A double-blind trial comparing an antimicrobial combination to standard care in hard-to-heal wounds.

OBJECTIVE: Excessive numbers of bacteria in hard-to-heal wounds impede wound healing. Numerous topical antiseptics have demonstrated effectiveness in benchtop studies; however, few clinical studies have demonstrated efficacy in the target population: patients with hard-to-heal wounds. This study addressed the clinical efficacy of a novel antibiofilm cleanser and gel in reducing bacterial load and improving wound outcomes. METHOD: Hard-to-heal wounds were photographed, measured and evaluated for bacterial load using fluorescence imaging weekly for four weeks. The target ulcers were randomised to be cleaned and treated with either a synergistic antibiofilm cleanser and antibiofilm gel with standard of care (AMC-AMG + SoC) or normal saline wash and an amorphous gel with standard of care (NSS-HG + SoC). RESULTS: A Chi-squared test of independence determined that the relationship between the treatment and the patient reaching 40% percentage area reduction (PAR) in four weeks was not significant (χ2(1, n=54)=0.73; p=0.39 at a significance level of 0.05); however, there was a strong trend favouring the antibiofilm cleanser and gel. A significant reduction (p<0.05) in bacterial load was observed in the antibiofilm group. CONCLUSION: This randomised controlled double-blind proof-of-concept study suggests that the performance of antibiofilm agents in vivo is comparable to that in vitro studies.

Proceedings of the Leaders in Wound Healing conference.

SerenaGroup Research Foundation, New Orleans, 17-19 April 2023.

Point-of-care fluorescence imaging reveals extent of bacterial load in diabetic foot ulcers.

Elevated levels of bacteria, including biofilm, increase the risk of chronic wound infection and inhibit healing. Addressing asymptomatic high bacterial loads is challenged by a lack of clinical terminology and diagnostic tools. This post-hoc multicenter clinical trial analysis of 138 diabetic foot ulcers investigates fluorescence (FL)-imaging role in detecting biofilm-encased and planktonic bacteria in wounds at high loads. The sensitivity and specificity of clinical assessment and FL-imaging were compared across bacterial loads of concern (104 -109 CFU/g). Quantitative tissue culture confirmed the total loads. Bacterial presence was confirmed in 131/138 ulcers. Of these, 93.9% had loads >104 CFU/g. In those wounds, symptoms of infection were largely absent and did not correlate with, or increase proportionately with, bacterial loads at any threshold. FL-imaging increased sensitivity for the detection of bacteria across loads 104 -109 (P < .0001), peaking at 92.6% for >108 CFU/g. Imaging further showed that 84.2% of ulcers contained high loads in the periwound region. New terminology, chronic inhibitory bacterial load (CIBL), describes frequently asymptomatic, high bacterial loads in diabetic ulcers and periwound tissues, which require clinical intervention to prevent sequelae of infection. We anticipate this will spark a paradigm shift in assessment and management, enabling earlier intervention along the bacterial-infection continuum and supporting improved wound outcomes.

Bacterial protease activity: a prognostic biomarker of early wound infection.

OBJECTIVE: High bacterial burden is one of several reasons that wounds fail to heal. At present, clinicians rely primarily on clinical signs and symptoms (CSS) to diagnose infection in hard-to-heal wounds; however, studies have demonstrated that CSS can be unreliable. This is especially true in the early stages of bacterial infection. Bacteria release proteases, virulence factors that promote invasive infection. This clinical trial evaluated the use of bacterial protease activity (BPA) as a biomarker to detect whether a wound was in the period of pathogenicity, prior to overt clinical signs. METHOD: Participants were drawn from six US wound centres and had their wounds assessed clinically for infection. In addition, wound fluid swabs were collected and analysed for BPA, inflammatory cytokines (interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α)), and cultured for quantitative microbiology. RESULTS: A total of 366 patients were recruited. The median BPA level increased with the increasing number of signs of infection. The majority of wounds tested positive for elevated BPA prior to exhibiting at least three CSS of infection, the level at which the criteria for infection are met. BPA tended to increase with the bioburden (colony forming unit (CFU)/ml) although some wounds with high bioburden were negative for BPA, and others with low bioburden were positive for BPA. The mean levels of IL-1ß and TNF-α were significantly higher in BPA-positive wounds (p<0.0001 and p=0.0002, respectively). CONCLUSION: The results of this clinical trial suggest that measuring BPA can lead to the early detection of pathogenic bacteria in the wound that impede wound healing and may progress to invasive infection. In a large percentage of cases, BPA detected virulent bacteria in the absence of CSS of infection. As a biomarker, BPA has an advantage over measuring bacterial load-hard-to-heal wounds are often colonised with non-pathogenic bacteria that do not inhibit wound healing and, conversely, a low number of highly virulent species could disrupt the healing process.

