Chronic Lower Extremity Ulcers Research Articles

Effective Management of Chronic Lower-Extremity Ulcers (CLEU) by Fu’s Subcutaneous Needling (FSN)

Effective Management of Chronic Lower-Extremity Ulcers (CLEU) by Fu’s Subcutaneous Needling (FSN)

Epidemiological profile of patients with chronic lower extremity ulcers in two public hospitals in southern Brazil

Epidemiological profile of patients with chronic lower extremity ulcers in two public hospitals in southern Brazil

Chronic wounds of the lower limbs: a guide for non-specialists

Chronic lower-extremity ulcers are a growing public health problem, resulting in significant costs for society and patients, and having a significant impact on the quality of life of patients and informal caregivers. As general practitioners are often solicited early on, the acquisition of basic knowledge regarding wound care management is therefore essential to initiate local care, to make an early diagnosis and identify emergencies and patients that need a referral. The CASE and TIMERS frameworks enable a holistic assessment of the patient and the wound, to propose a treatment of the wound based on its etiology combined with appropriate local wound care. This framework allows also to identify atypical, severe, or recalcitrant wounds requiring specialized advice.

Adipose-derived Mesenchymal Stem Cells are Ideal for the Cell-based Treatment of Refractory Wounds: Strong Potential for Angiogenesis.

Although Mesenchymal Stem Cells (MSCs)-based therapy has been proposed as a promising strategy for the treatment of chronic lower-extremity ulcers, their optimal sources, amounts, and delivery methods are urgently needed to be determined. In this study, we compared the heterogeneity of the human MSCs derived from bone marrow (BMSCs), umbilical cord (UCMSCs), and adipose tissue (ADSCs) in accelerating wound healing and promoting angiogenesis and explored the underlying mechanism. Briefly, a diabetic rat model with a full-thickness cutaneous wound on the dorsal foot was developed. The wound was topically administered with three types of MSCs. Additionally, we carried out in vitro and in vivo analysis of the angiogenic properties of the MSCs. Moreover, the molecular mechanism of the heterogeneity of the MSCs derived from the three tissues was explored by transcriptome sequencing. When compared with the BMSCs- and UCMSCs-treated groups, the ADSCs-treated group exhibited markedly accelerated healing efficiency, characterized by increased wound closure rates, enhanced angiogenesis, and collagen deposition at the wound site. The three types of MSCs formed three-dimensional capillary-like structures and promoted angiogenesis in vitro and in vivo, with ADSCs exhibiting the highest capacity for tube formation and pro-angiogenesis. Furthermore, transcriptome sequencing revealed that ADSCs had higher expression levels of angiogenesis-associated genes. Our findings indicate that MSCs-based therapy accelerates the healing of ischemia- and diabetes-induced lower-extremity ulcers and that adipose tissue-derived MSCs might be ideal for therapeutic angiogenesis and treatment of chronic ischemic wounds.

Reappraisal and updated review of maggot debridement therapy in chronic lower extremity ulcers.

Dating back to the mid-1500s, maggot debridement therapy (MDT) has been a viable treatment modality for chronic wounds. In early 2004, the sterile larvae of Lucilia sericata received FDA approval for medical marketing for neuropathic, venous, and pressure ulcers, traumatic or surgical wounds, and nonhealing wounds that have not responded to standard care. However, it currently remains an under-utilized therapy.The proven efficacy of MDT begs the question if this treatment modality should be considered as a first-line option for all or a subset of chronic lower extremity ulcers. This article aims to address the history, production, and evidence of MDT and discuss future considerations for maggot therapy in the healthcare field. A literature search using the PubMed database was conducted using keywords, such as wound debridement, maggot therapy, diabetic ulcers, venous ulcers, among others. MDT reduced short-term morbidity in non-ambulatory patients with neuroischemic diabetic ulcers and comorbidity with peripheral vascular disease. Larval therapy was associated with statistically significant bioburden reductions against both Staphylococcus aureus and Pseudomonas aeruginosa. Faster time to debridement was achieved when chronic venous or mixed venous and arterial ulcers were treated with maggot therapy versus hydrogels. The literature supports the use of MDT in decreasing the significant costs of treating chronic lower extremity ulcers, with emphasis on those of diabetic origin. Additional studies with global standards for reporting outcomes are necessary to substantiate our results.

