Successful Management of Chronic Wounds by an Autophagy-Activating Magnetized Water-Based Gel in Elderly Patients: A Case Series.

Chronic wounds pose a significant threat to human health, particularly for the elderly, and require extensive healthcare resources globally. Autophagy, a key molecular player in wound healing, not only offers a defense against infections but also contributes to the deposition of the extracellular matrix during the proliferative phase. Additionally, it promotes the proliferation and differentiation of endothelial cells, fibroblasts, and keratinocytes. We have recently shown that applying magnetized saline water topically can trigger autophagy in intact skin. In this case series, we document the successful management of five non-infected, difficult-to-heal wounds in elderly patients using a topical autophagy-stimulating gel containing 95% magnetized saline water. The treated wounds included pressure ulcers, venous ulcers, and trauma-related injuries that had shown minimal or no improvement with standard wound therapies over a prolonged period. Application of the autophagy-stimulating gel promoted wound healing, as indicated by reduced fibrous and necrotic tissue, granulation tissue formation, re-epithelialization, and partial or complete wound closure. These preliminary case studies suggest that a topical gel containing magnetized saline water, which promotes autophagy, may aid healing of chronic wounds in elderly patients. Further investigation is warranted to explore the potential of this novel approach, as it may offer a valuable addition to the existing arsenal of wound care treatments for the aging population, particularly in addressing difficult-to-heal wounds.

Assessing the Application and Effectiveness of Human Amniotic Membrane in the Management of Venous and Diabetic Ulcers: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

This study aimed to assess the efficacy of human amniotic membranes (HAM) in treating venous and diabetic ulcers, which often pose challenges in healing. A systematic review and meta-analysis were conducted, evaluating 10 relevant studies involving 633 participants. Findings revealed that HAM treatment significantly accelerated ulcer closure, demonstrating over 90% complete healing compared to standard care. Despite moderate heterogeneity among studies, the results strongly suggested the effectiveness and safety of HAM therapy for venous and diabetic leg ulcers. Further research with larger study cohorts is recommended to bolster the existing evidence supporting HAM in managing these challenging wounds.

Exploring causal correlations between inflammatory cytokines and varicose veins: A Mendelian randomization analysis.

This study aimed to investigate the causal relationship between inflammatory cytokines and the risk of varicose veins. The data were sourced from genome-wide association studies (GWAS) of European individuals. Multiple Mendelian randomization (MR) methods were used to evaluate the association between inflammatory cytokines and varicose veins. The study found significant associations between elevated levels of certain inflammatory biomarkers (e.g., CASP-8, Vascular endothelial growth factor A levels (VEGF_A)) and an increased risk of varicose veins, while others (e.g., 4EBP1, MMP-10) showed a protective effect. The MR-Egger Intercept and heterogeneity tests indicated no significant pleiotropy or heterogeneity. This comprehensive MR analysis identifies several cytokines as potential contributors to the pathogenesis of varicose veins, offering insights into novel therapeutic targets. Our findings underscore the importance of inflammation in varicose veins and suggest that targeting specific cytokines could be a promising strategy for the treatment and prevention of varicose veins.

Medical Management to Treat Chronic Non-healing Ulcers: A Case Series.

INTRODUCTION: Chronic non-healing leg ulcers are skin defects below the knee that resist healing for more than six weeks. They cause physical, emotional, and economic burdens to patients and society. OBJECTIVES: To introduce an innovative medical strategy that targets the chronic inflammation component in non-healing ulcers (NHUs) with rheumatic features and to evaluate its potential effectiveness in achieving complete healing. METHODS: We employed an empirical medical therapy regimen, which combined medications like deflazacort, colchicine, dapsone, hydroxychloroquine, and azathioprine. We retrospectively selected 25 patients with chronic pedal ulcers who underwent our therapy. RESULTS: The mean duration of ulcers was 7.84 years, and the time to heal was 5.97 months. Among 25 patients, 19 had atypical ulcers, four had venous ulcers, and two had diabetic neuropathy ulcers. Four patients with venous ulcers additionally underwent endovenous laser ablation. CONCLUSION: Our medical strategy showed promising results in healing chronic NHUs with rheumatic features without significant steroid-induced adverse effects.