Guidelines for the use of topical oxygen therapy in the treatment of hard-to-heal wounds based on a Delphi consensus.

A growing body of evidence supports the use of topical oxygen therapy (TOT) in the treatment of diabetic foot ulcers (DFUs). In addition, anecdotal evidence suggests that topical oxygen may be effective in the treatment of other wound types. In May 2021, experts in the field of wound healing from across the US assembled in New Orleans for the inaugural Leaders in Wound Healing conference. In an interactive session dedicated to TOT, several physicians presented and debated the evidence for TOT. Experts in the audience also shared their experiences in treating patients with TOT. The consensus of the experts recommended the use of TOT in DFUs and supported payer reimbursement for the modality. However, they stressed the need for a guidance document on the use of TOT in patients with hard-to-heal wounds. Following the conference, a Delphi method was employed to establish consensus guidelines for prescribing TOT. A multidisciplinary panel of 24 wound experts (15 wound specialists, six vascular surgeons, one plastic surgeon, one critical care provider and one PhD researcher) participated in two rounds of questionnaires. The Delphi survey questions focused on the indications for topical oxygen, when to prescribe the therapy, pretreatment work-up, visit frequency and length of therapy. A clinical workflow algorithm was also included as part of the Delphi. After two rounds, the Delphi participants were able to reach consensus of >77% on when to prescribe topical oxygen, the wound types that may benefit from the therapy, pretreatment wound preparation and work-up and length of therapy. The goal of the guidelines is to standardise the use of topical oxygen and inform further research efforts.

The efficacy of sodium hypochlorite antiseptic: a double-blind, randomised controlled pilot study.

OBJECTIVE: According to a recent clinical trial, 82% of hard-to-heal wounds harbour levels of bacteria that impede healing. A follow-up analysis of trial data revealed that the use of antiseptic cleansers did not correlate with bacterial burden. At a minimum, these findings suggest the need for clinical research into the efficacy of antiseptics in reducing bacterial burden. Evidence supporting the bacterial killing ability of antiseptics is largely derived from preclinical and laboratory studies. Few clinical trials have examined bacterial levels and healing rates in hard-to-heal wounds. Fortunately, the advent of fluorescence imaging to detect bacterial burden has simplified the conduct of clinical research examining the effectiveness of antiseptics in the clinic setting. The aim of this study was to evaluate the efficacy of a modified sodium hypochlorite (NaOCl) solution in reducing wound size and bacterial load in hard-to-heal wounds. METHOD: In this randomised, double-blind pilot study, patients were randomised to one of two groups: daily wound cleansing with either normal saline solution (NSS) or NaOCl. Patients and investigators were blinded to the allocation. All wound types were included. RESULTS: A total of 16 patients consented to participate. At the initial visit, the target ulcer was measured and a fluorescence image to evaluate bacterial load obtained. The wound was then cleansed with either NSS or NaOCl and fluorescence imaging repeated. Patients cleansed the wound daily in accordance with the randomisation schedule. They returned to the clinic weekly for four weeks, and on each visit the wound was measured and a fluorescence image captured. Patients receiving NaOCl had a greater percent reduction in wound area versus NSS; although the first phase of the study was not powered for statistical significance, there was a strong trend favouring NaOCl. In addition, there was greater bacterial reduction in the NaOCl group. CONCLUSION: Based on the results of this pilot study, enrolment has continued in order to increase the study's power. This pilot study suggests that sodium hypochlorite is efficacious in reducing bacterial burden and promoting healing.

A prospective clinical pilot study comparing two post-operative dressings in the treatment of surgical incisions in volunteers.

