Blue light photobiomodulation for reactivation of healing in wounds not responding to standard therapy.

OBJECTIVE: Blue light (410-430nm) has been suggested to be effective in the healing process of hard-to-heal wounds. The aim of this study was to test this hypothesis. METHOD: This single-centre observational study assessed the efficacy of photobiomodulation with blue light (120 seconds at a distance of 4cm from the wound bed once a week for four weeks) in activating healing in patients with hard-to-heal skin lesions (mean duration 23.9 months) of the lower limb that had not responded to four weeks of standard treatment. RESULTS: A total of 59 patients were assessed. Wounds were divided into groups according to aetiology: hard-to-heal venous wound (30.5%); hard-to-heal arterial and mixed wounds (16.9%); hard-to-heal inflammatory wound (22.0%); other hard-to-heal wounds (13.6%); and acute wound (16.9%). The mean reduction in wound area at the end of the four-week treatment period with blue light compared with baseline was 51.38% (p<0.001) across all wounds. Among subgroups, the best performance was obtained for hard-to-heal venous wounds, achieving a 63.36% (p<0.001) mean reduction in wound size, and acute wounds, achieving a mean reduction of 82.76% (p<0.001). The greatest mean change in wound bed score was seen at the end of the four-week treatment period with blue light, with an increase in the mean score from 8.6 at baseline to 12.8 at week four (77.2%; p<0.001). There was a clear decrease in pain during blue light treatment, achieving a reduction in the average numeric rating scale (NRS) from 4.3 at baseline to 1.8 at week 4 (53.23%; p <0.001). At week 4, the highest proportion of complete healing was seen in acute (100.0%) and venous wounds (83.3%). CONCLUSION: Based on these results, photobiomodulation with blue light appears to reactivate the healing process in acute and hard-to-heal wounds that do not respond to standard treatment. Photobiomodulation with blue light treatment is easy to perform and safe, with no reported adverse events or side-effects.

Best practice for wound repair and regeneration use of cellular, acellular and matrix-like products (CAMPs).

There are currently over 80 biomaterials derived from autologous, allogeneic, synthetic and xenogeneic sources, or a combination of any or all these types of materials, available for soft-tissue coverage to effect wound closure. Often generically referred to as cellular and/or tissue-based products (CTPs), they are manufactured under various trade names and marketed for a variety of indications.

What COVID-19 taught us: New opportunities and pathways from telemedicine and novel antiseptics in wound healing.

The COVID-19 pandemic deeply impacted the capacity of the health systems to maintain preventive and curative services, especially for the most vulnerable populations. During the pandemic, the wound healing centres in Italy assisted a significant reduction of the frequency of their hospital admission, since only urgencies, such as severe infections or wound haemorrhagic complications, were allowed to the hospital. The aim of this multidisciplinary work is to highlight the importance of a new pathway of wound care with patient-based therapeutic approach, tailored treatments based on the characteristics of the wound and fast tracks focused on the outpatient management, reserving hospital assessment only for patients with complicated or complex wounds. This analysis highlights the point that patients with chronic wounds need to be critically evaluated in order to find the best and most appropriate care pathway, which should vary according to the patient and, especially, to the characteristics of the wound. Moreover, the most adequate topic antiseptic should be started as soon as possible. An appropriate and correct management of the wound care will allow to link the knowledge based on years of clinical practice with the new challenges and the need to visit patients remotely, when possible.

Effectiveness of Blue light photobiomodulation therapy in the treatment of chronic wounds. Results of the Blue Light for Ulcer Reduction (B.L.U.R.) Study.

BACKGROUND: Lower limb ulcers not responding to standard treatments after 8 weeks are defined as chronic wounds, and they are a significant medical problem. Blue light (410-430 nm) proved to be effective in treating wounds, but there is a lack of data on chronic wounds in clinical practice. The aim of the study was to determine if blue light photobiomodulation with EmoLED (Emoled Srl, Sesto Fiorentino, Florence, Italy) medical device in addition to standard of care is more effective compared to standard of care alone in promoting re-epithelialization of chronic wounds of lower limbs in 10 weeks. METHODS: Ninety patients affected by multiple or large area ulcers were enrolled. To minimize all variabilities, each patient has been used as control of himself. Primary endpoint was the comparison of the re-epithelialization rate expressed as a percentage of the difference between the initial and final area. Secondary endpoints were: treatment safety, pain reduction, wound area reduction trend over time, healing rate. RESULTS: At week 10, the wounds treated with EmoLED in addition to standard care showed a smaller residual wound area compared to the wounds treated with standard of care alone: 42.1% vs. 63.4% (P=0.029). The difference is particularly evident in venous leg ulcers, 33.3% vs. 60.1% (P=0.007). 17 treated wounds and 12 controls showed complete healing at week 10. Patients showed a significant reduction in pain (P=2×10-7). CONCLUSIONS: Blue light treatment in addition to standard of care accelerates consistently the re-epithelialization rate of chronic wounds, especially venous leg ulcers and increases the chances of total wound healing in 10 weeks.

Wound bed preparation with hypochlorous acid oxidising solution and standard of care: a prospective case series.

