Leg Ulcers Research Articles

Liquid Crystal Elastomer for Compression Therapy.

Compression therapy is a widely used treatment for various disorders including venous leg ulcers. Traditional methods such as inelastic bandages and elastic stockings, have limitations in maintaining optimal pressure over time. Dynamic therapy devices offer intermittent pressure cycles but are often bulky or rigid. Here liquid crystal elastomer (LCE) is proposed for both static and dynamic compression therapy. Due to the soft elasticity of polydomain LCE, LCE-based static stocking can maintain consistent pressure over a wide range of leg diameters, permitting the tolerance of stocking application inconsistencies, various limb sizes, and interfacial pressure drop due to leg deswelling. The LCE-based dynamic stocking consists of monodomain LCEs with reversible thermal actuation, heating elements, and electronics. The dynamic stocking generates intermittent pressure from 20 to 60mmHg with a slight temperature increase above 33°C and offers pressure profile programmability. Furthermore, an untethered LCE-based dynamic compression device on a human leg is demonstrated. Both LCE-based static and dynamic stockings show minimal stress relaxation and reusability over 1000 cycles, ensuring long-term use in compression therapy applications.

527 PTEN is a master driver of healing inhibition in venous leg ulcers by targeting immune response, angiogenesis and lymphangiogenesis

527 PTEN is a master driver of healing inhibition in venous leg ulcers by targeting immune response, angiogenesis and lymphangiogenesis

A Review on Nanocarrier-based Polyherbal Drug Delivery Systems for Wound Healing

Background: Nanotechnology-based polyherbal drug delivery systems are considered a new and rapidly emerging area in the pharmaceutical field. They improved the drug loading capacity or enhanced encapsulation efficiency of herbal drugs and thus improved permeation efficiency, accelerated wound healing, promoted tissue remodelling, and reduced scarring. Objective: A wound on the skin is an injury of the skin tissues that arises due to a cut or damage and also by an impact, blow, or other forces like a cut, surgery, chemical, heat, cold, friction, or illness like leg ulcers or carcinomas. These wounds result in the loss of skin's protective function by the removal of epithelium or connective tissues (i.e., muscle, bone, nerves). The four sequential but overlapping phases of the typical wound healing process are hemostasis, inflammation, proliferation, and remodeling. By encouraging the growth and movement of fibroblasts and keratinocytes, as well as angiogenesis at the site of damage, it has been demonstrated that a polyherbal mixture composed of plant extraction accelerates the lesion recovery process. Polyherbal formulations contain phytoconstituents such as triterpenoids, flavonoids, coumarins, quinones, and carotenoids etc. All these phytoconstituents are used for anti-inflammatory, anti-microbial, antioxidant, and lesion recovery. At the same time, nanotechnology-based polyherbal formulation has the potential to overcome the limitations of traditional polyherbal formulation in wound healing. Wounds are better managed by polyherbal combination rather than an individual plant due to its synergism and fewer side effects. To include these polyherbal components and deliver them to the wound site in a more focused and sustained way, novel drug delivery systems are also being developed. Conclusion: This review discussed many nanotechnology-based polyherbal topical formulations for efficient and faster wound healing and recovery. Nanotechnology-based polyherbal formulations prove their success in promoting wound healing which is a unique approach to improving wound care and development of healthy skin.

Sub-ulcer foam sclerotherapy in patients with venous ulceration: A randomized controlled trial.

This trial analyzed the effect of sub-ulcer foam sclerotherapy in patients with venous leg ulcer (VLU). Randomized controlled trial. This trial recruited patients with VLUs to receive either sub-ulcer foam sclerotherapy and compression therapy (study group) or compression therapy only (control group). The primary outcome of this study was the change in the venous ulcer area at 4weeks. The feasibility, safety, and complications of the sub-ulcer foam sclerotherapy were recorded. Of 23 patients included, 12 were randomized to study group and 11 to control group. Preoperatively, the average ulcer areas were 5.8cm2 in both groups. At 4weeks, the average reductions in ulcer areas were 4.0cm2 (SD 3.1) in the study group (95% CI 2.0 to 5.9, p = .001) and 2.0cm2 (SD 3.1) in the control group (95% CI: -0.1 to 4.1, p = .051). No differences in complications were recorded. At 1-month sub-ulcer foam sclerotherapy and compression therapy reduced the ulcer area statistically significantly, whereas compression therapy alone did not. Sub-ulcer foam sclerotherapy could be a good addition to superficial venous insufficiency treatment in patients with VLU.ClinicalTrials.gov identifier NCT03795064.

