Wagner Grade Research Articles

Hyperbaric oxygen therapy for healing chronic foot wounds in diabetic patients: Randomised clinical trial

Introduction: foot wounds are highly prevalent in diabetic patients and can lead to limb amputation; thus, this pathology requires comprehensive treatment. Objective: the primary objective of this study was to evaluate the effectiveness of Hyperbaric oxygen therapy in improving the healing of diabetic foot ulcers. The secondary objective was to evaluate whether it reduces the number of amputations and enhances the quality of life. Methods: this non-blind randomized clinical study included diabetic patients who presented chronic foot ulcers classified as Wagner grades 2, 3, and 4. The sample consisted of 30 patients, 17 allocated to the control group and 13 to Hyperbaric oxygen therapy group. Hyperbaric oxygen therapy was applied once a day, five days a week for seven weeks; each session lasted 90min at 2.5 atmospheres absolute. The SF-36 quality of life questionnaire was administered to both groups. Results: the evaluation of foot wound healing in diabetic patients showed a better result in the Hyperbaric oxygen therapy group less than six months of follow-up (p = 0.04). There were two minor amputations in the control group with p=0.60. Furthermore, the quality of life was improved in the Hyperbaric oxygen therapy group compared to the control, with a statistically significant difference in most domains, except for mental health. Conclusions: our findings suggest that Hyperbaric oxygen therapy positively impacts the healing of foot wounds in diabetic patients who have undergone less than six months of follow-up. Data regarding the method’s benefit related to the reduction of minor or significant amputations are insufficient. Regarding quality of life, we obtained results that support the use of Hyperbaric oxygen therapy. Registration number RBR-7bd3xy (http://www.ensaiosclinicos.gov.br).

Comparative Outcomes of Conservative Surgery versus Early Surgical Intervention in Diabetic Foot Ulcers

Background: Diabetic foot ulcers (DFUs) are a severe complication of diabetes, often requiring intervention. Comparing conservative treatment and early surgical intervention is essential to optimize patient outcomes.Objectives: To evaluate the effectiveness of conservative surgery and early surgical intervention in the management of DFUs and to assess the association of clinical outcomes with biomarkers such as C-reactive protein (CRP) and glycated hemoglobin (HbA1c). Methods: A comparative study was conducted at different tertiary care center in Lahore between January 2024 and October 2024. A total of 300 patients with DFUs (Wagner grade 2-4) were included, with 150 receiving conservative surgery and 150 undergoing early surgical intervention. Outcomes measured included wound healing time, revision surgeries, and amputation rates. The association of these outcomes with CRP and HbA1c levels was analyzed.Results: Patients in the conservative surgery group had a higher rate of revision surgeries (53% vs. 41%, p = 0.04) and longer hospital stays (median 20 vs. 16 days, p < 0.01). Elevated CRP levels (median 58 mg/L, IQR 15–170) were significantly associated with clinical failure (HR = 1.8, p = 0.03), as were elevated HbA1c levels (median 8.2%, IQR 7.5–9.0; HR = 1.5, p = 0.02). Early surgical intervention was linked to lower revision rates and quicker recovery but at the cost of increased limb loss. Conclusion: Conservative surgery preserves limbs but often requires revisions and longer treatment durations, while early surgery shortens recovery time but raises amputation risks. Biomarkers like CRP and HbA1c are critical for guiding personalized treatment decisions.

Factors associated with severity and anatomical distribution of diabetic foot ulcer in a tertiary care hospital in Bangladesh: A cross-sectional study.

Diabetic foot ulcers are characterized by disturbances in the epidermis and/or a portion of the dermis in patients with the disease. With over a million amputations performed annually, it has also emerged as one of the primary causes of lower limb amputation globally. To better understand the severity and anatomical distribution of ulcerated areas in patients with type II diabetes mellitus, this study aimed to identify the factors associated with diabetic foot ulcers (DFUs). This descriptive cross-sectional study was conducted at M Abdur Rahim Medical College Hospital in Dinajpur, Bangladesh, from July to September 2023. The study population was selected using a purposive sampling technique based on the patients' availability during their usual and regular treatment at MARMCH. Using a Bangla questionnaire data was obtained to evaluate the DFUs, in addition to measuring blood pressure and assessing the affected area's neurological function. The severity of the ulcer is calculated by using the Wagner grading system. Data was analyzed by using STATS v15 and chi-square was applied. A total of 113 DFU patients took part in this study. The mean age in years was 56 ± 12 (SD + mean) and the male proportion was greater (61.9%). Most of them (93.91%) were negligent about foot care and suffered from severe DFU (86.37%). The majority of respondents (57.94%) had a right foot ulcer, of which 94.50% had severe ulcers. Almost all ulcers were severe (86.14%) and measured <5 cm in diameter (69.71%). The results highlight the tremendous burden of DFUs, which can have serious consequences and substantial mental and economic effects on patients' healthcare systems.