Patterns of use of advanced wound matrices in the Veterans Administration clinics.

Chronic wounds are a common and costly health issue affecting millions of individuals in the United States, particularly those with underlying conditions such as diabetes, venous insufficiency, and peripheral artery disease. When standard treatments fail, advanced wound care therapies, such as skin substitutes, are often applied. However, the clinical effectiveness, indications, and comparative benefits of these therapies have not been well established. In this study, we report on the usage of both acellular and cellular, single and bilayer, natural and synthetic, dermal, and epidermal skin substitutes in a VA hospital system. We performed a retrospective chart review to understand the ordering and usage patterns of advanced wound therapies for patients with chronic wounds at the VA Northern California Health Care System. We examined types of products being recommended, categories of users recommending the products, indications for orders, and rate of repeated orders. Neuropathic, venous, or pressure ulcers were the main indications for using advanced wound matrices. Only 15.6% of patients for whom the matrices were ordered had supporting laboratory tests. Exactly 34.3% of the ordered matrices were not applied. And the use of wound matrices resulted in increased costs per patient visit of $1018-$3450. Our study sheds light on the usage patterns of these therapies in a VA healthcare facility and highlights the need for more robust evidence-based studies to determine the true benefits, efficacy, and cost-effectiveness of these innovative treatment options.

Diagnosing and Managing Venous Stasis Disease and Leg Ulcers.

Venous insufficiency is a common medical condition that affects many individuals, especially those with advanced age. Chronic venous insufficiency can lead to secondary cutaneous changes that most commonly present as stasis dermatitis but can progress to more serious venous ulcers. Although venous ulcers are the most common cause of lower extremity ulcers, the differential diagnosis of leg ulcers is broad. This article will discuss clinical clues to help guide patient workup and will review basic clinical evaluation and management of common leg ulcers.

Risk of osteoporosis among individuals with varicose veins: a multi-institution cohort study.

The present study showed a significant association between varicose veins and the development of osteoporosis, especially women and patients older than 50 years. Physicians should be alerted to this issue and consider screening for osteoporosis in patients with varicose veins. PURPOSE: Osteoporosis might be associated with many skin diseases. However, only a paucity of data addressing the association between varicose veins and subsequent osteoporosis development. The study was aimed to evaluate whether there is an increased risk of osteoporosis among patients with varicose veins. METHODS: This multi-institution database study was based on Chang Gung Research Database from January 1, 2003, to December 31, 2015. Patients aged 20 years and older with varicose veins were enrolled. Participants in the control group were selected by matching in a 4:1 ratio by sex, age, index date, and comorbidities. The hazard ratios associated with osteoporosis were estimated using Cox regression analysis with competitive risk model. Incidence rate of osteoporosis was assessed in individuals with and without varicose veins. RESULTS: A total of 11,959 patients with varicose veins and 47,633 matched controls were enrolled in the study. The varicose veins group had higher incidence rates than the control group for osteoporosis (46.40 vs 31.92 per 10,000 person-years; adjusted HR 1.481 [95%CI, 1.314-1.669; P < 0.001]). Compared with matched controls, varicose veins patients with or without venous ulcers had 1.711- and 1.443-times increased risk of developing osteoporosis, respectively. Subgroup analysis showed varicose veins were associated with osteoporosis in women and patients older than 50 years. CONCLUSION: The present study demonstrated individuals with varicose veins had an increased risk of osteoporosis. Physicians should be alerted to this issue and consider screening for osteoporosis in patients with varicose veins, especially among women and patients older than 50 years.

Fluorescence-Based Evaluation of Bacterial Load in Perilesional Skin: A Comparison Between Short Stretch Bandage and Zinc Oxide Bandage.