The impact of dual-enrolee (Medicare/Medicaid) status on venous leg ulcer outcomes: a retrospective study.

To quantify race, sex, comorbidities, Medicaid status, and compare health outcomes for Medicare-only versus Medicare/Medicaid dual-enrolees who developed a hard-to-heal venous leg ulcer (VLU). Medicare Limited Data Standard analytic hospital inpatient and outpatient department files were used to follow episodes of medical care for a VLU from 1 October 2015-2 October 2019. In an earlier study, patients diagnosed concurrently with chronic venous insufficiency and a VLU were propensity-matched. In this current work, cohorts were split into patients enrolled in Medicare-only and those enrolled in Medicare and Medicaid (dual-enrolees). Treatment methods were compared and the most commonly used cellular, acellular and matrix-like product (CAMP) among Medicare beneficiaries-dehydrated human amnion chorion membrane (DHACM)-was evaluated. Episode claims were used to document demographics, comorbidities and treatments of Medicare enrolees who developed VLUs and outcomes such as time to ulcer closure, rates of complications and hospital usage rates. Quality of life (QoL) metrics, such as pain and time to VLU closure, were compared across the groups. Of the 555,284 Medicare beneficiaries evaluated in this analysis, 27% were Medicare/Medicaid dual-enrolees and 73% were Medicare-only enrolees. To qualify for Medicaid, patient income had to be ≤133% of the federal poverty level. Only 3% of Medicare-only patients and 6% of dual-enrolees had an Advantage plan, a lower rate than the general Medicare population. Dual-enrolees, compared to those covered by Medicare-only, demonstrated: a Charlson Comorbidity Index (CCI) score one point greater (p<0.0001); a higher percentage (16%) of patients from minority ethnic backgrounds; and significantly higher rates of emergency department visits (p<0.0001) and cellulitis (p=0.034). Dual-enrolees who received early and regularly applied CAMPs also reduced their treatment time by 21 days (p=0.0027), all of which can impact costs. The socioeconomic status of dual-enrolees included near poverty status, a higher percentage of patients from a minority ethnic background, and high rates of comorbidities compared to their Medicare-only counterparts. The VLUs of dual-enrolees took longer to close, developed more complications, and used significantly more hospital resources and expenses. Outcomes significantly improved when VLU episodes were treated with a CAMP, such as DHACM, while following parameters for use. Socioeconomic variables are associated with poor outcomes for patients with hard-to-heal (chronic) wounds. This should be tracked to find cost-effective interventions throughout their journey to provide equitable care and ensure they are not left behind. Greater access for dual-enrolees to CAMPs has the potential to improve clinical outcomes and patient QoL, while concomitantly reducing overall healthcare expenditure.

Genetic Evidence of Obesity-Induced Chronic Wounds Mediated by Inflammatory Biomarkers.

