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Diabetic foot ulcers (DFUs) are a severe complication of diabetes mellitus (DM), which often lead to hospitalization and non-traumatic amputations in the United States. Diabetes prevalence estimates in South Texas exceed the national estimate and the number of diagnosed cases is higher among Hispanic adults compared to their non-Hispanic white counterparts. San Antonio, a predominantly Hispanic city, reports significantly higher annual rates of diabetic amputations compared to Texas. The late identification of severe foot ulcers minimizes the likelihood of reducing amputation risk. The aim of this study was to identify molecular factors related to the severity of DFUs by leveraging a multimodal approach. We first utilized electronic health records (EHRs) from two large demographic groups, encompassing thousands of patients, to identify blood tests such as cholesterol, blood sugar, and specific protein tests that are significantly associated with severe DFUs. Next, we translated the protein components from these blood tests into their ribonucleic acid (RNA) counterparts and analyzed them using public bulk and single-cell RNA sequencing datasets. Using these data, we applied a machine learning pipeline to uncover cell-type-specific and molecular factors associated with varying degrees of DFU severity. Our results showed that several blood test results, such as the Albumin/Creatinine Ratio (ACR) and cholesterol and coagulation tissue factor levels, correlated with DFU severity across key demographic groups. These tests exhibited varying degrees of significance based on demographic differences. Using bulk RNA-Sequenced (RNA-Seq) data, we found that apolipoprotein E (APOE) protein, a component of lipoproteins that are responsible for cholesterol transport and metabolism, is linked to DFU severity. Furthermore, the single-cell RNA-Seq (scRNA-seq) analysis revealed a cluster of cells identified as keratinocytes that showed overexpression of APOE in severe DFU cases. Overall, this study demonstrates how integrating extensive EHRs data with single-cell transcriptomics can refine the search for molecular markers and identify cell-type-specific and molecular factors associated with DFU severity while considering key demographic differences.
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The dynamic wound microbiome
Abstract Background Diabetic foot ulcers (DFUs) account for the majority of all limb amputations and hospitalizations due to diabetes complications. With 30 million cases of diabetes in the USA and 500,000 new diagnoses each year, DFUs are a growing health problem. Diabetes patients with limb amputations have high postoperative mortality, a high rate of secondary amputation, prolonged inpatient hospital stays, and a high incidence of re-hospitalization. DFU-associated amputations constitute a significant burden on healthcare resources that cost more than 10 billion dollars per year. Currently, there is no way to identify wounds that will heal versus those that will become severely infected and require amputation. Main body Accurate identification of causative pathogens in diabetic foot ulcers is a critical component of effective treatment. Compared to traditional culture-based methods, advanced sequencing technologies provide more comprehensive and unbiased profiling on wound microbiome with a higher taxonomic resolution, as well as functional annotation such as virulence and antibiotic resistance. In this review, we summarize the latest developments in defining the microbiology of diabetic foot ulcers that have been unveiled by sequencing technologies and discuss both the future promises and current limitations of these approaches. In particular, we highlight the temporal patterns and system dynamics in the diabetic foot microbiome monitored and measured during wound progression and medical intervention, and explore the feasibility of molecular diagnostics in clinics. Conclusion Molecular tests conducted during weekly office visits to clean and examine DFUs would allow clinicians to offer personalized treatment and antibiotic therapy. Personalized wound management could reduce healthcare costs, improve quality of life for patients, and recoup lost productivity that is important not only to the patient, but also to healthcare payers and providers. These efforts could also improve antibiotic stewardship and control the rise of “superbugs” vital to global health.
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- Award ID(s):
- 2022382
- PAR ID:
- 10337966
- Date Published:
- Journal Name:
- BMC Medicine
- Volume:
- 18
- Issue:
- 1
- ISSN:
- 1741-7015
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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OBJECTIVES/GOALS: Target: Computationally identify the markers of ulcer severity and risk of amputation from datasets that include demographics data, clinical, laboratory data, and medical history over 6000 patients. METHODS/STUDY POPULATION: In this study we will use tables of demographics such as age, gender, and ethnicity/race. Inspired by previous research we’ll include wound age (duration in days), wound size, number of concurrent wounds of any etiology, evidence of bioburden/infection, Wagner grade, being non ambulatory, renal dialysis, renal transplant, peripheral vascular disease, and patient hospitalization. Another table will include laboratory vital signs to include physiological variables such as height, weight, body mass index, pulse rate, blood pressure, respiratory rate, and temperature. We’ll include also social data like smoking status, socio-economic status, housing condition. RESULTS/ANTICIPATED RESULTS: Our project aligns with previous efforts to identify high risk Diabetic Foot Ulcer individuals but also takes a different perspective by collecting and marking clinical data from a subset of patients (e.g., severity, Hispanic versus non-Hispanic) and computationally process these data to provide a tool that can identify DFU severity and high-risk patients. We will obtain samples from Hispanics and non-Hispanics because these two groups are likely to have significant differences in the progression of ulcer severity. The rationale is that by comparing these two groups, we will assess and study the factors that are differentially present. It is our expectation that the proposed project will provide an easy-to-use tool for DFU progression and risk of amputation and contribute to identify high-risk individuals. DISCUSSION/SIGNIFICANCE: Diabetes prevalence estimates in Bexar County, TX exceeds national estimates (15.5% vs. 11.3%) and diagnosed cases are higher among Hispanic adults (13.4%) compared to their non-Hispanic white counterparts (9.5%). Late identification of severe foot ulcers minimizes the likelihood of reducing amputation risk.more » « less
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Abstract Chronic wounds are one of the most devastating complications of diabetes and are the leading cause of nontraumatic limb amputation. Despite the progress in identifying factors and promising in vitro results for the treatment of chronic wounds, their clinical translation is limited. Given the range of disruptive processes necessary for wound healing, different pharmacological agents are needed at different stages of tissue regeneration. This requires the development of wearable devices that can deliver agents to critical layers of the wound bed in a minimally invasive fashion. Here, for the first time, a programmable platform is engineered that is capable of actively delivering a variety of drugs with independent temporal profiles through miniaturized needles into deeper layers of the wound bed. The delivery of vascular endothelial growth factor (VEGF) through the miniaturized needle arrays demonstrates that, in addition to the selection of suitable therapeutics, the delivery method and their spatial distribution within the wound bed is equally important. Administration of VEGF to chronic dermal wounds of diabetic mice using the programmable platform shows a significant increase in wound closure, re‐epithelialization, angiogenesis, and hair growth when compared to standard topical delivery of therapeutics.more » « less
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1186/s12916-020-01820-6