OBJECTIVE: Surgical site infections (SSIs) are one of the leading causes of post-operative morbidity and mortality worldwide. The original post-operative dressing, gauze taped in place, did not protect the incision from contamination. A recent clinical trial demonstrated that transparent films were superior to gauze in reducing SSIs. Transparent films are semi-occlusive (semi-permeable, transparent). They protect the incision from contamination; however, one of the drawbacks of current films is that they may become dislodged during daily activities, such as showering. Patients may not realise that the integrity of the dressing has been compromised, leading to soiling of the incision and possible infection. DrySee (DrySee Inc., US) is a novel film dressing with a colorimetric indicator that alerts the patient when the dressing has been compromised. METHOD: This trial compared the film dressing with the indicator (DSD) to a commonly used post-operative dressing comparator (Tegaderm + Pad; 3M, US). A 1.5cm incision was made in the volar forearm of volunteers. The incisions were randomly treated with the DSD or comparator dressing. RESULTS: A cohort of 20 volunteer patients was recruited. The DSD had a greater wear time and patients reported that the DSD dressing stayed in place better during activities compared to the comparator. CONCLUSION: Overall, 75% of patients preferred DSD and 25% preferred the comparator.

Antimicrobial stewardship: a JWC Masterclass.

This paper presents an overview of a Journal of Wound Care (JWC) webinar 'Antimicrobial Stewardship Masterclass' which took place on 17 June 2021, bringing together international experts in the field of wound care. The webinar was undertaken to provide an educational platform elucidating the basis of an effective antimicrobial strategy in wound care, and to demonstrate how it impacts on wound care clinicians and their day-to-day practice, using examples of 'real-life' patient outcomes.

A multicenter clinical trial evaluating the durability of diabetic foot ulcer healing in ulcers treated with topical oxygen and standard of care versus standard of care alone 1 year post healing.

Multiple clinical trials and real-world studies have demonstrated accelerated healing in diabetic foot ulcers (DFU) treated with advanced modalities, such as topical oxygen therapy (TOT). In addition to healing, the durability of wound closure is a crucial long-term endpoint for DFU clinical trials: an advanced treatment that does not confer a reasonable ulcer-free period will have limited clinical benefit and modest economic value. Preclinical studies suggest that DFUs receiving topical oxygen therapy will experience improved quality of healing: increased collagen deposition and angiogenesis. It is postulated that these changes will translate into a more long-lasting closure for ulcers treated with TOT and SOC compared to ulcers treated with SOC alone. At the conclusion of a recently completed randomised controlled DFU clinical trial evaluating the efficacy of TOT and SOC compared to SOC alone, patients with healed ulcers were asked to enrol in a long-term follow-up study. Healed patients completed four questionnaires through text messages or phone calls within 1-year post completion of the trial. Twenty-nine patients consented to participate in the long-term follow-up trial (17 TOT/SOC and 12 SOC). Only seven subjects were lost to follow up (5 TOT and 2 SOC). This is a surprisingly low number when factoring in the disruption caused by the COVID-19 pandemic that continued throughout the entire follow-up period. In the remaining patients, 85% of the TOT patients and 60% of the SOC remained healed at 1 year. There was one major amputation, which occurred in an SOC-treated patient. The numbers in the long-term follow-up were too small to reach statistical significance; however, there is a strong trend toward more durable closure in ulcers treated with TOT.

Uncovering the high prevalence of bacterial burden in surgical site wounds with point-of-care fluorescence imaging.

Detection of bacterial burden within or near surgical wounds is critical to reducing the occurrence of surgical site infection (SSI). A distinct lack of reliable methods to identify postoperative bioburden has forced reliance on clinical signs and symptoms of infection (CSS). As a result, infection management has been reactive, rather than proactive. Fluorescence imaging of bacterial burden (FL) is positioned to potentially flip that paradigm. This post hoc analysis evaluated 58 imaged and biopsied surgical site wounds from the multi-centre fluorescence imaging assessment and guidance clinical trial. Diagnostic accuracy measures of CSS and FL were evaluated. A reader study investigated the impact of advanced image interpretation experience on imaging sensitivity. Forty-four of fifty-eight surgical site wounds (75.8%) had bacterial loads >104  CFU/g (median = 3.11 × 105  CFU/g); however, only 3 of 44 were CSS positive (sensitivity of 6.8%). FL improved sensitivity of bacterial detection by 5.7-fold compared with CSS alone (P = .0005). Sensitivity improved by 11.3-fold over CSS among clinicians highly experienced with FL interpretation (P < .0001). Surgical sites that reach the stage of referral to a wound specialist frequently harbour asymptomatic high bacterial loads that delay healing and increase infection risk. Advanced imaging of pathological bacterial burden improves surgical site monitoring and may reduce the rate of SSIs.

