Evolving Strategies in the Management of Venous Leg Ulcers
Red Leg Dilemma: Development and Validation of Clinical Decision Tools for Non-Necrotizing Bacterial Dermohypodermitis, Necrotizing Fasciitis, and Eczematous Dermatitis
Diagnosing red legs on first presentation is challenging. There exists a lack of robustly developed and validated diagnostic red leg tools in clinical practice. Physicians fear missing cases of infectious red legs and treat many patients unnecessarily with antibiotics.
Screening for Diabetic Peripheral Neuropathy: Subjective Versus Objective Measures
This study compared subjective screening modalities recommended in diabetic foot screening guidelines for the detection of diabetic peripheral neuropathy (DPN) with an objective measure, the NC-Stat DPNCheck. We assessed 63 participants (mean age 54.5 years ± 10.5) utilising subjective screening tools (Semmes-Weinstein 10-g monofilament, 128-Hz traditional tuning fork, neurothesiometer, O'Brien 128-Hz electronic tuning fork) and compared results with the objective automated sural nerve conduction test NC-Stat DPNCheck. A significant difference was found in the number of limbs classified with DPN between all screening tools ( < .05). Therefore, this suggests that some screening modalities are more sensitive in diagnosing DPN than others, highlighting the importance of using multiple screening tools to a comprehensive understanding of the patient's neurological status. The findings also emphasize the need to incorporate objective measures in diabetic foot screening and encourage future research to establish a gold standard tool for DPN diagnosis.
Investigating Nonadherence in an Integrated Diabetic Limb Salvage Programme: Reasons, Associated Factors, and Impacts on Care Outcomes
Adherence to treatment plans is crucial for patients with diabetic foot ulcers (DFUs) to achieve positive outcomes. With limited understanding of nonadherence and its impacts on care outcomes, this study aimed to explore the reasons and factors associated with nonadherence in an integrated diabetic limb salvage (DLS) programme and evaluate its effects on care outcomes. This study included 2798 DFU patients who were enrolled in an integrated DLS programme across multiple institutions in central and northern Singapore from 2020 to 2021. Reasons for nonadherence were obtained via telephone interviews. Factors associated with nonadherence were identified using multiple logistic regression. Differences in one-year outcomes, including minor and major lower extremity amputation (LEA), mortality, LEA-free survival, and healthcare utilisation between adherent and nonadherent patients, were examined based on a significance level of < .05. Nonadherence was observed in 40.2% of patients, with higher rates among younger patients, Malays and Indians, and those with higher HbA1c levels. Patient-related factors were the most commonly reported reasons for missed appointments (50.4%). Compared to adherent patients, nonadherent patients exhibited a relatively higher minor LEA rate (13.0% vs 10.2%, OR = 1.18, 95% CI: 0.93, 1.51), lower mortality rate (8.6% vs18.1%, OR = 0.50, 95% CI: 0.39, 0.65), higher overall LEA-free survival (76.4% vs 71.1%, OR = 1.27, 95% CI: 1.06, 1.53), and more hospitalisations (IRR = 1.22, 95% CI: 1.11, 1.33) and emergency visits (IRR = 1.27, 95% CI: 1.16, 1.39). While nonadherent patients showed relatively higher minor LEA rates and more healthcare utilisation, they also exhibited lower mortality and higher LEA-free survival. This suggests that nonadherence in this population may be associated with complex patient characteristics and behaviours that warrant further investigation to tailor interventions effectively.
