Diabetic Foot Research Articles

Living without pain: A 10-year study of congenital insensitivity to pain with anhidrosis.

Congenital Insensitivity to Pain with Anhidrosis (CIPA) is a rare hereditary neuropathy caused by NTRK1 gene mutations, predisposing patients to recurrent infections and chronic wounds. Long-term studies on microbial and clinical outcomes in CIPA are limited. This study presents analysis of infection patterns, antibiotic resistance, and clinical outcomes in CIPA patients. A comprehensive ten-year retrospective cohort study was conducted at Soroka University Medical Center, Beer Sheva, Israel, from January 2014 to January 2023. Electronic medical records were reviewed to identify 63 CIPA patients, all were of consanguineous Bedouin families. Data collection included demographic details, clinical presentations, genetic analysis, documentation of infections, wound sites, hospital duration, and surgical interventions. Staphylococcus aureus, notably methicillin-resistant, dominated, with Gram-negative bacteria common in lower limbs. The study noted reduced extended-spectrum beta-lactamase bacteria and linked demographic factors to infection traits, antibiotic resistance, and surgical needs. This study provides valuable insights into the clinical and microbial patterns of CIPA, highlighting dynamic shifts in microbial compositions and antibiotic resistance profiles over time. Staphylococcus aureus, and Gram-negative bacteria particularly in lower limb infections, pose significant challenges in patient management. The findings underscore the importance of tailored approaches to address evolving microbial profiles and optimize patient care in CIPA. Key Message: This is the largest cohort study on CIPA to date, highlighting the dominance of Staphylococcus aureus, including methicillin-resistant strains, and significant Gram-negative bacterial infections in lower limbs. Contribution to Literature: It draws parallels between infection dynamics in CIPA and diabetic foot ulcers, emphasizing similar challenges due to neuropathy and ischemia, enhancing understanding of infection susceptibility and management in neuropathic conditions. The findings inform clinical practices by detailing infection and resistance patterns, supporting the development of targeted treatment strategies to improve outcomes for CIPA and similar conditions.

Mitochondrial Bioenergetics of Functional Wound Closure is Dependent on Macrophage-Keratinocyte Exosomal Crosstalk.

Tissue nanotransfection (TNT)-based fluorescent labeling of cell-specific exosomes has shown that exosomes play a central role in physiological keratinocyte-macrophage (mϕ) crosstalk at the wound-site. Here, we report that during the early phase of wound reepithelialization, macrophage-derived exosomes (Exomϕ), enriched with the outer mitochondrial membrane protein TOMM70, are localized in leading-edge keratinocytes. TOMM70 is a 70 kDa adaptor protein anchored in the mitochondrial outer membrane and plays a critical role in maintaining mitochondrial function and quality. TOMM70 selectively recognizes cytosolic chaperones by its tetratricopeptide repeat (TPR) domain and facilitates the import of preproteins lacking a positively charged mitochondrial targeted sequence. Exosomal packaging of TOMM70 in mϕ was independent of mitochondrial fission. TOMM70-enriched Exomϕ compensated for the hypoxia-induced depletion of epidermal TOMM70, thereby rescuing mitochondrial metabolism in leading-edge keratinocytes. Thus, macrophage-derived TOMM70 is responsible for the glycolytic ATP supply to power keratinocyte migration. Blockade of exosomal uptake from keratinocytes impaired wound closure with the persistence of proinflammatory mϕ in the wound microenvironment, pointing toward a bidirectional crosstalk between these two cell types. The significance of such bidirectional crosstalk was established by the observation that in patients with nonhealing diabetic foot ulcers, TOMM70 is deficient in keratinocytes of wound-edge tissues.

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.

Personalized and predictive strategies for diabetic foot ulcer prevention and therapeutic management: potential improvements through introducing Artificial Intelligence and wearable technology.