A prospective clinical trial evaluating changes in the wound microenvironment in patients with chronic venous leg ulcers treated with a hypothermically stored amniotic membrane.

Amniotic tissues have been long utilised to treat chronic wounds; however, there are few studies evaluating how the wound microenvironment responds to these therapies. The goal of this study was to evaluate the changes in wounds treated with a hypothermically stored amniotic membrane (HSAM). In this prospective single-arm study, 15 female patients with venous leg ulcers were treated with HSAM from male donors and standard of care for 12 weeks. Over the course of the study, wound exudate was collected and evaluated using proteomic microarrays. Biopsies were collected during the course of treatment to detect the presence of HSAM tissue. By 4 weeks, 60% of subjects achieved 50% or greater reduction in wound size, and by 12 weeks, 53% of subjects achieved 100% re-epithelialization. HSAM DNA was detected in 20% of biopsies as determined by the detection TSPY4, indicating HSAM was no longer present within the wound bed approximately 7 days from the last treatment for the majority of wounds. Proteomic analysis of wound exudate found that wounds on a healing trajectory had significantly higher levels of MMP-10, MMP-7, and TIMP-4 and significantly lower levels of CX3CL1, FLT-3 L, IL-1ra, IL-1a, IL-9, IL-2, IL-3, MCP-1, and TNF-b compared with other wounds.

Bacterial protease activity as a biomarker to assess the risk of non-healing in chronic wounds: Results from a multicentre randomised controlled clinical trial.

Millions worldwide suffer from chronic wounds challenging clinicians and burdening healthcare systems. Bacteria impede wound healing; however, the diagnosis of excessive bacterial burden or infection is elusive. Clinical signs and symptoms of infection are inaccurate and unreliable. This trial evaluated a novel, point-of-care, lateral flow diagnostic designed to detect virulence factors released by the most common bacteria found in chronic wounds. A multicentre prospective cohort clinical trial examined the efficacy of a diagnostic test in detecting bacterial proteases taken from swab samples of chronic venous, arterial, pressure and mixed aetiology chronic wounds. Two hundred and sixty six wounds were included in the analysis of the study. The wounds were tested at the start of the study after which investigators were permitted to use whatever dressings they desired for the next 12 weeks. Healing status at 12 weeks was assessed. The presence of elevated bacterial protease activity decreased the probability of wound healing at 12 weeks. In contrast, a greater proportion of wounds were healed at 12 weeks if they had little or no bacterial protease activity at study start. In addition, the presence of elevated bacterial protease activity increased the time it takes for a wound to heal and increased the risk that a wound would not heal, when compared to the absence of bacterial protease activity. The results of this clinical trial indicate that bacterial protease activity, as detected by this novel diagnostic test, is a valid clinical marker for chronicity in wounds. The diagnostic test offers a tool for clinicians to detect clinically significant bacteria in real time and manage bacteria load before the clinical signs and symptoms of infection are evident.

Evaluation of the combination of a biofilm-disrupting agent and negative pressure wound therapy: a case series.

OBJECTIVE: Approximately three million people in the US have hard-to-heal pressure ulcers (PUs), including 10% of hospitalised patients. Healing depends on ulcer stage and patient comorbidities. Despite advances in nutrition and wound care, PUs can take months or years to reach complete closure. To date, clinical studies have focused on single modality therapy. However, there is no one therapy that can address all of the deficits in these complex, hard-to-heal wounds. A commonly used treatment for PUs, negative pressure wound therapy (NPWT), has demonstrated improved healing in Stage 3 and 4 PUs. NPWT entails applying suction to a porous sponge fitted into the wound cavity and sealed with an occlusive dressing. Negative pressure facilitates wound healing by removing wound fluid containing harmful proteases, stimulating the formation of granulation tissue and promoting wound contracture. However, it does not affect biofilm formation. We hypothesised that adding an antibiofilm agent might increase the effectiveness of NPWT in recalcitrant PUs. METHOD: A prospective case series was conducted in outpatient wound care centres and a skilled nursing facility to examine the combination of a biofilm-disrupting antimicrobial agent (Blast-X, Next Science, US) in combination with NPWT (VAC, 3M, US) in healing and reducing bacterial burden in treatment-resistant pressure ulcers. Patients consented to application of the antibiofilm agent and NPWT three times per week for four weeks. The wounds were measured, imaged for bacteria and tested for host and bacterial protease activity weekly. RESULTS: Of the 10 patients, four dropped out of the study before the end of the four weeks. Of the remaining six, four patients experienced a reduction in wound surface area and volume, reduced protease activity and lower bacterial levels. CONCLUSION: The results of this study showed that multimodal therapy, including NPWT and biofilm disruption, may restart the healing of stagnant treatment-resistant PUs.

