Amputation-free survival in the long-term follow-up and gender-related characteristics in patients revascularized for critical limb ischemia.

OBJECTIVE: Patients with Critical Limb Ischemia (CLI) present a high risk of cardiovascular events and death. Revascularization is the cornerstone of therapy to relieve ischemic pain and prevent limb loss. Literature data suggest that women tend to present with worse outcomes after revascularization. The aim of the present study is to determine amputation-free survival in a long-term follow-up in women and men following endovascular revascularization procedure for CLI. METHODS: From November 2013 to December 2020, 357 consecutive patients were retrospectively included. Clinical and biological parameters were recorded at baseline before endovascular revascularization. During follow-up until February 2023, overall survival and amputation-free survival (freedom from major amputation) were analysed using the Kaplan-Meier method. Univariate and multivariate analyses were performed to study the parameters associated with amputation-free survival. A P<0.05 was considered as statistically significant. RESULTS: A total of 357 consecutive patients were included, 189 men and 168 women with CLI, with a mean age of 78.6±12 years. Treated hypertension (79%), diabetes mellitus (48%), coronary artery disease (39%) and protein malnutrition (61%) were the most prevalent comorbidities. Women were older than men with a mean age of 82.4±11.4 years (versus 75.4±11 years in men) and presented more frequently with protein malnutrition (70% of women). Prevalence of diabetes, tobacco use and history of coronary heart disease were significantly higher in men. During the 10-year follow-up period, 241 patients had died (68%) and 38 (11%) underwent major amputation, of whom 22 patients were still alive on February 2023. Median survival was 35.5 months [IQR: 29.5; 43] in the overall population, 38.5 [32; 50.4] months in women and 33.5 months [24.7; 43.5] in men. No gender-related differences were noted according to peri-procedural complications, survival probability and amputation-free survival. In multivariate analysis for amputation-free survival, age, previous coronary heart disease, C-reactive protein level, left ventricular ejection fraction (LVEF)<60% and albumin level<35g/L were correlated with poor outcome. In particular, protein malnutrition, as a treatable risk factor, appears significantly correlated with poor outcome in both men and women (HR=2.50 [1.16;5.38], P=0.0196 in men; HR=1.77 [1.00;3.13], P=0.049 in women). CONCLUSION: The present results highlight that mortality in patients after endovascular revascularization remains high with a mortality rate of 28% at 1 year, 40% at 2 years and 51% at 3 years. Women represented a distinct population, almost 10-year older than their male counterparts, with more prevalent protein malnutrition. However, no gender-related difference was noted according to amputation-free survival on the long-term follow-up. Associated risk factors are mainly age, a history of coronary heart disease, pre-procedural inflammatory syndrome and protein malnutrition. Correction of malnutrition could have the potential to improve functional and general long-term prognosis in patients with CLI together with optimal medical and interventional management.

Evaluation of the ankle brachial index and toe brachial index for peripheral arterial disease diagnosis in patients over 70 years with lower limb ulcers.

OBJECTIVE: The aim of our study was to evaluate the diagnostic performance of the ankle brachial index using pulsed Doppler, and the toe brachial index using laser Doppler, in comparison with the arterial Doppler ultrasound of the lower limbs as a reference test, in a population of non-diabetic subjects over 70 years old with lower limb ulcers and without chronic renal failure. METHODS: We included 50 patients, 100 lower limbs from the vascular medicine department of the Paris Saint-Joseph hospital from December 2019 to May 2021. RESULTS: We found a sensitivity of 54.5% for the ankle brachial index and a specificity of 67.6%. Regarding the toe brachial index, the sensitivity was 80.3% and the specificity 44.1%. We could explain the low sensitivity of the ankle brachial index in our population by the mediacalcosis of elderly subjects, avoidable with the measurement of the toe blood pressure index, which had a better sensitivity. CONCLUSION: In a population of subjects over 70 years of age with a lower limb ulcer, without diabetes and without chronic renal failure, it would seem judicious to use the ankle brachial index in association with the toe brachial index for the diagnosis of peripheral arterial disease, followed by an arterial Doppler ultrasound of the lower limbs in order to evaluate the lesion profile of patients with a result of less than 0.7 of toe brachial index.

Peri-procedural complications following endovascular revascularization for critical limb ischemia.