Analysis of clinical characteristics in patients with diabetic foot ulcers undergoing amputation and establishment of a nomogram prediction model

To assess the accuracy of a nomogram for predicting the risk of lower-extremity amputation (LEA) in individuals with diabetic foot ulcers (DFUs). We retrospectively analyzed data from 144 patients with DFUs at the Department of Orthopedics of the First Affiliated Hospital of Nanchang University, collected between January 2020 and December 2023. Univariate analysis determined primary predictive factors for amputation, followed by single and multifactor logistic regression analyses to indentify independent factors. These were utilized to develop a prediction model using R4.3.3, and a nomogram was created. Its performance was verified using receiver operating characteristic (ROC), corrected calibration, and clinical decision curves. Twelve primary predictive factors were identified from 20 variables, including age, Wagner grades, peripheral angiopathy of diabetes (PAD), chronic kidney disease(CKD), C-reactive protein(CRP) and the number of blood sugar abnormalities(BSA) etc. Multivariate logical regression analysis illustrated that Wagner grades, PAD, CRP, CKD, and the number of BSA were independent risk factors. The area under the curve (AUC) of the ROC curve was 0.967, and the revised calibration curve of the nomogram demonstrated strong fitting ability. This prediction model is a valuable tool for screening LEA risk and preventing DFU from progressing into amputation.

Association between inflammatory markers and anemia in patients with diabetic foot ulcer.

Aim: Anemia of inflammation (AI) is common among patients with diabetic foot ulcers (DFU). This study aimed to investigate the specific relationship between inflammation indicators and anemia in patients with DFU.Materials & methods: This cross-sectional study was carried out among patients with DFU between 2018 and 2023. Clinical data were gathered before treatment. Restricted cubic spline regression was employed to investigate the non-linear associations between inflammation and anemia.Results: A total of 395 patients with Wagner grades 2-4 were enrolled in the study. About 63.54% of the patients with DFU had anemia which was primarily presented with normocytic hypopigmentation anemia. Elevated IL-6 levels (39.10-369pg/ml) were significantly associated with an increased likelihood of anemia (OR=4.84; 95% CI: 1.97-11.90). Similarly, high CRP levels (48.56-385mg/l) were linked to a higher prevalence of anemia (OR=5.01; 95% CI: 2.35-10.68). Furthermore, a nonlinear relationship was observed between CRP levels and anemia, suggesting that CRP values exceeding 53.889mg/l may trigger anemia in patients with diabetic foot ulcers.Conclusion: Inflammation is identified as an independent risk factor for AI in patients with DFU. The inflammation indicators (CRP and IL-6) and anemia exhibit an L-shaped nonlinear correlation in patients with DFU.

Multidisciplinary Team-Led Management of Wagner Grade 3 Diabetic Foot Ulcer with MRSA Infection, Guided by Wound Care Specialists: A Case Report

Multidisciplinary Team-Led Management of Wagner Grade 3 Diabetic Foot Ulcer with MRSA Infection, Guided by Wound Care Specialists: A Case Report

The association of the perioperative neutrophil-to-lymphocyte ratio with wound healing in patients with Wagner grade 3 and 4 diabetic foot ulcers after tibial cortex transverse transport surgery: a prospective observational cohort study.

