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Diabetic Foot Ulcer Biofilm Infection and Recurrence

糖尿病足溃疡生物膜感染和复发

基本信息

批准号：
10376509
负责人：
GEOFFREY C GURTNER
金额：
$ 37.7万
依托单位：
INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-07 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10376509
关键词：
Address Amputation Animal Model Animals Area Award Bacteria Biological Caring Clinical Clinical Research Colony-Forming Units Assay Complication Complications of Diabetes Mellitus Data Data Collection Defect Diabetic Foot Ulcer Epithelial Epithelial Attachment Foot Ulcer Foundations Funding Gene Silencing Hospitalization Incidence Indiana Infection Infectious Skin Diseases Lead Leg Lower Extremity Measures Metabolic Methodology MicroRNAs Microbial Biofilms Molecular National Institute of Diabetes and Digestive and Kidney Diseases Non-Insulin-Dependent Diabetes Mellitus Patients Pilot Projects Recording of previous events Recurrence Reporting Research Research Design Rest Risk Series Site Skin Skin repair Techniques Testing Time Tissues Training Ulcer Universities Visit Water Work Wound Infection base chronic wound delta-catenin diabetic diabetic patient interest limb loss mortality risk novel pre-clinical premature primary endpoint recidivism recurrent infection repair function restoration skin barrier standard of care wound wound biofilm wound care wound closure wound healing

项目摘要

Abstract Diabetic foot ulcers (DFU) are one of the most common reason for hospitalization of diabetic patients and frequently it results in amputation of lower limbs. Of the one million people who undergo non-traumatic leg amputations annually worldwide, 75% are performed on people who have type 2 diabetes (T2DM). The risk of death at 10 years for a diabetic with DFU is twice as high as the risk for a patient without a DFU. The rate of amputation in patients with DFU is 38.4%. Infection is a common (>50%) complication of DFU. In those with DFU, 40% recur within one year after wound closure; 60% within 3 years, and 65% within 5 years. Thus, the strongest predictor of DFU is a previous foot ulcer. The proposed work rests on a series of pre-clinical and clinical findings laying the foundation to the hypothesis that biofilm infection of DFU compromises barrier function of the closed DFU. Such deficient closure paves the way to DFU recurrence. Biofilms are estimated to account for 60% of chronic wound infections. In the biofilm form, bacteria are in a dormant metabolic state. The standard clinical techniques like colony forming units (CFU) assay to detect infection may not detect biofilm infection. Thus, biofilm infection may be viewed as a silent maleficent threat in wound care. The proposed work is a two-center study – Indiana University and Stanford University – who were competitively funded with a pilot award by the NIDDK-DIACOMP mechanism to generate preliminary data on DFU closure and recurrence. The proposed work addresses a novel paradigm in DFU care that has never been tested in a fully powered patient- based study. Successful execution of the proposed work is likely to have direct impact on the current standards of wound care including re-defining the most important primary endpoint of wound care, wound closure itself. For the first time in a DFU patient-based study, mechanisms by which biofilm infection induces molecular mechanisms that compromise functional integrity of re-epithelialized DFU will be elucidated. In DFU care, the proposed work may identify that the current endpoint of wound closure (that does not account for any functional parameter) may be not the right time to stop caring for DFU. That such premature termination of care may be responsible for the high recurrence of DFU that is currently reported. The notion that continued care, until functional wound closure is achieved, is necessary to minimize recurrence and amputation would be of transformative value in the delivery of DFU care. This proposal, wholly based on the study of DFU patients seeks to conduct a two-centered robust clinical study testing whether wounds with a history of biofilm infection closes with deficient barrier function (Aim 2). Aim 3 tests whether such deficient wound closure which manifests as high TEWL is associated with greater wound recurrence. Aim 1 utilizes this patient-based study to address molecular mechanisms implicated in biofilm-induced loss of skin epithelial barrier integrity.

摘要