Bacterial proliferation plays a well-known role in delayed tissue healing. To date, the presence of microorganisms on the wound bed can be detected by skin swabs or skin biopsies. A novel noninvasive fluorescence imaging device has recently allowed real-time detection of bacteria in different types of wounds through endogenous autofluorescence. The fluorescence signals detected by the device provide health workers with a visual indication of the presence, load, and distribution of bacteria. The aim of our study was to evaluate the level of bacterial colonization in perilesional skin of patients affected by venous leg ulcers treated with 2 different types of bandages: short stretch bandage and zinc oxide bandage. We conducted a monocentric prospective study, enrolling 30 patients with venous leg ulcers, divided into 2 groups: group A was treated with short stretch bandage and group B with zinc oxide bandage. A complete patient's assessment was performed once a week for 3 weeks. Levels of potentially harmful bacteria in perilesional skin were detected using a fluorescent device by 2 experienced operators on the frames taken at individual injuries, while pain was evaluated with the Numerical Rating Scale. After 3 weeks, we observed a reduction in the bacterial colonization levels of the perilesional skin by 68.67% for group A and 85.54% for group B. All the patients had a statistically significant reduction in bacterial load (P < .001), and a statistically significant difference was identified between the 2 groups (P = .043). No statistically significant differences were found between the 2 groups in terms of pain relief (P = .114). Our study demonstrated that the application of zinc oxide bandage provides a higher reduction in bacterial load perilesional skin. On the other hand, we found no difference between the 2 bandages in terms of pain symptom reduction.

Lower-Extremity Vascular Ulcers: Assessment and Approaches to Management.

Healing of skin wounds of the lower extremities can be complicated by concomitant vascular disease. Dysfunction of the arterial, venous, and/or lymphatic systems can compromise the healing of skin ulcers of the legs, creating a burden for patients from painful, draining wounds and placing patients at risk for infection, amputation, and even death. Insights into vascular pathophysiology and an understanding of the processes of wound healing permit an evidence-based approach to patients with vascular leg ulcers. Clinical trials have demonstrated opportunities to improve the care of patients with vascular leg ulcers, thereby reducing morbidity and mortality and easing patients' burdens.

Implementing a new regimen to manage a difficult-to-heal lymphovenous leg ulcer.

The case study described in this article shows the use of different approaches and techniques that need to be utilised when treating patients presenting with a combination of venous and lymphatic disease (lymphovenous) in order to improve complex wound outcomes. The author highlights how lymphoedema can affect the wound healing process by increasing the risk of recurrent infection and a hardening of the tissues (fibrosis), reducing oxygenation and lymphatic flow to the wound, leading to chronic complex wounds.

Chronic Venous Insufficiency With Emphasis on the Geriatric Population.

The underpinning of Chronic Venous Insufficiency (CVI) is valvular dysfunction, which manifests on a spectrum depending on the severity of insufficiency and duration of the disease. The mainstay of treatment relies on compression therapy of a proper type and intensity. In older adults, special consideration must be taken during the patient encounter to account for age-related factors. This review discusses the clinical presentation, diagnosis, and mimicking of CVI, focusing mainly on older adults. The epidemiology, risk factors, disease burden, and grave complications -- such as thrombosis and ulceration, are reviewed. The physiological impacts of CVI are described, providing the background for treatment strategies, including non-invasive, medical, and surgical therapies. The findings show advanced age to be an important risk factor contributing to CVI and that other age-related factors add to the risk of severe complications. Clinical assessments combined with objective measurements that assess localized skin water using tissue dielectric constant values or whole limb assessments may aid in the differential diagnosis. Furthermore, understanding the mechanism of action of compression therapy, the mainstay of CVI treatment, and its physiological impacts, allows for its informed use in geriatric patients with increased risks of potential compression-related side effects.

The influence of different sub-bandage pressure values in the prevention of recurrence of venous ulceration-A ten year follow-up.

OBJECTIVE: The aim of this study was to establish the efficacy of three different strengths of compression systems in the prevention of venous leg ulcer (VLU) recurrences during a 10-year follow up period. METHODS: An open, prospective, randomized, single-center study included 477 patients (240 men, 237 women; mean age 59 years). Patients were randomized into three groups: Group A) 149 patients (allocated to wear elastic stocking 18-25 mmHg). Group B) 167 patients (wearing compression device exerting 25-35 mmHg), and Group C) 161 patients (treated with multilayer compression system exerting 35-50 mmHg). RESULTS: Overall, 65% (234/360) of patients had recurrent VLU within 10 years. Recurrence occurred in 120 (96%) of 125 in group A, in 89 (66.9%) of 133 patients in group B and in 25 (24.5%) of 102 patients in group C (p < 0.05). CONCLUSION: Compression systems with the higher compression class provide lower recurrence rate.

