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Chronic wounds, characterized by prolonged healing processes, pose a significant medical challenge with multifaceted aetiologies, including local and systemic factors. Here, it explores the complex pathogenesis of chronic wounds, emphasizing the disruption in the normal phases of wound healing, particularly the inflammatory phase, leading to an imbalance in extracellular matrix (ECM) dynamics and persistent inflammation. Senescent cell populations further contribute to impaired wound healing in chronic lesions. Traditional medical management focuses on addressing underlying causes, but many chronic wounds resist to conventional treatments, necessitating innovative approaches. Recent attention has turned to autologous orthobiologics, such as platelet-rich plasma (PRP), platelet-rich fibrin (PRF) and mesenchymal stem cells (MSCs), as potential regenerative interventions. These biologically derived materials, including bone marrow aspirate/concentrate (BMA/BMAC) and adipose tissue-derived stem cells (ADSCs), exhibit promising cytokine content and regenerative potential. MSCs, in particular, have emerged as key players in wound healing, influencing inflammation and promoting tissue regeneration. This paper reviews relevant scientific literature regarding basic science and brings real-world evidence regarding the use of orthobiologics in the treatment of chronic wounds, irrespective of aetiology. The discussion highlights the regenerative properties of PRP, PRF, BMA, BMAC and SVF, showcasing their potential to enhance wound healing. Despite advancements, further research is essential to elucidate the specific roles of each orthobiologic and determine optimal applications for different wound types. The conclusion underscores the evolving landscape in chronic wound management, with a call for more comprehensive studies to refine treatment strategies and maximize the benefits of regenerative medicine.
As the incidence of diabetic foot ulcers (DFU) increases, better treatments that improve healing should reduce complications of these ulcers including infections and amputations. We conducted a randomized controlled trial comparing outcomes between a novel purified reconstituted bilayer membrane (PRBM) to the standard of care (SOC) in the treatment of non-healing DFUs. This study included 105 patients who were randomized to either of two treatment groups (n = 54 PRBM; n = 51 SOC) in the intent to treat (ITT) group and 80 who completed the study per protocol (PP) (n = 47 PRBM; n = 33 SOC). The primary endpoint was the percentage of wounds closed after 12 weeks. Secondary outcomes included percent area reduction, time to healing, quality of life, and cost to closure. The DFUs that had been treated with PRBM healed at a higher rate than those treated with SOC (ITT: 83% vs. 45%, p = 0.00004, PP: 92% vs. 67%, p = 0.005). Wounds treated with PRBM also healed significantly faster than those treated with SOC with a mean of 42 versus 62 days for SOC (p = 0.00074) and achieved a mean wound area reduction within 12 weeks of 94% versus 51% for SOC (p = 0.0023). There were no adverse events or serious adverse events that were related to either the PRBM or the SOC. In comparison to the SOC, DFUs healed faster when treated with PRBM. Thus, the use of this PRBM is an effective option for the treatment of chronic DFUs.
This Phase 1b study was designed to evaluate the safety and efficacy of pravibismane, a novel broad-spectrum topical anti-infective, in managing moderate or severe chronic diabetic foot ulcer (DFU) infections. This randomized, double-blind, placebo-controlled, multicenter study consisted of 39 individuals undergoing pravibismane treatment and 13 individuals in the placebo group. Assessment of safety parameters included clinical observations of tolerability and pharmacokinetics from whole blood samples. Pravibismane was well-tolerated and exhibited minimal systemic absorption, as confirmed by blood concentrations that were below the lower limit of quantitation (0.5 ng/mL) or in the low nanomolar range, which is orders of magnitude below the threshold of pharmacological relevance for pravibismane. Pravibismane treated subjects showed approximately 3-fold decrease in ulcer size compared to the placebo group (85% vs. 30%, p = 0.27). Furthermore, the incidence of ulcer-related lower limb amputations was approximately 6-fold lower (2.6%) in the pooled pravibismane group versus 15.4% in the placebo group (p = 0.15). There were no treatment emergent or serious adverse events related to study drug. The initial findings indicate that topical pravibismane was safe and potentially effective treatment for improving recovery from infected chronic ulcers by reducing ulcer size and facilitating wound healing in infected DFUs (ClinicalTrials.gov Identifier NCT02723539).