A novel debridement device for the treatment of hard-to-heal wounds: a prospective trial.

OBJECTIVE: Debridement, the removal of nonviable tissue, forms the foundation of wound care practice. Clinicians have a variety of debridement methods at their disposal: sharp, biologic, enzymatic, autolytic and mechanical. The choice of debridement technique depends on the patient care setting, ulcer type and the clinician's experience, training, comfort level and licensure. This prospective study evaluated a novel debridement instrument, EZ-Debride (MDM Ventures, US). Cutting flutes on the head of the tool permit uniform removal of dead tissue while lessening the risk of deeper injury. It may also minimise pain during the debridement procedure. METHOD: Subjects with hard-to-heal wounds, drawn from a single wound care centre, participated in this institutional review board-approved prospective clinical study. Pain was measured before, during and after debridement using a numerical scale. Assessment of bacterial burden using fluorescence imaging (MolecuLight, Canada) was performed before and after debridement. RESULTS: Enrolment of 10 male and 12 female subjects, with a total of 28 wounds, was carried out over a two-month period by two investigators at a single institution. The average age of subjects was 64 years (range: 22-95 years). The average wound duration was 29 weeks (range: 6-142 weeks). Wound types included diabetic foot, venous leg and pressure ulcers, post-surgical and traumatic wounds. The average pain score at the time of enrolment was 3.9. Subjects reported an average increase in pain with debridement of 0.6 points (range: 0-8). Fluorescence imaging demonstrated a reduction in bacterial load in 69% of cases, with complete resolution in 19% of wounds. Haemostasis was achieved with direct pressure in all cases and the only adverse event was a wound infection that occurred four days after debridement. CONCLUSION: The results suggest that this novel debridement tool can safely remove nonviable tissue with minimal discomfort and reduce bacterial burden similar to results achieved by sharp debridement.

Efficacy and safety of a porcine peritoneum-derived matrix in diabetic foot ulcer treatment: a pilot study.

OBJECTIVE: A third of people with diabetes will develop a foot ulcer during their lifetime. The absence of pain secondary to neuropathy often leads to a delay in diagnosis and treatment. Diabetic foot ulcer (DFU) complications, such as infection and amputation, increase mortality and strain the financial resources of health systems across the world. Cellular and/or tissue products (CTPs) have played an important role in the closure of DFUs. Investigators continue to search for new CTPs that facilitate healing. The aim of this study was to assess the efficacy and safety of a porcine peritoneum-derived matrix in DFU treatment. METHOD: Patients with longstanding DFUs participated in this institutional review board-approved, multicentre, prospective pilot study evaluating the time to healing over 12 weeks. In addition to weekly assessments for wound size, investigators analysed bacterial burden using the MolecuLight procedure (MLiX) and bacterial protease (BPA) testing. Participants received a weekly application of Meso Wound Matrix Scaffold (MWM), a lyophilised porcine peritoneum-derived matrix (DSM Biomedical Inc., Exton, PA, US) for up to eight weeks. Descriptive statistics were chosen for this analysis. RESULTS: A total of 12 male patients and three female patients with an average age of 57 years were enrolled over a two-month period. The average wound duration was 30 weeks. Due to unrelated health issues, four participants were withdrawn. For the study endpoint of complete wound closure at 12 weeks, six (55%) of the remaining 11 patients achieved complete closure, and four (36%) patients healed during the 8-week treatment period. The average number of CTP applications was six. Patients who healed all had negative BPA by nine weeks and no fluorescence on MLiX, indicating low bacterial load. CONCLUSION: This small pilot study indicates that patients with longstanding DFUs may respond to a porcine peritoneal-derived CTP. In this study, the CTP appears to have inhibited bacterial growth in the wound; however, further research is needed.

Topical oxygen therapy in the treatment of diabetic foot ulcers: a multicentre, open, randomised controlled clinical trial.