Diabetic foot ulcers (DFUs) are severe complications of diabetes, involving multiple etiological factors including neuropathy, vascular insufficiency, and impaired wound healing. The global burden of DFUs is substantial, with significant morbidity and high management costs. Recent advancements have introduced the tibial cortex transverse transport (TTT) technique, which has shown promising results in the management of severe DFUs by promoting angiogenesis and immunomodulation. This prospective cohort study enrolled patients with Wagner grade 3 and 4 DFUs, treated using the TTT technique from May 2022 to September 2023 at MianYang Central Hospital. The study assessed the influence of TTT on the perioperative neutrophil-to-lymphocyte ratio (NLR), an established biomarker of systemic inflammation, and its correlation with wound healing outcomes. A total of 82 patients were enrolled, with 66 completing the study. The survival analysis revealed that patients with a lower preoperative NLR experienced significantly faster wound healing compared with a high NLR (log rank test P< 0.05; hazard ratio (HR) = 0.46; 95% CI: 0.26-0.83). The optimal NLR cutoff values (4.25) were established to predict wound healing times for DFUs. The median NLR was significantly different before TTT surgery, 3 days after TTT surgery, and 1 month after TTT surgery (P<0.05). The TTT technique significantly influences the perioperative NLR and is associated with improved wound healing in DFU patients. The perioperative NLR serves as an effective predictive biomarker for wound healing outcomes, highlighting the significance of interventions targeting NLR values in perioperative management strategies and postoperative monitoring protocols for the treatment of diabetic foot ulcers (DFUs) in clinical practice.

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.

ETS1 Expression in Diabetic Foot Ulcers: Implications for Fibroblast Phenotype and Wound Healing Through the PP2A/YAP Pathway.

Diabetic foot ulcers (DFUs) are a serious complication of diabetes, characterized by impaired wound healing and high morbidity and mortality risks. While ETS1 is known to influence fibroblast pathological remodeling, its specific role in DFU and fibroblast wound healing remains unclear. Skin tissue samples from DFU patients were categorized by Wagner grades to analyze ETS1 expression. Primary fibroblasts derived from diabetes mellitus wound (DMFBs) were collected from wound margins to test migration ability and analyze cell phenotype by immunofluorescence; they were further treated with siETS1 and the ETS1 inhibitor YK-4-279. Techniques including Western blotting, quantitative Real-Time PCR (qRT-PCR), and immunofluorescence were used to assess the expressionof ETS1, Collagen I, and phenotype in DMFBs. Additionally, the binding sites between human ETS1 and the PP2A promoter were predicted by the UCSC and JASPAR databases. It intended to explore the negative transcriptional regulation of PP2A by ETS1 and its implications in fibroblast function and wound healing. Fibroblasts derived from Wagner Grades II-IV exhibit differences in cell morphology, migratory ability, and phenotype. Our findings indicate a significant upregulation of ETS1 in Wagner III and IV. The downregulation of ETS1 was observed to enhance DMFB migration and increase the expression of Collagen I and α-SMA. These changes suggest a potential mechanism by which PP2A regulates the YAP/Hippo pathway in diabetic wound healing. ETS1 appears to impede the repair processes in DFUs, likely through the negative regulation of PP2A, affecting fibroblast function and wound healing.