Diabetic foot ulcers represent a serious and costly complication of diabetes, with significant morbidity and mortality. The purpose of this study was to explore advancements in Artificial Intelligence, and wearable technologies for the prevention and management of diabetic foot ulcers. Key findings indicate that Artificial Intelligence-driven predictive analytics can identify early signs of diabetic foot ulcers, enabling timely interventions. Wearable technologies, such as continuous glucose monitors, smart insoles, and temperature sensors, provide real-time monitoring and early warnings. These technologies promise to revolutionize diabetic foot ulcer prevention by offering personalized care plans and fostering a participatory healthcare model. However, the review also highlights challenges such as patient adherence, socioeconomic barriers, and the need for further research to validate these technologies' effectiveness. The integration of artificial intelligence and wearable technologies holds the potential to significantly improve diabetic foot ulcer outcomes, reduce healthcare costs, and provide a more proactive and personalized approach to diabetic care. Further investments in digital infrastructure, healthcare provider training, and addressing ethical considerations are essential for successful implementation.

Comprehensive validation of a compact laser speckle contrast imaging system for vascular function assessment: from the laboratory to the clinic.

Proper organ functioning relies on adequate blood circulation; thus, monitoring blood flow is crucial for early disease diagnosis. Laser speckle contrast imaging (LSCI) is a noninvasive technique that is widely used for measuring superficial blood flow. In this study, we developed a portable LSCI system using an 805-nm near-infrared laser and a monochrome CMOS camera with a 10 × macro zoom lens. The system achieved a high-resolution imaging (1280 × 1024 pixels) with a working distance of 10 to 35 cm. The relative flow velocities were visualized via a spatial speckle contrast analysis algorithm with a 5 × 5 sliding window. In vitro experiments demonstrated the system's ability to image flow velocities in a fluid model, and a linear relationship was observed between the actual flow rate and the relative flow rate obtained by the system. The correlation coefficient (R2) exceeded 0.83 for volumetric flow rates of 0 to 0.2 ml/min when channel widths were greater than 1.2 mm, and R2 > 0.94 was obtained for channel widths exceeding 1.6 mm. Comparisons with laser Doppler flowmetry (LDF) revealed a strong positive correlation between the LSCI and LDF results. In vivo experiments captured postocclusive reactive hyperemic responses in rat hind limbs and human palms and feet. The main research contribution is the development of this compact and portable LSCI device, as well as the validation of its reliability and convenience in various scenarios and environments. Future applications of this technology include evaluating blood flow changes during skin injuries, such as abrasions, burns, and diabetic foot ulcers, to aid medical institutions in treatment optimization and to reduce treatment duration.

New nano-chemotherapeutic chitosans-garlic oil-antibiotics against diabetic foot virulent Proteus spp.

Diabetes foot ulcer is recognized to have a major side effect that raises the risk of amputation. Diabetic ulcer bacterial infections caused by virulent and resistant bacteria like Proteus mirabilis lead to serious wounds that are incurable with conventional medications. In this study, we evaluated the antibacterial activity of a natural product nanochitosan - garlic oil against ten diabetic foot isolates of Proteus mirabilis. Various chitosans (Crab (CScr) - shrimp (CSsh) - squilla (CSsq)) in nano form were prepared and coated with garlic oil (GO). GC-MS analysis was carried out to determine the main components of the essential garlic oil. The physicochemical properties of GO-NCSsq were analyzed using dynamic light scattering (DLS), zeta potentials (ZP) and subsequently scan electron microscope (SEM). Additionally, the minimum inhibitory concentration (MIC) and fraction inhibitory concentration index (FICI) were determined. GC-MS analysis revealed the presence of major palmitic fatty acid. (GO) loaded on nanochitosan squilla (NCSsq) showed high activity. Although SEM showed lower nano-size, average size of the GO-NCSsq was 330.8 nm by DLS and its zeta potential formulation was +39.6 mV. The final formulation represented by GO-NCSsq + Pipercillin (Pi) inhibited the virulence factor of P. mirabilis and reduced the MIC value (p-value > 0.001). Moreover, the killing time at 9 h was found to be significantly higher for GO-NCSsq + pipercillin (Pi) against P. mirabilis. In order to manage diabetic foot infections, GO-NCSsq is a legitimate antibacterial agent that can be coupled with other antibiotics.