Background and aims: Bacteria in wounds can lead to stagnation of wound healing as well as to local or even systemic wound infections up to potentially lethal sepsis. Consequently, the bacterial load should be reduced as part of wound treatment. Therefore, the efficacy of simple mechanical wound debridement should be investigated in terms of reducing bacterial colonisation. Patients and methods: Patients with acute or chronic wounds were assessed for bacterial colonisation with a fluorescence camera before and after mechanical wound debridement with sterile cotton pads. If bacterial colonisation persisted, a second, targeted wound debridement was performed. Results: A total of 151 patients, 68 (45.0%) men and 83 (55.0%) women were included in this study. The male mean age was 71.0 years and the female 65.1 years. By establishing a new analysis method for the image files, we could document that the bacterial colonised areas were distributed 21.9% on the wound surfaces, 60.5% on the wound edges (up to 0.5 cm) and 17.6% on the wound surroundings (up to 1.5 cm). One mechanical debridement achieved a significant reduction of bacterial colonised areas by an average of 29.6% in the wounds, 18.9% in the wound edges and 11.8% in the wound surroundings and was increased by performing it a second time. Conclusions: It has been shown that even a simple mechanical debridement with cotton pads can significantly reduce bacterial colonisation without relevant side effects. In particular, the wound edges were the areas that were often most contaminated with bacteria and should be included in the debridement with special attention. Since bacteria remain in wounds after mechanical debridement, it cannot replace antimicrobial therapy strategies, but offer a complementary strategy to improve wound care. Thus, it could be shown that simple mechanical debridement is effective in reducing bacterial load and should be integrated into a therapeutic approach to wounds whenever appropriate.
Preserved allogeneic donor skin still represents one of the gold standard therapies in temporary wound coverage in severely burned patients or chronic wounds. Allogeneic skin grafts are currently commercially available as cryo- or glycerol-preserved allografts through skin tissue banks all over the world. Most of the skin tissue banks rely on human cadaveric skin donations. Due to the chronic shortage of human allogeneic transplants, such as skin, and increasing costs in the procurement of allografts from other skin tissue banks, Hannover Medical School has been building up its own skin tissue bank based on allogeneic skin grafts from living donors who underwent surgical treatment (i.e., body-contouring procedures, such as abdominioplasties). This article presents procedures and protocols for the procurement and processing of allogeneic skin grafts according to national legislation and European regulations and guidelines. Beside protocols, initial microbiological data regarding the sterility of the harvested grafts are presented. The results currently form the basis for further investigations as well as clinical applications. In summary, a microbiological testing and acceptance procedure is presented that ensures adequate patient safety and skin viability.
Complex, chronic or hard-to-heal wounds are a prevalent health problem worldwide, with significant physical, psychological and social consequences. This study aims to identify factors associated with the healing process of these wounds and develop a mobile application for wound care that incorporates these factors. A prospective multicentre cohort study was conducted in nine health units in Portugal, involving data collection through a mobile application by nurses from April to October 2022. The study followed 46 patients with 57 wounds for up to 5 weeks, conducting six evaluations. Healing time was the main outcome measure, analysed using the Mann–Whitney test and three Cox regression models to calculate risk ratios. The study sample comprised various wound types, with pressure ulcers being the most common (61.4%), followed by venous leg ulcers (17.5%) and diabetic foot ulcers (8.8%). Factors that were found to impair the wound healing process included chronic kidney disease (U = 13.50; p = 0.046), obesity (U = 18.0; p = 0.021), non-adherence to treatment (U = 1.0; p = 0.029) and interference of the wound with daily routines (U = 11.0; p = 0.028). Risk factors for delayed healing over time were identified as bone involvement (RR 3.91; p < 0.001), presence of odour (RR 3.36; p = 0.007), presence of neuropathy (RR 2.49; p = 0.002), use of anti-inflammatory drugs (RR 2.45; p = 0.011), stalled wound (RR 2.26; p = 0.022), greater width (RR 2.03; p = 0.002), greater depth (RR 1.72; p = 0.036) and a high score on the healing scale (RR 1.21; p = 0.001). Integrating the identified risk factors for delayed healing into the assessment of patients and incorporating them into a mobile application can enhance decision-making in wound care.