Leukocyte- and Platelet-rich Fibrin Treatment of Chronic Lower Extremity Ulcer in a Patient with Systemic Lupus Erythematosus: A Case Report

Introduction. Lower extremity ulcer is a severe complication in patients with autoimmune disease, and treatment is difficult and time-consuming. L-PRF has been widely used in mammalian regenerative medicine owing to its ease of use and low cost. However, few studies have been published on the application of L-PRF in autoimmune-associated ulcers. Case Report. This case report discusses a 26-year-old male patient with SLE who presented to the authors' institution with a chronic lower extremity ulcer of 8 months’ duration. He received once-weekly L-PRF treatment along with standard wound care. After 15 treatments, the ulcer was completely epithelialized, with a healing rate of 3.8 cm2 per week. Conclusions. This case report provides a promising therapeutic strategy for the treatment of autoimmune-associated ulcers. More robust data from case series and RCTs are required to further evaluate the clinical efficacy of L-PRF in refractory ulcers in patients with autoimmune disease.

Large Leg Ulcers After Swimming in the Ocean.

A 48-year-old man presented to the emergency department with pain in both legs after swimming in the ocean surrounding Florida 1 month prior to presentation. His medical history included skin graft treatment of burns during childhood and a chronic lower extremity ulcer that developed after trauma.

Stenotrophomonas maltophilia Infections in Geriatric Patients

We present Stenotrophomonas maltophilia infections in 317 hospitalized patients in a large health network over a 3-year period. The majority of patients were elderly. Most infections were polymicrobial: respiratory 95.2%, wound 91%, urinary 80.8% and blood 64.3%. Younger patients were small in number and were more common in those with otitis externa, infections from injection drug use and those with line infections. Most deaths were in patients with terminal conditions and polymicrobial infections and mortality could not be directly attributed to Stenotrophomonas maltophilia. None of the sputum, bronchial, urinary or wound culture positive patients had positive blood cultures. Only blood (14/317) or ear (7/317) culture positive patients had significant numbers of younger individuals with only 3 out of 14 over age 50 in blood culture positive patients and 1/7 in those with otitis externa. Those with bacteremia included patients with injection drug use, chronic pain syndromes and vascular catheter infections. 94% of urinary infections, 91.7% wound infections and 85.8% respiratory isolates were in those above age 50. Overwhelming majority of urinary infections were in males with drainage devices present in 75%. Recurrent infections were uncommon. Respiratory specimens were frequently associated with tracheostomies and endotracheal tubes. Most wound infections were in chronic lower extremity ulcers. Prior carbapenem use was not significant in this study. Isolates from all sites were over 98% susceptible to Trimethoprim/sulphamethoxazole. Limitations: The study group only had 1 organ transplant and 2 cystic fibrosis patients and no burn wound infections.

Perforator Free Flap Coverage of Chronic Lower Extremity Ulcers in Patients With Autoimmune Diseases Under Immunosuppression.

Objectives. Lower extremity ulcers are quite common in patients with autoimmune diseases. Due to chronic use of immunosuppressants, these wounds may develop into deeper wounds resulting in exposure of bone or tendon, which in turn may require free tissue transfers for coverage. The author reviewed perforator free flap transfers performed in this group of patients and analyzed the results. Methods. A retrospective review was performed on all patients who underwent perforator free flap transfer for coverage of lower extremity ulcers without trauma, over a 10-year period. Patient demographics, administered immunosuppressants, and flap and donor site complications were analyzed. Results. Twenty-two perforator free flap transfers were performed in patients with autoimmune diseases, including 18 thoracodorsal perforator flaps, 2 anterolateral thigh flaps, and 2 deep inferior epigastric artery flaps. There was no total flap loss, but there was a high rate of partial flap necrosis (40.9%) and wound dehiscence (40.9%). Intake of corticosteroids was significantly associated with postoperative complications (P < .05). Conclusion. As partial loss of flap and wound dehiscence is much more common in this group of patients, treatment may take longer, and a fully informed consent should be obtained preoperatively. Surgeons should not avoid performing perforator free flap transfers in patients with autoimmune diseases under immunosuppression; instead, much more preparation and caution are required.

COVID‐19 infection in patients with sickle cell disease

Severe acute respiratory syndrome coronavirus 2, also known as COVID-19, has spread to 184 countries with almost 1.5 million cases as of mid-April 2020 since first reported (1). The clinical features of this disease are not completely understood, however severe illness is thought to predominantly occur in adults with advanced age and those with underlying comorbidities (2). Sickle cell disease (SCD), an immunocompromised condition, puts patients at higher risk for respiratory infections and subsequent pulmonary complications such as acute chest syndrome (ACS) (3).