OBJECTIVES: Perfusion and blood oxygen levels are frequently insufficient in patients with hard-to-heal wounds due to poor circulation, vascular disruption and vasoconstriction, reducing the wound's capacity to heal. This study aimed to investigate the effect of topical oxygen on healing rates in patients with hard-to-heal diabetic foot ulcers (DFUs) (i.e., non-responsive over four weeks). METHOD: This multicentre, open-label, community-based randomised clinical trial compared standard care (SOC) with or without continuous topical oxygen therapy (TOT) for 12 weeks in patients with DFUs or minor amputation wounds. SOC included debridement, offloading with total contact casting (TCC) and appropriate moisture balance. Primary endpoints were the number of patients to achieve complete wound closure and percentage change in ulcer size. Secondary endpoints were pain levels and adverse events. RESULTS: For the study, 145 patients were randomised with index ulcers graded Infectious Diseases Society of America (IDSA) 1 or 2, or Wagner 1 or 2. In the intention-to-treat analysis, 18/64 (28.1%) patients healed in the SOC group at 12 weeks compared with 36/81 (44.4%) in the SOC plus TOT group (p=0.044). There was a statistically significant reduction in wound area between the groups: SOC group mean reduction: 40% (standard deviation (SD) 72.1); SOC plus TOT group mean reduction: 70% (SD 45.5); per protocol p=0.005). There were no significant differences in changes to pain levels or adverse events. CONCLUSION: This study suggests that the addition of TOT to SOC facilitates wound closure in patients with hard-to-heal DFUs.

Hyperbaric oxygen therapy in preventing mechanical ventilation in COVID-19 patients: a retrospective case series.

OBJECTIVE: A pandemic afflicts the entire world. The highly contagious SARS-CoV-2 virus originated in Wuhan, China in late 2019 and rapidly spread across the entire globe. According to the World Health Organization (WHO), the novel Coronavirus (COVID-19)has infected more than two million people worldwide, causing over 160,000 deaths. Patients with COVID-19 disease present with a wide array of symptoms, ranging from mild flu-like complaints to life threatening pulmonary and cardiac complications. Older people and patients with underlying disease have an increased risk of developing severe acute respiratory syndrome (SARS) requiring mechanical ventilation. Once intubated, mortality increases exponentially. A number of pharmacologic regimens, including hydroxychloroquine-azithromycin, antiviral therapy (eg, remdesevir), and anti-IL-6 agents (e.g., toclizumab), have been highlighted by investigators over the course of the pandemic, based on the therapy's potential to interrupt the viral life-cycle of SARS-CoV-2 or preventing cytokine storm. At present, there have been no conclusive series of reproducible randomised clinical trials demonstrating the efficacy of any one drug or therapy for COVID-19. CASES: COVID-19 positive patients (n=5) at a single institution received hyperbaric oxygen therapy (HBOT) between 13 and 20 April 2020. All the patients had tachypnoea and low oxygen saturation despite receiving high FiO2. HBOT was added to prevent the need for mechanical ventilation. A standard dive profile of 2.0ATA for 90 minutes was employed. Patients received between one and six treatments in one of two dedicated monoplace hyperbaric chambers. RESULTS: All the patients recovered without the need for mechanical ventilation. Following HBOT, oxygen saturation increased, tachypnoea resolved and inflammatory markers fell. At the time of writing, three of the five patients have been discharged from the hospital and two remain in stable condition. CONCLUSION: This small sample of patients exhibited dramatic improvement with HBOT. Most importantly, HBOT potentially prevented the need for mechanical ventilation. Larger studies are likely to define the role of HBOT in the treatment of this novel disease.

Use of a dual-layer amniotic membrane in the treatment of diabetic foot ulcers: an observational study.

BACKGROUND: Despite advances in the treatment, fewer than half of diabetic foot ulcers (DFUs) heal in 12 weeks and 85% of non-traumatic amputations follow the development of a DFU. The search for treatment options continues. Placental-derived products have shown promise in the treatment of DFUs. This study investigates Artacent (Tides Medical, US), a unique amniotic patch containing two layers of amnion and its potential to increase growth factor delivery. METHOD: This observational analysis included patients with DFUs with documented failure to heal by >50% after the protocol-defined run-in period (either two or four weeks) of standard of care (SOC), and who had been randomised in a larger clinical trial that had been discontinued earlier for logistical reasons. Patients were randomised to either weekly or biweekly application of the dual-layer amniotic membrane (DLAM) plus SOC and were included in per-protocol effectiveness analyses. Descriptive statistics were chosen for this analysis. Primary endpoint was complete closure at 12 weeks. RESULTS: A total of 26 patients were included in the analysis. Examination of baseline patient characteristics revealed that the ulcers were larger than in most DFU clinical trials (4.65±4.89cm2). For the primary endpoint, 17/26 (65%, 95% CI: 44-83%) of the combined treatment arms achieved complete closure. The small sample size precluded a meaningful comparison of healing between weekly and biweekly DLAM applications. CONCLUSION: The observations taken from the discontinued clinical trial suggest that the DLAM promotes healing of DFUs. The healing rates are similar to those in other placental-based tissue studies. In addition, the relatively larger size of the ulcers suggests that the DLAM may be effective in ulcers that are more resistant to standard of care. In the future, a revised clinical trial with a greater sample size is planned.