This systematic review and meta-analysis aimed to evaluate the relationship between body mass index (BMI) and mortality of burn patients. A comprehensive, systematic search was conducted in different international electronic databases, such as Scopus, PubMed, Web of Science and Persian electronic databases such as Iranmedex, and Scientific Information Database (SID) using keywords extracted from Medical Subject Headings such as “Body mass index”, “Burns” and “Mortality” from the earliest to the April 1, 2023. The quality of the studies included in this systematic review was evaluated using the appraisal tool for cross-sectional studies (AXIS tool). Finally, six articles were included in this systematic review and meta-analysis. A total of 16 154 burn patients participated in six studies. Their mean age was 46.32 (SD = 1.99). Of the participants, 71.7% were males. The mean length of hospitalization was 18.80 (SD = 8.08) days, and the average TBSA in burn patients was 38.32 (SD = 2.79) %. Also, the average BMI in burn patients was 27.10 (SD = 1.75). Results found mortality in patients with abnormal BMI (overweight to morbidity BMI) was 0.19 more than normal BMI (ES: 1.19, 95%CI: 0.76–1.87, Z = 0.75, I 2: 71.8%, p = 0.45). Results of linear dose–response showed each 5 kg/m2 increase in BMI was associated with a 5% increase in mortality that was marginally significant (ES: 1.05, 95%CI: 1.00–1.11, Z = 1.99, I 2: 22.2%, p = 0.047). There was a non-linear relationship between levels of BMI and mortality (Prob > χ 2 = 0.02). There was an increase in mortality from percentile 10 to 50, although it was not significant (Correlational coefficient: 0.01, p = 0.85). Also, there was an increase in mortality rate from percentile 50 to 90 that was statistically significant (correlational coefficient: 0.06, p = 0.047). Finally, the results of the study indicated BMI can increase the chance of mortality by 0.19, although it was not significant. As a result, more studies are needed to better judge the relationship between BMI and mortality in burn victims.
To systematically search and synthesise available literature on barriers and enablers to evidence-based care for patients with laparotomy wounds reported by acute care nurses. Specifically, we focused on wound assessment, infection control techniques, wound products used, escalation of care, dressing application, documentation and holistic care. The Preferred Reporting Items for Systematic review and Meta-Analyses extension for Scoping Reviews Checklist and explanation documents directed the review. The methodology framework created by Arksey and O'Malley, updated by Levac et al., and the Joanna Briggs Institute were utilised to assist the scoping review process. Data synthesis was guided by the Theoretical Domains Framework. Six qualitative and mixed methods studies were selected for the review. Most reported barriers and enablers were mapped to knowledge, skills, beliefs about consequences, environmental context and resources and beliefs about capability domains. The main barriers were limited access to and utilisation of wound assessment tools and clinical practice guidelines for wound management and suboptimal time management skills. Inconsistent management of laparotomy wounds was related to ward culture and nurses' lack of knowledge and skills in surgical wound assessment and aseptic technique during wound encounters. The reported enablers were knowledge of multi-factorial risk factors for surgical wound recovery, valuing education and reflective practice and believing that protocols should be utilised alongside comprehensive wound assessments. Holistic wound care included patient education on the role of mobilisation and nutrition in wound healing. Acute care nurses do not routinely incorporate comprehensive, evidence-based care recommendations for laparotomy wound management. Further research on evidence-based care behaviours in managing laparotomy wounds is required. The results indicate a need for standardising the practice of laparotomy wound management while acknowledging the current challenges faced in the ward environment.