Matrix therapy is a cost-effective solution to reduce amputation risk and improve quality of life: pilot and case studies.

Introduction: Chronic, non-healing ulcers remain one of the most challenging clinical situations for health care practitioners. Often, conventional treatments fail and lead to amputation, further decreasing the patient's quality of life and resulting in enormous medical expenditures for healthcare systems. Here we evaluated the use of and cost-effectiveness of the RGTA (ReGeneraTing Agents) medical device CACIPLIQ20 (OTR4120) for chronic lower-extremity ulcers in patients with Leriche and Fontaine Stage IV peripheral arterial disease who were not eligible for revascularization. Methods: This uncontrolled pilot study included 14 chronic lower extremity ulcers in 12 patients in one hospital. The pilot study included 12 patients with TcPO2 < 20 mm Hg and ABPI < 0.5 who had either a minimum of one chronic lower extremity ulcer or a chronic ulcer related to amputation. OTR4120 was applied twice a week or until complete healing, for up to 12 weeks. Ulcer surface area reduction (%)after 2, 4, 8 and 12 weeks, appearance after 4 weeks, and healing after 12 weeks were measured and recorded. Results: A 35% reduction in ulcer size was achieved after 4 weeks. 7 (50%) out of 14 ulcers completely healed within 1 to 3 months of treatment. Discussion: OTR4120 is an effective therapeutic option for patients with chronic lower extremity ulcers, can provide major improvement of quality of life and has the added benefit of being a significant cost-effective solution for healthcare systems.

A confirmatory study on the efficacy of dehydrated human amnion/chorion membrane dHACM allograft in the management of diabetic foot ulcers: A prospective, multicentre, randomised, controlled study of 110 patients from 14 wound clinics.

A randomised, controlled multicentre clinical trial was conducted at 14 wound care centres in the United States to confirm the efficacy of dehydrated human amnion/chorion membrane allograft (dHACM) for the treatment of chronic lower extremity ulcers in persons with diabetes. Patients with a lower extremity ulcer of at least 4 weeks duration were entered into a 2‐week study run‐in phase and treated with alginate wound dressings and appropriate offloading. Those with less than or equal to 25% wound closure after run‐in were randomly assigned to receive weekly dHACM application in addition to offloading or standard of care with alginate wound dressings, for 12 weeks. A total of 110 patients were included in the intent‐to‐treat (ITT) analysis, with n = 54 in the dHACM group and n = 56 in the no‐dHACM group. Of the participants, 98 completed the study per protocol, with 47 receiving dHACM and 51 not receiving dHACM. The primary study outcome was percentage of study ulcers completely healed in 12 weeks, with both ITT and per‐protocol participants receiving weekly dHACM significantly more likely to completely heal than those not receiving dHACM (ITT—70% versus 50%, P = 0.0338, per‐protocol—81% versus 55%, P = 0.0093). A Kaplan–Meier analysis was performed to compare the time‐to‐healing performance with/without dHACM, showing a significantly improved time to healing with the use of allograft, log‐rank P < 0.0187. Cox regression analysis showed that dHACM‐treated subjects were more than twice as likely to heal completely within 12 weeks than no‐dHACM subjects (HR: 2.15, 95% confidence interval 1.30–3.57, P = 0.003). At the final follow up at 16 weeks, 95% of dHACM‐healed ulcers and 86% of healed ulcers in the no‐dHACM group remained closed. These results confirm that dHACM is an efficacious treatment for lower extremity ulcers in a heterogeneous patient population.

Micrografting chronic lower extremity ulcers with mechanically disaggregated skin using a micrograft preparation system.

