Impaired microvascular function in patients with sickle cell anemia and leg ulcers improved with healing.

Leg Ulcer (LU) pathophysiology is still not well understood in sickle cell anaemia (SCA). We hypothesised that SCA patients with LU would be characterised by lower microvascular reactivity. The aim of the present study was to compare the microcirculatory function (transcutaneous oxygen pressure (TcPO2) on the foot and laser Doppler flowmetry on the arm) and several blood biological parameters between nine SCA patients with active LU (LU+) and 56 SCA patients with no positive history of LU (LU-). We also tested the effects of plasma from LU+ and LU- patients on endothelial cell activation. We observed a reduction of the TcPO2 in LU+ compared to LU- patients. In addition, LU+ patients exhibited lower cutaneous microvascular vasodilatory capacity in response to acetylcholine, current and local heating compared to LU- patients. Inflammation and endothelial cell activation in response to plasma did not differ between the two groups. Among the nine patients from the LU+ group, eight were followed and six achieved healing in 4.4 ± 2.5 months. Among thus achieving healing, microvascular vasodilatory capacity in response to acetylcholine, current and local heating and TcPO2 improved after healing. In conclusion, microcirculatory function is impaired in patients with LU, and improves with healing.

"Veins first" versus "artery first" approach for management of mixed arterial venous leg ulcers (MAVLU): Systematic review and meta-analysis.

INTRODUCTION: Mixed Arterial and Venous Leg Ulcers (MAVLU) are challenging. The optimal intervention sequence (artery-first vs vein first) is unclear. This review evaluates current evidence on surgical intervention sequencing. METHODS: MEDLINE, PUBMED, SCOPUS and EMBASE were searched using the term 'mixed arterial venous leg ulcers.' Studies were eligible if they reported ulcer healing outcomes in MAVLU patients. Pooled proportions were calculated by random effects modelling. RESULTS: The search yielded 606 studies, eight of which contained sufficient data to include in the analysis. There were no randomized controlled trials. Initial modified compression (MCT) and rescue revascularisation in MAVLU with ABI 0.5 to 0.85 achieved a pooled healing rate of 75% (95% CI 69% to 80%) compared to 79% (95% CI 61% to 93%) in patients with standard VLUs. The pooled rescue revascularisation rate for MAVLU patients with moderate arterial disease was 25% (95% CI 6% to 51%). Patients with severe arterial disease (ABI <0.5) who underwent arterial intervention first were less likely to heal (pooled proportion 40%; 95% confidence interval 16% to 66%). No studies compared either MCT or venous ablation with arterial revascularisation as first-line in patients with moderate arterial disease (ABI 0.5 to 0.85) alone or severe arterial disease (ABI <0.5) alone. There was marked heterogeneity between studies with respect to ulcer healing outcomes reported, definitions of ulcer healing, duration and size of ulcers at presentation, use of adjunct procedures such as skin grafting, unit of measurement (legs vs patients) and duration of follow up. CONCLUSION: A 'veins first' approach to MAVLU is plausible but robust data are lacking and should be evaluated in a randomized controlled trial.

Impact on healing of double-layered compression stocking in the treatment of severe venous leg ulcers: A prospective, multicenter, controlled trial.

Venous leg ulcer refers to chronic wounds, generally difficult to heal and often prone to recurrence. The objective of this research was to assess a double layered compression stocking VenoTrain® ulcertec on a population with mostly severe pathologies. This prospective, multicenter, interventional type II study was conducted between September 2018 and January 2022. Out of 124 patients enrolled, 97.6% had a history of previous leg ulceration, 72.6% were already being followed for leg ulcerations, 30.9% were severely overweight and 24.2% diabetic. Overall, a majority of target ulcers were present for 6months or more, and the ulcer surface area was larger than 8cm2 in nearly one in every five cases. The primary endpoint was the rate of closed ulcer after a maximum follow-up of 20weeks. While most of the treated venous leg ulcerations may be regarded as hard-to-heal wounds, closure rate at 20weeks ranged between 50.0% (two severity criteria) and 69.0% (no severity criteria) according to baseline wound severity criteria. Besides, VenoTrain® ulcertec device was particularly well accepted and tolerated by patients. In 93.2% of visits, patients stated using it every day. When managing venous ulcerations not requiring strongly thick absorbent dressings, VenoTrain® ulcertec device represents an efficient and more suitable alternative to venous compression bandaging.