OBJECTIVE: Revascularization procedures are considered the cornerstone of therapy in patients with critical limb ischemia (CLI) and multiple procedures are often required to attain limb salvage. The aim of the present study is to determine the prevalence of peri-procedural complications after endovascular procedure, and to determine the clinical and biological characteristics of patients associated to the risk of peri-procedural complications. METHODS: From November 2013 to May 2021, 324 consecutive patients were retrospectively included, of whom 99 underwent more than one revascularization procedure for contralateral CLI or clinical recurrence of CLI. A total of 532 revascularizations were performed. Clinical and biological parameters were recorded at baseline before endovascular revascularization. The occurrence of a peri-procedural complication (local complications, fatal and non-fatal major bleeding or cardiovascular events) was recorded up to 30days after revascularization. Univariate and multivariate analyses were performed to study the parameters associated with per-procedural complications. A P<0.05 was considered as statistically significant. RESULTS: A total of 324 consecutive patients were included, 177 men and 147 women with CLI, with a mean age of 77.6±11.9years. Most of these patients had cardiovascular comorbidities (41% with a history of coronary heart disease, 78% treated hypertensive patients, 49% diabetic patients). Peri-procedural mortality occurred in 13 patients (4%) and 9 patients (2.8%) experienced major amputation at one-month following revascularization. Among the 532 revascularization procedures, 99 major bleeding events (22.8% of the cohort population) and 31 cardiovascular events (8.6% of the cohort population), were recorded in the peri-procedural period. Cardiovascular events were associated with peri-procedural mortality. Complications at the puncture site occurred during 38 of the 532 procedures (10.2% of the cohort population). Compared with patients undergoing a single revascularization procedure, patients with multiple procedures presented a higher risk of major bleeding events (48.5% vs. 11.6%, P<0.0001) and access site complications (20.2% vs. 5.78%, P<0.0001). In multivariate analysis, pulse pressure <60mmHg and hemoglobin level <10g/dl were correlated with the occurrence of major bleeding events; left ventricular ejection fraction<60% and the absence of statin treatment were correlated with the occurrence of cardiovascular complications; a high chronological rank of revascularization was correlated with the occurrence of local complication. Finally, age and gender were not associated with the occurrence of peri-procedural complication. CONCLUSION: The present results highlight that multiple revascularization procedures for limb salvage are required in almost one third of the population with critical limb ischemia and were associated with the risk of major bleeding events and access site complications. The most frequent complications of peripheral vascular interventions were major bleeding events. Adverse cardiovascular events were related with peri-procedural mortality. Anemia, blood pressure, left ventricular ejection fraction and statin treatment are important parameters to consider for peri-procedural outcomes, independently of age, gender and the chronological rank of revascularization procedure.

Specific management of lipodermatosclerosis (sclerotic hypodermitis) in acute and chronic phase.

Lipodermatosclerosis or sclerotic hypodermitis is presented as a complication of venous insufficiency and in particular of post-thrombotic syndrome with a high risk of progression to leg ulcers. However, it has also been described in obese patients without venous insufficiency, and even in the course of various systemic diseases including scleroderma. It most often affects middle-aged women and is usually bilateral, with a typically "inverted champagne bottle" leg appearance. The pathogenic role of venous hypertension explains why compression with bands or stockings is the basis of treatment. In acute phase, which may precede or complicate chronic forms, the pain is so severe that compression is not tolerated. In acute phase, non-steroidal anti-inflammatory drugs, intra-lesional use of triamcinolone, and capsaicin transdermal patches indicated for neuropathic pain have been proposed. In chronic forms, the treatment of superficial venous insufficiency and/or incontinent perforating veins, documented during a Duplex ultrasound scan, is usually proposed, whenever possible. In association with elastic compression, pentoxifylline and colchicine have been used without clear evidence of clinical efficacy. Finally, in the most advanced clinical presentation with the appearance of a sclerotic gaiter associated with ulcerations, surgical treatment with excision-cutaneous grafting associated or not with perforating veins ligation and a fasciotomy may be discussed as a last resort for treatment.

Incident cardiovascular events and early mortality in patients with revascularized critical limb ischemia.

