an 710000 , China
| | - Yuewei Xi
- Frontier Institute of Science and Technology, Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology , Xi'an Jiaotong University , Xi'an 710000 , China
| | - Wei Cheng
- Frontier Institute of Science and Technology, Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology , Xi'an Jiaotong University , Xi'an 710000 , China
| | - Cong Mao
- Key Laboratory of Orthopedics of Zhejiang Province , Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University , Wenzhou 325027 , China
| | - Tianzhen Xu
- Key Laboratory of Orthopedics of Zhejiang Province , Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University , Wenzhou 325027 , China
| | - Xingxing Zhang
- Department of Burn , First Affiliated Hospital of Wenzhou Medical University , Wenzhou 325000 , China
| | - Cai Lin
- Department of Burn , First Affiliated Hospital of Wenzhou Medical University , Wenzhou 325000 , China
| | - Weiyang Gao
- Key Laboratory of Orthopedics of Zhejiang Province , Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University , Wenzhou 325027 , China
| | - Yi Guo
- Department of Biologic and Materials Science , University of Michigan , Ann Arbor , Michigan 48109 , United States
| | - Bo Lei
- Frontier Institute of Science and Technology, Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology , Xi'an Jiaotong University , Xi'an 710000 , China
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Pu D, Lei X, Leng W, Zheng Y, Chen L, Liang Z, Chen B, Wu Q. Lower limb arterial intervention or autologous platelet-rich gel treatment of diabetic lower extremity arterial disease patients with foot ulcers. ANNALS OF TRANSLATIONAL MEDICINE 2019; 7:485. [PMID: 31700921 PMCID: PMC6803174 DOI: 10.21037/atm.2019.07.87] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/31/2019] [Accepted: 07/24/2019] [Indexed: 11/06/2022]
Abstract
BACKGROUND To investigate whether lower limb vascular intervention or autologous platelet-rich gel (APG) treatment would benefit diabetic lower extremity arterial disease (LEAD) patients with foot ulcers. METHODS A total of 82 diabetic LEAD patients with foot ulcers were recruited and divided into three groups: group A (30 patients received basal treatment), group B (21 patients received basal and APG treatment), and group C (31 patients received basal and lower limb vascular intervention treatment). All patients underwent routine follow-up visits for 6 months. The baseline characteristics and parameters were examined. After treatment, changes in all parameters from baseline were recorded. The differences between groups and the relationship among each parameter were determined. RESULTS There were no differences in the ankle brachial index (ABI) or major amputation between groups A and B (P>0.05). Compared with groups A and B, the ABI and major amputation rate of group C were improved (P<0.05). There were no significant differences in transcutaneous oxygen partial pressure (TcPO2), the heal rate or minor amputation between groups A and C (P>0.05). Compared with groups A and C, TcPO2, the heal rate and minor amputation of group B were improved (P<0.05). The logistic regression analysis indicated that major amputation was mainly associated with the ABI, and minor amputation was mainly associated with TcPO2. Lower limb vascular intervention improves the ABI and reduces major amputation, and APG improves TcPO2 and reduces minor amputation. CONCLUSIONS In diabetic LEAD patients with foot ulcers, major amputation was mainly associated with the ABI, while minor amputation was mainly associated with TcPO2. Interventional surgery (angioplasty) mainly improves the ABI, reduces the incidence of major amputation and improves the macrovasculature, and APG mainly improves local TcPO2, reduces the incidence of minor amputation and improves the microcirculation.