Comparative Efficacy and Cost-Effectiveness of Two-Layer Versus Four-Layer Compression Bandages for Venous Leg Ulcers: A Prospective Study.

OBJECTIVE: This study aims to evaluate and compare the efficacy and cost-effectiveness of two-layer versus four-layer compression bandages in the treatment of venous leg ulcers (VLUs). METHODS: A prospective study was conducted at a tertiary hospital from August 2022 to July 2024. A total of 100 patients with chronic VLUs were sampled. Of the patients, 50 were given two-layer (group A) compression therapy, and the other 50 were given four-layer (group B) compression therapy. Outcomes after both therapies were analyzed. RESULTS: The mean age of the participants was 45.76 years, with a predominance of males (67%). Both bandaging systems demonstrated similar healing efficacy with no significant difference in ulcer size or healing time between groups. However, the four-layer bandage system required significantly fewer follow-ups (mean = 4.88) compared to the two-layer system (mean = 6.46) (p < 0.001). The mean total cost was higher for the four-layer system (₹3416) compared to the two-layer system (₹2907) (p = 0.004). Complications such as pain and pressure ulcers were comparable, though the four-layer system was associated with slightly higher discomfort and skin irritation. CONCLUSION: The four-layer bandage system may offer marginal advantages in wound healing and fewer follow-ups, but it is more expensive. The two-layer bandage system is more cost-effective and patient-friendly.

Patients with venous leg ulcers can be managed safely in the community ----results of an observational comparison study in Singapore.

AIM: To examine the healing outcomes of patients with venous leg ulcers requiring compression bandaging in community care versus tertiary care. METHOD: This was an analytical observational cohort study. Venous leg ulcer (VLU) patients who required compression bandaging were recruited from an outpatient vascular clinic between May 2021 and August 2022. Eligible patients received two-or four-layer compression bandaging and followed up with the community care or tertiary care centre nurses. The primary outcome was the difference in the total surface area of the VLU after 12 weeks, and the secondary outcome was the patient's quality of life, as measured by the Cardiff Wound Impact Schedule (CWIS). RESULTS: Forty-seven VLU patients were recruited; 27 received compression bandaging in the community care and 20 by the tertiary care centre. Mean age 70 years old (SD 11.04). The two most prevalent comorbidities were hypertension (51.06 %) and diabetes mellitus (38.29 %). Among those who completed follow-up (12 weeks), the median difference of the total surface area of the VLU between community-based care (p = 0.02) versus tertiary-based care (0.003) was significant. However, there was no difference in the healing status between community and tertiary-based care (p = 0.68). There was no difference in the quality of life of patients between groups. CONCLUSION: This first tropical study comparing VLU healing outcomes between community and tertiary care found no significant difference in healing with compression bandaging by nurses in either setting. However, the small sample size and high dropout rate limit the generalizability of the findings, necessitating a larger-scale study with longer follow-up. Despite these limitations, the study is a crucial step toward improving wound care services in Singapore, and highlights the need for further research to guide future community wound care implementation.

Axial Ablation versus Terminal Interruption of the Reflux Source (AAVTIRS): A Randomised Controlled Trial.