Incidence and Risk Factors for Amputations in Persons with Diabetes Mellitus: A Retrospective Cohort Study
The aim of this study was to identify and analyze the incidence rate of amputations and their risk factors in people with Diabetes Mellitus (DM) in two specialized outpatient clinics in Brazil. This is an epidemiological, retrospective cohort study using data collected from electronic health records of 281 adult diabetic patient types 1 or 2; attended in specialized outpatient service between 2015 and 2020. Statistical analyses were performed using the 2 sample t-test or Wilcoxon-Mann-Whitney test, for quantitative variables, and the Pearson's χ2 test or Fisher's exact test for categorical variables. The investigation of the risk factors for amputation was carried out through logistic regression. The study was approved by ethical committee. The sample mean age was 65.6 years (SD 13.05), predominating male gender n = 211 (75%), type 2 DM n = 223 (86.7%), with cardiovascular disease n = 143 (63.2%), and about 68.7% (n = 156) with peripheral arterial disease (PAD). Seventy-seven had lower limb amputation (LLA), with a rate incidence of 31.9% during five years. Logistic regression analysis showed the following associations with amputation: Diabetic peripheral neuropathy increased the rate of amputation by 3.6 times (OR = 3.631, 95% CI = 1.214-11.353; = .022), and peripheral arterial disease increased by 10 times (OR = 10.631; 95% CI = 2.969-57.029; = .001). The LLA in individuals with DM in two specialized outpatient services was higher compared to international literature; DPN and PAD were confirmed as risk factors for amputation, according to literature. This finding suggests that the study population faces an increased risk of amputation, highlighting the urgent need for targeted interventions and implementing robust preventive strategies to transform the current scenario and mitigate these severe outcomes. A comprehensive approach is essential to proactively address the underlying issues and reduce the prevalence and impact of amputations in Brazil.
Corrigendum to "Ultrasound in the Modern Management of the Diabetic Foot Syndrome: A Multipurpose Versatile Toolkit"
The Infected Diabetic Foot: Does Negative Pressure Wound Therapy with Irrigation Reduce Bioburden and Improve Wound Healing?
The aim of this study was to compare the microbial loads of patients with diabetic foot infections treated with negative pressure wound therapy (NPWT) with and without irrigation with polyhexamethylene biguanide (NPWTi-P). This is a post hoc analysis of combined data of two randomized clinical trials. We evaluated people with diabetes treated with moderate and severe diabetic foot infections that required surgery. Tissue specimens were obtained after the initial surgery and following a second planned return to the operating room after 48-72 h of NPWT or NPWTi-P, prior to the second surgery. We used quantitative polymerase chain reaction (qPCR) to determine the total microbial loads (Log 16S copies per gram of tissue). There was no difference in mean quantitative bacterial cultures among patients that received NPWT and NPWTi-P (before first surgery Log: NPWT = 6.4 ± 1.8, NPWTi-P = 7.5 ± 1.7 vs before second surgery Log: NPWT = 6.7 ± 1.8, NPWTi-P = 7.6 ± 1.9 p = .12). There was no difference in wound healing (59.5% vs 50.0%, p = .51) or time to heal (127 ± 109.3 vs 143 ± 95.9), p = .71). There were fewer re-infections in people that received traditional NPWT (28.6% vs 56.3%, p = .05). Level 1.
Effectiveness of Stem Cell Therapy for Diabetic Foot Ulcers: Cell Therapy Alone is Not Enough for Effective Management of Chronic Wounds
We read with great interest the meta-analysis by Mudgal et al. (2024) regarding the effectiveness and safety assessment of stem cell therapy for diabetic foot ulcers. Indeed, The management of chronic wounds requires innovative approaches to avoid unsuccessful outcomes, and stromal cell therapies have emerged as a potential solution for soft tissue repair. A critical aspect of this therapeutic strategy is the role of mast cells in stimulating delayed inflammation through their interactions with various cells as well as the extracellular matrix. Mast cells are critical in orchestrating the inflammatory response and their activation can influence macrophage behavior and secondary healing efficacy. The use of mesenchymal stromal cells in regenerative medicine for diabetic foot ulcers treatment is often limited by their time-limited anti-inflammatory responses. However, these time-limited effects could not achieve the prolonged effects and impact of cell therapy efficacy and the potential enhancement of cell function by biologically active factors such as growth factors or gene therapeutics for prolonged release. The integration of cell and prolonged release gene therapeutics is a promising approach that goes beyond regenerative medicine by preventing secondary inflammatory complications. While mesenchymal stromal cells have shown promising results in experimental and clinical studies, there are limitations to their efficacy in regenerative medicine for diabetic foot ulcers. These limitations include the heterogeneity of cell populations used in the studies, the difficulty in determining the contribution of cells when used in combination with materials, the lack of data on optimal cell numbers for tissue repair, the effect of culture conditions on cell therapy efficacy, and the potential enhancement of cell efficacy by the use of additional biologics such as growth factors or gene therapeutics. The combination of cell and gene therapy is seen as a promising approach that goes beyond regenerative medicine into the field of molecular surgery of chronic wounds.
