Relationship between healing status and microbial dissimilarity in wound and peri-wound skin in pressure injuries.

AIM: Wound infection is the most serious cause of delayed healing for patients with pressure injuries. The wound microbiota, which plays a crucial role in delayed healing, forms by bacterial dissemination from the peri-wound skin. To manage the bioburden, wound and peri-wound skin care has been implemented; however, how the microbiota at these sites contribute to delayed healing is unclear. Therefore, we investigated the relationship between healing status and microbial dissimilarity in wound and peri-wound skin. METHODS: A prospective cohort study was conducted at a long-term care hospital. The outcome was healing status assessed using the DESIGN-R® tool, a wound assessment tool to monitor the wound healing process. Bacterial DNA was extracted from the wound and peri-wound swabs, and microbiota composition was analyzed using 16S rRNA gene analysis. To evaluate microbial similarity, the weighted UniFrac dissimilarity index between wound and peri-wound microbiota was calculated. RESULTS: Twenty-two pressure injuries (7 deep and 15 superficial wounds) were included in the study. For deep wounds, the predominant bacteria in wound and peri-wound skin were the same in the healing wounds, whereas they were different in all cases of hard-to-heal wounds. Analysis based on the weighted UniFrac dissimilarity index, there was no significant difference for healing wounds (p = 0.639), while a significant difference was found for hard-to-heal wounds (p = 0.047). CONCLUSIONS: Delayed healing is possibly associated with formation of wound microbiota that is different in composition from that of the skin commensal microbiota. This study provides a new perspective for assessing wound bioburden.

Expression levels of NPPB, ITGB6, CPNE4, EML5, and ITSN1 in fresh exudates swabbed from critically colonised and infected full-thickness wounds in rats.

Pressure injury management requires reliable identification of critical colonisation due to lack of infection signs. Our research group previously proposed the mRNAs natriuretic peptide B (Nppb), integrin subunit beta 6 (Itgb6), copine 4 (Cpne4), echinoderm microtubule-associated protein like 5, and intersectin 1 as candidate markers in pooled exudates of critically colonised wounds. However, it is unclear whether mRNAs or proteins of the candidate genes would be suitable as biomarkers in fresh exudate. Therefore, this study aimed to evaluate the validity of the mRNAs and proteins as fresh exudate markers for critical colonisation. Three wound models of normal healing, critical colonisation, and infection were created in rats. Fresh swab-collected exudates were collected, and mRNA and protein expression levels were measured. In the fresh wound exudates, the detection frequency of Itgb6 tended to decrease in the critically colonised and infected wounds (P = .067), and those of Cpne4 and Nppb tended to be lower in the infected wounds than in the normal healing and critically colonised wounds (P = .006 and .067, respectively). In contrast, there was no difference in protein expression in the exudates. This study suggests that Itgb6 mRNA in fresh exudates is a promising biomarker for critical colonisation.

Bacterial invasion into the epidermis of rats with sodium lauryl sulphate-irritated skin increases damage and induces incontinence-associated dermatitis.

Incontinence-associated dermatitis (IAD) is caused by prolonged exposure to urine/liquid stool. It is a common and often painful skin condition in older incontinent adults because of poor prevention. Patients with urinary infections are at risk of developing IAD, and to guide the development of novel prevention strategies, we aimed to develop an animal model of IAD by urine and bacteria. First, contralateral sites on the dorsal skin of Sprague-Dawley rats were compromised by sodium lauryl sulphate (SLS), simulating frequent cleansing with soap/water. Filter discs were then placed inside ring-shaped chambers on foam dressings, inoculated with or without Pseudomonas aeruginosa, covered with agarose gels immersed in cultured filtrated urine, and secured in place with an occlusive dressing for 3 days. Untreated and SLS-compromised sites served as controls. The IAD was developed at bacteria-inoculated sites, characterised by severe IAD-like redness that persisted for up to 3 days post-exposure and higher disruption of the skin barrier function compared with non-inoculated sites. Pathological changes included epidermal thickening, partial skin loss, inflammatory cell infiltration, accumulation of red blood cells, and invasion of bacteria into the epidermis. This novel, clinically relevant IAD rat model can serve for future prevention developments.

An in vivo critically colonised wound model with dysbiotic wound microbiota.