OBJECTIVE: This prospective case series aims to evaluate the clinical impact of a hypochlorous acid oxidising solution (AOS) in association with usual standard of care (SoC) on wound bed preparation (WBP) in patients with hard-to-heal ulcers of various aetiologies. The AOS (Nexodyn, APR Applied Pharma Research S.A., Switzerland) comprises three main features: highly pure and stabilised hypochlorous acid, acidic pH and high reduction-oxidation potential. METHOD: Between February 2015 and February 2017, patients who met the inclusion criteria were treated with AOS and usual SoC. Data collection ran for 70 days: T0-T70. A baseline assessment was undertaken at T0; parameters assessed at fortnightly visits included: WBP score, area and depth of ulcer, duration, pain, Bates-Jensen score and infection status. RESULTS: A total of 60 patients took part in the study. By T70, 68.3% of wounds had healed or improved and a significant wound size reduction of 21% was observed (p<0.001), despite a mean wound duration of 20.6 months. All wounds were free of local infection and cellulitis; 10% were colonised. WBP scores improved, while Bates-Jensen and pain scores fell significantly over time. CONCLUSION: This evaluation suggests that AOS might represent a valuable therapeutic addition for an optimal WBP in the routine management of hard-to-heal ulcers of different aetiologies. DECLARATION OF INTEREST: ER worked as a consultant for APR Applied Pharma Research S.A. The authors have no other conflicts of interest.

Hard-to-heal ulcers treated with hypochlorous acid oxidising solution and standard of care: a 32-week follow-up.

OBJECTIVE: Immediately following a two-year prospective case series in which the wounds of 60 patients with hard-to-heal ulcers were treated with a hypochlorous acid oxidising solution (AOS) in addition to standard of care (SoC) for 70 days (T0-T70), a subset of 31 patients (51.7%) whose wounds had not fully healed by T70 opted to continue with treatment for a further 22 weeks (days T70-T224, a total treatment time of 32 weeks (224 days). The objective was to provide long-term evidence on the clinical performance and safety of AOS when used in association with the usual SoC in patients with stalled, hard-to-heal ulcers of various aetiologies. METHOD: As per the main study, wounds were formally assessed by the study lead at 28 days (±14 days, depending on patient attendance). Parameters assessed at fortnightly visits included area, depth and duration of ulcer; pain; wound bed preparation (WBP) score; and infection status. Wounds were managed in accordance with the SoC protocol. RESULTS: By T224, 35.5% (n=11) of wounds healed completely and 83.9% showed some types of improvement. All wounds were free of infection and colonisation, the WBP score improved (100% A1-A2 at T196), and pain scores fell. Use of AOS in combination with several types of dressing (SoC) for such a long period confirmed a good safety profile. CONCLUSION: This follow-up evaluation, coupled with the primary study, suggests that AOS might represent a valuable therapeutic addition for the management of hard-to-heal ulcers for long periods of treatment. DECLARATION OF INTEREST: ER worked as a consultant for APR Applied Pharma Research S.A. The authors have no other conflicts of interest.

AI technology for remote clinical assessment and monitoring.

OBJECTIVE: To report the clinical validation of an innovative, artificial intelligence (AI)-powered, portable and non-invasive medical device called Wound Viewer. The AI medical device uses dedicated sensors and AI algorithms to remotely collect objective and precise clinical data, including three-dimensional (3D) wound measurements, tissue composition and wound classification through the internationally recognised Wound Bed Preparation (WBP) protocol; this data can then be shared through a secure General Data Protection Regulation (GDPR)- and Health Insurance Portability and Accountability Act (HIPAA)-compliant data transfer system. This trial aims to test the reliability and precision of the AI medical device and its ability to aid health professionals in clinically evaluating wounds as efficiently remotely as at the bedside. METHOD: This non-randomised comparative clinical trial was conducted in the Clinica San Luca (Turin, Italy). Patients were divided into three groups: (i) patients with venous and arterial ulcers in the lower limbs; (ii) patients with diabetes and presenting with diabetic foot syndrome; and (iii) patients with pressure ulcers. Each wound was evaluated for area, depth, volume and WBP wound classification. Each patient was examined once and the results, analysed by the AI medical device, were compared against data obtained following visual evaluation by the physician and research team. The area and depth were compared with a Kruskal-Wallis one-way analysis of variations in the obtained distribution (expected p-value>0.1 for both tests). The WBP classification and tissue segmentation were analysed by directly comparing the classification obtained by the AI medical device against that of the testing physician. RESULTS: A total of 150 patients took part in the trial. The results demonstrated that the AI medical device's AI algorithm could acquire objective clinical parameters in a completely automated manner. The AI medical device reached 97% accuracy against the WBP classification and tissue segmentation analysis compared with that performed in person by the physician. Moreover, data regarding the measurements of the wounds, as analysed through the Kruskal-Wallis technique, showed that the data distribution proved comparable with the other methods of measurement previously clinically validated in the literature (p=0.9). CONCLUSION: These findings indicate that remote wound assessment undertaken by physicians is as effective through the AI medical device as bedside examination, and that the device was able to assess wounds and provide a precise WBP wound classification. Furthermore, there was no need for manual data entry, thereby reducing the risk of human error while preserving high-quality clinical diagnostic data.