The Effect of a HealiAid ® Collagen Wound Dressing on Wound Healing in Patients: A Randomized Double-Blind Pilot Clinical Trial

Wound healing is a complex, multi-phase process. With rising healthcare costs, an aging population, and increasing chronic disease prevalence, the burden of wound care is escalating. Thus, finding safe and effective methods to accelerate wound healing is crucial. This study aims to explore the safety and efficacy of HealiAid® Collagen Wound Dressing in treating various types of wounds, including venous ulcers, diabetic foot ulcers, pressure ulcers, and burns. A clinical trial was conducted on 18 subjects with venous ulcers, diabetic foot wounds, pressure ulcers, and burn wounds. The study assessed the effectiveness of HealiAid in different wound types by analyzing its thermal stability, porous structure, biocompatibility, and clinical efficacy. Wound healing was strictly monitored, and the safety and tolerability of the dressing were evaluated. The results showed that HealiAid Collagen Wound Dressing has excellent thermal stability and structural integrity. Its porous microstructure enhances cell adhesion and tissue regeneration, demonstrating significant healing effects across various wound types, including venous ulcers, diabetic foot wounds, pressure ulcers, and burns. No serious adverse reactions were reported, and endotoxin levels were well below safety standards. This study confirms the safety and efficacy of HealiAid Collagen Wound Dressing in treating multiple wound types. Its outstanding thermal stability, porous structure, and biocompatibility make it a promising option for clinical wound care

Ultrasonic cavitation for managing wounds in patients with purulent-necrotic complications of diabetic foot syndrome

Ultrasonic cavitation for managing wounds in patients with purulent-necrotic complications of diabetic foot syndrome

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.

Analysis of mRNA expression profile in the treatment of diabetic foot ulcer healing by tibial cortex transverse distraction

To investigate mRNA Expression profile and associated signaling pathways in the treatment of diabetic foot ulcer healing by tibial cortex transverse distraction. Tissue samples were collected from the wound edge before and after the surgery. After reference genome transcriptome sequencing and subsequent bioinformatics analysis, the differentially expressed genes and related pathways were explored, and functional analysis of important genes and pathways was conducted. qRT-PCR was used to verify the significantly expressed genes-HLA-DRB1, HLA-DRB5, CXCL5 and IGFL1. There were 2441 significantly up-regulated and 3904 significantly down-regulated genes in the postoperative group. The qRT-PCR results showed the expression of HLA-DRB1, HLA-DRB5 and CXCL5 was consistent with the transcriptional sequencing results. CXCL5 and CXCL6 differentially up-regulated genes are involved in the process of neovascularization, and HLA-DRB1 is involved in the improvement of the degree of diabetic peripheral nerve degeneration. Pathway analysis showed that differential genes were most significantly enriched in Adherens junction, Inflammatory mediator regulation of TRP channels and Wnt signaling pathway. Inflammatory mediator regulation of TRP channels is involved in the improvement of peripheral neurodegeneration, VEGF signaling pathway is involved in the process of neovascularization, and Wnt signaling pathway is involved in the process of bone healing. Significantly up-regulated CXCL5 and CXCL6 and enriched VEGF signaling pathway analyzed are involved in postoperative lower limb neovascularization. The HLA-DRB1 and the enriched Inflammatory mediator regulation of TRP channels may be related to the improvement of postoperative peripheral neurodegeneration. The differentially expressed genes and related pathways can provide objective basis for further mechanism study.

ATUAÇÃO DA FISIOTERAPIA NA PREVENÇÃO DO PÉ DIABÉTICO

Physical therapy plays a comprehensive role in diabetic foot prevention by providing education, assessment, exercise, pain management, and footwear advice. This bibliographic review includes studies published from 2015 to 2024, selected through the Medline/PubMed, SciELO and LILACS databases. 31 articles were found and 10 met the inclusion criteria to be used in the results and discussion. The participation of physiotherapy in the prevention of diabetic foot is crucial, as physiotherapists play a fundamental role in promoting health and preventing complications in patients with diabetes.

Investigating the Inhibitory Effect of Animal Antimicrobial Peptides on Gram-Positive and Gram-Negative Bacteria in Diabetic Foot Ulcers

Investigating the Inhibitory Effect of Animal Antimicrobial Peptides on Gram-Positive and Gram-Negative Bacteria in 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.