The Rigenera system is a new standardised micrograft preparation system. It works by means of automated mechanical disaggregation of small tissue samples, extracting only the smallest cells (<50µm). The aim of this study was to retrospectively evaluate patients affected by chronic ulcers and who were treated with the micrograft preparation method. Chronic ulcers have been included regardless of the cause. The specimen was collected with a 3mm diameter biopsy punch and immediately dissociated by means of the Rigenera System. The obtained suspension was placed on a scaffold of equine collagen. We included 15 patients (four males, 11 females) with a mean age of 72.2±8.41 (mean±standard deviation) years. In seven patients the ulcers were related to the complications of diabetes, post-traumatic in a further three diabetic patients, vasculitis in one patient, and four patients had venous leg ulcers (VLUs). The median main diameter was 5.0cm and the median estimated area was 43.96cm2. The ulcers were present from a mean of 4.50±2.30 months before inclusion in this study. At the second week the wounds were reduced by 37.33%±19.35%, at the week eight, nine patients (60.0%) were healed, and at week 16, 13 (86.7%) were healed. The quality of scars was good and did not deteriorate at the six month follow-up. The simplicity of the approach, the minimal invasiveness of the specimen collection, and the good quality of scarring of healed wounds, confirmed in the follow-up, makes this micrograft preparation method a useful tool to use on large or complex wounds.

Treatment of Chronic Lower Extremity Ulcers with A New Er:Yag Laser Technology.

Chronic lower extremity ulcers (CLEUs) have a high prevalence and are difficult to treat due to their various aetiologies. The aim of this study is to evaluate the results achieved in treating CLEUs using an Erbium: YAG (Er:YAG) laser with RecoSMA technology. This laser emits thousands of microbeams of energy causing superficial epidermal ablation and a separation of dermal fibres due to a mechanical-acoustic and resonance effect. The evaluation of the results achieved was carried out by questionnaires completed by 18 patients enrolled in the study. Histological studies and photographs taken before each session (16 sessions in total) were analysed to visually monitor the clinical progress. The analyses were carried out with the help of computer software. The results after 16 treatment sessions showed the complete healing of ulcers or a decrease in their initial area of at least 55% in over 65% of the patients treated. The Student's t-test and Fisher's exact test were used for statistical analysis. The Er:YAG laser and RecoSMA technology ablates few epidermal cell layers, producing a mechanical-acoustic effect with resonance action leading to tissue regeneration mechanisms. This technology offers an effective and safe alternative for treating CLEUs.

Vasculitic and autoimmune wounds.

Chronic wounds are a major cause of morbidity and mortality. Approximately 20% to 23% of nonhealing wounds that are refractory to vascular intervention have other causes, including vasculitis, pyoderma gangrenosum, and other autoimmune diseases. The purpose of this article was to review the literature across medical and surgical specialties with regard to refractory chronic wounds associated with vasculitis and autoimmune diseases and to delineate clinical outcomes of these wounds in response to vascular and other interventions. An electronic search encompassing MEDLINE, PubMed, Cochrane Library, and Scopus was completed using the following search terms: rheumatoid arthritis; systemic sclerosis; systemic lupus erythematosus; antineutrophil cytoplasmic antibody-associated vasculitis; mixed connective tissue disease; antiphospholipid syndrome; pyoderma gangrenosum; thromboangiitis obliterans; cryoglobulinemia; hydroxyurea; sickle cell; atrophie blanche; livedoid vasculitis; cholesterol emboli; calciphylaxis; antiphospholipid antibodies; prothrombotic; combined with the terms: chronic wound and leg ulcer. Full-text articles published in English up to March 1, 2016, that investigated the clinical outcomes of chronic wounds associated with autoimmune diseases were included. Review articles and evaluations of management of chronic wounds were also reviewed. Primary outcomes included in the review were amputation, ulcer healing, reduction in wound size, overall survival, and freedom from reintervention. Owing to the heterogeneity of data reporting among articles, qualitative analysis is also reported. Vasculitis and autoimmune diseases play a role in 20% to 23% of patients with chronic lower extremity ulcers. Furthermore, patients with autoimmune disease have a significantly high rate of split thickness skin graft failure (50%compared to 97% in patients without autoimmune disease; P = .0002). The management of leg ulcers associated with autoimmune diseases is discussed. Autoimmune and vasculitic causes should be considered in patients with chronic wounds who do not respond to appropriate vascular intervention and standard local wound care. A multidisciplinary approach with the involvement of rheumatologists allows investigation for underlying systemic disease and improves clinical outcomes for many of these challenging patients.

The PCS Evidence-based Clinical Practice Guidelines on the Diagnosis and Treatment of Chronic Lower Extremity Ulcers

The PCS Evidence-based Clinical Practice Guidelines on the Diagnosis and Treatment of Chronic Lower Extremity Ulcers

Effectiveness of Autologous Stem Cell Therapy for the Treatment of Lower Extremity Ulcers: A Systematic Review and Meta-Analysis.