In critically colonised wounds, many of the signs of infection are often absent, and delayed healing may be the only clinical sign. The prevention of critical colonisation is important, but its pathophysiology has not yet been elucidated. We have previously reported that dysbiotic microbiota dissimilar to the peri-wound skin microbiota may develop in critically colonised wounds. To investigate the role of dysbiotic microbiota, this study aimed to develop a critically colonised wound model by transplantation of dysbiotic microbiota. To transplant microbiota, a bacterial solution (dysbiosis group) or with Luria-Bertani medium (commensal group) was inoculated to full-thickness wounds of rats. The bacterial solution was prepared by anaerobically culturing bacteria from donor rats on an artificial dermis in Luria-Bertani medium for 72 hours. As a result, the degree of the change in the microbial similarity between pre- and post-transplantation of microbiota was significantly higher in the dysbiosis group (P < .001). No signs of infection were observed in any rat in either group. The wound area in the dysbiosis group was significantly larger (P < .001), and there was a significant infiltration of neutrophils (P < .001). All rats of the dysbiosis group represented the clinical features of critically colonised wounds. Furthermore, there were significantly fewer regulatory T cells in the wounds of the dysbiosis group. This is the first study to develop a novel animal model that represents the clinical features of critically colonised wounds and will be useful in investigating the pathogenesis of critical colonisation via regulatory T cells.

Which objective itch-assessment tools are applicable to patients with advanced cognitive impairments? A scoping review.

BACKGROUND: Itching is an irritating and uncomfortable sensation that has a profound effect on patients' physical and mental health. It is a major under-recognised problem in older patients who cannot express their pain due to advanced cognitive impairment. Therefore, objective itch-assessment tools that do not rely on patients' reports of itching may be of value for this patient group. OBJECTIVE: To summarise the characteristics of validated objective itch-assessment tools for patients with advanced cognitive impairment. METHODS: This scoping review was conducted according to the PRISMA extension for scoping reviews checklist. The PubMed, CINAHL and Cochrane Library databases were searched, via database-specific search strategies, for articles published in English between January 1, 1990 and March 11, 2020. Based on the eligibility criteria, two authors independently screened the articles for inclusion. Thereafter, the lead author performed data extraction and analysis. RESULTS: Three validated scratch-monitoring using accelerometers and a sound sensor and one validated scratch-mark assessment have been reported. The Actiwatch Plus, ActiTrac® , body-conducted sound sensor and Scoring Atopic Dermatitis index for scratching (SCORAD-scratch) had positive criterion validity outcomes. The Actiwatch Plus, ActiTrac® and body-conducted sound sensor were significantly correlated with scratch behaviour (r = 0.91, p < 0.001; r = 0.71, p = 0.042; r = 0.99, and p-value not shown, respectively). The SCORAD-scratch was significantly correlated with subjective itch-assessment scores (r = 0.78-0.80, p = <0.0001-0.010). CONCLUSIONS: This scoping review summarises the characteristics of validated objective itch-assessment tools to investigate which of these are applicable to older patients with advanced cognitive impairments. Although there are limitations and further verification is required, the ActiTrac® , Actiwatch Plus and body-conducted sound sensor may be useful for measuring scratch movements and itching. IMPLICATIONS FOR PRACTICE: Nurses and patients' families may better understand the characteristics and validity of each objective itch-assessment tool and select the optimal tool for patients with advanced cognitive impairment who cannot express their discomfort caused due to itching.

An Exploratory Study of the Effects of the pH of Synthetic Urine on Skin Integrity in Healthy Participants.

BACKGROUND: Incontinence-associated dermatitis (IAD) develops from prolonged exposure of skin to urine and/or stool and represents a common complication in older adults, reducing the quality of life. Increased pH is an important etiologic factor of IAD; however, the relationship between urinary pH and skin barrier disruption remains unclear. OBJECTIVE: The aim of this study is to examine the effects of synthetic urine (s-urine) at various pHs on transepidermal water loss (TEWL), stratum corneum hydration (SCH), and skin surface pH. METHODS: S-urine solutions (pH 5.0-9.0) were applied to the volar forearms of 15 healthy participants for 2 h, with another site serving as the untreated control. Measurements of TEWL, SCH, and skin surface pH were obtained at baseline (BL) and after each challenge. Skin buffering capacity was also examined in 5 volunteers by recording skin pH at BL, after 2 h exposure and every 5 min for 40 min. RESULTS: TEWL and SCH were increased following exposure to s-urine compared to BL values. Although there was a tendency for pH to increase after exposure, further investigation showed that changes are only temporal as pH value is restored to BL within 5 mins. There were no significant differences between solutions. CONCLUSIONS: This study revealed that urine disrupts healthy skin integrity; however, its effects are not pH dependent. Transient changes were observed on the acid mantle of the skin due to its innate buffering capacity. Future studies need to examine the effects of urine combined with bacteria responsible for pH elevation in patients with urinary incontinence.