Background: Obese patients are increasingly recognized as being at higher risk for skin diseases, particularly chronic wounds. While the exact mechanisms remain unclear, obesity is suspected to influence the development of chronic injuries via inflammatory biomarkers. Single nucleotide polymorphisms (SNPs) may further influence gene expression, protein function, and levels of inflammatory biomarkers through various mechanisms, thereby modulating inflammatory responses that contribute to wound pathogenesis. Methods: A two-sample two-step Mendelian Randomization (MR) was employed to explore the causal relationship between obesity and chronic wounds, focusing on the mediating role of inflammatory biomarkers. SNPs were used as instrumental variables (IVs) to infer causality. Obesity-related genetic data were sourced from the UK Biobank and GIANT consortium. Genome-wide association studies provided data on 92 inflammatory biomarkers, involving 14,824 and 575,531 individuals. Pressure injuries, lower limb venous ulcers, and diabetic foot ulcer data were obtained from FinnGen R10 and the Pan-UK Biobank. Results: Obesity significantly increased the risk of pressure injuries, lower limb venous ulcers, and diabetic foot ulcers. CCL19, hGDNF, IL-12B, and TNFRSF9 were identified as mediators in obesity-induced lower limb venous ulcers. Conclusion: This study provides genetic evidence that obesity leads to lower limb venous ulcers via inflammatory biomarkers, suggesting potential therapeutic targets for intervention.

Adjustable compression wraps: back to the future

Adjustable Compression Wraps (ACWs) are used to treat a variety of conditions, in particular venous leg ulcers, edema and lymphedema. Publications on the use of these devices are ultimately few and far between, with limitations or biases (small sample sizes, methodological weaknesses, non-comparative studies, lack of interface pressures). A development model like that used in the study of a drug could be more rational. We propose five phases: phase 1) discovery and development, phase 2) in vitro testing, phase 3) clinical trials, phase 4) real-life data analysis, medico-economic investigation using Artificial Intelligence (AI), and phase 5) preparation of regulatory dossiers. This lack of coherence in development could be an obstacle to widespread clinical use. Using AI to analyse large quantities of data could reduce the cost and number of clinical trials needed to generate more robust evidence. This would make it possible to better define the clinical effects of ACWs in specific situations (e.g., leg wounds in the elderly, diabetic wounds, mixed leg ulcers, secondary lymphedema of the upper limb, efficacy, and comfort...) and to compare treatment costs between bandages and ACWs. If we don't explore the future with AI, we'll never know what will be useful for the present - hence the title “Back to the Future”.

Hidden Diagnosis - Chronic Non-Healing Leg Ulcer

Chronic ulcers present a significant clinical challenge, often necessitating tailored, multi-faceted interventions and strict adherence to treatment protocols. Accurate diagnosis and management require a thorough understanding of the ulcer's etiology and associated systemic conditions. This case report highlights a 35-year-old male with a chronic non-healing leg ulcer, compounded by a history of deep vein thrombosis (DVT) and pulmonary thromboembolism. Despite negative findings for common vasculitic and procoagulant profiles, a biopsy revealed leukocytoclastic vasculitis, and subsequent HLA-B51 testing confirmed the diagnosis of Behçet’s disease. The patient was treated with a combination of prednisolone, mycophenolate mofetil, and rivaroxaban, resulting in notable regression of the ulcer. This case underscores the importance of considering Behçet’s disease in young male patients presenting with chronic non-healing ulcers and thromboembolic events. Early diagnosis and vigilant, multidisciplinary management are essential to mitigate complications such as pulmonary artery hemorrhage and neuro-Behçet’s disease. This report emphasizes the need for comprehensive diagnostic approaches and long-term follow-up to prevent irreversible organ damage and improve patient outcomes.

Atypical Leg Ulcer in an Elderly Patient.

N/A.

Umbilical cord mesenchymal stem cells combined with autologous platelet-rich plasma for lower extremity venous ulcers: A case report and literature review.

