Special Issue "Chronic Wounds or Hard to Heal Ulcers: Updating Epidemiology, Physiopathology, and Therapies"

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Epidemiology & Public Health".

Deadline for manuscript submissions: closed (25 May 2022) | Viewed by 10298

Special Issue Editor

Prof. Dr. José Verdú-Soriano
E-Mail Website
Guest Editor
Community Nursing, Preventive Medicine, Public Health and History of Science Department, Faculty of Health Sciences, University of Alicante, Alicante, Spain
Interests: wound care; pressure ulcers; lower leg ulcers; diabetic foot ulcers; wound infection; wound biofilm; hard-to-heal wounds; prevention and treatment; quantitative research

Special Issue Information

Dear Colleagues,

Currently, there is an intense debate about the terminology, etiology, epidemiology, and current strategies for the prevention and management of so-called chronic wounds. Researchers have usually used, indistinctly, the terms “chronic wound”, “skin ulcer”, “hard-to-heal wound or ulcer”, etc. Specifically, for certain types of wounds, the terminology is changing due to new insights into the physiopathology and etiology, leading to new theoretical models of wound development, for instance, the trend from decubitus or bed sores to pressure ulcers and, now, to pressure injuries. The case is similar for leg or lower extremity wounds, where different etiologies could be present.

Nevertheless, such types of lesions are a remarkable public health problem due to the high numbers of people suffering from them, leading to a high impact on the direct cost burden and indirect indicators such as the quality of life of people suffering from wounds, and their families. On the other hand, the current prevention and treatment strategies are still limited and often less effective, or have little reported evidence to back them up.

This highlights the urgent need for new approaches and new research with better quality, requiring a further understanding of the whole process, from the etiology to wound healing.

This Special Issue of the Journal of Clinical Medicine on Chronic or Hard-to-Heal Wounds is intended to present cutting-edge original research and systematic, integrative, or scoping reviews on the epidemiology, risk factors, and physiopathology of those wounds; those on the existing strategies and emerging advanced clinical approaches for prevention and treatment management are also welcome.

Prof. Dr. José Verdú-Soriano
Guest Editor

Manuscript Submission Information

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Keywords

  • epidemiology
  • physiopathology
  • advanced therapies
  • hard-to-heal wounds
  • chronic wounds
  • skin ulcers
  • new theoretical models
  • etiology research
  • risk factors
  • prevention strategies

Published Papers (9 papers)