Machine Learning Algorithm-Aided Determination of Predictors of Mortality from Diabetic Foot Sepsis at a Regional Hospital in South Africa During the COVID-19 Pandemic.

Background and Objectives: Diabetic foot sepsis (DFS) accounts for approximately 60% of hospital admissions in patients with diabetes mellitus (DM). Individuals with DM are at risk of severe COVID-19. This study investigated factors associated with major amputation and mortality in patients admitted with DFS during the COVID-19 pandemic. Materials and Methods: Demographic information, COVID-19 and HIV status, clinical findings, laboratory results, treatment and outcome from records of patients with diabetic foot sepsis, were collected and analysed. Supervised machine learning algorithms were used to compare their ability to predict mortality due to diabetic foot sepsis. Results: Overall, 114 records were found and 57.9% (66/114) were of male patients. The mean age of the patients was 55.7 (14) years and 47.4% (54/114) and 36% (41/114) tested positive for COVID-19 and HIV, respectively. The median c-reactive protein was 168 mg/dl, urea 7.8 mmol/L and creatinine 92 µmol/L. The mean potassium level was 4.8 ± 0.9 mmol, and glycosylated haemoglobin 11.2 ± 3%. The main outcomes included major amputation in 69.3% (79/114) and mortality of 37.7% (43/114) died. AI. The levels of potassium, urea, creatinine and HbA1c were significantly higher in the deceased. Conclusions: The COVID-19 pandemic led to an increase in the rate of major amputation and mortality in patients with DFS. The in-hospital mortality was higher in patients above 60 years of age who tested positive for COVID-19. The Random Forest algorithm of ML can be highly effective in predicting major amputation and death in patients with DFS.

Correlating Climate Conditions With Pseudomonas aeruginosa Prevalence in Diabetic Foot Infections Within the United States.

The 2023 "International Working Group on the Diabetic Foot/Infectious Disease Society of America Guidelines on the Diagnosis and Treatment of Diabetes-Related Foot Infections" (DFIs) provides recommendations for Pseudomonas coverage based on the climate region. This was a retrospective national study of veterans between 1/1/2010 and 3/23/2024 with diabetes mellitus and a culture below the malleolus wound. Prevalence of Pseudomonas was categorized based on climate zones according to the International Energy Conservation Code. Multivariable logistic regression was used to determine odds ratios and 97.5% CIs. The prevalence of Pseudomonas significantly varied between US climates. Pseudomonas was most prevalent within the Hot Humid climate, where it was isolated in 11.6% of DFI cultures. Pseudomonas was least prevalent within the Very Cold climate, where it was isolated in 6.2% of cultures. In the multivariable logistic regression model, hot and humid climates were associated with an odds of P. aeruginosa of 1.92 (97.5% CI, 1.69-2.20), a hot, dry climate was associated with an odds of 1.65 (97.5% CI, 1.44-1.90), and a humid climate was associated with an odds of 1.65 (97.5% CI, 1.45-1.89). A lower Charlson Comorbidity Index, inpatient admission, recent antipseudomonal antibiotic use, and swabs were less likely to have Pseudomonas. Recent admission increased the odds of P. aeruginosa (odds ratio [OR], 1.34; 97.5% CI, 1.27-1.41). History of P. aeruginosa was associated with an increase in P. aeruginosa (OR, 8.90; 97.5% CI, 8.29-9.56). The prevalence of DFI organisms varies within different US climates. Utilization of local climate information may allow for more accurate and targeted empiric antibiotic selection when treating DFIs.