Acupuncture artery technique at Zusanli (ST 36) for Wagner grade 0 diabetic foot

To observe the clinical efficacy of acupuncture artery technique at Zusanli (ST 36) for Wagner grade 0 diabetic foot. Sixty patients with Wagner grade 0 diabetic foot were randomly divided into an observation group and a control group, with 30 patients in each group. Both groups selected bilateral Zusanli (ST 36). In the control group, the needle was inserted about 10 mm under ultrasound guidance to avoid blood vessels in the Zusanli (ST 36) area, with needle retention for 5 min without manipulation. In the observation group, the needle was inserted about 25 mm under ultrasound guidance to the anterior tibial artery branch below Zusanli (ST 36), followed by lifting and thrusting manipulation for 5 min before withdrawing the needle. Both groups were treated twice a week for 4 weeks. The traditional Chinese Medicine (TCM) syndrome scores were observed; infrared thermography was used to measure the temperature difference between the left and right sides in four areas, i.e. the medial malleolus, lateral malleolus, and upper and lower parts of the sole of the foots; Doppler ultrasound was used to measure the logarithm of the peak systolic velocity (ln PS) and the logarithm of the time average maximum velocity (ln TAMAX) of the anterior tibial artery below the right Zusanli (ST 36); the ankle-brachial index (ABI) was measured using Doppler blood flow detector and blood pressure monitor before treatment, after the first treatment, and at the end of treatment. Clinical efficacy was compared between the two groups. Compared before treatment, the TCM syndrome scores in both groups were reduced after the first treatment and at the end of treatment (P<0.01, P<0.05), and the scores in the observation group were lower than those in the control group (P<0.01). In the observation group, compared before treatment, the maximum, minimum, and average temperature differences between the left and right sides of the upper and lower parts of the sole of the foots, medial malleolus, and lateral malleolus were reduced after the first treatment and at the end of treatment (P<0.05, P<0.01). After the first treatment, the maximum temperature difference between the left and right sides of the upper part of the sole of the foots and the medial malleolus in the observation group was lower than that in the control group (P<0.05). At the end of treatment, except for the average temperature difference of the medial malleolus, the maximum, minimum, and average temperature differences between the left and right sides of the upper and lower parts of the sole of the foots, medial malleolus, and lateral malleolus in the observation group were lower than those in the control group (P<0.01, P<0.05). After the first treatment and at the end of treatment, the ln PS, ln TAMAX, and ABI of the anterior tibial artery below the right Zusanli (ST 36) in the observation group were higher than those before treatment (P<0.01) and higher than those in the control group (P<0.01). The total effective rate in the observation group was 96.7% (29/30), higher than 3.3% (1/30) in the control group (P<0.05). Acupuncture artery technique at Zusanli (ST 36) could effectively improve the clinical symptoms of patients with Wagner grade 0 diabetic foot, increase blood flow velocity in the lower limb vessels, and reduce the temperature difference between the left and right lower limbs.

A multicentre clinical trial evaluating the outcomes of two application regimens of a unique keratin-based graft in the treatment of Wagner grade one non-healing diabetic foot ulcers.

Diabetic foot complications that lead to lower extremity amputations pose a significant challenge to the entire global health system. In this multicentre clinical trial, 26 patients with chronic Wagner one diabetic foot ulcers (DFUs) were treated with a unique human keratin matrix graft applied either weekly or bi-weekly, in addition to standard of care. The hypothesis was that bi-weekly application would be similar to weekly application. The primary endpoint was complete wound closure by 12 weeks, and secondary endpoints included healing time, percent area reduction and weekly changes in peripheral neuropathy, pain and quality of life. In the intent-to-treat population, 77% (10/13) of DFUs treated with bi-weekly application healed compared with 69% (9/13) treated with weekly application. The mean time to heal within 12 weeks in the bi-weekly group was 61 days and in the weekly group was 54 days. The mean percent area reduction at 12 weeks was 94.7% in the bi-weekly group compared with 84.8% in the weekly group. The number of grafts used in the bi-weekly group was 3.9 compared with 6.2 in the weekly group. The results of this trial confirm our hypothesis that whether bi-weekly or weekly application of the unique keratin matrix graft is used to treat nonhealing indolent DFUs, there is a high rate of complete healing. Based on these results, future studies should be conducted that further investigate the use of this novel human keratin matrix graft for the treatment of chronic DFUs.

Development and Validation of a Risk Prediction Model for Prolonged Hospitalization in Patients With Diabetic Foot Ulcers