INTRODUCTION: Treatment of reflux has been shown to improve time to healing of Venous Leg Ulcers (VLU). Terminal Interruption of the Reflux Source (TIRS) treats reflux within the plexus of veins around an active VLU using foam sclerotherapy. The efficacy of TIRS in managing VLU has never been tested. METHODS: We performed a pragmatic, single centre, assessor-blinded, randomised controlled trial comparing endovenous ablation of the axial superficial veins (Axial Ablation-AA) vs TIRS. Patients of any age with VLU of any duration were eligible. RESULTS: 98 Participants were randomised to AA or TIRS. 39/55, 70.9% (95%CI; 57.1-82.37) healed their VLU in the AA group, while 29/39, 74.36% (95%CI; 57.87-86.96) healed their VLU in the TIRS group, P = 0.45.4 were lost to follow-up. Median time to ulcer healing was 84 days (95%CI; 74.67-93.33) in the axial ablation group and 84 days (95%CI; 73.02-94.98) in the TIRS group. Hazard Ratio for ulcer healing with AA vs TIRS was 0.96 (95%CI 0.59-1.56). There were no significant quality of life differences. CONCLUSION: The AAVTIRS trial did not show that axial ablation was superior to TIRS in the primary outcome of number of VLU healed in 6 months, or time to VLU healing. This trial is not powered to show non-inferiority. TIRS is a viable option for treatment of VLU. Further investigation is necessary before it can be recommended as an alternative to axial ablation.Trial registered at clinicaltrials.gov NCT04484168.

Wound Healing Society 2023 update on guidelines for arterial ulcers.

The Wound Healing Society guidelines for the treatment of arterial insufficiency ulcers were originally published in 2006, with the last update in 2014. These guidelines provided recommendations, along with their respective levels of evidence, on seven categories: diagnosis, surgery, infection control, wound bed preparation, dressings, adjuvant therapy and long-term maintenance. Over the last 9 years, additional literature regarding these aspects of arterial ulcer management has been published. An advisory panel comprised of academicians, clinicians and researchers was chosen to update the 2014 guidelines. Members included vascular surgeons, internists, plastic surgeons, anaesthesiologists, emergency medicine physicians and dermatologists, all with expertise in wound healing. The goal of this article is to evaluate relevant new findings upon which an updated version of the guidelines will be based.

A Double-Blind Study on the Effectiveness of Polarized Light Therapy in the Treatment of Venous leg Ulcers-Pilot Study.

Vein diseases are one of the most common civilization diseases. The most advanced form chronic venous insufficiency are venous leg ulcers. The study included 40 patients, 20 male (50%) and 20 female (50%) in age between 52 and 88 years (mean age: 68.00 ± 8.55 years) with venous leg ulcers lasting 12.50 ± 5.45 months. Patients were distributed randomly in a double-blind study into two equal groups including 20 patients each (group 1-polarized light therapy and group 2-sham exposure). Patients from both groups received routine pharmacological treatment, specialistic medical dressings and compression therapy. In addition, patients were exposed to a cycle of polarized light therapy procedures or to sham exposures (30 procedures performed in two series of 15 procedures). Wound surface area was evaluated by computerized planimetry and pain intensity was assessed with the use of Visual Analog Scale (VAS) before and after therapy (2.5 months). The analysis showed a statistically significant reduction of surface ulcers area between groups 1 and 2. The median (IQR) size of wounds in group 1 was 2.4 (1.95-2.9) cm2, in group 2; 2.8 (2.6-3.1) cm2 (p = 0.038). The level of pain (VAS) after treatment was assessed in group 1, median (IQR): 2 (2-3) points, in group 2 4.5 (4-5) points; and the observed difference was also statistically significant (p < 0.001). In group 1, after treatment, the area of ulcers decreased-median (IQR): 33.05 (28.7-41.48) %, in group 2 by 18.99 (15-24.4) % (p < 0.001). In group 1, the pain intensity measured using the VAS scale decreased with a median (IQR): 71.42 (61.25-71.42) %, in group 2: 37.5 (28.57-50) % (p < 0.001). Complex therapy with polarized light therapy added to standard care was more effective than standard care alone in reducing of ulcers surface area and intensity of pain ailments in patients with chronic venous leg ulcers.

Arterial Leg Ulcers in the Octogenarian.

Arterial leg ulcers are a debilitating sequela of chronic ischemia, and their management, particularly in the octogenarian, is an immense challenge. ALUs are frequently a manifestation of end-stage peripheral arterial disease, and their presence portends a high morbidity and mortality. Management primarily relies on restoration of flow, but in the geriatric population, interventions may carry undue risk and pathologies may not be amenable. Adjunctive therapies that improve quality of life and decrease morbidity and mortality are therefore essential, and understanding their benefits and limitations is crucial in developing a multimodal treatment algorithm of care for the uniquely challenging octogenarian population.