Identification of microRNAs responsive to shear loading in rat skin.

Pressure injuries (PIs) are localised skin injuries that result from pressure with or without shear force. Shear force is more destructive than pressure in clinical settings. Therefore, determining the critical external forces is important for selecting the appropriate care to prevent PIs. To quantitatively distinguish pressure and shear loading with high specificity, we focused on microRNAs (miRs). This study aimed to identify the miRs that are distinguishable between pressure with and without shear loading in rat skin. Microarray analysis identified six candidate miRs from the comparisons among the pressure, shear, and unloaded groups. We analysed the expression levels of the candidate miRs in the process of PI development using real-time reverse transcriptase polymerase chain reaction. In the pressure and shear groups, miR-92b expressions at 6 hours after loading were 2.3 ± 1.3 and 2.9 ± 1.0, respectively, which were significantly higher than those in the control group (P = .014 and .004, respectively). miR-877 expression at 6 hours after loading was significantly increased only in the shear group (2.8 ± 0.9) compared with the control group (P = .016). These results indicate that miR-92b and miR-877 are promising biomarkers to determine for which external force healthcare professionals should intervene.

Assessing absorbent products' effectiveness for the prevention and management of incontinence-associated dermatitis caused by urinary, faecal or double adult incontinence: A systematic review.

OBJECTIVE: Adults who suffer from incontinence are at substantial risk of developing incontinence-associated dermatitis (IAD). In healthcare settings, several interventions have been implemented to prevent or manage IAD, and several absorbent products have been developed for incontinent patients; however, there is no systematic review that has reported on which absorbent products are effective for the prevention or management of incontinence-associated dermatitis. We conducted a systematic review to investigate the effectiveness of absorbent products in the prevention and management of IAD. METHODS: MEDLINE (1946-August 31, 2020), CINAHL (1982-August 31, 2020), and Cochrane Library (August 31, 2020) were searched for relevant articles. RESULTS: Eight studies met the eligibility criteria and were included in this review, including two randomized controlled trials that were designed to evaluate the efficacy of absorbent products on the prevention or management of incontinence-associated dermatitis. Quality of evidence was assessed as low or very low. The findings revealed that some outcomes related to IAD prevention or improvement of IAD can be positively affected by the introduction of a new absorbent product or a difference in the frequency of pad changing, which can control the overhydration of the skin. CONCLUSIONS: The studies included in this review indicated that the problem of control of overhydration of the skin associated with urine and/or faeces can be controlled by absorbent products and these products may be effective for the prevention or management of incontinence-associated dermatitis. Future research with high-quality studies is required.

Investigating the release of inflammatory cytokines in a human model of incontinence-associated dermatitis.

Incontinence-associated dermatitis (IAD) is a painful complication in elderly patients, leading to reduced quality of life. Despite recent attention, its underlying inflammatory mechanisms remain poorly understood. This study was designed to quantify the release of inflammatory cytokines in a human model of IAD. The left volar forearm of ten healthy volunteers was exposed to synthetic urine and synthetic faeces for 2 h, simulating the effects of urinary and faecal incontinence, respectively, and the subsequent cytokine response compared to that of an untreated control site. Inflammatory cytokines were collected using both the Sebutape® absorption method and dermal microdialysis and quantified using immunoassays. Results from the former demonstrated an upregulation in IL-1α, IL-1RA and TNF-α. Synthetic urine caused a higher median increase in IL-1α from baseline compared to synthetic faeces, whereas synthetic faeces were associated with significantly higher median TNF-α levels compared to synthetic urine (p = 0.01). An increase in IL-1α/IL-1RA ratio was also observed with significant differences evident following exposure to synthetic urine (p = 0.047). Additionally, microdialysis revealed a time-dependent increase in IL-1ß and IL-8 following exposure of up to 120 min to synthetic urine and synthetic faeces, respectively. This study demonstrated the suitability of both sampling approaches to recover quantifiable cytokine levels in biofluids for the assessment of skin status following exposure to synthetic fluids associated with incontinence. Findings suggest some differences in the inflammatory mechanisms of IAD, depending on moisture source, and the potential of the cytokines, IL-1α and TNF-α, as responsive markers of early skin damage caused by incontinence.