To investigate the risk factors associated with prolonged hospitalization in patients diagnosed with diabetic foot ulcers (DFU), to develop a predictive model, and to conduct internal validation of the model. The clinical data of DFU patients admitted to West China Hospital, Sichuan University between January 2012 and December 2022 were retrospectively collected. The subjects were randomly assigned to a training cohort and a validation cohort at a ratio of 7 to 3. Hospital stays longer than 75th percentile were defined as prolonged length-of-stay. A thorough analysis of the risk factors was conducted using the training cohort, which enabled the development of an accurate risk prediction model. To ensure robustness, the model was internally validated using the validation cohort. A total of 967 inpatients with DFU were included, among whom 245 patients were identified as having an extended length-of-stay. The training cohort consisted of 622 patients, while the validation cohort comprised 291 patients. Multivariate logistic regression analysis revealed that smoking history (odds ratio [OR]=1.67, 95% confidence interval [CI], 1.13 to 2.48, P=0.010), Wagner grade 3 or higher (OR=7.13, 95% CI, 3.68 to 13.83, P<0.001), midfoot ulcers (OR=1.99, 95% CI, 1.07 to 3.72, P=0.030), posterior foot ulcers (OR=3.68, 95% CI, 1.83 to 7.41, P<0.001), multisite ulcers (OR=2.91, 95% CI, 1.80 to 4.69, P<0.001), wound size≥3 cm2 (OR=2.00, 95% CI, 1.28-3.11, P=0.002), and white blood cell count (OR=1.11, 95% CI, 1.05 to 1.18, P<0.001) were associated with an increased risk of prolonged length of stay. Additionally, a nomogram was constructed based on the identified risk factors. The areas under the receiver operating characteristic (ROC) curves for both the training cohort and the validation cohort were 0.782 (95% CI, 0.745 to 0.820) and 0.756 (95% CI, 0.694 to 0.818), respectively, indicating robust predictive performance. Furthermore, the calibration plot demonstrated optimal concordance between the predicted probabilities and the observed outcomes in both the training and the validation cohorts. Smoking history, Wagner grade≥3, midfoot ulcers, posterior foot ulcers, multisite ulcers, ulcer area≥3 cm2, and elevated white blood cell count are identified as independent predictors of prolonged hospitalization. Therefore, it is imperative that clinicians conduct a comprehensive patient evaluation and implement appropriate diagnostic and therapeutic strategies to effectively shorten the length of stay for DFU patients.

Analysis of factors influencing the recurrence of diabetic foot ulcers.

The aim of this study is to investigate the factors influencing the recurrence of diabetic foot ulcers (DFU) and provide guidance for reducing the recurrence rate. A total of 211 patients diagnosed with DFU who were hospitalized and discharged from the hospital from October 2015 to January 2020 were included as the study cohort. Participants were divided into two groups according to whether the foot ulcer recurred during the 2-year follow-up period: a recurrence group (n=84) and a non-recurrence group (n=127). The following data were collected and analyzed for the two groups of patients: general information, foot information, laboratory indicators, diabetes comorbidities, and complications. (1) The overall recurrence rate of diabetic foot ulcers (DFU) within 2 years was 39.8%, indicating a high recurrence rate. (2) Significant differences were observed between the two patient groups in terms of BMI, HbA1c, TBIL, CRP, financial situation, foot deformity, first ulcer on the sole of the foot, previous amputation history, Wagner grade of the first ulcer, osteomyelitis, DFU duration(>60 days), lower limb vascular reconstruction, peripheral arterial disease (PAD), and diabetic peripheral neuropathy (DPN) (t=2.455; Z=-1.988, -3.731, -3.618; χ2=7.88, 5.004, 3.906, 17.178, 16.237, 5.007, 24.642, 4.782, 29.334, 10.253). No significant differences were found for the other indicators. (3) Logistic regression analysis revealed that TBIL (OR=0.886, p=0.036) was a protective factor against ulcer recurrence. In contrast, PAD, previous amputation history, DPN, and the first ulcer on the sole of the foot (OR=3.987, 6.758, 4.681, 2.405; p<0.05 or p<0.01) were identified as risk factors for ulcer recurrence. Early screening and preventive education targeting high-risk factors such as DPN, PAD and the initial ulcer location on the sole of the foot are essential to mitigate the high long-term recurrence rate of DFU. Furthermore, the protective role of TBIL in preventing ulcer recurrence underscores the importance of monitoring bilirubin levels as part of a comprehensive management strategy for DFU patients.

Correlation analysis of patients with diabetic foot ulcers treated with tibial cortex transverse transport surgery and platelet-to-lymphocyte ratio and monocyte-to-neutrophil ratio.