Other Wounds Encountered in Clinical Practice.

This chapter delves into uncommon wounds including pyoderma gangrenosum, sickle cell disease ulcers, vasculitic wounds, Martorell hypertensive ischemic leg ulcers, and malignant ulcers. Emphasizing a multidisciplinary approach, it covers diagnostics, treatments, and challenges, with case studies illustrating complexities in managing these conditions. The discussion extends to radiation-related wounds, underscoring the need for patient-centered care, interdisciplinary collaboration, and realistic goal setting. Overall, the chapter navigates the intricacies of uncommon wounds, emphasizing the importance of tailored approaches for improved outcomes in patients with diverse underlying conditions.

A clinical observational case series evaluation of a superabsorbent dressing on exudating wounds.

The annual cost to the NHS of managing 3.8 million patients with a wound was estimated in 2020 to be £8.3 billion, of which £5.6 billion was spent on the 30% of wounds that did not heal and £2.7 billion on the 70% of wounds that healed (Guest, 2020). One of the main symptoms associated with chronic 'hard-to-heal' wounds is the production of excess exudate (Atkin et al, 2019). This is due to a prolonged chronic inflammatory response stimulated by a physiological cause. This article describes what exudate is and its importance in the wound healing process, highlighting the consequences of too little or excessive wound exudate associated with any wound. The article goes on to describe a case series observational study involving a range of patients (n=47; 33 male/14 female), aged between 33 and 91 years (mean 67.4 years), with a variety of acute (n=11) and chronic exuding wounds (n=44). In total, 55 wounds of various aetiologies were managed with DryMax Super (a dressing whose design includes superabsorbent polymers) in order to evaluate and report on the absorption and fluid-handling properties of the product.

Diagnosis and treatment of venous leg ulcers: S2k Guideline of the German Society of Phlebology and Lymphology (DGPL) e.V.

This S2k guideline on venous leg ulcers was created on the initiative and under the leadership of the German Society of Phlebology and Lymphology (DGPL). The guideline group also consisted of representatives from the German Society for Phlebology and Lymphology, German Dermatological Society, German Society for General Medicine, German Society for Angiology, German Society for Vascular Surgery and Vascular Medicine, German Society for Surgery, German Society for Dermatosurgery, German Society for Wound Healing and Wound Treatment, Professional Association of Phlebologists and Lymphologists and Initiative Chronische Wunden. The aim of this guideline is to combine the different approaches and levels of knowledge of the respective professional groups on the basis of consensus, so that a basic concept for the best possible treatment of patients with venous leg ulcers can be provided. A total of 70 specific recommendations were formulated and agreed upon, divided into the subject areas of diagnostics, therapy, prevention of recurrences, and everyday challenges. The guideline thus reflects the current state of scientific knowledge and is intended to be widely used as the best available document for the treatment of patients with venous leg ulcers in everyday clinical practice.

Review of Mixed Arterial Venous Leg Ulcers (MAVLU) Disease in Contemporary Practice.

BACKGROUND: Mixed Arterial and Venous Leg Ulcers (MAVLU) are challenging. Clinical evidence specific to MAVLU management is scarce. We evaluated our recent experience with MAVLU patients and reviewed current data regarding MAVLU epidemiology, aetiology, diagnostic assessment and management options. METHODS: A prospective leg ulcer database was retrospectively interrogated to determine the prevalence and clinical outcome of MAVLU over 2-year period (2021-2022). The literature was reviewed to determine if optimal treatment strategies. RESULTS: 307 patients attended the ulcer clinic over a 2-year period. Most were venous leg ulcers (71%), 24% were arterial and 5% were MAVLU. The highest healing rate was in MAVLU (93%), followed by (74%) and (41%), in arterial and venous leg ulcer groups, respectively. CONCLUSION: Evidence-based guidelines for MAVLU remain lacking. Well-developed randomised controlled trials are warranted to guide current clinical practice.