A limited understanding of the pathology underlying chronic wounds has hindered the development of effective diagnostic markers and pharmaceutical interventions. This study aimed to elucidate the molecular composition of various common chronic ulcer types to facilitate drug discovery strategies. We conducted a comprehensive analysis of leg ulcers (LUs), encompassing venous and arterial ulcers, foot ulcers (FUs), pressure ulcers (PUs), and compared them with surgical wound healing complications (WHCs). To explore the pathophysiological mechanisms and identify similarities or differences within wounds, we dissected wounds into distinct subregions, including the wound bed, border, and peri-wound areas, and compared them against intact skin. By correlating histopathology, RNA sequencing (RNA-Seq), and immunohistochemistry (IHC), we identified unique genes, pathways, and cell type abundance patterns in each wound type and subregion. These correlations aim to aid clinicians in selecting targeted treatment options and informing the design of future preclinical and clinical studies in wound healing. Notably, specific genes, such as PITX1 and UPP1, exhibited exclusive upregulation in LUs and FUs, potentially offering significant benefits to specialists in limb preservation and clinical treatment decisions. In contrast, comparisons between different wound subregions, regardless of wound type, revealed distinct expression profiles. The pleiotropic chemokine-like ligand GPR15L (C10orf99) and transmembrane serine proteases TMPRSS11A/D were significantly upregulated in wound border subregions. Interestingly, WHCs exhibited a nearly identical transcriptome to PUs, indicating clinical relevance. Histological examination revealed blood vessel occlusions with impaired angiogenesis in chronic wounds, alongside elevated expression of genes and immunoreactive markers related to blood vessel and lymphatic epithelial cells in wound bed subregions. Additionally, inflammatory and epithelial markers indicated heightened inflammatory responses in wound bed and border subregions and reduced wound bed epithelialization. In summary, chronic wounds from diverse anatomical sites share common aspects of wound pathophysiology but also exhibit distinct molecular differences. These unique molecular characteristics present promising opportunities for drug discovery and treatment, particularly for patients suffering from chronic wounds. The identified diagnostic markers hold the potential to enhance preclinical and clinical trials in the field of wound healing.
Chronic wounds contribute to significant healthcare and economic burden worldwide. Wound assessment remains challenging given its complex and dynamic nature. The use of artificial intelligence (AI) and machine learning methods in wound analysis is promising. Explainable modelling can help its integration and acceptance in healthcare systems. We aim to develop an explainable AI model for analysing vascular wound images among an Asian population. Two thousand nine hundred and fifty-seven wound images from a vascular wound image registry from a tertiary institution in Singapore were utilized. The dataset was split into training, validation and test sets. Wound images were classified into four types (neuroischaemic ulcer [NIU], surgical site infections [SSI], venous leg ulcers [VLU], pressure ulcer [PU]), measured with automatic estimation of width, length and depth and segmented into 18 wound and peri-wound features. Data pre-processing was performed using oversampling and augmentation techniques. Convolutional and deep learning models were utilized for model development. The model was evaluated with accuracy, F1 score and receiver operating characteristic (ROC) curves. Explainability methods were used to interpret AI decision reasoning. A web browser application was developed to demonstrate results of the wound AI model with explainability. After development, the model was tested on additional 15 476 unlabelled images to evaluate effectiveness. After the development on the training and validation dataset, the model performance on unseen labelled images in the test set achieved an AUROC of 0.99 for wound classification with mean accuracy of 95.9%. For wound measurements, the model achieved AUROC of 0.97 with mean accuracy of 85.0% for depth classification, and AUROC of 0.92 with mean accuracy of 87.1% for width and length determination. For wound segmentation, an AUROC of 0.95 and mean accuracy of 87.8% was achieved. Testing on unlabelled images, the model confidence score for wound classification was 82.8% with an explainability score of 60.6%. Confidence score was 87.6% for depth classification with 68.0% explainability score, while width and length measurement obtained 93.0% accuracy score with 76.6% explainability. Confidence score for wound segmentation was 83.9%, while explainability was 72.1%. Using explainable AI models, we have developed an algorithm and application for analysis of vascular wound images from an Asian population with accuracy and explainability. With further development, it can be utilized as a clinical decision support system and integrated into existing healthcare electronic systems.