Cleansing versus tailored deep debridement, a fresh approach to wound cleansing: an Italian experience.

OBJECTIVE: To evaluate if cleansing, using a solution containing the antimicrobial polyhexanide and the surfactant betaine (polyhexanide propylbetaine [PP], Prontosan Solution, B. Braun), can aid effective wound bed preparation (WBP). METHOD: A solution containing the PP was used in two different treatment regimens. Group A was treated with a single application at different time durations (2, 5, 10 and 15 minutes) to evaluate efficacy in the removal of residues from the wound bed. Group B was treated with PP for 10 minutes, followed by application of an inert dressing, at daily dressing changes for 14 days, to evaluate efficacy of debridement. RESULTS: A total number of 70 patients took part in the study. In Group A (n=40), after the two and five minute application, no change was observed. At 10 minutes, an improvement was seen in 4/10 cases and at 15 minutes the improvement was in 5/10 patients. In Group B (n=30), over the 14 days, an improvement in the condition of the tissue, i.e. the wound bed was cleaned and debrided in 73% of cases, was observed. Patients experienced a reduction in pain and no adverse effect or complication was reported. Periwound skin was improved in 29/30 cases, with only one case where the tissue deteriorated, as determined by the presence of maceration. CONCLUSION: PP is effective in helping debridement during wound cleansing. Efficacy depends on time of application. However, randomisation and further study is required to confirm these results.

A large Italian observational multicentre study on vascular ulcers of the lower limbs (Studio Ulcere Vascolari).

An observational study of 2 years was promoted by the Italian Association for Cutaneous Ulcers (AIUC) in order to monitor the epidemiology of leg ulcers, the trend of healing and the more frequent therapeutic approaches in lower limb ulcers. Fifty-nine sites in 14 different Italian regions involved in the study, with 1333 enrolled patients (1163 patients fully evaluated and followed up for 9 months). A prevalence of females (62%) was observed with a mean age of 70 years and a high rate of hypertension (62%), diabetes (38%) and obesity (29%). Venous ulcer was most frequent (55%), followed by mixed (25%) and diabetic (8·3%) ulcers. Basically, all patients received a local therapy (LT) (compression and advanced local therapies), while 63% of patients have an associated systemic pharmaceutical treatment. Ulcer healing rates progressively increased throughout the study and despite the type of observational study does not allow conclusions on the treatment, it was observed that the patients receiving additional systemic drugs were associated with a more rapid acceleration of healing rates of ulcers compared to LT alone (3 months: 39·7% versus 29·2%; 6 months: 62·0% versus 47·0%; 9 months: 74·7% versus 63·8%). In particular, the Studio Ulcere Vascolari (SUV) study showed that a combination treatment with sulodexide and compression therapy allows for a greater increase in the healing rates in venous ulcers.

A novel composition for in vitro and in vivo regeneration of skin and connective tissues.

The particular combination of polydeoxyribonucleotides, l-carnitine, calcium ions, proteolytic enzyme and other ingredients acts in a synergetic way in the regeneration of skin and connective tissues. This new formulation of active principles was tested in vitro as a cell and tissue culture medium and in vivo for various preparations in support of tissue regeneration. In vitro, the new blend allowed the maintenance of skin biopsies for more than 1 year in eutrophic conditions. Immunocytochemical analyses of fibroblasts isolated from these biopsies confirmed a significant increase of the epidermal and connective wound-healing markers such as collagen type I, collagen type IV, cytokeratin 1 (CK1), CK5, CK10 and CK14 versus controls. To examine the effects of the new compound in vivo, we studied impaired wound healing in genetically diabetic db/db mice. At day 18, diabetic mice treated with the new composition showed 100% closure of wounds and faster healing than mice treated with the other solutions. This complex of vital continuity factors or life-keeping factors could be used as a tissue-preserving solution or a cosmetic/drug/medical device to accelerate wound healing in the treatment of patients with deficient wound repair to promote the regeneration of cutaneous and connective tissues (injuries-wound, dermatitis) and prevent the recurrent relapses.

Microcrystalline cellulose membrane for re-epithelisation of chronic leg wounds: a prospective open study.

Treatment of chronic leg ulcers remains a major health care issue. Although many reports have examined different topical dressings, none have specifically looked at microcrystalline cellulose (MCC). We aimed to evaluate in a prospective, open study the safety and performance of a MCC membrane (Veloderm) in a series of chronic leg wounds of different aetiology. Fifty-five patients participated in this study. The membrane was applied every 5-10 days for 1 month, immediately after surgical debridement. The wound bed was assessed on days 7, 15 and 30 for erythema, pain, exudate level and infection. The wound size change at 30 days was the primary efficacy parameter and any adverse events were collected and analysed. A wound size change of 55% was achieved at the end of follow-up, with an improvement in all the collected parameters, but the erythema, which showed a mild increase. To date, this is the largest experience with a MCC product in chronic wounds. Our study suggests that this treatment may be safe and useful and deserves further investigation.