Evaluation of a Semi-Automated Wound-Halving Algorithm for Split-Wound Design Studies: A Step towards Enhanced Wound-Healing Assessment.

Background: Chronic leg ulcers present a global challenge in healthcare, necessitating precise wound measurement for effective treatment evaluation. This study is the first to validate the "split-wound design" approach for wound studies using objective measures. We further improved this relatively new approach and combined it with a semi-automated wound measurement algorithm. Method: The algorithm is capable of plotting an objective halving line that is calculated by splitting the bounding box of the wound surface along the longest side. To evaluate this algorithm, we compared the accuracy of the subjective wound halving of manual operators of different backgrounds with the algorithm-generated halving line and the ground truth, in two separate rounds. Results: The median absolute deviation (MAD) from the ground truth of the manual wound halving was 2% and 3% in the first and second round, respectively. On the other hand, the algorithm-generated halving line showed a significantly lower deviation from the ground truth (MAD = 0.3%, p < 0.001). Conclusions: The data suggest that this wound-halving algorithm is suitable and reliable for conducting wound studies. This innovative combination of a semi-automated algorithm paired with a unique study design offers several advantages, including reduced patient recruitment needs, accelerated study planning, and cost savings, thereby expediting evidence generation in the field of wound care. Our findings highlight a promising path forward for improving wound research and clinical practice.

Integrating new approaches to care in a vascular wound clinic.

INTRODUCTION: An evidence-based approach is essential in the treatment of wounds to optimise healing, reduce costs and improve patient outcomes. AIM: This case study aimed to demonstrate our model of care, which assesses and manages patients with venous disease and complex wounds. In this case, venous leg ulcer (VLU) was treated with TLC-NOSF dressing and therapeutic compression. The wound was serially assessed using a smart App that gave the patient a graphic representation of their progress. DESIGN: Descriptive Observational Case Study. CLINICAL CARE: An evidence-based approach for managing a chronic, severe VLU. The patient was initially seen at the Outpatient Vascular Wound Clinic twice weekly, then every two weeks for conservative sharp wound debridement, skin care, dressing change, and compression therapy using a compression (Ready) wrap. Wound progress was monitored by the digital application 'Tissue Analytics', a "purposedesigned digital wound management platform that records, tracks, and analyses wounds". RESULTS: Week 1: On initial review, ulcer length was 3.15cm, width was 3.1 cm, and total surface area was 6.31 cm2. The wound base was mildly sloughy (<25%), with areas of good granulation tissue on view. Week 12: Length was 1.32 cm, width 1.50 cm, and total surface area of 1.45 cm2, a 77% reduction in wound size. Week 24: The length was 0.48 cm, the width was 0.64 cm, and the total surface area was 0.18 cm2. This represented a 97% reduction in wound size. Week 36: Length was 0.01 cm, the width 0.06 cm, with a total surface area of 0.00 cm2. This represented a 99.99% reduction in wound size. CONCLUSION: The patient's treatment for a complex venous leg ulcer included the application of TLC-NOSF dressing in combination with individualised therapeutic compression therapy. We found TLC-NOSF was very effective in combination with the best standard of VLU care (i.e. therapeutic graduated compression therapy). The clinician and patient were impressed with the healing rate at 12 weeks, as the wound dimensions were the lowest since the wound started six years ago. This dramatically improved patient concordance and engagement in care. Despite incomplete healing at 36 weeks, the wound-healing journey over the 36 weeks indicated wound closure was close. In addition, using a wound assessment App, the patient could immediately see the benefits of the new treatment, facilitating patient compliance with the treatment.

Comparison of two ablation procedures combined with high ligation and foam sclerotherapy and compression therapy for patients with venous leg ulcers.