The impact of hyperbaric oxygen therapy on the redox balance of patients with diabetic foot syndrome

Diabetic foot wounds associated with oxidative stress are treated with hyperbaric oxygen (HBO), but that may also induce the stress itself; therefore, we studied the effect of HBO treatments on the oxidant–antioxidant balance in the venous blood of patients with diabetic foot syndrome. In addition, blood counts were also examined. 14 male patients (24–74 years), at risk of lower limb amputation were treated with 30 HBO procedures (60 min of the inhalation of pure oxygen at a pressure of 2.5 atm per day, 5 days a week). The control group consisted of 29 healthy male volunteers aged 25–69 years. No members of the group had been subjected to HBO therapy previously (ClinicalTrials.gov, no. NCT06401941). The analyzed redox parameters did not change during the experiment in the patients (p > 0.05). The concentration of thiobarbituric acid reactive substances (TBARS) in the plasma was higher in the patients before the first and after the thirtieth HBO treatments when compared to the control group. In contrast, the TBARS concentration in erythrocytes was lower in the patients after the first treatment vs. the controls. Moreover, the higher activity of catalase in the patients’ erythrocytes was noted before the therapy and after the first and last treatments compared to the controls. HBO therapy increased the percentage of monocytes and platelet volume, but it decreased the volume of platelets in the patients’ blood. HBO therapy does not affect the oxidant–antioxidant balance disturbed in diabetic foot patients.

NIR-II Image-Guided Wound Healing in Hypoxic Diabetic Foot Ulcers: The Potential of Ergothioneine-Luteolin-Chitin Hydrogels.

Hypoxic diabetic foot ulcers (HDFUs) pose a challenging chronic condition characterized by oxidative stress damage, bacterial infection, and persistent inflammation. This study introduces a novel therapeutic approach combining ergothioneine (EGT), luteolin (LUT), and quaternized chitosan oxidized dextran (QCOD) to address these challenges and facilitate wound healing in hypoxic DFUs. In vitro, assessments have validated the biosafety, antioxidant, and antimicrobial properties of the ergothioneine-luteolin-chitin (QCOD@EGT-LUT) hydrogel. Furthermore, near-infrared II (NIR-II) fluorescence image-guided the application of QCOD@EGT-LUT hydrogel in simulated HDFUs. Mechanistically, QCOD@EGT-LUT hydrogel modulates the diabetic wound microenvironment by reducing reactive oxygen species (ROS). In vivo studies demonstrated increased expression of angiogenic factors mannose receptor (CD206)and latelet endothelial cell adhesion molecule-1 (PECAM-1/CD31), coupled with decreased inflammatory factors tumor necrosis factor-α (TNF-α) and Interleukin-6 (IL-6), thereby promoting diabetic wound healing through up-regulation of transforming growth factor β-1 (TGF-β1).

Effect of Treatment of Neuropathic and Ischemic Diabetic Foot Ulcers with the Use of Local Ozone Therapy Procedures-An Observational Single Center Study.

Background: Diabetes ranks high among worldwide global health problems, and diabetic foot ulcer syndrome (DFU) is considered as one of its most serious complications. The purpose of this study was to evaluate the impact of local ozone therapy procedures on the wound healing process in patients with two DFU types: neuropathic and ischemic. Material and Methods: In the retrospective study reported here, the treatment outcomes of 90 patients were analyzed: 44 males (48.8%) and 46 females (51.2%), in the age range between 38 and 87 years of age, with neuropathic (group 1) and ischemic (group 2) diabetic foot ulcers treated by means of local ozone therapy. The assessment of therapeutic effects in both groups of patients included an analysis of the rate of ulcer healing using planimetry and an analysis of the intensity of pain associated with ulcers performed using the VAS scale. Results: After the application of ozone therapy procedures, a statistically significant decrease in the surface area of the ulcers was obtained in both groups of patients, respectively: in group 1 from 7 (6-7.5) cm2 to 3 (2-3.5) cm2 and in group 2 from 7.5 (6.5-8) cm2 to 5 (4.5-5.5) cm2 (p < 0.001), with a complete healing of ulcers not observed in any patients from groups 1 and 2. After treatment, the surface area of the assessed ulcers was smaller in the neuropathic group. The intensity of pain experienced after treatment also decreased with statistical significance in both groups (p < 0.001). Conclusions: Short-term local ozone therapy was effective in promoting wound healing and alleviating pain in patients with DFUs of both neuropathic and ischemic etiology. The effectiveness of therapy in the neuropathic type of DFUs was significantly higher than in the ischemic type, in which patients had a higher incidence of risk factors and more advanced lesions, characterized by a larger initial ulcer area and greater intensity of pain.