Cold Environment-Associated Extremity Lesions or Severe Hypothermia Help Differentiate Between Frostbitten and Trench Foot (Immersion Foot)
Cold associated foot injuries, such as frostbite and trench foot (immersion foot) are relatively common in cold environments. The former is classified as a freezing cold injury, and the latter as a nonfreezing cold injury. Trench foot is sometimes misdiagnosed as frostbite, and rapid rewarming exacerbates the condition. This paper aims to help differentiate between frostbitten foot and trench foot. This study included patients with frostbitten foot or trench foot treated at our hospital between December 2005 and May 2023. The differences in sex, age, month of injury, conditions at the time of injury, injury distribution, foot lesion laterality, other complications upon arrival (finger frostbite, immersion hand, or hypothermia), and presence and distribution of sensory disturbance at discharge were noted among the groups. A total of 16 patients (14 men) with frostbitten foot and 3 patients (3 men) with trench foot were identified. Finger frostbite observed in nine and zero patients with frostbitten foot and trench foot, respectively; and severe hypothermia on arrival observed in five and zero patients with frostbitten foot and trench foot, respectively. Physical findings at the initial examination showed that the frostbitten feet were dry, and the lesions were distal and clearly demarcated, whereas feet with trench foot were wet, and the lesions covered the entire sole and were not clearly demarcated. Accurate differentiation between frostbitten foot and trench foot and appropriate initial treatment are important. The presence of finger frostbite, immersion hand or severe hypothermia may help to differentiate between frostbitten foot and trench foot.
Comparative Effectiveness of Diode Laser Therapy and Topical Turmeric Extract Ointment in Promoting Healing of Wounds in a Murine Model
The intricate biological process of wound healing is influenced by a wide range of therapeutic techniques. In this work, the effects of topical turmeric extract ointment and diode laser therapy on wound healing in a mouse model were investigated. Out of the sixty mice, three groups of twenty male mice each were created. Three groups received treatment: the first was a control group that got no treatment; the second group received topical application of 5% curcumin twice a day; and the third group received diode laser therapy, which involved direct laser beam therapy for five minutes a day at an output power of 100 mW at an 810 nm wavelength. Over the course of two weeks, the study examined histological changes and wound closure rates. On days 0 through 14, the wound area was measured with digital calipers to provide quantifiable statistics about the process of healing. In histological analyses, epithelializations, and collagen deposition, in addition to inflammatory cells, were investigated using hematoxylin and eosin staining. It was demonstrated by comparing the outcomes to those of a control group that diode laser therapy and turmeric extract ointment are both successful therapeutic options. The results demonstrate that different therapies, while with differing degrees of effectiveness, greatly quicken the healing process of wounds. According to these results, topical turmeric extract ointment could be used as an additional or supporting therapy to aid in the healing of wounds during medical treatments.