AIM: To compare the ablation techniques' efficacy of endovenous microwave ablation (EMA) combined with high ligation (HL), foam sclerotherapy (FS) and compression therapy (CT) and endovenous laser ablation (EVLA) combined with HL-FS-CT in the treatment of VLUs. METHOD: 301 consecutive patients with VLUs from 2013 to 2022 in a 3200-bed hospital were intervened by EMA combined with HL-FS-CT and EVLA combined with HL-FS-CT were retrospectively compared. RESULTS: One hundred thirty-four patients underwent EMA+HL-FS-CT and 167 patients underwent EVLA+HL-FS-CT. The primary outcome of the ulcer healing time was 1.45(0.75-1.5) months and 1.86(0.5-2.5) months, respectively, in the two groups (HR for ulcer healing was 1.26, 95% CI [0.96-1.66], p = 0.097). Secondary outcomes included that no significant difference was found in ulcer recurrence and GSV recanalization and complications between the two groups, and the postoperative VCSS and AVVQ were significantly lower than the baseline values in the respective groups (p = 0.0001). CONCLUSION: EMA+HL-FS-CT and EVLA+HL-FS-CT are both effective at treating VLUs. Both of the two comprehensive treatments were beneficial to the healing of ulcers, but no evidence showed which one was superior in the ulcer healing time.

Controversies in the pathophysiology of leg ulcers in sickle cell disease.

Patients with sickle cell disease (SCD) often experience painful vaso-occlusive crises and chronic haemolytic anaemia, as well as various acute and chronic complications, such as leg ulcers. Leg ulcers are characterized by their unpredictability, debilitating pain and prolonged healing process. The pathophysiology of SCD leg ulcers is not well defined. Known risk factors include male gender, poor social conditions, malnutrition and a lack of compression therapy when oedema occurs. Leg ulcers typically start with spontaneous pain, followed by induration, hyperpigmentation, blister formation and destruction of the epidermis. SCD is characterized by chronic haemolysis, increased oxidative stress and decreased nitric oxide bioavailability, which promote ischaemia and inflammation and consequently impair vascular function in the skin. This cutaneous vasculopathy, coupled with venostasis around the ankle, creates an ideal environment for local vaso-occlusive crises, which can result in the development of leg ulcers that resemble arterial ulcers. Following the development of the ulcer, healing is hindered as a result of factors commonly observed in venous ulceration, including venous insufficiency, oedema and impaired angiogenesis. All of these factors are modulated by genetic factors. However, our current understanding of these genetic factors remains limited and does not yet enable us to accurately predict ulceration susceptibility.

Whole genome-based antimicrobial resistance and virulence profiling of Staphylococcus aureus isolates from chronic leg ulcer patients in Kilimanjaro, Tanzania.

BACKGROUND: Chronic leg ulcers are hard to treat and can be a burden, particularly in resource-limited settings where diagnosis is a challenge. Staphylococcus aureus is among the common bacteria isolated from chronic wounds with a great impact on wound healing, particularly in patients with co-morbidities. Antimicrobial resistance genes and virulence factors in Staphylococcus aureus isolates were assessed to support healthcare professionals to make better therapeutic choices, and importantly to curb the development and spread of antibiotic resistance. METHODS: A cross-sectional study involved both inpatients and outpatients with chronic leg ulcers was conducted from August 2022 to April 2023 in 2 health facilities in Kilimanjaro region in Tanzania. Antimicrobial susceptibility testing was done using the disk diffusion method. Further, whole genome sequencing was performed to study the genotypic characteristics of the isolates. RESULTS: A total of 92 participants were recruited in which 9 participants were only positive for 10 Staphylococcus aureus isolates upon culture. Five STs among 9 isolates were identified. Most of them belonged to ST8 (44%), with 1 isolate does not belong to any ST. Additionally, 50% of the isolates were methicillin-resistant Staphylococcus aureus (MRSA). All S. aureus isolates had almost similar virulence factors such as hemolysin, proteases and evasions that promote toxin production, protease production and host immune evasion respectively. Moreover, all mecA positive S. aureus isolates were phenotypically susceptible to cefoxitin. CONCLUSION: Presence of mecA positive S. aureus isolates which are also phenotypically susceptible to cefoxitin implies the possibility of classifying MRSA as MSSA. This may result in the possible emergence of highly cefoxitin - resistant strains in health care and community settings when subsequently exposed to beta-lactam agents. Therefore, combination of whole genome sequencing and conventional methods is important in assessing bacterial resistance and virulence to improve management of patients.