Diabetic foot ulcers (DFUs) represent one of the most severe late-stage complications of diabetes. Tibial cortex transverse transport (TTT) surgery stands as the prevailing method for addressing DFUs. This surgical intervention holds the promise of expediting DFU wound healing and diminishing the rate of amputations, with the mitigation of inflammatory responses playing a pivotal role. In this study, we aim to explore the correlation between inflammation and TTT surgery, with the overarching goal of facilitating swift prognostic assessments in clinical practice. The correlation between the severity of DFUs and clinical test results remains ambiguous. A clinical prediction model was devised to explore the connection between DFU severity and the efficacy of TTT surgery, utilizing straightforward and efficient clinical indicators. Clinical data and examination results were gathered by tracking hospitalized DFU patients who underwent TTT surgery at the First Affiliated Hospital of Guangxi Medical University (Nanning, China). Indicators associated with DFU severity and wound healing time post-surgery were identified through logistic regression and least absolute shrinkage and selection operator (LASSO) regression analyses. Subsequently, a clinical prediction model was constructed. Finally, the intersection of these 2 sets of indicators revealed factors correlated with wound severity and post-operative healing duration. Our study was comprised of 202 patients who were categorized into 2 groups based on Wagner's grading classifications. Utilizing Student's t-tests, LASSO regression and logistic regression analyses, we identified 3 factors indicative of DFU severity: platelet-to-lymphocyte ratio (PLR), mixed lymphocyte reaction (MLR) and hemoglobin (HGB). Univariate COX regression analysis revealed 12 factors such as: white blood cells (WBC), neutrophils (NEUT), monocytes (MO), PLR, MLR, neutrophil-to-lymphocyte ratio (NLR), erythrocyte sedimentation rate (ESR), age, lymphocytes (LY), monocyte-to-neutrophil ratio (MNR), uric acid (UA), and albumin (ALB) associated with the postoperative healing duration. Ultimately, we identified 2 factors, PLR and MNR, at the intersection of these 2 datasets. Platelet-to-lymphocyte ratio and MNR were identified as factors associated with both the severity of DFUs and the prognosis following TTT surgery.

Autologous Platelet-Rich Gel Accelerates Diabetic Wound Healing Through Inhibition of Ferritinophagy.

Aims: The objective was to examine the efficacy of autologous platelet-rich gel (APG) in treating diabetic wound and investigate the association between APG and ferritinophagy. Methods: A total of 32 patients with diabetic foot (DF) and Wagner grade 1 to 2 were included. Within the APG group, individuals with DF received weekly APG treatment. In the non-APG group, DF patients received daily dressing changes. Flow cytometry quantified the proportion of endothelial progenitor cells (EPCs) in peripheral blood on days 0 and 10. The diabetic rat model was induced using Streptozotocin. Two circular skin wounds were created on the backs of rats. The normal glucose group received daily dressing changes on the wound. In the diabetic group, the left wound underwent daily dressing changes, whereas the right wound was treated with APG once a week. CD34 levels were tested 7 days after the skin damage. The levels of glutathione peroxidase 4 (GPX4), Nuclear Receptor Coactivator 4 (NCOA4), Light chain 3 (LC3), and Masson staining were quantified on 14 days. The wound area and wound healing rate were separately measured at 0 and 14 days after the injury, regardless of DF patients or diabetic rats. Results: The wound healing rate was higher in the APG group than in the non-APG group, regardless of DF patients or diabetic rats. The APG group had a greater ΔEPCs% in DF patients than the non-APG group. Regarding rat experiment, the APG group exhibited lower levels of NCOA4, and LC3 expressions and a shorter wound healing time. However, the APG group showed higher levels of CD34 expression, GPX4 protein, and collagen fibers than the non-APG group. Conclusions: Autologous platelet-rich gel accelerated the wound healing rate in diabetic populations and rats. Autologous platelet-rich gel promoted EPCs counts, collagen fiber volume, and vessel numbers. Autologous platelet-rich gel decreased LC3 and NCOA4 expression, but increased GPX4 protein expression. The possible mechanism was the inhibition of ferritinophagy.

Therapeutic Effectiveness of Leukocyte- and Platelet-rich Fibrin for Diabetic Foot Ulcers: A Retrospective Study.

