Does exercise improve healing of diabetic foot ulcers? A systematic review

Abstract

Background: For patients with diabetic foot ulcers, offloading is one crucial aspect of treatment and aims to redistribute pressure away from the ulcer site. In addition to offloading strategies, patients are often advised to reduce their activity levels. Consequently, patients may avoid exercise altogether. However, it has been suggested that exercise induces an increase in vasodilation and tissue blood flow, which may potentially facilitate ulcer healing. The aim of this systematic review was to determine whether exercise improves healing of diabetic foot ulcers.

Review: We conducted a systematic search of MEDLINE, CINAHL and EMBASE between July 6, 2009 and July 6, 2019 using the key terms and subject headings diabetes, diabetic foot, physical activity, exercise, resistance training and wound healing. Randomised controlled trials were included in this review.

Three randomised controlled trials (139 participants) were included in this systematic review. All studies incorporated a form of non-weight bearing exercise as the intervention over a 12-week period. One study conducted the intervention in a supervised setting, while two studies conducted the intervention in an unsupervised setting. Two studies found greater improvement in percentage wound size reduction in the intervention group compared with the control group, with one of these studies achieving statistically significant findings (p < 0.05). The results of the third study demonstrated statistically significant findings for total wound size reduction (p < 0.05), however results were analysed within each treatment group and not between groups.

Conclusion: This systematic review found there is insufficient evidence to conclusively support non-weight bearing exercise as an intervention to improve healing of diabetic foot ulcers. Regardless, the results demonstrate some degree of wound size reduction and there were no negative consequences of the intervention for the participants. Given the potential benefits of exercise on patient health and wellbeing, non-weight bearing exercise should be encouraged as part of the management plan for treatment of diabetic foot ulcers. Further research is required to better understand the relationship between exercise and healing of diabetic foot ulcers.

Keywords: Diabetic foot ulcer, Exercise, Physical therapy, Wound healing.

International comparison of pressure ulcer measures in long-term care facilities: Assessing the methodological robustness of 4 approaches to point prevalence measurement

Introduction: Pressure ulcer indicators are among the most frequently used performance measures in long-term care settings. However, measurement systems vary and there is limited knowledge about the international comparability of different measurement systems. The aim of this analysis was to identify possible avenues for international comparisons of data on pressure ulcer prevalence among residents of long-term care facilities. Material and methods: A descriptive analysis of the four point prevalence measurement systems programs used in 28 countries on three continents was performed. The criteria for the description and analysis were based on the scientific literature on criteria for indicator selection, on issues in international comparisons of data and on specific challenges of pressure ulcer measurements.

Results: The four measurement systems use a prevalence measure based on very similar numerator and denominator definitions. All four measurement systems also collect data on patient mobility. They differ in the pressure ulcer classifications used and the requirements for a head-to-toe resident examination. The regional or country representativeness of long-term care facilities also varies among the four measurement systems.

Conclusions: Methodological differences among the point prevalence measurement systems are an important barrier to reliable comparisons of pressure ulcer prevalence data. The alignment of the methodologies may be improved by implementing changes to the study protocols, such as aligning the classification of pressure ulcers and requirements for a head-to-toe resident skin assessment. The effort required for each change varies. All these elements need to be considered by any initiative to facilitate international comparison and learning.

The potential of a canister-based single-use negativepressure wound therapy system delivering a greater and continuous absolute pressure level to facilitate better surgical wound care

Abstract

       Two types of single-use negative-pressure wound therapy systems are currently available to treat surgical wounds: Canister-based and canisterless. This work was aimed to evaluate the performance of a canister-based vs a canisterless system, each with a different negative-pressure setting and technology for fluid management. Continuous delivery of a specified level of negative pressure to the wound bed is hypothesised to be important for promoting surgical wound healing, by achieving continuous reduction of lateral tension in the wound, particularly through decrease of skin stress concentrations around suture insertion sites. To test the above hypothesis, we developed a computational modelling framework, a laboratory bench-test for simulated clinical use and had further conducted a pre-clinical study in a porcine model for closed incision. We specifically focussed on the impact of effective fluid management for continuous delivery of a stable, consistent negative pressure and the consequences of potential losses of the pressure level over the therapy period. We found that a greater (absolute) negative-pressure level and its continuous, consistent delivery through controlled fluid management technology, by removing excess fluid from the dressing, provides far superior biomechanical performances. These conditions are more likely to result in better quality of the repaired tissues.