OBJECTIVES: Patients with critical limb ischemia (CLI) present a high risk of cardiovascular events and death. This study aimed to investigate the incidence of major adverse cardiovascular events (MACE) and one-year mortality in patients undergoing percutaneous revascularization procedure for CLI. METHODS: This investigation is a retrospective analysis of an ongoing cohort study in patients with CLI undergoing endovascular revascularization, hospitalized in the vascular medicine department from November 2013 to December 2018. Major cardiovascular events were collected during the first year after revascularization procedure and were defined as heart failure, acute coronary syndrome, ischemic stroke and sudden death. Mortality and major limb amputations, defined as above-the-ankle amputation, were determined during the one-year follow-up period. Multivariate logistic regression analyses were performed to identify factors independently associated with the occurrence of MACE and one-year mortality after revascularization procedure. A P≤0.05 was considered as statistically significant. RESULTS: The study included 285 consecutive patients, 157 men (55%) and 128 women (45%), with a mean age of 77.8±12 years. Treated hypertension was present in 222 (78%) patients; diabetes was present in 137 (48%) patients; 112 (39%) patients had known coronary heart disease and 20 (7%) patients were dialysis dependent. During the one-year follow-up after revascularization procedure, 75 (26.3%) patients presented an incident cardiovascular event, of whom 19 (6.7%) patients in the perioperative period. Cumulative mortality rate was 26.7% (76 patients) mostly from cardiovascular causes. Twenty-five patients (8.8%) experienced major amputation. In multivariate analysis, the occurrence of MACE was associated with an increased mortality risk (HR 6.96 (2.99-16.94), P<0.001). Other variables associated with an increased mortality were living in a nursing home and malnutrition. Decompensated heart failure and coronary heart disease were both associated with incident MACE in multivariate analysis, independently of confounders. CONCLUSION: In the present study population, incident MACE were prevalent in the year following endovascular revascularization procedure in patients with CLI and were associated with an increased risk of mortality. Coronary heart disease and decompensated heart failure are important contributors for the occurrence of MACE. In this elderly patient population with CLI, these results should be taken into account during the multidisciplinary team meeting before consideration of revascularization procedure.

Characteristics and outcomes of octogenarians with revascularized critical limb ischemia: Impact of altered cardiac function for early mortality.

OBJECTIVE: Patients with critical limb ischemia (CLI) present with advanced age and end-stage organ damage, in particular heart failure. The aim of the present study is to describe clinical and biological characteristics in octogenarian patients with CLI compared to their younger counterparts and to determine the peri-procedural risk and early mortality after endovascular procedure. METHODS: From November 2013 to May 2019, 315 consecutive patients were retrospectively included. Clinical and biological parameters were recorded at baseline before endovascular revascularization. The main outcome was total 1-year mortality. RESULTS: The study included 170 octogenarians and 145 non-octogenarians. The mean age of octogenarian patients was 86.9±4.8 years, almost 20 years higher than that registered in non-octagenarians patients (67.4±8.6 years). Octogenarian patients were mostly women (59.4%), presented with lower body mass index (23.8±4.4kg/m2), lower serum albumin level (31.5±5.4g/L) and lower creatinine clearance (66.1±24.5mL/mn) than younger counterparts. They were more likely to be institutionalized in a nursing home (27.1%). In the peri-procedural period, major bleeding occurred in 40 patients (12.7%), without statistical significance between the two age groups. Peri-procedural mortality occurred in 12 patients (3.8%), of whom 10 patients (83%) were octogenarians. Cumulative mortality rate was 25.4% (80 patients) during the one-year follow-up period: 58 octogenarians died (34.1%) compared to 22 non-octogenarian patients (15.2%), P<0.001. Cardiovascular events were highly prevalent, accounting for 40% of overall mortality. Twenty-five patients (8%) experienced major amputation, without significant difference between the two age groups. In octogenarian population, institutionalized status (P=0.004) and BNP level (P=0.001) were positively correlated with mortality whereas systolic blood pressure (P<0.001), left ventricular ejection fraction (P=0.003), serum albumin (P=0.020), C-Reactive protein (P=0.020) and renin-angiotensin system inhibitors at hospital discharge were negatively correlated with mortality. In multivariate analysis for mortality, only BNP level≥500pg/mL (HR 3.27; 95% CI 1.04-10.97; P=0.04), was correlated with mortality, independently of other confounders. CONCLUSION: In the present study population, octogenarians represent a rather distinct CLI population, 20 years of age older as compared to non-octogenarians, with prevalent malnutrition and institutionalized status. The present results underline a substantial one-year mortality rate of 34.1% in this elderly population following revascularization procedure with a 6% peri-procedural mortality. Decompensated heart failure is an important contributor for mortality.

Innovative endovascular approach for limb salvage in critical limb ischemia.