Primary studies in animal models and humans have suggested the therapeutic potential of autologous stem cell for treating chronic lower extremity ulcers. However, the results of pilot randomized controlled trials (RCTs) in humans have been inconsistent.A meta-analysis of RCTs was performed to evaluate the role of autologous stem cell-based therapy for lower extremity ulcers.Studies were identified during a systematic search of Medline, Embase, Cochrane's library, and references cited in related reviews and studies.Studies were included if they were RCTs published in English, recruited patients with lower extremity ulcers who were assigned to either a group for the topical therapy with autologous stem cells, and reported data regarding the healing of the ulcers.Relative risks (RRs) for healing rate and standardized mean differences (SMDs) for the changes in the mean sizes of ulcers were evaluated with a random-effects model.Overall, autologous stem cell-based therapy was associated with better healing of lower extremity ulcers (12 comparisons, 290 patients, RR for partial healing = 3.07, 95% confidence interval [CI] = 1.14–8.24, P = 0.03; RR for complete healing = 2.26, 95% CI = 1.48–3.16, P < 0.001) with little heterogeneity (I2 = 0%). Moreover, autologous stem cell-based therapy was associated with a greater reduction in mean ulcer size (SMD = −0.63, 95% CI = −1.03 to −0.22, P = 0.002). Subgroup analyses indicated that stem cells from peripheral blood and bone marrow seemed to exert similar beneficial effects on the healing of ulcers. Stem cell therapy was not associated with any increased risks for adverse events.The optimized sources, amounts, and delivery methods of stem cell -based therapy for patients with chronic lower extremity ulcers need to be determined, and the long-term effects of stem cell-based therapy on clinical outcomes need further exploration.Autologous stem cell-based therapy is effective and safe for improving the healing of chronic lower extremity ulcers and large-scale RCTs are needed to confirm our findings.

Tratamiento de las úlceras crónicas de las piernas con láser de Er: YAG y tecnología RecoSMA

Chronic lower extremity ulcers (CLEU) have a high prevalence,present various aetiologies and are difficult to heal.The aim of the present study is to evaluat...

Study of etiology and outcome of chronic lower extremity ulcer

Clinical research is driving the improved prognosis for patients with systemic vasculitis. The major progress has been in ANCA-related vasculitis, where the need now is to incorporate the lessons from limited term controlled trials into evidence-based treat-to-target regimes related to individual responses over a prolonged period. This perspective examines the research aimed to establish the biomarkers needed for such an approach to succeed. It also looks at the more basic research needed to establish the aetio-pathogenesis of other major forms of vasculitis so that rational treatments can be devised for them too.

Phenotypic, molecular and antimicrobial susceptibility assessment in isolates from chronic ulcers of cured leprosy patients: a case study in Southern Brazil.

BACKGROUND One of the most stigmatizing physical sequelaeof leprosy in cured patients is the development of chronic lower extremity ulcers. The bacterial diversity present in ulcers is considered one of the factors that can delay the healing process, as well as serve as a focus for severe secondary infections. OBJECTIVE To identify the microbiota and antimicrobial resistance profile of bacteria isolated from skin ulcers in patients cured of leprosy. METHODSAfter obtaining informed consent, material was collected from ulcers of 16 patients treated at the Outpatient Public Health Dermatology Clinic of Rio Grande do Sul and Hospital Colônia Itapuã. Sampleswere collected during dressing, and the material sent to the Microbiology Laboratory of the Federal University of Health Sciences of Porto Alegre for microbiological culture. Methicillin-resistant Staphylococcus aureus (MRSA) was characterized by two molecular methods, including detection of the mecA gene by PCR and SCCmecgene typing. RESULTS Cultures revealed microorganisms in all ulcers: Gram-negative bacilli in 80%, Gram-positive cocci in 63%, and mixed microflora in 36%. Staphylococcus aureus and Pseudomonas aeruginosa were the most prevalent bacteria. Assessment of the antimicrobial resistance profile was notable for the presence of MRSA. Molecular analysis of this isolate revealed presence of the mecA gene contained in a type IV staphylococcal cassette chromosome mec (SCCmec). CONCLUSIONS In patients with leprosy, laboratory culture of skin ulcers is essential for correct antibiotic selection and to control emerging pathogens, such as MRSA carrying SCCmec type IV.