Extracellular matrix and cellular senescence in venous leg ulcers.
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ABSTRACT:
SUBMITTER: Lim DXE
PROVIDER: S-EPMC8505655 | biostudies-literature |
REPOSITORIES: biostudies-literature
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| S-EPMC9354941 | biostudies-literature
Project description:IntroductionLow-frequency, low-intensity ultrasound has been previously shown to promote healing of chronic wounds in humans, but mechanisms behind these effects are poorly understood. The purpose of this study was to evaluate gene expression differences in debrided human venous ulcer tissue from patients treated with low-frequency (20 kHz), low-intensity (100 mW/cm2) ultrasound compared to a sham treatment in an effort to better understand the potential biological mechanisms.MethodsDebrided venous ulcer tissue was collected from 32 subjects one week after sham treatment or low-frequency, low-intensity ultrasound treatment. Of these samples, 7 samples (3 ultrasound treated and 4 sham treated) yielded sufficient quality total RNA for analysis by ultra-high multiplexed PCR (Ampliseq) and expression of more than 24,000 genes was analyzed. 477 genes were found to be significantly differentially expressed between the ultrasound and sham groups using cut-off values of p < 0.05 and fold change of 2.Results and discussionThe top differentially expressed genes included those involved in regulation of cell metabolism, proliferation, and immune cell signaling. Gene set enrichment analysis identified 20 significantly enriched gene sets from upregulated genes and 4 significantly enriched gene sets from downregulated genes. Most of the enriched gene sets from upregulated genes were related to cell-cell signaling pathways. The most significantly enriched gene set from downregulated genes was the inflammatory response gene set. These findings show that therapeutic ultrasound influences cellular behavior in chronic wounds as early as 1 week after application. Considering the well-known role of chronic inflammation in impairing wound healing in chronic wounds, these results suggest that a downregulation of inflammatory genes is a possible biological mechanism of ultrasound-mediated venous chronic wound healing. Such increased understanding may ultimately lead to the enhancement of ultrasound devices to accelerate chronic wound healing and increase patient quality of life.
| S-EPMC10098114 | biostudies-literature
Project description:ObjectiveTo review the evidence of effectiveness of dressings applied to venous leg ulcers.DesignSystematic review and meta-analysis.Data sourcesHand searches of journals and searches of electronic databases, conference proceedings, and bibliographies up to April 2006; contacts with dressing manufacturers for unpublished studies.Studies reviewedAll randomised controlled trials that evaluated dressings applied to venous leg ulcers were eligible for inclusion. Data from eligible studies were extracted and summarised independently by two reviewers using a data extraction sheet. Methodological quality was assessed independently by two reviewers.ResultsThe search strategy identified 254 studies; 42 of these fulfilled the inclusion criteria. Hydrocolloids were no more effective than simple low adherent dressings used beneath compression (eight trials; relative risk for healing with hydrocolloid 1.02, 95% confidence interval 0.83 to 1.28). For other comparisons, insufficient evidence was available to allow firm conclusions to be drawn. None of the dressing comparisons showed evidence that a particular class of dressing healed more ulcers. Some differences existed between dressings in terms of subjective outcome measures and ulcer healing rates. The results were not affected by the size or quality of trials or the unit of randomisation. Insufficient data were available to allow conclusions to be drawn about the relative cost effectiveness of different dressings.ConclusionsThe type of dressing applied beneath compression was not shown to affect ulcer healing. The results of the meta-analysis showed that applying hydrocolloid dressings beneath compression produced no benefit in terms of ulcer healing compared with applying simple low adherent dressings. No conclusive recommendations can be made as to which type of dressing is most cost effective. Decisions on which dressing to apply should be based on the local costs of dressings and the preferences of the practitioner or patient.