In the absence of feasible revascularization, nearly one third of patients with critical limb ischemia experienced major amputation at 6 months. In patients with an independent living status, this decision is difficult to support without exhausting all chances to attain limb salvage and preserve functional autonomy. The present report describes a new procedure of revascularization by performing a full endovascular extra-anatomic femoropopliteal bypass for the treatment of limb-threatening ischemia. The patient presented with extensive tissue loss and a short-term risk of major amputation. She had experienced previous failure of conventional surgical and endovascular revascularization procedures and ligation of proximal femoral artery precluded any further revascularization attempt. Limb salvage was achieved with this endovascular revascularization procedure with complete wound closure. The patient still presents an independent living status and preserved functional autonomy without wound recurrence after a follow-up of more than 5 years.

Endovascular Extra-Anatomic Femoro-Popliteal Bypass for Limb Salvage in Chronic Critical Limb Ischemia.

PURPOSE: To report the initial clinical experience with fully endovascular extra-anatomic femoro-popliteal bypass (FPB) for limb salvage in patients with critical limb ischemia (CLI) and no traditional endovascular or surgical revascularization options. METHODS: Between June 2013 and May 2018, endovascular procedure was proposed for limb salvage during multidisciplinary team meeting in fifteen hospitalized patients (median age 67 years; 73% men) with CLI and a high risk of major amputation. Primary outcome was amputation-free survival at 1 year. Secondary outcomes included mortality, cardiovascular (CV) events and major limb amputation at 1 year, primary/secondary bypass patency and wound healing at the last follow-up visit. Procedure-related complications (deaths, CV events, hemorrhages) were recorded through 30 days. RESULTS: Technical procedure success rate was 100%. Major peri-procedural outcomes occurred in two patients (13%): One patient died secondary to cardiogenic shock; one patient suffered acute coronary syndrome associated with iliopsoas bleeding. No major amputation occurred through 30 days. Median follow-up period was 21.5 (18.25-45.5) months (last follow-up visits on April 2019). Amputation-free survival at 1-year and at the last follow-up visit was 80% and 53%, respectively. Cumulative mortality at 1-year and at the last follow-up visit was 13% and 33%, respectively. Primary and secondary bypass patency was 27% and 60%, respectively. Complete wound healing was achieved in 11 patients (73%). CONCLUSION: Endovascular extra-anatomic FPB represents an innovative approach for limb salvage in CLI with no traditional endovascular or surgical revascularization options. Our clinical experience highlights that this technique remains challenging because of frequent comorbidities and fragility of this patient population. LEVEL OF EVIDENCE: Level 4, Case series.

[Necrotic leg ulcers after topical application of chlormethine]. / Ulcères de jambe nécrotiques après application locale de chlorméthine.

BACKGROUND: Topical chlormethine has been widely used in the early stages of mycosis fungoides for many years. Cutaneous reactions (skin irritation and itch) are the most frequent adverse effects. Herein we report a rare side effect: severe necrotic leg ulcers. PATIENTS AND METHODS: An 82-year-old woman with a history of high blood pressure developed hyperalgesic necrotic ulcers on the lower limbs following local trauma one month after initiation of topical chlormethine (Valchlor®) to treat mycosis fungoides. Aetiological examination showed moderate peripheral arterial disease which, while constituting an aggravating factor, did not account fully for these skin ulcers. Moreover, drug-induced ulcer was suspected on account of the chronology. Dermal corticoids and topical treatment were prescribed in place of chlormethine and led to a favourable outcome. CONCLUSION: Incrimination of chlormethine was based on the chronological and semiological criteria. This is the first published case of leg ulceration induced by Valchlor®.

[A post-thrombotic pelvic congestion syndrome]. / Un syndrome de congestion pelvienne post-thrombotique.

INTRODUCTION: Pelvic congestion syndrome is a chronic pelvic pain syndrome related to pelvic varices developed in the setting of primary venous insufficiency or secondary to venous obstruction. OBSERVATION: We report the case of a 35-year-old patient undergoing anticoagulant therapy for an extensive unprovoked left iliac vein thrombosis, who developed a disabling pelvic congestion syndrome secondary to chronic obstruction of the left iliac vein. Recanalization with stenting of the left iliac vein, combined with antithrombotic treatment with antiplatelet therapy (aspirin 100mg) and anticoagulation (rivaroxaban 20mg) for three months, followed by antiplatelet therapy alone, led to a complete and lasting regression of symptoms. DISCUSSION: Management of pelvic congestion syndrome secondary to post-thrombotic lesions must take into account its pathophysiology. It involves iliac venous angioplasty with stent placement in combination with antithrombotic therapy, which modalities remain to be specified in long-term follow-up.