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Affiliation(s)
- Danlan Pu
- Endocrinology and Nephrology Department, Chongqing University Cancer Hospital and Chongqing Cancer Institute and Chongqing Cancer Hospital, Chongqing 400030, China
| | - Xiaotian Lei
- Endocrinology Department, the First Affiliated Hospital of the Third Military Medical University (Army Medical University), Chongqing 400038, China
| | - Weiling Leng
- Endocrinology Department, the First Affiliated Hospital of the Third Military Medical University (Army Medical University), Chongqing 400038, China
| | - Yanling Zheng
- Endocrinology Department, the First Affiliated Hospital of the Third Military Medical University (Army Medical University), Chongqing 400038, China
| | - Liu Chen
- Endocrinology Department, the First Affiliated Hospital of the Third Military Medical University (Army Medical University), Chongqing 400038, China
| | - Ziwen Liang
- Endocrinology Department, the First Affiliated Hospital of the Third Military Medical University (Army Medical University), Chongqing 400038, China
| | - Bing Chen
- Endocrinology Department, the First Affiliated Hospital of the Third Military Medical University (Army Medical University), Chongqing 400038, China
| | - Qinan Wu
- Endocrinology and Nephrology Department, Chongqing University Cancer Hospital and Chongqing Cancer Institute and Chongqing Cancer Hospital, Chongqing 400030, China
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Zhang M, Wen X, Zhou C, Huang J, He Y. Carotid intima-media thickness and plaques in internal carotid artery as surrogate markers of lower limb arterial lesions in Chinese patients with diabetic foot. ACTA ACUST UNITED AC 2019; 52:e8432. [PMID: 31314853 PMCID: PMC6644526 DOI: 10.1590/1414-431x20198432] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2019] [Accepted: 05/03/2019] [Indexed: 02/05/2023]
Abstract
Peripheral arterial disease (PAD) can impair healing of diabetic foot (DF) in patients with diabetes mellitus. To determine whether carotid intima-media thickness (CIMT) can predict lower limb arterial lesions in patients with DF, this cross-sectional study enrolled patients with DF at West China Hospital (China) between January 2012 and December 2015. Ultrasonography was used to measure CIMT, assess the internal carotid arteries (ICA) for plaques, and evaluate lower limb segmental arteries for stenosis. The optimal CIMT cutoff for detecting lower limb PAD was determined by receiver operating characteristic (ROC) curve analysis. Factors associated with PAD were identified by logistic regression analyses. A total of 167 patients (mean age: 69.7±10.3 years; 102 men) were included. Patients with PAD were older and had higher levels of total cholesterol and low-density lipoprotein than patients without PAD (P<0.05). The area under the ROC curve was 0.747 (P<0.001). At the optimal CIMT cutoff of 0.71 mm, the sensitivity, specificity, positive predictive value, and negative predictive value were 79.65, 61.11, 81.08, and 58.93%, respectively. Compared with those without PAD, more patients with PAD had CIMT ≥0.71 mm (79.65 vs 38.89%; P<0.001) and ICA plaques (66.37vs 11.11%; P<0.001). Multivariate logistic regression revealed that age (odds ratio [OR]: 1.118; 95% confidence interval [95%CI]: 1.056–1.183; P<0.001), ICA plaques (OR: 13.452; 95%CI: 4.450–40.662; P<0.001), and CIMT ≥0.71 mm (OR: 2.802; 95%CI: 1.092–7.188; P=0.032) were associated with PAD.CIMT may be a surrogate marker of PAD in patients with DF.
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Affiliation(s)
- Mei Zhang
- Department of Ultrasound, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Xiaorong Wen
- Department of Ultrasound, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Chenyun Zhou
- Department of Ultrasound, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Jing Huang
- Department of Ultrasound, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Ying He
- Department of Ultrasound, West China Hospital, Sichuan University, Chengdu, Sichuan, China
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Wang Y, Cao HJ, Wang LQ, Lu CL, Yan YQ, Lu H, Zhang K, Zhang HM, Liu JP. The effects of Chinese herbal medicines for treating diabetic foot ulcers: A systematic review of 49 randomized controlled trials. Complement Ther Med 2019; 44:32-43. [PMID: 31126573 DOI: 10.1016/j.ctim.2019.03.007] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2018] [Revised: 02/22/2019] [Accepted: 03/12/2019] [Indexed: 01/01/2023] Open
Abstract
OBJECTIVE To assess the effects and associated risks of Chinese herbal medicine (CHM) for diabetic foot ulcer (DFU). METHODS We systematically searched seven electronic databases for randomized controlled trials (RCTs) about Chinese herbal medicines for treating diabetic foot ulcers. The methodological quality of RCTs was assessed by the Cochrane risk of bias tool. Data was synthesized using review manager (RevMan) 5.3. Meta-analysis was conducted if the data were available. A summary of finding table was generated by The GRADEpro Guideline Development Tool (GDT) online. RESULTS Forty-nine RCTs, all conducted in China, involving 3646 participants were included. Most of the included trials had unclear or high risk of bias. Twenty-six trials could be pooled in five Meta-analyses, the remaining trials could not be pooled due to the obvious clinical heterogeneity. Only low evidence showed CHM therapy may have 42%-60.4% participants healed completely after treatment, approximately twice (RR 1.42-1.76) as much as the healed rates in conventional therapy (or plus hot water foot bath) group. Majority of the included trials reported benefit of CHM group on shortening healing time (4-23 days) and reducing ulcer wound size (at least 2 cm2). No serious adverse events were reported related to the medication in all trials. CONCLUSION Weak evidence showed benefit of CHM as add-on treatment of conventional therapy on increasing number of ulcer heals in patients with DFU. That's about twice the healing rate of the conventional treatment (or plus hot water foot bath) group. With insufficient information, we could not draw confirmative conclusion on safety of CHM administration. These findings need to be tested in further large, rigorous trials.
