Diabetic Foot Ulcers Research Articles

The relationship between dietary phytochemical index and novel anthropometric indices and the severity of diabetic foot ulcers in adults with type 2 diabetes: a cross-sectional study

BackgroundResearch on the relationship between dietary phytochemical intake and the anthropometric indices as well as the diabetic foot ulcers (DFUs) remains inconsistent. We aimed to investigate the associations of dietary phytochemical index (DPI) with the novel anthropometric indices and the severity of DFUs.MethodsThis cross-sectional study was conducted on 339 adults with type 2 diabetes. Dietary intake was assessed using three 24-hour dietary recalls. To quantify the phytochemical content of the diet, the DPI estimation was done through an equation proposed by McCarty. The International Working Group on the Diabetic Foot (IWGDF) criteria and Wagner classification system were applied to assess DFUs. New anthropometric indices including a body shape index (ABSI), body roundness index (BRI) and abdominal volume index (AVI) were calculated based on formulas. We employed analysis of variance (ANOVA), analysis of covariance (ANCOVA) and logistic regression to explore associations between DPI and the anthropometric indices and DFU variables.ResultsOur results revealed no significant association between DPI and the foot ulcer indices, following adjusting for the possible covariates. Furthermore, we also examined the relationship between diabetic neuropathy, as measured by monofilament score, and the DPI. Similarly, we did not find any substantial relationship between the DPI and monofilament score (OR: 1.18; 95% CI: 0.66–2.09; Ptrend = 0.56), as well as biochemical indices. Our analysis did not reveal any significant associations between the DPI and ABSI (OR: 0.70; 95% CI: 0.35–1.38; Ptrend = 0.30), BRI (OR: 0.80; 95% CI: 0.33–1.95; Ptrend = 0.59), and AVI (OR: 1.99; 95% CI: 0.92–4.33; Ptrend = 0.08).ConclusionsOur study revealed no significant links between the DPI and foot ulcer indices, neuropathy measures, and anthropometric indices. These findings imply that factors beyond dietary phytochemical intake may exert greater influence on the development of foot ulcers in diabetes.

Clinical Efficacy of a Contralateral Shoe Lift in Patients with Diabetic Foot Ulcers and Induced Limb-Length Discrepancies: A Randomized Controlled Trial.

Objective: To evaluate the clinical efficacy of combining an offloading device with a contralateral shoe lift to compensate for induced limb-length discrepancies in participants with plantar diabetes-related foot ulcers. Approach: Between March 2021 and December 2023, 42 consecutive patients with active plantar diabetic foot ulcers (DFUs) were randomly assigned (1:1) to the treatment group (limb-length discrepancy compensation with a shoe lift in the therapeutic footwear of the contralateral limb) or a control group that did not receive limb-length discrepancy compensation. Primary outcomes included the 20-week wound-healing rate and wound area reduction. Secondary outcomes included minor amputation, new ulcers in the contralateral limb, perceived comfort, and hip pain. Results: On an intention-to-treat basis, 15 participants in the control and 19 in the treatment group showed ulcer healing (p = 0.0023). In those with >80% adherence to the offloading device, multivariate analysis showed that the shoe lifts improved ulcer healing time. The use of a shoe lift reduced the number of minor amputations and the occurrence of new ulcers in the contralateral limb (p = 0.035; p = 0.033 respectively). Hip pain and perceived comfort improved with the use of shoe lifts (p < 0.001). Innovation: It validates the use of shoe lifts for patients with DFUs, as it is the first largest study of its kind to establish a clear reference standard to guide clinician decision-making. Conclusion: The use of shoe lifts reduced healing time in participants with diabetes and active plantar foot ulcers. Shoe lifts reduce late complications, including new ulcers in the contralateral limb and minor amputations.

Effect of aspirin on platelet-rich plasma of diabetes mellitus with lower extremity atherosclerosis.