Supervised short-stretch compression therapy in mixed leg ulcers.

OBJECTIVES: This study was conducted to determine hemodynamic and clinical tolerance under short-stretch compression therapy in elderly patients suffering from mixed-etiology leg ulcers. DESIGN: Transversal observational study conducted in 25 hospitalized patients with a moderate peripheral arterial occlusive disease defined as an ankle-brachial pressure index>0.5, an ankle pressure of>70mmHg and a toe cuff pressure (TP)>50mmHg. MATERIAL AND METHODS: Short-stretch bandages were applied daily with pressures from 20 to 30mmHg. Ankle-brachial pressure, great toe laser Doppler flowmetry (LDF) and transcutaneous oxygen pressure (TcPO2) on dorsum of the foot were measured at baseline and after its removal at 24hours. Great toe LDF was also measured at 10minutes after bandage application. Compression pressure (CP) was measured with a sub-bandage device at baseline, at 10minutes and before bandage removal at 24hours. Clinical tolerance was evaluated taking into account the patient's pain and skin tolerance. RESULTS: Mean age of patients was 80±15 years. Median duration of ulcers was 18 months. Hypertension was highly prevalent. One third of patients had diabetes. Toe pressure index and TcPO2 values did not significantly change under compression therapy (P=0.51 and P=0.09, respectively) whereas CP decreased significantly during 24hours. The loss of CP was significant 10minutes after bandage application (P<0.001). Nearly all ulcers were painful prior to placement of compression therapy and required level 1 analgesics. One patient required level 2 analgesic for pain relief. No increase in pain and no ischemic skin damage occurred under compression therapy. CONCLUSIONS: In elderly patients with mixed leg ulcers and with an absolute TP>50mmHg, short-stretch compression of up to 30mmHg does not adversely affect arterial flow and appears clinically well tolerated. Such bandages with appropriate levels of compression may aid ulcer healing by treating the venous part of the disease.

[Identifying barriers to screening for abdominal aortic aneurysm in general practice: Qualitative study of 14 general practitioners in Paris]. / Identification des freins au dépistage de l'anévrisme de l'aorte abdominale en médecine générale : étude qualitative auprès de 14 médecins généralistes exerçant à Paris.

INTRODUCTION: Abdominal aortic aneurysm (AAA) is a silent pathology with often fatal consequences in case of rupture. AAA screening, recommended in France and many other countries, has shown its effectiveness in reducing specific mortality. However, AAA screening rate remains insufficient. OBJECTIVE: To identify barriers to AAA screening in general practice. MATERIAL AND METHOD: Qualitative study carried out during 2016 among general practitioners based in Paris. RESULTS: Fourteen physicians were included. Most of the barriers were related to the physician: unawareness about AAA and screening recommendations, considering AAA as a secondary question not discussed with the patient, abdominal aorta not included in cardiovascular assessment, no search for a familial history of AAA, AAA considered a question for the specialist, lack of time, lack of training, numerous screenings to propose, oversight. Some barriers are related to the patient: unawareness of the pathology and family history of AAA, refusal, questioning the pertinence of the doctor's comments, failure to respect the care pathway. Others are related to AAA: source of anxiety, low prevalence, rarity of complications. The remaining barriers are related to screening: cost-benefit and risk-benefit ratios, sonographer unavailability, constraint for the patient, overmedicalization. CONCLUSION: Information and training of general practitioners about AAA must be strengthened in order to optimize AAA screening and reduce specific mortality.

[When to ask for a skin biopsy in a patient with leg ulcer? Retrospective study of 143 consecutive biopsies]. / Quand poser l'indication d'une biopsie cutanée chez un patient porteur d'ulcère de jambe ? Étude rétrospective sur 143 biopsies consécutives.