Nonhealing ulcers are difficult to manage because they deviate from the normal wound healing process. Conventional therapy cannot achieve satisfactory therapeutic effects. To verify the effectiveness of combined treatment with human umbilical cord mesenchymal stem cells (hUMSCs) and platelet-rich plasma (PRP) for nonhealing ulcers, we studied a patient with left lower limb venous ulcer (LEVU) treated with combined injection therapy. We present the case of a LEVU patient who has not healed for a long period of time (up to 1 year). LEVU was diagnosed with clinical symptoms. The hUMSCs plus PRP were injected into the wound edge and base (1 µL of cells/cm2 of wound surface), 0.5 mL at each point, with a distance of approximately 1 to 3 cm between points. The injection point was determined according to the extent of wound involvement. Seven days after hUMSC + PRP application, the wound area decreased by nearly 50%. The ulcers had almost completely healed by day 62, and no serious treatment-related toxic side effects were observed. hUMSCs can improve wound healing through re-epithelialization, increased angiogenesis, and granulation tissue formation. PRP has also been suggested to promote wound healing through the secretion of various nutritional factors. The combination of hUMSCs and PRP has a mutually reinforcing effect, which may achieve a 1 + 1 > 2 effect. Therefore, the combination of hUMSCs and PRP may be a safe and effective treatment option for LEVU.

Comprehensive treatment of the patient with venous trophic ulcer

Improving the results of treatment for patients with varicose veins in the lower extremities, complicated by trophic ulcers, is an urgent task for modern medicine. A long-term, recurrent course of the disease leads to a reduction in working capacity and deterioration in quality of life, as well as permanent disability for patients, whose treatment causes special economic problems. At present, there are virtually no effective methods for conservative therapy, leading to prolonged unsuccessful treatment of such patients. This article presents the clinical case of a 63-year-old patient undergoing complex treatment for chronic lower limb venous insufficiency of class C6 according to the CEAP classification. Conclusion. An effective complex method for treating trophic ulcers in patients with chronic venous disease involves the correction of venous hemodynamic disorders (in this case, through radiofrequency ablation), as well as primary surgical treatment for the ulcerative defect, and simultaneous autodermaplasty with a perforated skin flap.

A Case Study on Dushta Vrana w.s.r to Venous Ulcer

Vrana in Ayurveda is defined as a structural deformity in the skin and deeper structures, it’s of 2 types - Dushtavrana and Shudhavrana. Dushta Vrana with foul smell has abnormal color with profuse discharge from wound, intense pain and takes long period to heal is said to be Dushta Vrana. The features will vary according to the predominant Dosha. It can be correlated to Chronic wound based on underlying pathology. Chronic wounds are termed ulcers and can be defined as wounds with full thickness in depth and slow healing tendency. In this single case study Dusta Vrana is considered as venous ulcer is one among 4 types of Chronic wound. Venous Ulcer occurs due to abnormal hypertension in the lower third of the leg, ankle and dorsum of foot. Acharya Sushruta has mentioned Shashti Upakrama for the management of Vrana. Here to evaluate the combined effect of Shodhana and Shamana Chikitsa, Classical Virechana, Jalaukaavacharana as a Shodhananga, Shamanaushadi by Kaishora Guggulu, Triphala Guggulu, Gandhaka Rasayana, and Manjishtadi Kashaya, Sthanika Chikitsa by Panchavalkala Kashaya Pariseka and Jathyadi Ghrita. The medicines having Tridosha Shamaka, Vrana Shodhana, Ropana, Vedana Shamaka, Shothahara, Rasayana property showed successful result in treating Dushtavrana.

New insights into the role of cellular senescence and chronic wounds.

Chronic or non-healing wounds, such as diabetic foot ulcers (DFUs), venous leg ulcers (VLUs), pressure ulcers (PUs) and wounds in the elderly etc., impose significant biological, social, and financial burdens on patients and their families. Despite ongoing efforts, effective treatments for these wounds remain elusive, costing the United States over US$25 billion annually. The wound healing process is notably slower in the elderly, partly due to cellular senescence, which plays a complex role in wound repair. High glucose levels, reactive oxygen species, and persistent inflammation are key factors that induce cellular senescence, contributing to chronic wound failure. This suggests that cellular senescence may not only drive age-related phenotypes and pathology but also be a key mediator of the decreased capacity for trauma repair. This review analyzes four aspects: characteristics of cellular senescence; cytotoxic stressors and related signaling pathways; the relationship between cellular senescence and typical chronic non-healing wounds; and current and future treatment strategies. In theory, anti-aging therapy may influence the process of chronic wound healing. However, the underlying molecular mechanism is not well understood. This review summarizes the relationship between cellular senescence and chronic wound healing to contribute to a better understanding of the mechanisms of chronic wound healing.