Diabetic foot ulcer (DFU) is one of the most serious complications of diabetes. Leukocyte- and platelet-rich fibrin (L-PRF) is a second-generation autologous platelet-rich plasma. This study aims to investigate the clinical effects of L-PRF in patients with diabetes in real clinical practice. Patients with DFU who received L-PRF treatment and standard of care (SOC) from 2018 to 2019 in Tongji Hospital were enrolled. The clinical information including patient characteristics, wound evaluation (area, severity, infection, blood supply), SOC of DFU, and images of ulcers was retrospectively extracted and analyzed. L-PRF treatment was performed every 7±2 days until the ulcer exhibited complete epithelialization or an overall percent volume reduction (PVR) greater than 80%. Therapeutic effectiveness, including overall PVR and the overall and weekly healing rates, was evaluated. Totally, 26 patients with DFU were enrolled, and they had an ulcer duration of 47.0 (35.0, 72.3) days. The severity and infection of ulcers varied, as indicated by the Site, Ischemia, Neuropathy, Bacterial Infection, and Depth (SINBAD) scores of 2-6, Wagner grades of 1-4, and the Perfusion, Extent, Depth, Infection and Sensation (PEDIS) scores of 2-4. The initial ulcer volume before L-PRF treatment was 4.94 (1.50, 13.83) cm3, and the final ulcer volume was 0.35 (0.03, 1.76) cm3. The median number of L-PRF doses was 3 (2, 5). A total of 11 patients achieved complete epithelialization after the fifth week of treatment, and 19 patients achieved at least an 80% volume reduction after the seventh week. The overall wound-healing rate was 1.47 (0.63, 3.29) cm3/week, and the healing rate was faster in the first 2 weeks than in the remaining weeks. Concurrent treatment did not change the percentage of complete epithelialization or healing rate. Adding L-PRF to SOC significantly improved wound healing in patients with DFU independent of the ankle brachial index, SINBAD score, or Wagner grade, indicating that this method is appropriate for DFU treatment under different clinical conditions.

Effects of ON101 for Hard-to-Heal Diabetic Foot Ulcers in a Randomized Phase III Trial: A Post Hoc Analysis.

Objective: Hard-to-heal diabetic foot ulcers (DFUs) are associated with higher mortality rates and an increased medical burden for patients. ON101, a new topical cream, exhibited better healing efficacy than the control dressing in a Phase III trial. In this post hoc analysis, we further identify whether ON101 can improve the healing of ulcers with hard-to-heal risk factors in this cohort of DFU patients. Approach: To compare the efficacy of ON101 with absorbent dressing among various hard-to-heal wounds in patients with DFU, a post hoc analysis of a randomized Phase III trial that included 276 DFU patients was performed by subgrouping those patients based on ulcer depth, location, size, duration, and patients' glycated hemoglobin (HbA1c) levels and body mass index (BMI). Results: In the full analysis set, the proportion of patients achieving healing was 61.7% in the ON101 group and 37.0% in the comparator (p = 0.0001). In subgroup analysis according to risk factors, ON101 demonstrated superior healing capacity on Wagner grade 2 ulcers (p < 0.0001); plantar ulcers (p = 0.0016), ulcer size ≥5 cm2 (p = 0.0122), ulcer duration ≥3 months (p = 0.0043); for patients with HbA1c ≥9% (p = 0.0285); and patients with BMI ≥25 (p = 0.0005). Innovation: ON101, a novel therapeutic drug, can modulate the functions of macrophages and demonstrate superior healing rates to conventional absorbent dressing in patients with hard-to-heal DFUs. Conclusions: The results of this post hoc study suggest that ON101 is a better therapeutic option than conventional dressing used in treatment for DFU patients with higher HbA1c, BMI, or ulcers with complex conditions such as longer duration, deeper wounds, larger size, and plantar location.

Bacteriological analysis and antibiotic resistance in patients with diabetic foot ulcers in Dhaka.

The primary objective of this study was to isolate bacteria from diabetic foot ulcers and subsequently assess their antibiotic resistance capabilities. Seventy-five patients diagnosed with diabetic foot ulcers were investigated. A number of these patients (97.33%) had type 2 diabetes, with a significant proportion of them having been diagnosed for 1-5 years (29.33%). Notably, a substantial number of these individuals were on insulin usage (78.66%). Among the patients under examination, 49.33% reported having no use of tobacco products, alcohol, or betel leaf. The ulcers analyzed in this study were classified into grades 1-5 according to the Wagner scale. Wagner grade 2 diabetic foot ulcers had the highest number of culture-positive patients, at 33.33%. Pus samples collected from patients were cultured on selective media, and bacterial identity was confirmed by biochemical tests and polymerase chain reaction. A total of 141 isolates were isolated. Among the isolates, 82.97% gram-negative bacteria and 17.02% gram-positive bacteria were detected. Klebsiella pneumoniae was the most common isolate. Proteus spp., Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus were also detected. Approximately 61.33% of the ulcers exhibited were polybacterial. In this study, it was observed that all bacterial isolates, except for Proteus spp., were primarily detected in patients classified under Wagner's grade 2. Moreover, antibiotic susceptibility was also tested on these 141 isolates. Among them, Escherichia coli showed the highest multidrug resistance, 81.81%. Most of the gram-negative bacteria were resistant to ampicillin. All of the gram-negative isolates exhibited high levels of susceptibility to piperacillin-tazobactam, and these levels were Klebsiella pneumoniae (97.56%), Pseudomonas aeruginosa (95.24%), Escherichia coli (81.82%), and Proteus spp. (80%). On the other hand, gram-positive Staphylococcus aureus mostly showed sensitivity towards vancomycin and norfloxacin (79.17%).