Aim: Platelet-rich plasma (PRP), enriched with multiple growth factors, is a promising adjunctive therapy for diabetic foot ulcers (DFUs). As a classic anti-platelet drug for diabetic patients, the effects of aspirin on the content of growth factors in PRP remains unclear.Methods: Our study enrolled diabetic patients who were currently taking or not taking aspirin as the research subjects, with healthy volunteers as the control. PRP from these individuals was activated with glucose calcium and thrombin. Growth factors levels in PRP activated supernatant (PRP-AS) and wound healing ability of platelet gel (PG) in the full-thickness skin defect diabetic mouse model were compared.Results: We found the level of growth factors in PRP-AS derived from two groups of diabetic patients were not statistically different, whereas both lower than that from healthy volunteers. Similarly, we found better wound healing ability of PG from healthy volunteers than those from diabetic patients, but no difference between the two groups of diabetic patients in the mouse model.Discussion: Aspirin does not interfere with autologous PRP therapy when using calcium gluconate and thrombin as agonists. However considering the content of growth factors, PRP from healthy volunteers is a preferable option for promoting DFU repair.

A Comprehensive Approach for Diabetic Foot Ulcer Management

Objectives: This study aims to evaluate the efficacy of a comprehensive management plan in the treatment of diabetic foot ulcers (DFUs). Evaluating the effects of wound debridement on the outcomes of diabetic foot ulcers, advanced dressings, blood sugar control, and offloading strategies are the main objectives. The study also intends to investigate the function of surgery in managing chronic ulcers and preventing recurrences. The goal is to offer advice for managing DFUs optimally and lowering related morbidity based on evidence. Method: The intervention program includes techniques like wound debridement, advanced dressings, unloading modalities, blood sugar level control, and, where necessary, surgical treatments. Growth factors, electrical stimulation, negative pressure wound therapy, bio-engineered skin, and hyperbaric oxygen therapy are among the many treatments that are included. Regression models are among the statistical analyses used to assess the efficacy of the overall management strategy. Results: Significant findings are presented in the results section, which shows how the holistic management strategy improves DFU outcomes. Improved wound healing rates, reduced infection incidents, and enhanced patient-reported outcomes are highlighted. The results underscore the significance of maintaining blood sugar levels, wound debridement, and incorporating various therapeutic modalities in DFU management. Conclusion: This study concludes by recommending a thorough and interdisciplinary approach to DFU management. Maintaining blood sugar levels, debridement of the wound, sophisticated dressings, unloading techniques, and surgical procedures are among the effective strategies that help reduce morbidity and prevent serious complications related to diabetic foot ulcers. Additional investigation is necessary to enhance and broaden these results for ongoing progress in the management of diabetic foot ulcers.

Factors Influencing Outcomes of Diabetic Foot Management: Retrospective Study at Mwananyamala Regional Referral Hospital

Background: Diabetic foot ulcers (DFUs) contribute to significant morbidity and mortality worldwide, with the global prevalence of diabetes expected to rise to 12.2% by 2045, an increasing number of people are at risk for complications like DFUs, which affect 19% to 34% of diabetic patients. People with DFUs carry a 20% lifetime risk of limb amputation and mortality rate of 50% to 70%. In Tanzania DFUs account for 41.9% of major limb amputations and mortality rate of 54%. Methods: A retrospective observational study aimed to investigate the clinical factors, and treatment modalities that influence the management outcomes of diabetic foot among patients attending Mwananyamala Regional Referral Hospital (MRRH). The study reviewed existing patient records. Results: A total of 143 participants were enrolled in the study, of which 94 (65.73%) were female. The participants had a mean age of 57 ± 13.9 years. And approximately half (50.35%) were married. Nearly, all patients, 140 (97.90%), underwent surgical treatment, nearly half (41.96%) had DFU Wagner Class 3 while most of participants (69.93%) had hypertension. The mean hospital stay was 9.2 days. In binary logistic regression model output, marital status, level of education, working diagnosis, surgical management, patient progress and number of readmissions were identified as determinants of the outcome (P-value &lt; 0.05). Conclusion: This study identified key factors influencing diabetic foot outcomes, including gender, marital status, co-morbidities and ulcer grade. These findings underscore the importance of early diagnosis, targeted interventions, and comprehensive management to improve patient outcomes.