The Differential Diagnosis of Leg Ulcers.

Chronic wounds on the leg (below the knee) are called leg ulcers. They have many causes, and thus patients with leg ulcers are treated by many different kinds of medical specialist. Appproximately 80% of sufferers have chronic venous insufficiency (CVI) and/or peripheral arterial occlusive disease (PAOD). Knowledge of the relevant differential diagnoses is important for appropriate treatment, particularly for patients with atypical findings or an intractable course. This article is based on publications retrieved by a selective search in PubMed, including current guidelines and expert recommendations. The diagnostic evaluation of a leg ulcer can be structured according to the ABCDE rule. This involves individualized, targeted history-taking (anamnesis); bacteriological testing; clinical examination; ancillary testing, particularly for perfusion (defective vascular system); and extras, such as biopsies. Specifically, we present in this article the main aspects of the complex diagnostic evaluation of venous leg ulcers, arterial leg ulcers, vasculitis, vasculopathy, calciphylaxis, pyoderma gangrenosum, necrobiosis lipoidica, ecthyma, and squamous cell carcinoma. There remain many unsolved problems, including interactions between the various areas of clinical treatment and the relative paucity of relevant high-quality research. A timely differential-diagnostic evaluation for the many diseases that can cause leg ulcers, which require treatment from representatives of many different medical specialties and health professions, is a prerequisite for their effective individualized treatment.

Biofilm and Its Characteristics in Venous Ulcers.

The aim of the study was to analyze the characteristics of the biofilm of venous ulcers in terms of location and formation and to relate the presence of the biofilm to ulcer characteristics including duration, injured area, and necrotic tissue. Descriptive clinical study. We obtained 2 biopsy fragments (tissue samples) from 44 patients with venous ulcers treated at a public outpatient clinic in a university hospital in Belo Horizonte, Brazil. Ulcers were photographed and classified according to the duration. In addition, the wound size and proportion of wound surface covered by necrotic tissue were measured. One fragment from each ulcer underwent microbiological analysis, while the other was analyzed using transmission electron microscopy. Data analysis was limited to fragments from patients with bacteria in the microbiological analysis. Data analysis is based on samples obtained from 21 ulcers in 21 patients who had bacteria in their ulcer based on microbiologic analysis of a tissue sample. Most ulcers were open for 2 to 10years, 57% (n=12) were 16 cm2 or smaller, and the proportion of the wound bed covered by necrotic tissue coverage varied widely. Of the 21/44 patients (48%) with bacteria in their ulcers, only 3 patients had bacterial biofilm present in the transmission electron microscopy, corresponding to 7% of the 44 patients. Pseudomonas aeruginosa was the most frequent bacterium, identified in 10 fragments. The biofilm was not present on the surface but in a layer slightly below it. The detection of biofilms was not directly related to the duration of the ulcer. It was not possible to establish a correlation between the size of the lesion and the presence of these microorganisms due to the small sample size. Our findings indicate that detecting biofilm in venous ulcers is challenging, as it does not uniformly occur throughout the wound bed, can occur at different depths, and is often not present on the wound surface. There is a need to develop studies that can contribute to the detection of biofilm in clinical practice.

An Early-Stage Economic Evaluation of Superabsorbent Wound Dressings for the Management of Moderately to Highly Exuding Leg Ulcers in Slovakian Settings