The Wound-QoL assesses the impact of chronic wounds on patients' health-related quality of life (HRQoL). A 17-item and a shortened 14-item version are available. The Wound-QoL-17 has been validated for multiple languages. For the Wound-QoL-14, psychometric properties beyond internal consistency were lacking. We aimed to validate both Wound-QoL versions for international samples representing a broad range of European countries, including countries for which validation data had yet been pending. Patients with chronic wounds of any aetiology or location were recruited in Austria, Lithuania, the Netherlands, Poland, Slovakia, Spain, Switzerland and Ukraine. Psychometric properties were determined for both Wound-QoL versions for the overall sample and, if feasible, country-wise. We included 305 patients (age 68.5 years; 52.8% males). Internal consistency was high in both Wound-QoL-17 (Cronbach's α: 0.820–0.933) and Wound-QoL-14 (0.779–0.925). Test–retest reliability was moderate to good (intraclass correlation coefficient: 0.618–0.808). For Wound-QoL-17 and Wound-QoL-14, convergent validity analyses showed highest correlations with global HRQoL rating (r = 0.765; r = 0.751) and DLQI total score (r = 0.684; r = 0.681). Regarding clinical data, correlations were largest with odour (r = −0.371; r = −0.388) and wound size (r = 0.381; r = 0.383). Country-wise results were similar. Both Wound-QoL versions are valid to assess HRQoL of patients with chronic wounds. Due to its psychometric properties and brevity, the Wound-QoL-14 might be preferrable in clinical practice where time is rare. The availability of various language versions allows for the use of this questionnaire in international studies and in clinical practice when foreign language patients are being treated.
A novel autologous heterogeneous skin construct (AHSC) was previously shown to be effective versus standard of care (SOC) treatment in facilitating complete wound healing of Wagner 1 diabetic foot ulcers in an interim analysis of 50 patients previously published. We now report the final analysis of 100 patients (50 per group), which further supports the interim analysis findings. Forty-five subjects in the AHSC treatment group received only one application of the autologous heterogeneous skin construct, and five received two applications. For the primary endpoint at 12 weeks, there were significantly more diabetic wounds closed in the AHSC treatment group (35/50, 70%) than in the SOC control group (17/50, 34%) (p = 0.00032). A significant difference in percentage area reduction between groups was also demonstrated over 8 weeks (p = 0.009). Forty-nine subjects experienced 148 adverse events: 66 occurred in 21 subjects (42%) in the AHSC treatment group versus 82 in 28 SOC control group subjects (56.0%). Eight subjects were withdrawn due to serious adverse events. Autologous heterogeneous skin construct was shown to be an effective adjunctive therapy for healing Wagner 1 diabetic foot ulcers.
Pyoderma gangrenosum (PG) is a non-infectious, neutrophilic dermatosis that was difficult to diagnose in clinical practice. Today, the PARACELSUS score is a validated tool for diagnostics. Based on this score, patients with clearly diagnosed PG were examined with regard to predilection sites. In this retrospective study, the data of patients from the University Hospitals of Essen and Erlangen were analysed in whom the diagnosis of PG could be clearly confirmed using the PARACELSUS score. A total of 170 patients, 49 men (29%) and 121 women (71%) with an average age at first manifestation of 55.5 years, could be included in the analysis. The predilection sites were identified as the lower legs in 80.6% of the patients and the extensor sides in 75.2%. Other localisations of PG were the thighs in 14.1%, mammae and abdomen in 10.0% each, back and gluteal in 7.1% each, feet in 5.9%, arms in 4.7%, genital in 3.5% and head in 2.9%. This retrospective study is the first to identify a collective of PG patients with the highest data quality using the PARACELSUS score. It could be shown that PG can basically occur on the entire integument. However, the predilection sites of PG, which have now been reliably identified for the first time, are the lower legs and in particular the extensor sides.
Chronic wounds can severely limit patient's social life. This cross-sectional study investigated quantitatively social support of patients with chronic wounds, its association with health-related quality of life as well as qualitatively changes in social participation of these patients. Overall, 263 patients from seven countries participated. The most frequent wound class was leg ulcer (49.2%). Results revealed generally high levels of social support (mean global score: 5.5) as measured with the Multidimensional Scale of Perceived Social Support. However, individuals differed considerably (range 1.0–7.0). All dimensions of social support differed by patients' family and living situations (p < 0.001 to p = 0.040) and were positively correlated with generic health-related quality of life (r = 0.136–0.172). Having children, living with others and being in a relationship were significant predictors of having higher global social support. Patients reported great support from family members. Many participants reported no changes in relationships with friends. Wound care managers took an important role and provided additional emotional support. Patients reported a range of discontinued activities. Despite the high overall level of social support, inter-individual differences should be acknowledged. The importance of family carers should be acknowledged to be able to reduce caregiver burden and to ensure high-qualitative wound care.