Structural analysis and accelerating wound healing function of a novel galactosylated glycosaminoglycan from the snail Helix lucorum

Diabetic foot ulcers (DFUs) as a nonhealing wound remain a clinical challenge, and the development of pro-healing and cost-effective drugs is in urgent need. Herein, we reported a novel galactosylated glycosaminoglycan (GAG) from the snail Helix lucorum, as an effective pro-healing compound. The snail GAG is composed of a heparan sulfate-like main chain and galactose side chains at C-3 of GlcNAc residue. Its main chain has a repeating disaccharide structure of → 4)-α-D-GlcNAc-(1 → 4)-α-L-IdoA2S(1 →. This is the first example of glycosaminoglycan with galactose branches from mollusks. Pharmacological experiments showed that the H. lucorum GAG significantly promoted skin wound healing in both healthy and diabetic mice by accelerating granulation tissue regeneration, angiogenesis, and collagen deposition. The distinctive galactosylated substitution may play an important role on its pro-healing activity. Our discovery enriches the diversity of non-anticoagulant heparan sulfate-like glycosaminoglycans, and provides a potential candidate of pro-healing drug for treating diabetic wound.

Molecular Detection of Beta-Lactamase Genes (KPC and CTX-M) of Pseudomonas aeruginosa in Diabetic Foot Ulcers Patients

Background: diabetic foot ulcers (DFUs ) are an inflammatory disease caused by a bacterial infection such as Pseudomonas aeruginosa (P. aeruginosa), provided with genetic virulence factors. This study aims to detect KPC and CTX-M genes of P. aeruginosa isolated from chronic DFU patients. Methods: One hundred twenty DFU patients were recruited from Al-Sader Medical City and Al-Hakim General Hospital in Najaf province from September to January 2021 to collect ear swaps. The Primary identification depends on Gram stain and biochemical tests. We also used the Vitek 2 system to make another identification and examine resistance to antibiotics. A polymerase chain reaction (PCR) was used to amplify the required genes. Furthermore, gel electrophoresis was performed to show the amplified genes. Results: The results have revealed that 100 samples (83.3%) give a positive outcome, while 20 samples (16.6%)are negative for culture bacteria. Only 17(17 %) of the 100 clinical specimens showed positive tests for P. aeruginosa. However, the gene, CTX-M gene is found in 58.8% of P. aeruginosa isolates, while the KPC gene is not found in the isolates. Conclusion: Our findings suggest that P. aeruginosa is one of the most common causes of DFU infection in Iraqi patients and The levels of MDR of P. aeruginosa isolates in Najaf hospitals were undoubtedly high. Most bacterial isolates show the presence of the CTX-M gene. The presence of these genes is one of the virulence factors and probably partly explains the resistance to antibiotics.

Multifactorial analysis of risk factors for foot ulcers in patients with neurovascular complications of diabetes.

Diabetic foot ulcers (DFU) are a major complication associated with significant morbidity and mortality. While numerous studies have investigated risk factors for these ulcers in general, few have focused specifically on patients with Neurovascular Complications of Diabetes. This study aimed to evaluate the prevalence and risk factors for DFU in this specific population. We analyzed data from the National Institutes of Health (NIS) database for the years 2017-2019, involving a cohort of 161,834 patients aged over 18 who were diagnosed with neurovascular complications of diabetes. Demographic characteristics (age, gender, ethnicity), hospital characteristics, comorbidities, and other relevant data were included for analysis. A binary logistic regression model was generated to identify independent risk factors for DFU. The prevalence of DFU among patients with neurovascular complications of diabetes was 29.4% during the period from 2017 to 2019. Compared to patients without DFU, those with DFU had longer hospitalization times and higher costs. The multiple regression analysis revealed that Iron-deficiency anemia (OR, 1.10; 95% CI, 1.01-1.11; P=0.019), Hypertension (OR, 1.07; 95% CI, 1.03-1.11; P=0.001), Obesity (OR, 1.08; 95% CI, 1.06-1.11; P<0.001), Peripheral vascular disorders (PVD) (OR, 1.69; 95% CI, 1.65-1.74; P<0.001), Osteomyelitis (OR, 7.10; 95% CI, 6.89-7.31; P<0.001), Tinea pedis (OR, 1.89; 95% CI, 1.59-2.26; P<0.001), Sepsis (OR, 1.24; 95% CI, 1.20-1.28; P<0.001), and onychomycosis (OR, 1.26; 95% CI, 1.13-1.42; P<0.001) were independent predictors for DFU in this population. The study found a high prevalence of DFU in patients with neurovascular complications of diabetes. Identifying and addressing risk factors such as deficiency anemia, hypertension, obesity, PVD, infections, and foot conditions may contribute to reducing the prevalence of DFU in this vulnerable population.