Heel Raises and Calf Stretches Exercises Versus Medication Only in Ischemic Intermittent Claudication: A Randomized Controlled Trial
Intermittent claudication is a primary symptom of peripheral artery disease (PAD). a chronic progressive disease caused primarily by atherosclerosis. It is usually characterized by leg pain, aches, cramps, or fatigue when walking, which improves with rest. Physical therapy, including a supervised exercise program, is often recommended as the first treatment for sprains. This study aims to evaluate the short-term effects of incorporating heel raise and calf stretch exercises with standard medical therapy compared to medical therapy alone in managing intermittent claudication. From May 2022 to November 2023, 160 patients with Stage II Fontaine PAD were randomly assigned to two equal groups. Group A (80 patients) received heel raise and calf stretch exercises in addition to medical treatment, while Group B (80 patients) received only medical treatment. Both groups underwent treadmill walking tests before and after three months to measure absolute walking distance (ACD), peak walking time (PWT), and Walking Impairment Questionnaire (WIQ) scores, including distance, speed, and symptom severity. At baseline, there were no significant differences between the groups in terms of ACD, peak walking time, ankle-brachial index, distance, speed, and symptoms. At follow-up, Group A showed significantly greater improvements in ACD (312.00 ± 45.43 m), peak walking time (8.54 ± 1.55 min), distance (29.46 ± 4.63 km), speed (20.01 ± 3.13 kph), and WIQ symptoms (22.10 ± 1.02) compared to Group B, which had ACD (276.55 ± 29.07 m), peak walking time (6.72 ± 1.70 min), distance (23.68 ± 3.89 km), speed (15.71 ± 2.71 kph), and WIQ symptoms (20.80 ± 1.47) ( < .001). The ankle-brachial index remained similar between the groups ( > .05). We concluded that integrating standard physical therapy exercises, such as calf raises and leg stretches, with medical therapy significantly enhances walking function in patients with ischemic intermittent claudication.
COVID-19 and COVID-19 Vaccine-Related Skin Ulcerations in the Lower Extremities: A Case Report and Literature Review
A 53-year-old male patient presented to the dermatology clinics with a three-week history of painful necrotic patches coalescent of the lateral malleolus of the right and left ankles. History goes back to when the patient reported developing pruritic papules two weeks after receiving his second shot of the Pfizer BioNTech COVID-19 vaccine (BNT162b2). Punch biopsy was consistent with leukocytoclastic vasculitis. He was prescribed a four-week course of systemic corticosteroids and antibiotics as per cultures. Vascular assessment confirmed normal peripheral arterial and venous system. Two months later, the patient re-presented with fever and worsening of his lower extremity ulcers. He underwent debridement of his wounds. Intra-operative cultures revealed multidrug resistant bacteria. He required an additional debridement session a few days later and a 14-day course of Piperacillin-Tazobactam. The patient was subsequently discharged on corticosteroids and Azathioprine and followed up in the vascular surgery and rheumatology clinics. At four months follow-up, the patient's wounds were almost completely healed.
A Randomized Clinical Trial Study on the Prevention Strategy and Early Detection of Ulcer Recurrence in Patients with Type 2 Diabetes Mellitus Using the Risk of Recurrence Ulcer Tool
ClinicalTrials.gov Identifies: NCT06434922.
Free Flap Limb Salvage and Ulcer Recurrence in Chronic Limb-threatening Ischemia
Free flap transfer is a well-established treatment for foot reconstruction in patients with chronic limb-threatening ischemia (CLTI) and can achieve prolonged amputation-free survival. However, reports on ulcer recurrence after free flap transfer are scarce, with most focusing on trauma patients. Therefore, we retrospectively reviewed patients with CLTI who underwent free flap reconstruction at our institution over a 17-year period. Patient characteristics, ulcer recurrence rates, activity level, and variables associated with ulcer recurrence were investigated in patients who met the following criteria: successful reconstructive surgery, complete wound healing, and at least 1 year of follow-up. Free flap foot reconstruction was performed in 42 patients (92.9% male, 7.1% female; mean age 57.1 years, range 37-81 years). Among them, 39 patients (92.9%) had diabetes mellitus, 15 (35.7%) had critical limb ischemia, and 15 (35.7%) had end-stage renal disease/hemodialysis. Mean postoperative follow-up was 60.5 (range 12.0-208.0) months. The 5-year primary ulcer recurrence-free survival rate was 48.7%. High activity level and selection of the posterior tibial artery as the recipient artery were significantly associated with ulcer recurrence [hazard ratio, 3.59 and 9.81; = .046 and < .001, respectively]. Activity levels were not significantly different before and 1 year after surgery. In conclusion, survival analysis revealed that ulcer recurrence is most likely to occur within the first 2 years after surgery. Although recurrence occurred in approximately half of the patients, most patients maintained activity levels comparable to their preoperative levels.