KEYWORDS

       animal study, bioengineering laboratory research, closed incision, finite element modelling, lateral tension sutures

Single cell transcriptomic landscape of diabetic foot ulcers

Diabetic foot ulceration (DFU) is a devastating complication of diabetes whose pathogenesis remains incompletely understood. Here, we profifile 174,962 single cells from the foot, forearm, and peripheral blood mononuclear cells using single-cell RNA sequencing. Our analysis shows enrichment of a unique population of fifibroblasts overexpressing MMP1, MMP3, MMP11, HIF1A, CHI3L1, and TNFAIP6 and increased M1 macrophage polarization in the DFU patients with healing wounds. Further, analysis of spatially separated samples from the same patient and spatial transcriptomics reveal preferential localization of these healing associated fifibroblasts toward the wound bed as compared to the wound edge or unwounded skin. Spatial transcriptomics also validates our fifindings of higher abundance of M1 macrophages in healers and M2 macrophages in non-healers. Our analysis provides deep insights into the wound healing microenvironment, identifying cell types that could be critical in promoting DFU healing, and may inform novel therapeutic approaches for DFU treatment.

Hyaluronic Acid/Collagenase Ointment in the Treatment of Chronic Hard-to-Heal Wounds: An Observational and Retrospective Study

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. The TIME framework (tissue, inflflammation/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 effificacy 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 effificacy 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.

Keywords: chronic wounds; hyaluronic acid; collagenase; Vibrio alginolitycus; Bionect Start; Hyalo4 Start

Contribution of antimicrobial photosonodynamic therapy in wound healing: an in vivo efect of curcumin-nisin-based poly (L-lactic acid) nanoparticle on Acinetobacter baumannii bioflms

Abstract

Background: The bioflm-forming ability of Acinetobacter baumannii in the burn wound is clinically problematic due to the development of antibiotic-resistant characteristics, leading to new approaches for treatment being needed. In this study, antimicrobial photo-sonodynamic therapy (aPSDT) was used to assess the anti-bioflm efcacy and wound healing activity in mice with established A. baumannii infections.

Methods: Following synthesis and confrmation of Curcumin-Nisin-based poly (L-lactic acid) nanoparticle (CurNisNp), its cytotoxic and release times were evaluated. After determination of the sub-signifcant reduction (SSR) doses of CurNisNp, irradiation time of light, and ultrasound intensity against A. baumannii, anti-bioflm activity and the intracellular reactive oxygen species (ROS) generation were evaluated. The antibacterial and anti-virulence efects, as well as, histopathological examination of the burn wound sites of treated mice by CurNisNp-mediated aPSDTSSR were assessed and compared with silver sulfadiazine (SSD) as the standard treatment group.

Results: The results showed that non-cytotoxic CurNisNp has a homogeneous surface and a sphere-shaped vesicle with continuous release until the 14th day. The dose-dependent reduction in cell viability of A. baumannii was achieved by increasing the concentrations of CurNisNp, irradiation time of light, and ultrasound intensity. There was a time-dependent reduction in bioflm growth, changes in gene expression, and promotion in wound healing by the acceleration of skin re-epithelialization in mice. Not only there was no signifcant diference between aPSDTSSR and SSD groups in antibacterial and anti-virulence activities, but also wound healing and re-epithelialization occurred more efciently in aPSDTSSR than in the SSD group.

Conclusions: In conclusion, CurNisNp-mediated aPSDT might be a promising complementary approach to treat burn wound infections.

Keywords: Antimicrobial photodynamic therapy, Antimicrobial sonodynamic therapy, Bioflms, Burn wound infection, Curcumin, Nisin, Silver sulfadiazine