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Research

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Article
One-Stage Coverage of Leg Region Defects with STSG Combined with VAC Dressing Improves Early Patient Mobilisation and Graft Take: A Comparative Study
J. Clin. Med. 2022, 11(12), 3305; https://doi.org/10.3390/jcm11123305 - 09 Jun 2022
Cited by 1 | Viewed by 450
Abstract
Lower limb skin defects are very common and can result from a wide range of aetiologies. Split thickness skin graft (STSG) is a widely used method to address these problems. The role of postoperative dressing is primary as it permits one to apply [...] Read more.
Lower limb skin defects are very common and can result from a wide range of aetiologies. Split thickness skin graft (STSG) is a widely used method to address these problems. The role of postoperative dressing is primary as it permits one to apply a uniform pressure over the grafted area and promote adherence. Focusing on lower limb reconstruction, our clinical study compares the application of V.A.C. (Vacuum Assisted Closure) Therapy vs. conventional dressing in the immediate postoperative period following skin grafting. We included in the study all patients who received skin grafts on the leg region between January 2015 and December 2018, despite the aetiology of the defect. Only reconstructions with complete preoperative and postoperative follow-up data were included in the study. Patients were divided into two groups depending on if they received a traditional compressive dressing or a VAC dressing in the immediate postoperative period. We could retain 92 patients, 23 in the No VAC group and 69 in the VAC group. The patients included in the VAC group showed a statistically significant higher rate of graft take together with a lower immobilisation time (p < 0.05). Moreover, a lower rate of postoperative infection was recorded in the VAC group. This study represents the largest in the literature to report in detail surgical outcomes comparing the use of VAC therapy vs. conventional dressing after STSG in the postoperative management of lower limb reconstruction using skin grafts. VAC therapy was used to secure the grafts in the leg region, increasing the early graft take rate while at the same time improving patient mobilisation. Full article
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Article
Superiority of a Novel Multifunctional Amorphous Hydrogel Containing Olea europaea Leaf Extract (EHO-85) for the Treatment of Skin Ulcers: A Randomized, Active-Controlled Clinical Trial
J. Clin. Med. 2022, 11(5), 1260; https://doi.org/10.3390/jcm11051260 - 25 Feb 2022
Cited by 1 | Viewed by 908
Abstract
This 8-week, multicenter, randomized, active-controlled, observer-blinded clinical trial was designed to demonstrate the accelerating effect on wound healing of the novel Olea europaea leaf extract hydrogel (EHO-85) by comparing it to a widely used amorphous hydrogel. Results showed that EHO-85 significantly accelerated wound [...] Read more.
This 8-week, multicenter, randomized, active-controlled, observer-blinded clinical trial was designed to demonstrate the accelerating effect on wound healing of the novel Olea europaea leaf extract hydrogel (EHO-85) by comparing it to a widely used amorphous hydrogel. Results showed that EHO-85 significantly accelerated wound healing, regardless of ulcer etiology (pressure, venous leg or diabetic foot) and prognosis, doubling the median wound area reduction compared with a reference amorphous hydrogel (79.4% vs. 39.7%; difference: −39.7%, 95% CI: −71.1 to −21.3%; p < 0.001). The intention-to-treat analysis was conducted on 195 patients from 23 Spanish health centers/nursing homes. This novel treatment balances the ulcer microenvironment by modulating reactive oxygen species and pH. These actions complement the moistening and barrier functions inherent to amorphous hydrogels, whilst also conferring EHO-85 its documented granulation formation and pain relief properties. Furthermore, efficacy was achieved safely and in a cost-efficient manner due to its multi-dose format, which reduced the amount of product needed by 85.8% over 8 weeks compared to single-use hydrogel. The present randomized controlled trial is a relevant milestone in evidence-based practice for being the first to demonstrate (i) the effectiveness of an amorphous hydrogel in accelerating wound healing and (ii) the superiority of a specific hydrogel over another. Full article
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Article
EHO-85: A Multifunctional Amorphous Hydrogel for Wound Healing Containing Olea europaea Leaf Extract: Effects on Wound Microenvironment and Preclinical Evaluation
J. Clin. Med. 2022, 11(5), 1229; https://doi.org/10.3390/jcm11051229 - 24 Feb 2022
Viewed by 826
Abstract
The prevalence of chronic wounds is increasing due to the population aging and associated pathologies, such as diabetes. These ulcers have an important socio-economic impact. Thus, it is necessary to design new products for their treatment with an adequate cost/effectiveness ratio. Among these [...] Read more.
The prevalence of chronic wounds is increasing due to the population aging and associated pathologies, such as diabetes. These ulcers have an important socio-economic impact. Thus, it is necessary to design new products for their treatment with an adequate cost/effectiveness ratio. Among these products are amorphous hydrogels. Their composition can be manipulated to provide a favorable environment for ulcer healing. The aim of this study was to evaluate a novel multifunctional amorphous hydrogel (EHO-85), containing Olea europaea leaf extract, designed to enhance the wound healing process. For this purpose, its moistening ability, antioxidant capacity, effect on pH in the wound bed of experimental rats, and the effect on wound healing in a murine model of impaired wound healing were assessed. EHO-85 proved to be a remarkable moisturizer and its application in a rat skin wound model showed a significant antioxidant effect, decreasing lipid peroxidation in the wound bed. EHO-85 also decreased the pH of the ulcer bed from day 1. In addition, in mice (BKS. Cg-m +/+ Leprdb) EHO-85 treatment showed superior wound healing rates compared to hydrocolloid dressing. In conclusion, EHO-85 can speed up the closure of hard-to-heal wounds due to its multifunctional properties that are able to modulate the wound microenvironment, mainly through its remarkable effect on reactive oxygen species, pH, and moistening regulation. Full article
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Article
Content Validity and Reliability of the Pressure Ulcer Knowledge Test and the Knowledge Level of Portuguese Nurses at Long-Term Care Units: A Cross-Sectional Survey
J. Clin. Med. 2022, 11(3), 583; https://doi.org/10.3390/jcm11030583 - 24 Jan 2022
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Abstract
(1) Background: Improvement in pressure ulcer care depends both on the dissemination of knowledge and its implementation. This study aims to translate the Pressure Ulcer Knowledge Test into Portuguese from Portugal and evaluate the internal consistency of the questionnaire. The second aim is [...] Read more.
(1) Background: Improvement in pressure ulcer care depends both on the dissemination of knowledge and its implementation. This study aims to translate the Pressure Ulcer Knowledge Test into Portuguese from Portugal and evaluate the internal consistency of the questionnaire. The second aim is to assess nurses’ pressure ulcer knowledge level. (2) Methods: The Pressure Ulcer Knowledge Test was translated into Portuguese, and the translated test’s internal consistency and content validity were assessed. Further, the authors conducted a cross-sectional survey using the test among 221 nurses working in long-term care units. (3) Results: The Cronbach’s alpha internal coefficient of reliability recorded for the 47 items was 0.738, which is higher than the minimum acceptable level of 0.7. The Cronbach’s alpha for the subscales was 0.709 for prevention/risk and less than 0.5 for staging and wound description. Only two of the 221 nurses achieved a score of 90% correct answers or more. The nurses scored lower in questions related to prevention/risk (Me = 67.4%, IQR = 60.6–75.8% vs. staging: ME = 85.7%, IQR = 71.4–85.7%, description: ME = 85.7%, IQR = 71.4–85.7%, p < 0.001). (4) Conclusion: The internal consistency of the instrument was acceptable. The instrument can accurately measure Portuguese nurses’ knowledge of pressure ulcers, and its information can help improve education and implementation of best practices. Full article