| S-EPMC1939774 | biostudies-literature
Project description: Not available
| S-EPMC8210978 | biostudies-literature
Project description:BACKGROUND:Individuals with venous leg ulcers (VLUs) suffer disproportionately with multiple chronic conditions, are often physically deconditioned, and demonstrate high levels of physical inactivity. OBJECTIVE:The primary objective of this randomized controlled trial was to establish the feasibility of a mobile health (mHealth) physical activity exercise app for individuals with VLUs to improve lower leg function. METHODS:In a 6-week study, adults with VLUs were recruited from 2 wound centers in South Carolina, United States, and enrolled if they were aged 18 years or older with impaired functional mobility and an ankle-brachial index between 0.8 and 1.3. Participants were randomized 1:1 to receive evidence-based, phased, nonexertive physical conditioning activities for lower leg function (FOOTFIT) or FOOTFIT+ with an added patient-provider communication feature. The mHealth Conditioning Activities for Lower Leg Function app also provided automated educational and motivational messages and user reports. Foot movement on the VLU-affected leg was tracked by a Bluetooth-enabled triaxial accelerometer. The study was guided by the Reach, Effectiveness, Adoption, Implementation, and Maintenance framework to assess the feasibility of reach, adherence, acceptability, implementation, and maintenance. RESULTS:A total of 24 patients were recruited, enrolled, and randomized in the study. Most patients reported difficulty following the protocol for exercising and using the accelerometer and mobile phone and did not use the provider contact feature. However, all patients were adherent to the 6-week exercise program more than 85% of the time for duration, whereas 33% (8/24) of patients adhered more than 85% for the frequency of performing the exercises. Across the three exercise levels, adherence did not differ between the two groups. Confidence limits around the difference in proportions ranged from -0.4 to 0.7. Providers in FOOTFIT+ were inconsistent in checking participant progress reports because of lack of time from competing work commitments. The technology became outdated quickly, making maintenance problematic. Participants said they would continue to exercise their foot and legs and liked being able to follow along with the demonstrations of each level of exercise provided through the app. CONCLUSIONS:The findings of this study suggest that despite initial interest in using the app, several components of the program as originally designed had limited acceptability and feasibility. Future refinements should include the use of more modern technology including smaller wearable accelerometers, mobile phones or tablets with larger screens, an app designed with larger graphics, automated reporting for providers, and more engaging user features. TRIAL REGISTRATION:ClinicalTrials.gov NTC02632695; https://clinicaltrials.gov/ct2/show/NCT02632695.
| S-EPMC7260657 | biostudies-literature
Project description:Recent advancements in near-infrared fluorescence lymphatic imaging (NIRFLI) technology provide opportunities for non-invasive, real-time assessment of lymphatic contribution in the etiology and treatment of ulcers. The objective of this study was to assess lymphatics in subjects with venous leg ulcers using NIRFLI and to assess lymphatic impact of a single session of sequential pneumatic compression (SPC).Following intradermal microdoses of indocyanine green (ICG) as a lymphatic contrast agent, NIRFLI was used in a pilot study to image the lymphatics of 12 subjects with active venous leg ulcers (Clinical, Etiologic, Anatomic, and Pathophysiologic [CEAP] C6). The lymphatics were imaged before and after a single session of SPC to assess impact on lymphatic function.Baseline imaging showed impaired lymphatic function and bilateral dermal backflow in all subjects with chronic venous insufficiency, even those without ulcer formation in the contralateral limb (C0 and C4 disease). SPC therapy caused proximal movement of ICG away from the active wound in 9 of 12 subjects, as indicated by newly recruited functional lymphatic vessels, emptying of distal lymphatic vessels, or proximal movement of extravascular fluid. Subjects with the longest duration of active ulcers had few visible lymphatic vessels, and proximal movement of ICG was not detected after SPC therapy.This study provides visible confirmation of lymphatic dysfunction at an early stage in the etiology of venous ulcer formation and demonstrates the potential therapeutic mechanism of SPC therapy in removing excess fluid. The ability of SPC therapy to restore fluid balance through proximal movement of lymph and interstitial fluid may explain its value in hastening venous ulcer healing. Anatomical differences between the lymphatics of longstanding and more recent venous ulcers may have important therapeutic implications.