Effect of electrospun poly (L-lactide-co-caprolactone) and formulated porcine fibrinogen for diabetic foot ulcers

Diabetic foot ulcers were a significant complication of diabetes and were accompanied by delayed wound healing. To compare the effect of topical application electrospun poly (L-lactide-co-caprolactone) and formulated porcine fibrinogen (PLCL/Fg) dressing with alginate dressing when treating diabetic foot ulcers (DFUs). A single-center, prospective, randomized, patient-blinded clinical trial was conducted from July 1, 2023, to December 26, 2023. The clinical trial registration was completed on August 28, 2023 (ClinicalTrials.gov Identifier: NCT06014437). The eligible patients with DFUs of 1–20 cm2 present for at least 1 month and with Wagner grade 1 or 2. They were randomized 1:1 to receive PLCL/Fg or alginate dressing. Participants received PLCL/Fg dressing 1–3 times per week or alginate dressing 3 times per week for 12 weeks. A total of 52 patients (33 men [63.5 %]; mean [SD] age, 63.1 [11.9] years; mean [SD] diabetes time, 8.3 [4.6] years) with DFUs were assessed for this study. The DFUs classified as Wagner grade 1 or 2 (mean [SD] ulcer area, 3.8 [3.2] cm2) were randomized to receive either the PLCL/Fg dressing (n = 26) or the alginate dressing (n = 26) for as long as 12 weeks. In this study, the incidence of complete healing included 22 patients (91.7 %) in the PLCL/Fg group and 14 (63.6 %) in the alginate group during the 12-week treatment period (P = 0.003). The treatment-related adverse events that occurred were 5 (20.8 %) in the PLCL/Fg group and 4 (18.1 %) in the comparator group.In this randomized clinical trial, PLCL/Fg dressing showed beneficial effects in DFUs treatment of wound surface reduction and regulating the wound microenvironment.

The Efficacy of Diabetic Foot Treatment in a "TOSF" Pattern: A Five-Year Retrospective Study.

To evaluate the advantages and problems in the diagnosis and treatment of diabetic foot (DF) patients by analyzing the results of a 5-year follow-up of the organ system based (TOSF) treatment model. A retrospective study was conducted in 229 patients with diabetic foot. Chi-square test and rank-sum test were used to analyze the effects of patients' general condition, behavioral and nutritional status, degree of infection (inflammatory markers), comorbidity, diabetic foot grade/classification, and revascularization on readmission rate, amputation rate, all-cause mortality, incidence of other complications, and wound healing time. Logistic regression was used to analyze the risk factors affecting the prognosis of diabetic foot. Kaplan-Meier survival curve was used to analyze the differences in amputation rate and mortality rate at each time point. This study showed that nutritional status, degree of infection, and revascularization influenced readmission rates. General condition, behavior and nutritional status, degree of infection, Wagner grade and revascularization affect the amputation rate. General conditions, behavioral and nutritional status, degree of infection, comorbidities, classification and revascularization affect the mortality of patients. Age and white blood cell(WBC) count affected the incidence of other complications. Influence of infection degree and Wagner grade and revascularization in patients with wound healing time. Revascularization was an independent protective factor for readmission, amputation, and mortality.Elevated serum inflammatory markers are an independent risk factor for amputation. Hypoproteinemia is an independent risk factor for mortality. In the "TOSF" diagnosis and treatment pattern, diabetic foot patients have a good prognosis. Special attention should be paid to the screening and revascularization of lower extremity vascular disease in patients with diabetic foot.