SFRP2 modulates functional phenotype transition and energy metabolism of macrophages during diabetic wound healing.

Diabetic foot ulcer (DFU) is a serious complication of diabetes mellitus, which causes great health damage and economic burden to patients. The pathogenesis of DFU is not fully understood. We screened wound healing-related genes using bioinformatics analysis, and full-thickness skin injury mice model and cellular assays were used to explore the role of target genes in diabetic wound healing. SFRP2 was identified as a wound healing-related gene, and the expression of SFRP2 is associated with immune cell infiltration in DFU. In vivo study showed that suppression of SFRP2 delayed the wound healing process of diabetic mice, impeded angiogenesis and matrix remodeling, but did not affect wound healing process of control mice. In addition, suppression of SFRP2 increased macrophage infiltration and impeded the transition of macrophages functional phenotypes during diabetic wound healing, and affected the transcriptome signatures-related to inflammatory response and energy metabolism at the early stage of wound healing. Extracellular flux analysis (EFA) showed that suppression of SFRP2 decreased mitochondrial energy metabolism and increased glycolysis in injury-related macrophages, but impeded both glycolysis and mitochondrial energy metabolism in inflammatory macrophages. In addition, suppression of SFRP2 inhibited wnt signaling-related genes in macrophages. Treatment of AAV-SFRP2 augmented wound healing in diabetic mice and demonstrated the therapeutic potential of SFRP2. In conclusions, SFRP2 may function as a wound healing-related gene in DFU by modulating functional phenotype transition of macrophages and the balance between mitochondrial energy metabolism and glycolysis.

The role of vitamin D in diabetic foot ulcer; an umbrella review of meta-analyses.

Complications related to diabetic foot ulcers (DFU) due to diabetes are increasing. One of the factors influencing the management and treatment of complications related to DFU is the vitamin D serum levels of patients. Therefore, we sought to comprehensively review meta-analyses from randomized controlled trials and observational studies examining the link between serum vitamin D levels and DFU outcomes in diabetic patients. We searched PubMed, Scopus, and ISI Web of Science until September 2024 and extracted the required data from related articles according to Inclusion criteria. The certainty of the evidence and the quality of conduct of the published meta-analyses were rated using the ASMTAR 2 tools, respectively. A total of 8 meta-analyses studies that met inclusion criteria were included. Based on the obtained results, it has been noted that individuals with DFU exhibit serum vitamin D levels significantly lower, ranging from -7.14 (5.44, 8.83) to -0.93 (95% CI: 0.17, 1.68) ng/ml, compared to those with diabetes but without DFU. Furthermore, individuals exhibiting severe vitamin D deficiency are found to be at least 1.82 times more susceptible to developing DFU. Conversely, administering varying doses of vitamin D supplementation has been shown to positively affect the size and number of ulcers in DFU patients. This study suggests a potential link between lower levels of vitamin D in the blood and the risk of DFU, hinting at the benefits of vitamin D supplementation in improving outcomes associated with DFU. However, caution is warranted due to the potential bias present in the included studies.