Identification of High-Risk Lower Extremity Wounds Using Point-of-Care Test for Bacterial Protease Activity; A Single-Centre, Single-Blinded, Prospective Study
Clinician observation is the mainstay to determine if wound infection is present, and focuses on presence of erythema, purulence, and odour. However, non-visible bacterial protease activity can delay wound healing and lead to complications. In this study, a point-of-care test to detect the presence of bacterial protease activity (BPA, tested with Woundchek Bacterial Status test) was appraised. A total of 130 patients with lower extremity wounds were recruited in vascular and podiatry clinics, and across two time-points 182 BPA tests were conducted subsequent to initial (blinded) clinician's wound appraisal. Clinical opinion ('no infection', 'possible' or 'definite' infection) and BPA result (negative or positive test) had a moderate Kendall's tau-c rank correlation coefficient of 0.32 (< 0.001). Binary logistic regression analysis and principal component analysis showed that infection determined by clinical opinion was significantly associated with abovementioned clinical signs and a positive BPA test. However, a positive BPA result was also significantly linked with wound severity, such as number of lesions, chronicity and size. Throughout a 12-week follow-up period, median ulcer size was larger for wounds positive for BPA test at baseline ( 0.001) and week-12 ( 0.036; both Mann-Whitney U-test) respectively. As a pilot initiative, clinical staff were allowed to act on the BPA result if they wished; in 11 out of 71 test-positive cases (15%) this happened and antimicrobial dressing was applied instead of planned standard dressing. These results show that protease-releasing bacteria may be active in ulcers that do not (yet) exhibit hallmark signs of infection, and are associated with delayed healing. Targeted point-of-care testing for bacterial protease activity may have the potential to identify and enable pro-active (antimicrobial) management of these high-risk wounds.
Manifestations of Endocrine Disease in the Lower Extremities: Beyond the Diabetic Foot
The aim of this narrative review was to discuss manifestations of endocrine disease other than diabetic foot in the lower extremities. Acromegaly, Addison's disease, Cushing's syndrome, hypo- and hyperthyroidism, hypo- and hyperparathyroidism, autoimmune polyglandular syndrome, hypopituitarism, and glucagonoma are among the endocrine diseases that may present with clinical manifestations in the lower extremities. Clinical signs vary depending on the underlying condition. Clinical suspicion is necessary for early diagnosis. Treatment of the underlying endocrine disease usually results in improvement of lower-extremity manifestations.
Analysis of Genetic Risk Factors Associated with Charcot Foot Based on the FinnGen Study R9 Data: A Wide-angle Mendelian Randomization Study
Charcot foot or Charcot neuropathic joint disease (CN) is a rare and complex foot disease with unknown pathogenesis, hindering early identification and intervention. The study aimed to clarify the causal association between all predominant risk factors and CN.