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Affiliation(s)
- Ying Wang
- Center for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China.
| | - Hui-Juan Cao
- Center for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China.
| | - Li-Qiong Wang
- School of acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, 100029, China.
| | - Chun-Li Lu
- Center for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China.
| | - Yu-Qian Yan
- Center for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China.
| | - Hao Lu
- Department of Endocrinology, Shuguang Hospital affiliated to Shanghai TCM University, Shanghai, 200020, China.
| | - Kang Zhang
- Center for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China.
| | - Hui-Min Zhang
- School of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China.
| | - Jian-Ping Liu
- Center for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China; Institute of Integrated Traditional Chinese Medicine and Western Medicine, Guangzhou Medical University, Guangzhou, Guangdong, 510182, China.
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Vein conduit for end-to-side anastomosis of a calcified vessel in lower extremity free flap reconstruction. J Plast Reconstr Aesthet Surg 2019; 72:1100-1109. [PMID: 31036502 DOI: 10.1016/j.bjps.2019.02.021] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2018] [Revised: 12/26/2018] [Accepted: 02/12/2019] [Indexed: 01/18/2023]
Abstract
BACKGROUND As the microsurgical and interventional revascularization techniques are evolving, traditionally amputated limbs are now challenged to salvage. However, a calcified recipient vessel is a common but challenging problem encountered in lower extremity reconstruction. METHODS An end-to-side anastomosis of a vein graft (1.5-3.5 cm in length) was performed to the recipient vessel when it was difficult to clamp the recipient vessel near the defect because of the inelastic and hard vessel wall. The vascular clamp was applied to the vein graft, and the flap's pedicle was anastomosed to the vein graft. RESULTS A total of 18 free flaps (10 ALT cases, 4 TDAP cases, 2 PAP cases, and 2 SCIP cases) were anastomosed with a bridge vein graft to the heavily calcified recipient vessels (7 ATA cases, 3 PTA cases, 7 DPA cases, and 1 MPA case). Overall flap survival rate was 83.3%. Limb salvage rate was 93.7%, and anastomosis patency rate was 94.4% CONCLUSION: Vein conduit in an end-to-side anastomosis of severely calcified recipient vessels shows a reasonable limb salvage rate. It acts as a buffer, which makes microscopic vessel manipulation easier. If vessel calcification is the only drawback for a free flap reconstruction, then a vein graft needs to be prepared instead of an amputation. This method may extend the surgical option to more high-risk patients in lower extremity microsurgical reconstruction and increase the limb salvage rate.
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Biological Mechanisms of Chronic Wound and Diabetic Foot Healing: The Role of Collagen. SERBIAN JOURNAL OF EXPERIMENTAL AND CLINICAL RESEARCH 2019. [DOI: 10.2478/sjecr-2018-0077] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
Abstract
The treatment of chronic wounds is a continuously developing research focus. The problems of excessive mechanical forces, infection, inflammation, reduced production of growth factors, and lack of collagen will affect the results of treatment. The purpose of this study was to analysse the elements that lead to long-term non-healing of chronic wounds and trophic ulcers, including diabetic foot syndrome, by determining the optimal treatment algorithm. The paper presents an analysis of the world literature on the etiopathogenesis and principles of chronic wound treatment in diabetic foot syndrome. The epidemiology of chronic wounds of different genesis is presented. The issues of physiological and metabolic disorders in chronic ulcers affecting the process of wound healing are discussed. Particular attention is paid to collagen, which is a protein that forms the basis of connective tissue; collagen ensures the strength and elasticity of the skin, which confirms the importance of its role not only in aesthetics but also in the process of wound healing. Different types of collagen and their roles in the mechanisms of chronic wound healing in diabetic foot syndrome are described. The results of clinical studies evaluating the effectiveness of medical products and preparations, consisting of collagen with preserved (native collagen) and fractionated structures, in treating chronic wounds of diabetic foot syndrome are analysed. It has been shown that the use of native collagen preparations is a promising treatment for chronic ulcers and wounds, including diabetic foot syndrome, which makes it possible to increase the effectiveness of treatment and reduce the economic costs of managing these patients.
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