A comparative analysis of vacuum assisted closure therapy and conventional dressings: outcomes in chronic diabetic foot ulcers among Indian patients

Background: India faces a growing diabetes epidemic, with approximately 77 million individuals affected. Chronic non-healing diabetic foot ulcers (DFUs) are a common complication of diabetes and a major healthcare challenge in Conventional wound care methods often result in prolonged healing times, increasing the risk of infection, hospitalization, and amputations. Vacuum-assisted closure (VAC) therapy, a modern treatment modality, offers a potentially more effective approach to managing these ulcers. Methods: This prospective, observational study was conducted at a tertiary care hospital in India from March 2022 to March 2024. One hundred patients with chronic non-healing DFUs were randomized into VAC therapy or conventional dressing groups. The primary outcomes included wound size reduction and healing time, while secondary outcomes involved patient satisfaction and cost-effectiveness. Results: VAC therapy significantly reduced wound size (65.2% vs. 40.5%) and shortened healing time (6.2 vs. 10.9 weeks) compared to conventional dressings. Additionally, VAC therapy led to higher patient satisfaction and proved more cost-effective due to fewer dressing changes and shorter hospital stays. Conclusions: VAC therapy outperforms conventional dressings in managing DFUs, offering faster healing, better patient satisfaction, and cost-effectiveness. Expanding its use in India could greatly improve diabetic foot care outcomes.

6909 Mortality and Readmission Rates for Inpatients with Diabetic Foot Ulcer in a Tertiary, Urban Medical Center: A Five-Year Retrospective Review

Abstract Disclosure: A. Herrera Chancay: None. R. Lopez Fanas: None. H. Tabassum: None. J. Daily: None. A. Myers: None. Background: Diabetic Foot Ulcer (DFU) is a severe complication of diabetes mellitus and is associated with high rates of morbidity and mortality. The incidence of DFUs and amputation disproportionately impact Black and Hispanic populations. DFU is also associated with a high rate of hospital readmissions and prolonged length of stay (LOS). The goal of this study was to examine 1-year mortality data, LOS and readmission rate. Methods: This study was a retrospective chart review of 1348 patients admitted to three hospitals in our system in the Bronx from 6/1/16 to 5/31/21. Data was extracted from the EPIC® electronic health records, based on the diagnoses ICD 10 codes, E10.621 and E11.622. Inclusion criteria was patients admitted with an active DFU regardless of other admission diagnosis, age 18 years or above. The index admission was defined as the first admission in our medical records within the date range. Patients were excluded if their index admission was not accessible through our EMR. Simple logistic regression and multiple logistic regression were used to analyze the association between variables of interest and mortality at index admission and at 1-year, LOS and re admissions. Results: Of the 650 eligible patients, the mean age was 59 + 13 years, 70% of patients were male, and majority were non-White (88%). Mortality was 1% during the index admission and the risk increased to 6% at 1 year after the index admission. Readmission with an active DFU from the index admission occurred in 15% of patients within 30-days, 32% of patients within 90 days, and 55% of patients within 1 year. The mean length of stay was 9 +7.5 days. Discussion: Our study in an urban region has identified high rates of mortality and costs associated with DFU, which has been reported in many settings. This patient population is high risk for poor outcomes and targeted programs are needed to reduce mortality and provide care to reduce readmissions. Future studies that explore the challenges of DFU health care and that test interventions are needed to improve DFU related health outcomes. Presentation: 6/2/2024