Venous, Arterial, and Neuropathic Leg Ulcers With Emphasis on the Geriatric Population.

Leg ulcers are a common and often serious problem in older adults. Underlying conditions that increase risk include age-related increases in chronic venous insufficiency, peripheral artery disease, connective tissue and autoimmune conditions, reduced mobility, and diabetes mellitus (DM). Geriatric patients have a higher risk of multiple wound-related complications including infection, cellulitis, ischemia, and gangrene, any of which may lead to further complications including amputation. The very presence of these lower extremity ulcers in the elderly negatively impacts their quality of life and ability to function. Understanding and early identification of the underlying conditions and wound features are important for effective ulcer healing and complication mitigation. This targeted review focuses on the three most common types of lower extremity ulcers: venous, arterial, and neuropathic. The goal of this paper is to characterize and discuss the general and specific aspects of these lower extremity ulcers and their relevancy and impact on the geriatric population. The top five main results of this study can be summarized as follows. (1) Venous ulcers, caused by inflammatory processes secondary to venous reflux and hypertension, are the most common chronic leg ulcer in the geriatric population. (2) Arterial-ischemic ulcers are mainly due to lower extremity vascular disease, which itself tends to increase with increasing age setting the stage for an age-related increase in leg ulcers. (3) Persons with DM are at increased risk of developing foot ulcers mainly due to neuropathy and localized ischemia, both of which tend to increase with advancing age. (4) In geriatric patients with leg ulcers, it is important to rule out vasculitis or malignancy as causes. (5) Treatment is best made on a case-by-case basis, considering the patient's underlying condition, comorbidities, overall health status, and life expectancy.

First pilot case-control interventional study using autologous extracellular vesicles to treat chronic venous ulcers unresponsive to conventional treatments.

Current therapeutic approaches for chronic venous ulcers (CVUs) still require evidence of effectiveness. Diverse sources of extracellular vesicles (EVs) have been proposed for tissue regeneration, however the lack of potency tests, to predict in-vivo effectiveness, and a reliable scalability have delayed their clinical application. This study aimed to investigate whether autologous serum-derived EVs (s-EVs), recovered from patients with CVUs, may be a proper therapeutic approach to improve the healing process. A pilot case-control interventional study (CS2/1095/0090491) has been designed and s-EVs recovered from patients. Patient eligibility included two or more distinct chronic lesions in the same limb with 11 months as median persistence of active ulcer before enrollment. Patients were treated three times a week, for 2 weeks. Qualitative CVU analysis demonstrated that s-EVs-treated lesions displayed a higher percentage of granulation tissue compared to the control group (Sham) (s-EVs 3 out of 5: 75-100 % vs Sham: none), further confirmed at day 30. s-EVs-treated lesions also displayed higher sloughy tissue reduction at the end of treatment even increased at day 30. Additionally, s-EV treatment led to a median surface reduction of 151 mm2 compared to 84 mm2 in the Sham group, difference even more evident at day 30 (s-EVs 385 mm2vs Sham 106 mm2p = 0.004). Consistent with the enrichment of transforming growth factor-ß1 in s-EVs, histological analyses showed a regenerative tissue with an increase in microvascular proliferation areas. This study first demonstrates the clinical effectiveness of autologous s-EVs in promoting the healing process of CVUs unresponsive to conventional treatments.

Clinical validation of a smartphone application for automated wound measurement in patients with venous leg ulcers.