ABSTRACT BACKGROUND The management of chronic leg ulcers, including venous leg ulcers (VLUs), causes a considerable economic and clinical burden to healthcare systems. Factors such as nursing time, hospital care, and wound dressings account for approximately 85% of the total cost. Superabsorbent dressings (eg, superabsorbent polymers [SAPs]) are recommended as a first-line treatment for moderately to highly exuding VLUs. OBJECTIVE To assess the cost-effectiveness of utilizing SAPs compared with the standard of care (SoC) for managing patients with moderately to highly exuding VLUs within the Slovakia healthcare settings. METHODS The decision-analytic modeling method used a Markov process as microsimulation, with a time horizon of 6 months, from the perspective of the third-party payer in Slovakia. All model inputs were based on data identified through systematic literature reviews. RESULTS According to model predictions, the use of SAPs instead of SoC in patients with moderately to highly exuding leg ulcers in Slovakian settings would lead to an improved healing rate of 2.2%, incremental health-related quality of life of 0.143 quality-adjusted life-weeks, and total direct cost savings of €75 (USD $82) per patient over a 6-month period. CONCLUSIONS The evaluation’s results align with clinical recommendations that endorse superabsorbent wound dressings as the preferred first-line treatment for moderately to highly exuding VLUs. The findings support the use of these dressings as a cost-saving solution for the National Insurance in Slovakia, when compared with SoC.

Treatment of 50 Acute and Chronic Wounds of Multiple Etiologies: A Case Series Looking at Outcomes and Utility of an Extended-Wear Transforming Powder Dressing

ABSTRACT Increasing healthcare costs, limited healthcare resources, an aging population, and lifestyle-related diseases make wound management a growing clinical, social, and economic burden. This case series investigated the use of a novel, biocompatible, polymer-based transforming powder dressing (TPD) that transforms in situ to a shape-retentive wound matrix upon hydration for treating wounds of various etiologies. In this institutional review board-approved single-center retrospective case series, the researchers evaluated various acute and chronic wounds treated with TPD over a period of 2 years. Wounds were followed from the first TPD application up to 1 month after the last TPD application or until the wound healed or the patient was lost to follow-up, whichever came first. The researchers evaluated wound etiology, location, number of applications, change in wound surface area, and comorbidities. The researchers identified 50 patients who were treated with TPD and had at least one follow-up visit during the retrospective study period. The majority of wounds treated with TPD were venous leg ulcers (n = 27) followed by traumatic wounds (n = 11) and skin tears (n = 7). Normal rates of wound healing (&gt;10% per week) were observed in the majority of patients (36/50, 72%) over their duration of treatment. Complete healing during the study period was observed in 43% of venous leg ulcers, 55% of traumatic wounds, 71% of skin tears, and 80% of other wound types. No adverse effects of TPD administration were observed. Treatment with TPD resulted in significant reductions in wound area of nearly all wounds, regardless of etiology.

Construction of nomogram for wound recurrence in elderly patients with venous leg ulcers.

Venous Leg Ulcers (VLUs) are one of the most serious and intractable complications of chronic venous insufficiency. This study aims to develop a nomogram based on a theoretical model to predict the probability of wound recurrence in older patients with VLUs. The elderly patients with VLUs attending the five hospitals between September 2021 and October 2022 were enrolled in this research, and randomized to the training and validation cohorts based on the corresponding ratio (7:3). Recurrent events were recorded during a six-month follow-up after the baseline data collection. The univariate analysis, the least absolute shrinkage and selection operator (LASSO) regression method were used to screen variables, and multiple logistic regression was used to establish a risk prediction model, which was presented by nomogram. Receiver operating curves (ROC), Hosmer-Lemeshow test, as well as calibration curves, were adopted to assess the effectiveness of the nomogram. The prognostic value of the nomogram was also examined. A total of 608 elderly patients with VLUs were included in the study. They were randomly divided into the training cohort (N = 421) and the validation cohort (N = 187). In the training cohort, Lasso regression and multivariate logistic regression analysis indicated that previous recurrence number, last ulcer duration, lower extremity DVT history, and frailty were independent risk factors for wound recurrence in elderly patients with VLUs, while daily exercise time and self-efficacy were protective factors. A nomogram was established with a good discrimination capacity and predictive efficiency with and the area under the curve (AUC) of 0.869 (95%CI: 0.831-0.908) in the training set and 0.890 (95%CI: 0.841-0.938) in the validation set. The p values of the Hosmer-Lemeshow test for both sets were 0.887 and 0.772, respectively, both greater than 0.05. The calibration degree charts showed that the data point connection was similar to the diagonal, indicating that the model's prediction probability of wound recurrence in elderly VLUs patients is close to the actual probability. This study constructed a new nomogram to predict the risk of wound recurrence in elderly patients with VLUs. The nomogram has excellent accuracy and reliability, which can help healthcare workers and patients actively monitor and follow up with patients to prevent the recurrence of ulcers and make clinical decisions.