6663 Amputation Rate in Hospitalized Patients With Diabetic Foot Ulcer at Montefiore Medical Center, Bronx, NY

Abstract Disclosure: R. Lopez Fanas: None. A. Herrera Chancay: None. H. Tabassum: None. J. Milosavljevic: None. S. Xu: None. J. Daily: None. A.K. Myers: None. Introduction: Diabetic foot ulcers (DFU) are associated with poor outcomes including lower extremity amputations and death in individuals with diabetes. Our study aims to define health outcomes and explore the association of sociodemographic and clinical factors on amputation rates in patients hospitalized with DFU addressing an existing knowledge gap in our population. Methods: This was a retrospective review of the electronic health record of adult patients hospitalized with DFU at one of the three major Montefiore Medical Center hospitals in the Bronx, New York between 06/01/2016 and 05/30/2021. Patient data extracted from the index admission included demographics, comorbidities, and laboratory values. Survival and amputation rates were calculated for each patient over the five-year study period. Results: In our analysis of 650 patients, 88% self-identified as non-white, and only 23% had commercial insurance. The amputation rate during the initial DFU admission was 44%, with 76% experiencing at least one amputation over five years. Male sex, low BMI, and smoking were associated with amputation during the study period, with an OR of 0.62 (p=0.01), 0.98 (p=0.05), and 1.45 (p=0.05) respectively. Patients with history of osteomyelitis had a higher risk of any amputation during the index admission (OR 2.05, p&amp;lt;0.0001), and the 5-year study period (OR 3.03, p&amp;lt;0.0001). PAD or prior history of amputation increased the risk of any amputation during the study period, OR 2.11 (p=0.0002) and OR 7.92 (p&amp;lt;0.001) ESRD was associated with a higher risk of AKA and BKA during the index admission (OR 2.31, p=0.05). Elevated ESR, CRP, WBC, and low albumin were associated with amputation during admission, with ORs of 1.01 (p=0.0006), 1.05 (p&amp;lt;0.0001), 1.11 (p&amp;lt;0.0001), and 0.41 (p&amp;lt;0.0001), respectively. Discussion: This study revealed a 44% amputation rate during the initial DFU admission, with 76% experiencing at least one amputation within five years. Bivariate analyses identified male sex, lower BMI, and smoking as correlated with a heightened amputation risk, consistent with previous studies. Prior amputation, PAD, ESRD, and osteomyelitis were also associated with an increased risk. Multiple regression analysis found significant associations between elevated ESR, CRP, WBC, and low albumin with amputations. As a result, interventions need to be devised for patients with these characteristics to prevent this high rate of amputation. Presentation: 6/2/2024

6914 Footing the Bill: Analysis of DFU-related amputation cost expenditure in a sample of HealthFirst Insured Patients

Abstract Disclosure: M. Hashmi: None. C. Schechter: None. A. Herrera Chancay: None. H. Tabassum: None. N. Shiraliyeva: None. J. Daily: None. A.K. Myers: None. Objective Diabetes complications, especially diabetic foot ulcers (DFU), are a leading cause of health care expenditures. This study examined the total cost of amputations and subsequent procedures in Health First insured (HF) patients initially treated at Montefiore Medical Center (MMC) for DFU. Using the database of HF, a large-scale Medicaid managed insurance organization, we captured healthcare utilization beyond the scope of one hospital system, obtaining a more comprehensive understanding of expenditures. We also explored the associations of demographic and lab values with expenditures. Methods The HF data extraction covered calendar years 2021 and 2022 plus YTD 2023. Amputations were identified by CPT codes 27880, 27590, 28810, and 28820. One hundred twenty patients were included in the sample as they had HF insurance and their initial admission for DFU was at one of three hospitals at MMC. Demographic and laboratory data were extracted from the EHR. Demographics, lab values within 3 months of the index admission, and total costs were summarized, and paid amounts per capita per year were calculated. Expenditures included amputation, labs, wound care, surgery, hyperbaric therapy, interpreter services, emergency department visits, home care visits, and outpatient follow-up (in-person and telehealth). We explored demographic, comorbidity, and lab values as predictors of expenditure levels using a bivariate analysis. Results The mean age was 60.6 ± 12 years with majority being male (n=79, 65.3%) and having Type 2 Diabetes (n=103, 96.3%). A significant portion identified their race as other (n=58, 53.7%) or ethnicity as Hispanic-Latino (n=60, 56.1%). Common comorbidities in this group were current or former tobacco use (n=64, 59.2%), chronic kidney disease (n=62, 57.9%), and hypertension (n=94, 86.2%). Glycemic control was suboptimal with an average Hemoglobin A1c of 9.1% (SD 3.1%) and average admission glucose of 232.2 mg/dL. C-reactive protein 17.1 (SD 34.1) and erythrocyte sedimentation rate 88.8 (SD 36.3) were both elevated for most patients. The DFU-related amputation cost was higher for Hispanic-Latino individuals, RR 1.97 (CI 1.04, 3.71) and for those with chronic kidney disease, RR 1.36 (1, 1.86). Female sex, serum glucose and BMI were moderately associated with increased relative cost. The study was limited by not having access to subsequent visits outside our health system and the retrospective nature of the study. Conclusions Our study highlights disparities among patients who underwent a DFU related amputation, with higher costs for Hispanic-Latino individuals, those with chronic kidney disease , and women, emphasizing the need for tailored interventions for these populations to ameliorate the high cost of DFU-related care. Presentation: 6/2/2024