Chronic wounds are associated with significant clinical, economic and quality-of-life burden. Despite the variety of wound imaging systems available in the market for wound assessment and surveillance, few are clinically validated among patients of Asian ethnicity. We aimed to clinically validate the accuracy of a smartphone wound application (Tissue Analytics [TA], Net Health Systems Inc, Florida, USA), versus conventional wound measurements (visual approximation and paper rulers), in patients of Asian ethnicity with venous leg ulcers (VLU). A prospective cohort study of patients presenting with VLU to a specialist wound nurse clinic over a 5-week duration was conducted. Each patient received seven wound measurements: one by a trained wound nurse clinician, and three separate wound measurements using TA on each of the iOS and Android operating systems. Inter-rater and intra-rater reliability between clinical and TA-based measurements were analysed using intra-class correlation statistics, with values of <0.5, 0.5 to 0.75, 0.75 to 0.9, and >0.9 indicating poor, moderate, good and excellent reliability, respectively. 82 patients (51% males), with a mean age at 65.8 years, completed the 5-week study duration. 25 (30%) had underlying diabetes mellitus. Chinese, Malay and Indian ethnicity comprised 68%, 12% and 11%, respectively. The VLU healed in 26 (32%) of patients within the study period. In total, 358 wound episodes with 2334 wound images were analysed. Inter-rater reliability for length, width and area between wound nurse measurements and TA application measurements was good (range 0.799-0.919, P < 0.001). Separate measurements of intra-rater reliability for length, width and area within the iOS or Android systems were excellent (range 0.967-0.985 and range 0.977-0.984 respectively, P < 0.001). Inter-rater reliability between TA used on the iOS and Android systems was also excellent (0.987-0.989, P < 0.001). Tissue Analytics, a smartphone wound application, is a useful adjunct for wound assessment and surveillance in VLU patients of Asian ethnicity.

Clinical Study of Platelet-Rich Plasma (PRP) for Lower Extremity Venous Ulcers: A Meta-Analysis and Systematic Review.

To systematically evaluate the clinical effects of platelet-rich plasma in the treatment of lower limb venous ulcers by applying a meta-analysis method. The Pubmed, Cochrance Library, Embase, and OVID EBM Reviews databases were searched for the search terms'platelet-rich plasma" or "Plasma, Platelet-Rich" or "Platelet Rich Plasma" and "lower extremity venous ulcers' or "Leg Ulcers' or "Ulcer, Leg", and a meta-analysis was performed on the published research literature on platelet-rich plasma for lower extremity venous ulcers from January 1900 to April 2021. The outcome indicators were: post-treatment trauma area and healing rate. Revman 5.3 statistical software was applied for meta-analysis. A total of 294 patients with lower extremity venous ulcers were included in six publications, including 148 patients in the experimental group treated with PRP versus 146 patients in the control group treated with conventional therapy. There was a statistically significant difference in the Formula of an ellipse at the end of treatment (CM²) between the experimental group and the control group, with a mean difference of -1.19 (95% CI -1.80 to -0.58, P = .0001; 6 studies, 294 participants moderate quality of evidence). The difference between the healing rate of the experimental group and the control group was statistically significant, with a risk ratio (RR) of 5.73 (95% CI 3.29 - 9.99, P < .00001; 5 studies, 248 participants moderate quality of evidence).There may be publication bias for both Formula of an ellipse at the end of treatment and healing rate. This comprehensive meta-analysis of available evidence suggests that the application of PRP for lower extremity venous ulcers accelerates the wound healing process and improves wound healing rates.

Carboxymethyl Cellulose-Based Hydrogel Film Combined with Umbilical Cord Blood Platelet gel as an Innovative Tool for Chronic Wound Management: A Pilot Clinical Study.

Treatment of chronic leg ulcers remains a major challenge and it is a substantial financial burden on individuals, families, caregivers, and health care system. There is increasing evidence on using of autologous Platelet-rich-plasma in wound repair but limited clinical data are available on the efficacy and safety of the use of umbilical cord blood platelet gel (CBPG). In our pilot study, for the first time, we aimed to evaluated the safety and efficacy of the use of umbilical CBPG combined with a hydrogel dressing in 10 patients with chronic venous ulcers (VU). The protocol consisted of application of umbilical cord blood platelet-rich plasma (PRP) combined with a Carboxymethyl cellulose (CMC)-based hydrogel dressing once a week for 4 weeks. The 80% of patients after 4 weeks of treatment had a significantly decrease in wound size. Moreover, we obtained an improvement in terms of mean Wound Bed Score (WBS), numeric rating scale (NRS) value and the EQ-5D index score. This pilot study showed that the topically therapeutic administration of umbilical CBPG associated with a CMC-based hydrogel dressing has the potential to accelerate the healing of chronic lesions without adverse reaction. However, additional studies with larger sample size and longer follow-up periods are required to confirm our findings.

Radiofrequency ablation of varicose veins in combination with ultrasonic-assisted wound debridement and platelet-rich plasma as well as platelet-rich fibrin technologies in treatment of lower extremity venous ulcers in office-based surgery.