A Network Meta-Analysis of Randomized Controlled Trials on the Comparative Efficacy of Stem Cells Therapy for Diabetic Foot Ulcer Healing
Stem cell therapy in diabetic foot ulcer has emerged as a promising treatment option to promote ulcer healing. This network meta-analysis was undertaken to evaluate how they compete with each other and their ranking with respect to chances of ulcer healing. A systematic search strategy to retrieve data from five databases, were used to identify potential studies. Randomized controlled trial or clinical controlled trial, published in English, using any type of stem cells as intervention in individuals aged over 18 years diagnosed with diabetic foot ulcers were included. This network meta-analysis was performed using frequentist method using R version 4.2.1. Eighteen clinical trials were included in the study which included 13 interventions. The study found that most of the stem cells were significantly promoting ulcer healing chances with human viable wound matrix (hVWM) [RR 2.91; CI: 1.28, 6.64], peripheral blood mononuclear cells (PBMNC) [RR 2.35; CI: 1.21, 4.55], bone marrow mesenchymal stem cells (BMMSCs) [RR 2.20; CI: 1.34, 3.60], were top three stem cell options among all. P score also suggested the same. Risk of bias study suggested that there was "some concern or "high risk'' among majority of studies. It is evident from this study that bone marrow mononuclear cells were found to be most effective in wound healing in cases of diabetic foot ulcer in that order. Though there was no significant difference between these and more studies were required to ascertain whether they differ in term of efficacy for the clinical outcome of ulcer healing.
Real-Life Data on Wound Healing Speed and Duration to Wound Closure by Different Aetiology in a Primary Care Centre in the Netherlands
Correct classification of wounds is of paramount importance for diagnostic and therapeutic pathways. The aim of this study was to provide insight in the incidence of different aetiology of wounds and the healing time in a primary care setting. All patients with a wound presented in Primary Care (PC) practice from January 2017 through 2020 were included. A retrospective analysis related to age, sex, duration of wound healing, healing-rates, aetiology and comorbidity of the patients was performed. The prevalence of wounds in primary care was is 3.9 per 1000. In more than 90% of the wounds heal within 37 days. The wound healing speed and duration to closure differ significantly ( = .002) between aetiology. This study shows that 90% of wounds that enter a Dutch GP practice heal within 37 days. This study provides unique data on wound healing rates differentiated by etiology.
Application of Continuous Care Pattern Based on Information-Motivation-Behavioral Skills Model in out-of-Hospital Rehabilitation of Diabetic Foot Ulceration Patients: A Randomized Controlled Trial
To explore the effect of information-motivation-behavioral skills model (IMB)-based continuous nursing model on the out-of-hospital rehabilitation of diabetic foot ulceration (DFU) patients, and to provide a theoretical basis for long-term disease management of DFU patients.
Early Tissue Resection Versus Watchful Waiting After Revascularization for Chronic Limb-Threatening Ischemia: A Meta-Analysis
No consensus or guideline has been established regarding the optimal timing of tissue resection after revascularization in patients with chronic limb-threatening ischemia (CLTI). This study aimed to compare early tissue resection and watchful waiting after revascularization regarding the outcomes of patients with CLTI. We searched PubMed, the Cochrane Library, and EMBASE for relevant randomized trials and observational studies published from their inception to May 1, 2024. In total, five articles were analyzed. The results showed that the early tissue resection group had a higher wound healing rate than the watchful waiting group (I= 26%, odds ratio [OR] = 2.80, 95% confidence interval [CI] 1.32 to 5.92, = 0.007). However, the rate of major amputation was significantly higher in the early tissue resection group than in the watchful waiting group (I= 5%, OR = 1.48, 95% CI 1.18 to 1.86, < 0.001), and wound recurrence rate in the early tissue resection group was relatively higher than that in the watchful waiting group (I= 0%, OR = 2.42, 95% CI: 0.99 to 5.93, = 0.05). No statistical significance was found in the rate of postoperative mortality (I= 2%, OR = 0.99, 95% CI: 0.69 to 1.41, = 0.94) and wound healing time (I= 97%, standardized mean difference = -105.92, 95% CI -232.96 to 21.13, = 0.10) between the early tissue resection and watchful waiting groups. For patients without signs of infection, a watchful waiting strategy could reduce the risk of major amputation.