| S-EPMC4782606 | biostudies-literature
Project description:Venous leg ulcers (VLUs) are an important health problem, and the size of ulcers often affects patient care, healing time, and quality of life. However, the risk factors associated with ulcer size have been rarely reported. The aim of this study was to establish the risk factors for the size of venous ulceration by analyzing the patient demographics and the results of duplex ultrasonography.This study was an in-patient population-based cross-sectional study conducted at a single center during the period from 2013 to 2017. Men and women aged >18 years, who consecutively presented to our hospital with VLU, were included. According to the size of the ulcer, patients were divided into two groups, those with ulcers≤2 cm and those with ulcers >2 cm. Demographic, anthropometric, and clinical data were collected. For the analysis, univariate and multivariate logistic regressions were used.A total of 232 patients with VLUs were admitted to our hospital from 2013 to 2017, including 117 patients (50.4%) with ulcer diameters ≤2 cm and 115 patients (49.6%) with ulcer diameters >2 cm. According to the results of the multivariate analysis, the ulcer duration (P = .001), the diameter of perforating veins (PVs) around the ulcers (P = .025), the reflux time of common femoral veins (CFVs) (P = .013), the reflux time of great saphenous veins (GSVs) (P = .021), and the reflux time of PVs around the ulcers (P = .001) were independent risk factors for VLUs.These findings provide evidence that the size of VLU was significantly related to the ulcer duration, the diameter of PV around the ulcers, the CFV reflux time, the GSV reflux time, and the PV reflux time.
| S-EPMC6380848 | biostudies-literature
Project description:IntroductionChronic venous leg ulcer (VLU) healing is a complex clinical problem. It requires intervention from skilled, costly, multidisciplinary wound-care teams, working with patients to manage their care. Compression therapy has been shown to help heal venous ulcers and to reduce recurrence, with some evidence suggesting the value of exercise as well. These activities require health education and health literacy (HL) as patients must process, understand and consistently apply health information for successful self-management. Research suggests that those most vulnerable to VLUs also tend to have limited HL, but there have been no reviews examining the state of HL in patients with previous or active VLUs. This scoping review aims to examine the level of HL in VLU patients and how HL may link to self-management behaviours (particularly exercise and compression adherence), and their VLU healing generally.Methods and analysisWe will use Preferred Reporting Items for Systematic Reviews and Meta-Analyses Scoping Review guidelines and the Levac methodology framework to explore eligible papers that examine the effect of HL on their exercise and compression adherence. Electronic databases will be searched (MEDLINE, EMBASE, the Cochrane Library, PsycInfo and Health, OpenGray), examining for all papers on these subjects published between 2000 and 2020. All studies describing compression and or exercise during VLU management will be included. Study characteristics will be recorded; qualitative data will be extracted and evaluated. Quantitative data will be extracted and summarised.Ethics and disseminationWe will disseminate results through peer-reviewed publications. We will use data (ie, journal articles) from publicly available platforms; so, this study does not require ethical review. The consultation step will be carried out with patients, carers and health professionals as part of an established wound consumer group.
| S-EPMC8117997 | biostudies-literature
Project description: Not available
| S-EPMC10830917 | biostudies-literature
Project description:ObjectiveThe aim of this review was to identify, and assess the quality of, published model-based economic evaluations relating to treatments for patients with venous leg ulcers to help inform future decision-analytic models in this clinical area.MethodsA systematic literature search was performed on six electronic databases, from database inception until 21 May 2018. Search results were screened against predefined criteria by two independent reviewers. Data was then extracted from the included studies using a standardised form, whilst the decision-analytic model-specific Philips Checklist was used to assess quality and to inform model critique.ResultsA total of 23 models were identified, 12 studies used a Markov modelling approach, five used decision trees and six studies did not detail the model type. Studies were predominantly from the National Health Service (NHS)/payer perspective, with only two taking a societal perspective. Interventions were wide ranging, but dressing technologies (11/23) were most common. The intervention studied was found to be dominant in 22/23 studies. The reporting quality of papers was mostly low, with evidence behind model structures, time horizons and data selection consistently underreported across the included papers.ConclusionsThis review has identified a sizeable literature of model-based economic evaluations, evaluating treatments for venous leg ulcers. However, the methods used to conduct such studies were generally poorly reported. In particular, the reporting of evidence surrounding the model structure, justification of the time horizon used and the rationale for selecting data inputs should be focused on in any future models developed.
| S-EPMC7248160 | biostudies-literature