OBJECTIVE: A vascular cause is found in around 85% of leg ulcer patients, but non-vascular causes are also observed. Their diagnosis is based on a set of clinical arguments and skin biopsy with histological analysis. The aim of this study was to analyze the results of these biopsies and to find common criteria for ulcers whose skin biopsies had led to the diagnosis of a non-vascular ulcer. MATERIAL AND METHOD: A retrospective study was carried out on the analysis of 143 skin biopsies of leg ulcers. The reasons for the biopsy were mainly atypical clinical signs and/or the lack of improvement in care after 6 months, as advocated by the French health authorities. RESULTS: The skin biopsies led to a diagnosis of non-vascular ulcer in 4.9% of cases (7/143), including skin cancer (n=5, 3.5%), cutaneous leishmaniasis (n=1, 0.7%) and Pyoderma gangrenosum (n=1, 0.7%). The univariate statistical analysis revealed that an elevated rim and abnormal excessive granulation tissue were significantly more frequently found in these ulcers. All patients with a positive skin biopsy had associated vascular involvement. CONCLUSION: This study found a 5% rate of non-vascular causes of ulcers, mainly skin cancer. Elevated rims and abnormal excessive granulation tissue were the unusual features most commonly found in these ulcers. All patients whose skin biopsy revealed a non-vascular cause had associated vascular involvement. This information confirms the need to perform a skin biopsy, even in the presence of a vascular disease.

Ranibizumab and digital ischemia.

Case report of a patient with age-related macular degeneration whose digital ischemia can most plausibly be attributed to ranibizumab. PURPOSE: To report ranibizumab as the probable cause of digital ischemia in a patient treated for age-related macular degeneration. METHODS: Single-patient case report. RESULTS: An 83-year-old woman with an unremarkable medical history suffered acute ischemia in her left hand with necrosis of the distal phalange of the fifth finger after six intravitreal injections of ranibizumab. Her etiological work-up was negative. Her condition improved after endovascular revascularization and remained good at six months' follow-up after three months of dual antithrombotic therapy (low molecular weight heparin then rivaroxaban, both with aspirin) followed by rivaroxaban alone and four courses of intravenous iloprost. CONCLUSION: The increased incidence of peripheral arterial thromboembolic events in patients under ranibizumab treatment is slight but significant, with 0.8-5% of patients affected, most of which suffer strokes. These events seem to occur at a random time after ranibizumab treatment is initiated and no reliable marker has yet been identified. The most probable cause of digital ischemia in our patient was ranibizumab.

Quality of life in patients with leg ulcers: results from CHALLENGE, a double-blind randomised controlled trial.

OBJECTIVE: We recently showed the superiority of a matrix metalloproteinase (MMP) modulating dressing (foam impregnated with NOSF, nano-oligosaccharide factor) compared with a lipidocolloid matrix (TLC) control dressing in median wound area reduction (WAR). Here we report the results from the same study assessing the performance and safety of TLC-NOSF in the local management of venous leg ulcers (VLUs) or mixed leg ulcers and determining its impact on the patient's health-related quality of life (HRQoL). METHOD: A superiority randomised double-blind controlled trial was conducted on patients presenting with a non-infected leg ulcer (VLUs or mixed leg ulcers) of predominantly venous origin (ABPI >0.8), with a surface area ranging from 5 to 50cm2 and a duration of 6 to 36 months. Patients were randomly allocated to either the TLC-NOSF matrix foam (UrgoStart) dressing group or to the neutral TLC foam dressing group (UrgoTul Absorb). All received appropriate compression therapy and the wounds were assessed blindly (clinical examination, wound area tracing and photographic record) every 2 weeks for a period of 8 weeks, or until complete closure. A secondary endpoint, described here, was the patient's HRQoL, documented by the patient, through the EuroQol 5D tool (EQ-5D) questionnaire and visual analogue scale (VAS). RESULTS: In total, 187 patients were randomised to either the TLC-NOSF group (n=94) or the control dressing group (n=93). The two groups were well balanced at baseline with regard to wound and patient characteristics. In the HRQoL questionnaire (EQ-5D), the pain/discomfort and anxiety/depression dimensions were significantly improved in the TLC-NOSF group versus the control one (pain/discomfort: 1.53±0.53 versus 1.74±0.65; p=0.022, and anxiety/depression: 1.35±0.53 versus 1.54±0.60, p=0.037). The VAS score was better in the test group compared with the control group (72.1±17.5 versus 67.3±18.7, respectively), without reaching significance (p=0.072). Acceptability and tolerance of the two products were similar in both groups. CONCLUSION: The double-blind clinical trial has demonstrated that the TLC-NOSF matrix dressing promotes faster healing of VLUs and mixed leg ulcers and significantly reduces the pain/discomfort and anxiety/depression experienced by the patients. These results suggest that acceleration of VLU healing could improve the HRQoL of the patients and reduced the emotional and social burden of these chronic wounds.