Multimodal Identification of Molecular Factors Linked to Severe Diabetic Foot Ulcers Using Artificial Intelligence.

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.

A novel approach for the treatment of diabetic foot ulcers using a multimodal wound matrix: a clinical study.

Innovation in wound healing, particularly regarding diabetic foot ulcers (DFUs), is needed to reverse the number of diabetes-related amputations. This study evaluated a novel approach and performance of a multimodal wound matrix in converting stalled DFUs into a healing trajectory. Patients with either type 1 or 2 diabetes and with foot ulcers (Wagner grade 1 and 2), were screened to determine eligibility for treatment. Ulcers improving >30% in area during a two-week screening phase were not eligible for the study treatment phase. The study was an open-label trial conducted in three phases: screening, treatment and healing confirmation. Patients enrolled in the study received a treatment protocol that included application of a wound matrix to the ulcer and offloading. A total of 19 patients (15 males, four females) with a median age of 60 years, and a median ulcer duration of 36 weeks took part in the study. Patients showed an average four-week percentage area reduction (PAR) of 62%, a 12-week PAR of 94%, and a 12-week healing rate of 57% (8/14). Results of this study support the viability and potential of a novel approach to treating DFUs that includes use of a multimodal wound matrix.

Efficacy of combined hyperbaric oxygen therapy and topical haemoglobin spray in treating hard-to-heal sloughy wounds.

This study examined the effectiveness of a combination of hyperbaric oxygen therapy (HBOT) and topical haemoglobin spray in treating hard-to-heal, sloughy diabetic foot ulcers (DFUs). Patients with hard-to-heal DFUs at least 25% sloughy or necrotic were included in the study. We compared the results of patients who received standard of care and HBOT with topical haemoglobin spray (oxygen group) to an equal number of patients who only received standard personalised wound care (control group). The initial values of haemoglobin A1C and C-reactive protein, wound culture results and SINBAD (site, ischaemia, neuropathy, bacterial infection, area, depth) scores were documented. Wounds were considered healed when completely closed within 16 weeks. The oxygen group (n=21) had a mean SINBAD score of 5.00±0.89, while the control group (n=21) had a mean score of 4.62±0.80 (p=0.155). After 16 weeks, 85.7% of wounds in the oxygen group showed complete recovery, compared with 52.4% in the control group (p=0.02). In this study, a greater number of wounds in the oxygen group healed. Combining HBOT with topical haemoglobin spray provides oxygenation to the wound for longer, primarily because patients can receive 90 minutes of HBOT daily. This ensures that patients benefit from both systemic and local oxygen. This combination therapy may effectively address the problem of hypoxia and promote healing in hard-to-heal wounds.

Granular Porous Nanofibrous Microspheres Enhance Cellular Infiltration for Diabetic Wound Healing.

Diabetic foot ulcers (DFUs) are a significant challenge in the clinical care of diabetic patients, often necessitating limb amputation and compromising the quality of life and life expectancy of this cohort. Minimally invasive therapies, such as modular scaffolds, are at the forefront of current DFU treatment, offering an efficient approach for administering therapeutics that accelerate tissue repair and regeneration. In this study, we report a facile method for fabricating granular nanofibrous microspheres (NMs) with predesigned structures and porosities. The proposed technology combines electrospinning and electrospraying to develop a therapeutic option for DFUs. Specifically, porous NMs were constructed using electrospun poly(lactic-co-glycolic acid) (PLGA):gelatin short nanofibers, followed by gelatin cross-linking. These NMs demonstrated enhanced cell adhesion to human dermal fibroblasts (HDF) during an in vitro cytocompatibility assessment. Notably, porous NMs displayed superior performance owing to their interconnected pores compared to nonporous NMs. Cell-laden NMs demonstrated higher Young's modulus values than NMs without loaded cells, suggesting improved material resiliency attributed to the reinforcement of cells and their secreted extracellular matrix. Dynamic injection studies on cell-laden NMs further elucidated their capacity to safeguard loaded cells under pressure. In addition, porous NMs promoted host cell infiltration, neovascularization, and re-epithelialization in a diabetic mouse wound model, signifying their effectiveness in healing diabetic wounds. Taken together, porous NMs hold significant potential as minimally invasive, injectable treatments that effectively promote tissue integration and regeneration.