Introduction: for the treatment of varicose ulcer performed clinical and laboratory reasoning of the use of ultrasonic-assisted venous ulcer debridement and Platelet-rich plasma with radiofrequency ablation in an outpatient setting, was carried out. Methods: ultrasonic-assisted debridement of trophic ulcer were performed for 50 patients with lower extremity varicose veins at decompensation stage. The effectiveness of ultrasonic-assisted debridement was evaluated by indicators of bacteriological, morphological, cytological study and assessment of trophic ulcers according to the MEASURE system. After ultrasonic-assisted debridement, the patients were divided into two groups: 30 patients, who underwent combined Platelet-rich plasma to stimulate wound regeneration and 20 patients, for whom the Granuflex hydrocolloid bandage was applied for the same purpose. Results: a comparative analysis of ulcer regeneration in two groups of patients proved that in cases of platelet rich plasma the time of transition from inflammatory-regenerative type to regenerative one is much shorter than when using a hydrocolloid dressing. In 28 patients undergoing Platelet-rich plasma (PRP) and Platelet-rich fibrin (PRF), the radiofrequency ablation of the principal superficial and perforating veins was performed. Another 22 patients performed autodermoplasty of trophic ulcers after radiofrequency ablation. Conclusion: our experience has shown that in a one-day inpatient surgical clinic such a multidisciplinary approach to treatment of venous ulcers, including ultrasonic-assisted debridement that is stimulation of wounded process by Platelet-rich plasma with further surgeries to remove the causes of decompensated chronic insufficiency, is promising regarding low costs of treatment and rehabilitation of these patients.

microRNA-301a-3p is a potential biomarker in venous ulcers vein and gets involved in endothelial cell dysfunction.

Venous ulcer is a common contributor to chronic venous insufficiency (CVI) of lower limbs, which seriously affects the life quality of patients. In this study, we researched the expression characteristics of microRNA-301a-3p (miR-301a-3p) in patients with CVI and investigated the impact of miR-301a-3p on the dysfunction of human umbilical vein endothelial cells (HUVECs). The plasma level of miR-301a-3p in normal controls, patients with varicose great saphenous vein, and patients with the venous ulcer of lower limbs were measured. We adopted Interleukin-1ß (IL-1ß), H2O2, and oxygen and glucose deprivation (OGD) to induce endothelial cell injury in vitro. In this way, we evaluated the influence of miR-301a-3p on HUVEC viability, apoptosis, inflammatory response, and oxidative stress. Our data showed that miR-301a-3p was substantially overexpressed in patients with lower limb venous ulcers. The viability of HUVECs decreased, and miR-301a-3p was up-regulated after IL-1ß, H2O2, and OGD treatment. miR-301a-3p inhibition greatly ameliorated the dysfunction and cell damage of HUVECs, promoted IGF1/PI3K/Akt/PPARγ, and down-regulated NF-κB/MMPs. The phosphatidylinositol 3-kinase (PI3K) inhibitor (LY294002) or the peroxisome proliferator-activated receptor-γ (PPARγ) inhibitor (GW9661) reversed the anti-inflammatory, antioxidant, and anti-apoptotic effects mediated by miR-301a-3p down-regulation. The nuclear factor-κB (NF-κB) inhibitor lessened cell injury mediated by miR-301a-3p overexpression. In terms of the mechanism, miR-301a-3p targeted the 3'UTR of Insulin-like growth factor-1 (IGF1) and repressed the profile of IGF1. Thus, miR-301a-3p mediates venous endothelial cell damage by targeting IGF1 and regulating the IGF1/PI3K/Akt/PPARγ/NF-κB/MMPs pathway.

Chronic venous insufficiency: a comprehensive review of management.

Chronic venous insufficiency is an extensive progressive disease in need of public health attention. This insidious disease is a growing burden on patient quality of life and the health economy. Chronic venous insufficiency has become more pronounced in global populations, especially in regions exhibiting a higher rate of risk factors. It is critical for healthcare providers to recognise and intervene early to prevent ongoing and debilitating complications. This article provides a comprehensive review of chronic venous insufficiency outlining the anatomy, pathophysiology, clinical presentation, assessment and management options.