Does the presence of bacterial urinary infection contribute to the development of incontinence-associated dermatitis? A scoping review.

OBJECTIVE: Incontinence-associated dermatitis (IAD) is an inflammatory skin condition caused by the repeated exposure to urine and faeces. It is not common for urinary incontinence only to cause IAD, however patients with urinary tract infections (UTIs) are also at increased risk for IAD. This scoping review aimed to provide a summary of the relationship between bacterial urinary infections and IAD. METHODS: We conducted a scoping review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. PubMed, CINAHL, Medline, and Web of Science were searched for relevant articles from January 2007 through February 2020. RESULTS: Based on eligibility criteria, 13 research studies and review articles were included. Despite the acknowledged role of bacterial infections can play in IAD and the importance of eradicating infections for the prevention of skin breakdown, there have been limited studies that have investigated how uropathogenic bacteria, in combination with urine, lead to skin damage and IAD. The use of urinary catheters also predisposes to UTIs; however, prevalence/incidence rates of IAD in these patients are not clear, as they were considered as continent of urine in the included studies. CONCLUSION: Further research is needed to elucidate the mechanisms of how bacteria, in combination with urine, lead to IAD.

Effectiveness of ultrasonic debridement on reduction of bacteria and biofilm in patients with chronic wounds: A scoping review.

Chronic wounds are defined as "hard-to-heal" wounds that are caused by disordered mechanisms of wound healing. Chronic wounds have a high risk of infection and can form biofilms, leading to the release of planktonic bacteria, which causes persistent infections locally or remotely. Therefore, infection control and removal of the biofilm in chronic wounds are essential. Recently, ultrasonic debridement was introduced as a new method to reduce infection and promote the healing of chronic wounds. This scoping review aimed to evaluate the effectiveness of ultrasonic debridement on the changes in bacteria and biofilms, and consequently the wound healing rate of chronic wounds. A total of 1021 articles were identified through the database search, and nine papers were eligible for inclusion. Findings suggest that non-contact devices are useful for wound healing as they reduce the inflammatory response, although the bacterial load is not significantly changed. Ultrasonic debridement devices that require direct contact with the wound promote wound healing through reduction of biofilm or bacterial load. The optimum settings for ultrasonic debridement using a non-contact device are relatively consistent, but the settings for devices that require direct contact are diverse. Further studies on ultrasonic debridement in chronic wounds are required.

Elevated Skin pH Is Associated With an Increased Permeability to Synthetic Urine.

PURPOSE: The aim of this study was to investigate the permeability of the skin following cleansing activities and its susceptibility to synthetic urine penetration. SUBJECTS AND SETTING: Ten healthy volunteers (aged 22-58 years) participated in the study, which was conducted in a university bioengineering laboratory. METHODS: Tape stripping and sodium lauryl sulfate were used to simulate the physical and chemical irritation exacerbated by frequent cleansing activities, respectively. An untreated site also was selected to evaluate responses of intact skin. Synthetic urine was then applied for a period of 2 hours. Measurements of transepidermal water loss and skin pH were taken at baseline and after each challenge. To quantify the permeability of the skin following exposure, desorption curves of transepidermal water loss were measured and skin surface water loss was calculated. RESULTS: Chemically irritated skin, characterized by increased pH (7.34 ± 0.22), demonstrated an increased permeability to urine, as reflected by a significant increase in mean skin surface water loss (46,209 ± 15,596 g/m2) compared to both the intact (14,631 ± 6164 g/m2) and physically irritated (14,545 ± 4051 g/m2) skin (P = .005 in both cases). In contrast, the differences between the intact and physically irritated skin were not significant (P = .88). CONCLUSION: Permeability of the skin to irritants is influenced by the status of the skin and its acid mantle. These highlight the need to reevaluate the frequency of cleansing activities, along with the choice of product in clinical settings, favoring the use of pH-balanced cleansers.

Knowledge Gaps in the Etiology and Pathophysiology of Incontinence-Associated Dermatitis: A Scoping Review.