Comparing near infrared spectroscopy and transcutaneous oxygen measurement in hard-to-heal wounds: a pilot study.

OBJECTIVE: Oxygen plays an integral role in all phases of the wound healing process and tissue oxygenation is a key determinant of wound healing. A comprehensive evaluation of patients with hard-to-heal wounds must include measurement of oxygenation in and around the area of skin breakdown. The current gold standard, transcutaneous oxygen measurement (TCOM), has numerous drawbacks and as a result has fallen into disuse. METHOD: This study compared measurement of tissue oxygenation of near infrared spectroscopy (NIRS) with TCOM in patients with acute and hard-to-heal wounds. The Shapiro-Wilk test was used to evaluate the normality of the data. The level of agreement between NIRS and TCOM was determined using Bland-Altman analysis. The relationship between TCOM and NIRS was examined using Pearson correlation. RESULTS: A total of 24 observations were obtained from 10 patients using TCOM and NIRS. The weighted mean partial pressure of oxygen (pO2) in the study population was 39.54mmHg (8.96 standard deviation). Bland-Altman analysis showed that mean difference was positive (18.75), suggesting an overestimation of oxygen measurements using TCOM compared with NIRS. The oxygen levels measured by TCOM and NIRS showed a strong correlation (r=0.74). CONCLUSION: The wound and hyperbaric community would benefit from a simplified procedure for measuring tissue oxygenation. These findings suggest a strong trend toward correlation between NIRS and TCOM. A further study in a larger population is recommended. NIRS offers several advantages over TCOM. Clinicians have immediate point-of-care visualisation of tissue oxygenation using a handheld device. The procedure takes minutes to perform and is less operator-dependent than TCOM. Finally, NIRS allows measurement of oxygenation in the wound bed, while TCOM does not.

Real-time bacterial fluorescence imaging accurately identifies wounds with moderate-to-heavy bacterial burden.

OBJECTIVE: Clinical evaluation of signs and symptoms (CSS) of infection is imperative to the diagnostic process. However, patients with heavily colonised and infected wounds are often asymptomatic, leading to poor diagnostic accuracy. Point-of-care fluorescence imaging rapidly provides information on the presence and location of bacteria. This clinical trial (#NCT03540004) aimed to evaluate diagnostic accuracy when bacterial fluorescence imaging was used in combination with CSS for identifying wounds with moderate-to-heavy bacterial loads. METHODS: Wounds were assessed by study clinicians using NERDS and STONEES CSS criteria to determine the presence or absence of moderate-to-heavy bacterial loads, after which the clinician prescribed and reported a detailed treatment plan. Only then were fluorescence images of the wound acquired, bacterial fluorescence determined to be present or absent and treatment plan adjusted if necessary. RESULTS: We examined 17 VLUs/2 DFUs. Compared with CSS alone, use of bacterial fluorescence imaging in combination with CSS significantly improved sensitivity (22% versus 72%) and accuracy (26% versus 74%) for identifying wounds with moderate-to-heavy bacterial loads (≥104 CFU/g, p=0.002). Clinicians reported added value of fluorescence images in >90% of study wounds, including identification of wounds incorrectly diagnosed by CSS (47% of study wounds) and treatment plan modifications guided by fluorescence (73% of study wounds). Modifications included image-guided cleaning, treatment selection, debridement and antimicrobial stewardship. CONCLUSION: Findings from this pilot study suggest that when used in combination with CSS, bacterial fluorescence may: (1) improve the diagnostic accuracy of identifying patients with wounds containing moderate-to-heavy bacterial loads and (2) guide more timely and appropriate treatment decisions at the point-of-care.