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Article
Hyaluronic Acid/Collagenase Ointment in the Treatment of Chronic Hard-to-Heal Wounds: An Observational and Retrospective Study
J. Clin. Med. 2022, 11(3), 537; https://doi.org/10.3390/jcm11030537 - 21 Jan 2022
Cited by 2 | Viewed by 770
Abstract
Background: Wound bed preparation is an important concept in clinical practice and is related to adequate debridement. The use of proteolytic enzymes is an established method of enzymatic wound debridement, especially in hard-to-heal ulcers that are unresponsive to normal healing procedures and progress. [...] Read more.
Background: Wound bed preparation is an important concept in clinical practice and is related to adequate debridement. The use of proteolytic enzymes is an established method of enzymatic wound debridement, especially in hard-to-heal ulcers that are unresponsive to normal healing procedures and progress. The TIME framework (tissue, inflammation/infection, moisture balance, and edge of wound) offers an appropriate strategy to eliminate resistance to healing, as well as maximizing the healing process. Maintenance debridement, as opposed to sporadic debridement, may be proposed in preserving an adequate wound bed towards complete recovery. Collagenase has been effective in debridement due to its ability to degrade collagen and elastin. In this clinical context, collagenase taken from Vibrio alginolitycus is the most favorably expressed enzymatic debriding agent. Methods: This retrospective observational study evaluates the efficacy of an ointment based on hyaluronic acid and collagenase (Bionect Start®), considering a reduced healing time and greater healing quality. We included 70 patients with chronic wounds of different etiologies, including diabetes mellitus (20), post-traumatic ulcers (35), chronic burns of degrees I and II (10), and pressure ulcers (5). We analyzed wound characteristics using the wound bed score (WBS) concept, healing time, as well as operator and patient satisfaction. Results: Frequency of debridement efficacy in terms of wound bed cleansing varied from 26% after 2 weeks to 93% after 4 weeks. We observed complete healing in 62 patients within an eight-week period. The overall operator and patient satisfaction after 8 weeks were 100% and 90%, respectively. Moreover, all patients reported less pain. Conclusions: A combined action of hyaluronic acid and collagenase ointment demonstrated a reduction in healing time while improving healing quality, with a decrease in pain. Full article
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Article
Infection Probability Index: Implementation of an Automated Chronic Wound Infection Marker
J. Clin. Med. 2022, 11(1), 169; https://doi.org/10.3390/jcm11010169 - 29 Dec 2021
Viewed by 463
Abstract
The number of people suffering from chronic wounds is increasing due to demographic changes and the global epidemics of obesity and diabetes. Innovative imaging techniques within the field of chronic wound diagnostics are required to improve wound care by predicting and detecting wound [...] Read more.
The number of people suffering from chronic wounds is increasing due to demographic changes and the global epidemics of obesity and diabetes. Innovative imaging techniques within the field of chronic wound diagnostics are required to improve wound care by predicting and detecting wound infections to accelerate the application of treatments. For this reason, the infection probability index (IPI) is introduced as a novel infection marker based on thermal wound imaging. To improve usability, the IPI was implemented to automate scoring. Visual and thermal image pairs of 60 wounds were acquired to test the implemented algorithms on clinical data. The proposed process consists of (1) determining various parameters of the IPI based on medical hypotheses, (2) acquiring data, (3) extracting camera distortions using camera calibration, and (4) preprocessing and (5) automating segmentation of the wound to calculate (6) the IPI. Wound segmentation is reviewed by user input, whereas the segmented area can be refined manually. Furthermore, in addition to proof of concept, IPIs’ correlation with C-reactive protein (CRP) levels as a clinical infection marker was evaluated. Based on average CRP levels, the patients were clustered into two groups, on the basis of the separation value of an averaged CRP level of 100. We calculated the IPIs of the 60 wound images based on automated wound segmentation. Average runtime was less than a minute. In the group with lower average CRP, a correlation between IPI and CRP was evident. Full article
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Article
Higher Periwound Temperature Associated with Wound Healing of Pressure Ulcers Detected by Infrared Thermography
J. Clin. Med. 2021, 10(13), 2883; https://doi.org/10.3390/jcm10132883 - 29 Jun 2021
Cited by 8 | Viewed by 1136
Abstract
Visual and empirical assessments do not enable the early detection of wound deterioration or necroses. No suitable objective indicator for predicting poor wound-healing is currently available. We used infrared thermography to determine the association between wound temperature and pressure-wound healing. We examined patients [...] Read more.
Visual and empirical assessments do not enable the early detection of wound deterioration or necroses. No suitable objective indicator for predicting poor wound-healing is currently available. We used infrared thermography to determine the association between wound temperature and pressure-wound healing. We examined patients with grades 2–4 pressure ulcers from a medical center in southern Taiwan and recorded the temperatures of the wound bed, periwound, and normal skin using infrared thermographic cameras. A total of 50 pressure ulcers and 248 infrared-thermography temperature records were analyzed. Normal skin temperature was not related to pressure ulcer wound healing. In a multivariate analysis, higher malnutrition universal-screening-tool scores were associated with poor wound-healing (p = 0.020), and higher periwound-temperature values were associated with better wound-healing (p = 0.028). In patients who had higher periwound-skin temperature than that of the wound bed, that result was also associated with better wound-healing (p = 0.002). Wound-bed and periwound temperatures differed significantly with the grade of the pressure ulcer, and a high periwound temperature was positively correlated with wound healing. Infrared thermography can objectively serve as indicators for assessing pressure-ulcer healing. Full article
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Article
Multicentre Study of Chronic Wounds Point Prevalence in Primary Health Care in the Southern Metropolitan Area of Barcelona
J. Clin. Med. 2021, 10(4), 797; https://doi.org/10.3390/jcm10040797 - 16 Feb 2021
Cited by 4 | Viewed by 1448
Abstract
Background: Chronic wounds give rise to major costs and resource consumption in health care systems, due to their protracted healing time. Incidence and prevalence data are scarce or nonexistent in community settings. Objective: The aim of the present epidemiological study was to analyse [...] Read more.
Background: Chronic wounds give rise to major costs and resource consumption in health care systems, due to their protracted healing time. Incidence and prevalence data are scarce or nonexistent in community settings. Objective: The aim of the present epidemiological study was to analyse and determine the prevalence of chronic wounds in the community in the south of the province of Barcelona (Spain). Design: A cross-sectional, multicentre secondary data analysis study was conducted in the community (excluding nursing homes) in Barcelona between 16 April and 13 June 2013. It included 52 primary care centres that serve a total population of 1,217,564 inhabitants. Results: The observed prevalence was 0.11%. Venous ulcers presented the highest prevalence, at 0.04%, followed by pressure injuries, at 0.03%. The >74 age group presented the highest frequency of chronic wounds, accounting for 69.4% of cases. Conclusion: The results obtained are consistent with those reported in previous similar studies conducted in Spain and elsewhere. As with most studies that adjusted their variables for age and sex, we found that the prevalence of ulcers increased with age and was higher in women, except in the case of diabetic foot ulcers and ischaemic ulcers, which were more frequent in men. Full article