Venous ulcers affect up to 3% of the global population, with a high impact on economies and quality of life. This is exacerbated by its recurrence rates, which reach 70% at 12 months after healing. The perpetuation of these cycles of healing and recurrence is not interrupted or even attenuated by the self-care activities recommended and directed toward their prevention. In this context, we sought to identify the effectiveness of interventions that promote adherence to self-care to prevent venous ulcer recurrence. In August 2022, we conducted a literature search via EBSCO in the following databases: CINAHL Complete, MEDLINE Complete, Cochrane Database of Systematic Reviews, Scopus, and Web of Science. The inclusion criteria were researched in the form of randomised controlled trials or systematic literature reviews, and 99 studies were identified. During the different times of selection, four studies met the defined inclusion criteria and were included. As the main conclusions, the emphasis goes to the importance of the use of compression and the greater effectiveness of higher compression classes for the prevention of recurrence. Different educational methodologies seem to be important to increase knowledge about prevention, specifically regarding the aetiology of recurrence and the implementation of prevention measures.
Wound care is a complex procedure and the related research may include many variables. Deficiencies in the sample inclusion and exclusion criteria may limit the generalizability of randomized controlled trials (RCTs) for wound patients in the real world. This study aimed to evaluate deficiencies in reporting the inclusion and exclusion criteria and the characteristics of patients in RCTs of pressure injuries (PI) therapeutic interventions. We conducted a systematic methodological review in which 40 full text RCTs of PI treatment interventions published in English, from 2008 to 2020, were identified. Data on the general characteristics of the included RCTs and data about inclusion/exclusion criteria and characteristics of patients were collected. The inclusion/exclusion criteria were categorized into five domains (definition of disease, precision, safety, ethical/legal and administrative). Study duration (in weeks) was 8.0 (quartile 1: 2.0; quartile 3: 48.0); only 5.0% of the trials mentioned race, skin colour or ethnicity, and 37.5% reported the duration of the wound. Only 9 (22.5%) studies reported the drugs that the included patients were using and 10 (25.0%) RCTs reported adverse events. The presence of the five domains was observed only in 12.5% of RCTs and only 12 (30.0%) had the precision domain. Much more research is required in systematic assessments of the external validity of trials because there is substantial disparity between the information that is provided by RCTs and the information that is required by clinicians. We concluded that there are deficiencies in reporting of data related to inclusion/exclusion criteria and characteristics of patients of RCTs assessing PI therapeutic interventions.
The meta-analysis aimed to assess the efficiency of platelet-rich plasma (PRP) in the management of burn wounds (BWs). Using dichotomous or contentious random- or fixed-effects models, the outcomes of this meta-analysis were examined and the odds ratio (OR) and the mean difference (MD) with 95% confidence intervals (CIs) were computed. Thirteen examinations from 2009 to 2023 were enrolled for the present meta-analysis, including 808 individuals with BWs. PRP had significantly shorter healing time (MD, −5.80; 95% CI, −7.73 to −3.88, p < 0.001), higher healing rate (OR, 3.14; 95% CI, 2.05–4.80, p < 0.001), higher healed area percent (MD, 12.67; 95% CI, 9.79–15.55, p < 0.001) and higher graft take area percent (MD, 4.39; 95% CI, 1.51–7.26, p = 0.003) compared with standard therapy in patients with BW. However, no significant difference was found between PRP and standard therapy in graft take ratio (OR, 1.70; 95% CI, 0.86–3.34, p = 0.13) and infection rate (OR, 0.55; 95% CI, 0.20–1.47, p = 0.23) in patients with BW. The examined data revealed that PRP had a significantly shorter healing time, a higher healing rate, a higher healed area percent and a higher graft take area percent; however, no significant difference was found in graft take ratio or infection rate compared with standard therapy in patients with BW. Yet, attention should be paid to its values since all of the selected examinations had a low sample size and some comparisons had a low number of selected studies.
FreshRSS 