The prevalence of depression among patients with diabetic foot ulcers at King Khalid University Hospital, Riyadh, Saudi Arabia

ABSTRACT Background and Aim: The prevalence rates of depression and anxiety among diabetic patients with diabetic foot ulcers (DFU) vary from one study to the other. We aimed to determine the prevalence of depression and the associated risk factors among patients with DFU. Methods: We conducted a cross-sectional study using a self-reported questionnaire on adult patients aged 18 years old and above with DFU at our institution. We used the 9-item Patient Health Questionnaire to evaluate the presence of depressive symptoms. Results: A total of 75 patients, 56 (74.7%) males and 19 (25.3%) females, participated in the study; 33 (44.0%) were more than 60 years old. The prevalence of moderate to severe depression among our patients was 35 (46.7%). Patients who had DFU for more than 1 year had a higher proportion of moderate to severe depression (P = 0.032). There were no significant differences in the proportion of patients who had depression according to age groups (P = 0.456), gender (P = 0.095), level of education (P = 0.145), employment (P = 0.514), type of diabetes (P = 0.561), duration of diabetes (P = 0.704), level of HbA1c (P = 0.525), smoking history (P = 0.163), and previous history of DFU (P = 0.713). Logistic regression analysis showed that patients who had DFU for more than 1 year were three times more at risk to have moderate to severe depression (P = 0.049). Conclusion: Patients with DFU have a high frequency of moderate to severe depression regardless of age, gender, or other sociodemographic characteristics, with patients with long-standing DFU having triple the risk of depression as those with freshly diagnosed DFU. Diabetic persons should be thoroughly assessed to reduce the diabetes result, and preventative actions and patient education about DFU are crucial.

Topical Anti-ulcerogenic Effect of the Beta-adrenergic Blockers on Diabetic Foot Ulcers: Recent Advances and Future Prospectives.

Patients with diabetes suffer from major complications like Diabetic Retinopathy, Diabetic Coronary Artery Disease, and Diabetic Foot ulcers (DFUs). Diabetes complications are a group of ailments whose recovery time is especially delayed, irrespective of the underlying reason. The longer duration of wound healing enhances the probability of problems like sepsis and amputation. The delayed healing makes it more critical for research focus. By understanding the molecular pathogenesis of diabetic wounds, it is quite easy to target the molecules involved in the healing of wounds. Recent research on beta-adrenergic blocking drugs has revealed that these classes of drugs possess therapeutic potential in the healing of DFUs. However, because the order of events in defective healing is adequately defined, it is possible to recognize moieties that are currently in the market that are recognized to aim at one or several identified molecular processes. The aim of this study was to explore some molecules with different therapeutic categories that have demonstrated favorable effects in improving diabetic wound healing, also called the repurposing of drugs. Various databases like PubMed/Medline, Google Scholar and Web of Science (WoS) of all English language articles were searched, and relevant information was collected regarding the role of beta-adrenergic blockers in diabetic wounds or diabetic foot ulcers (DFUs) using the relevant keywords for the literature review. The potential beta-blocking agents and their mechanism of action in diabetic foot ulcers were studied, and it was found that these drugs have a profound effect on diabetic foot ulcer healing as per reported literatures. There is a need to move forward from preclinical studies to clinical studies to analyze clinical findings to determine the effectiveness and safety of some beta-antagonists in diabetic foot ulcer treatment.