Review

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Review
The Role of Antioxidants on Wound Healing: A Review of the Current Evidence
J. Clin. Med. 2021, 10(16), 3558; https://doi.org/10.3390/jcm10163558 - 13 Aug 2021
Cited by 36 | Viewed by 2070
Abstract
(1) Background: Reactive oxygen species (ROS) play a crucial role in the preparation of the normal wound healing response. Therefore, a correct balance between low or high levels of ROS is essential. Antioxidant dressings that regulate this balance are a target for new [...] Read more.
(1) Background: Reactive oxygen species (ROS) play a crucial role in the preparation of the normal wound healing response. Therefore, a correct balance between low or high levels of ROS is essential. Antioxidant dressings that regulate this balance are a target for new therapies. The purpose of this review is to identify the compounds with antioxidant properties that have been tested for wound healing and to summarize the available evidence on their effects. (2) Methods: A literature search was conducted and included any study that evaluated the effects or mechanisms of antioxidants in the healing process (in vitro, animal models or human studies). (3) Results: Seven compounds with antioxidant activity were identified (Curcumin, N-acetyl cysteine, Chitosan, Gallic Acid, Edaravone, Crocin, Safranal and Quercetin) and 46 studies reporting the effects on the healing process of these antioxidants compounds were included. (4) Conclusions: this review offers a map of the research on some of the antioxidant compounds with potential for use as wound therapies and basic research on redox balance and oxidative stress in the healing process. Curcumin, NAC, quercetin and chitosan are the antioxidant compounds that shown some initial evidence of efficacy, but more research in human is needed. Full article
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