PURPOSE: Incontinence-associated dermatitis (IAD) due to the prolonged exposure of the skin to urinary, fecal, or double incontinence represents a major clinical practice challenge. The aim of this review was to identify and critically appraise the results of published studies on the etiology and pathophysiology of IAD and highlight the current gaps in empirical evidence. METHODS: Scoping literature review. SEARCH STRATEGY: The electronic databases PubMed, Cumulative Index to Nursing and Allied Health Literature, MEDLINE, and Embase were searched for relevant articles published from 1996 to April 2018. Thirteen studies and review articles related to the etiology and pathophysiology of IAD were identified in our initial review, and 3 studies published subsequent to our initial review were evaluated and included in our final review. FINDINGS: These studies suggest that several etiologic factors contribute to the development of IAD including exposure to urine, stool, or a combination of these substances (dual incontinence), the duration and frequency of exposure, frequent cleaning, and inflammatory responses. Results from the current scoping review showed that despite the increasing interest in IAD, evidence related to the underlying mechanisms causing IAD remains sparse. This paucity represents a clear gap in knowledge and indicates a need for additional research. IMPLICATIONS: Future studies should aim at elucidating: (1) the role of urine and its inherent pH on skin integrity, (2) the role of stool, specific digestive enzymes, and fecal bacteria on skin integrity, (3) the permeability and susceptibility of the skin to damage following frequent cleansing activities and occlusion, and (4) the specific inflammatory response triggered following exposure to urine and fecal matter.

The Effect of Absorbent Pad Design on Skin Wetness, Skin/Pad Microclimate, and Skin Barrier Function: A Quasi-experimental Open Cohort Study.

PURPOSE: The main aims of this study were to describe the effects of incontinence pad composition on skin wetness, the skin/pad microclimate, and skin barrier function. We also evaluated the potential utility of our methods for future clinical investigation of absorbent pad design. DESIGN: Single-blind, quasi-experimental, open cohort design. SUBJECTS AND SETTING: Twenty healthy older volunteers (mean age = 72.8 years, SD = 5.8 years; 8 male and 12 female) tested 2 absorbent pad types, with acquisition layers of different compositions (A and B) applied to different sites on the volar aspect of the forearms. One type A pad served as control (A dry) versus 3 pad samples wetted with 3 volumes of saline (A 15 mL, A 35 mL, and B 15 mL). The study was conducted within the clinical laboratory of a university nursing research group in the United Kingdom. METHODS: Skin barrier function was assessed by measuring transepidermal water loss (TEWL), stratum corneum (SC) hydration by corneometry, and skin surface pH using a standard skin pH electrode. Skin water loading (excess water penetration into the skin) was quantified by measuring TEWL and creating a desorption curve of the water vapor flux density. Calculating the area under the curve of the desorption curve to give skin surface water loss reflected excess water penetration into the skin. In a subgroup of the sample, the temperature and relative humidity (microclimate) at the interface between the skin and test pads were measured using a wafer-thin sensor placed between the skin and pad sample. Proinflammatory cytokine release from the SC was assessed using a noninvasive lipophilic film. The main outcome measures in this study were the differences in biophysical measurements of skin barrier function (TEWL, corneometer, and pH) before and after the application of the different pads. RESULTS: Mean ± SD baseline TEWL across all test sites was 10.4 ± 4.4 g/h/m. This increased to 10.6 ± 3.8 g/h/m at the control site, 15.3 ± 6.3 g/h/m for the A 15-mL pad, 15.3 ± 3.9 g/h/m for the A 35-mL pad, and 15.6 ± 3.2 g/h/m for the B 15-mL pad. The mean baseline skin surface pH was 5.9 ± 0.04; cutaneous pH increased to a mean of 6.1 ± 0.06 following all pad applications (P = .16). Mean SC hydration remained unchanged at the control site (A dry). In contrast, SC hydration increased following the application of all wetted pads. Target cytokines were detected in all samples we analyzed. The IL-1RA/IL-1α ratio increased following pad application, except for the wettest pad. CONCLUSION: Study findings suggest that absorbent pad design and composition, particularly the acquisition layer, affect performance and may influence skin health. Based on our experience with this study, we believe the methods we used provide a simple and objective means to evaluate product performance that could be used to guide the future development of products and applied to clinical settings.