Retrospective clinical study on the efficacy and complications of interventional embolization in the treatment of scalp arteriovenous fistula.

Scalp arteriovenous fistula (AVF) is a rare and intricate vascular anomaly characterized by a direct connection between an artery and a vein, without an intervening capillary system. This anomaly can induce significant local hemodynamic changes and is associated with various complications, such as pain, a pulsatile mass, increasing swelling, and venous hypertension skin ulcerations which may be non-healing. This study aimed to evaluate the efficacy and safety of interventional embolization treatments for scalp AVF at Shandong Provincial Hospital. This retrospective clinical analysis assessed 21 patients who underwent interventional embolization between 2018 and 2024. Patients included were those treated in the vascular surgery department at Shandong Provincial Hospital, who had comprehensive medical records and follow-up data. Treatment methods, outcomes, and complications were thoroughly analyzed through patient medical records. Among the patients studied, direct puncture was the most prevalent treatment method, employed in 42.86% (9/21) of cases, followed by various combinations of arterial, venous, and direct approaches. Ethanol, used in 85.71% (18/21) of the cases, demonstrated its broad efficacy and application in clinical settings. Immediate imaging post-treatment confirmed a cure rate of 85.71% (18/21). The main postoperative complications included swelling, with some patients also experiencing nodules, scabbing, or hair loss. Interventional embolization has proven to be a safe and effective method for managing scalp AVF, significantly minimizing complications. Future research should focus on further optimizing these treatment methods to enhance efficacy and improve patient quality of life.

The use of p-toluenesulfonic acid in the removal of biofilm in chronic ulcers

Background: Bacterial biofilms represent a topic of great concern due to their ability to cause chronic, sometimes fatal infections. Considering the prevalence and pathogenicity of biofilms in chronic ulcers, an observational study was designed to evaluate the anti-biofilm capabilities of p-toluenesulfonic acid, using it in the chronic ulcers of patients belonging to the Diabetic Foot clinic. Methods: Preliminary analysis of an observational study on patients attending the diabetic foot clinic with leg ulcers for at least 4 weeks. 17 patients treated with p-toluenesulfonic acid on a weekly basis for a maximum of 16 weeks. The primary outcome was 100% granulation tissue formation at week 16 and 50% reduction in initial chronic ulcer size. Results: The average treatment time was 10 ± 4.8 weeks. 8 patients healed, 7 are undergoing treatment, 1 required reoperation due to post-operative complications and 1 spontaneously dropped out of the study after 6 weeks. In the sample of healed patients, the average treatment time was 10.5 weeks with 100% granulation present at the 6th week. The reduction in the overall size of the ulcer and of the granulation area is not significant in the total sample. The data improves in the sample of healed patients even if it does not reach significance (lesion p-value 0.094, granulation p-value 0.13). Applying the analysis to the delta of the two variables, a measurement of the area that coincides with the margins of the ulcer, a p-value of 0.069 is obtained. The behaviour of the sample does not change when stratified by the dressings applied after treatment with p-toluenesulfonic acid. Conclusions: Treatment with p-toluenesulfonic acid promotes tissue granulation regardless of the type of dressing subsequently applied. The data on the evolution of the size of the lesions were not significant due to the smallness of the sample but in the sample of healed persons, the formation of granulation after an average of 6 applications transforms the "chronic" ulcer into an "active" ulcer, promoting closure within the subsequent 4 weeks. The appearance of granulation confirms healing. Elimination of biofilm with p-toluenesulfonic acid can reduce healing times and the risk of reinfection.