A model for diabetic foot ulcer clinical trials on advanced therapies.

DECLARATION OF INTEREST: TS is a consultant for Inotec AMD Ltd., UK. The authors have no other conflicts of interest to declare.

Remote assessment and monitoring with advanced wound therapy to optimise clinical outcomes, access and resources.

OBJECTIVE: Patients in rural communities may have limited access to wound care; however, this may be mitigated by using a shared care approach. This study assessed the impact of a remote assessment and monitoring tool in combination with adjunctive continuous topical oxygen therapy (cTOT) in patients with diabetes and hard-to-heal wounds. METHOD: Patients with hard-to-heal wounds (defined as no visible improvement in the previous four weeks) were enrolled to this 12-week pilot study to validate a shared care approach using an Advanced Digital Wound Care Platform-telehealth (ADWCPt) system (eKare Inc., US) coupled with cTOT. Patient and wound assessments were reviewed by the clinician either remotely, via telehealth calls, or at the clinic, and the number of face-to-face clinic visits was recorded. Patient health status scores were captured before and after the study, along with feedback on usability of the remote platform and cTOT device. RESULTS: The wounds in all eight patients studied reduced in size over 12 weeks (mean percentage area reduction 92.0%), and two wounds were completely re-epithelialised. Another wound almost healed (99.2% wound area reduction). Clinical interactions consisted of self-assessments (n=80, 50.0%), video assessments with the clinician (n=27, 16.9%), and face-to-face interactions in clinic (n=53, 33.1%). Operational efficiencies encompassed a 54.0% increase in the number of clinical interactions, whereas clinical time was reduced by 25.8%. Health status scores improved across all eight patients and feedback on the shared approach and cTOT device was favourable. CONCLUSION: A shared care model with ADWCPt coupled with an innovative cTOT device saved time and resources, improving patient access and engagement, along with a marked improvement in the wound healing trajectory.

Proceedings of the Leaders in Wound Healing conference.

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

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.

Consenso de expertos sobre la eficacia clínica y directrices sobre la terapia de oxígeno transdérmico continuo para la cicatrización de las heridas complejas o difíciles de cicatrizar.

INTRODUCTION: Oxygen is pivotal for wound healing. Its lack or hypoxia can delay this process, especially in individuals with comorbidities, potentially resulting in complex or hard-to-heal wounds. The Colombian Association of Diabetes (ACD) and the Colombian Association of Internal Medicine (ACMI) collaborated with a diverse group of experts to provide recommendations on the efficacy and best practices of continuous transdermal oxygen therapy (TOTc) in the care of such wounds. METHOD: A modified Delphi technique was employed to obtain controlled feedback and responses. Experts from various disciplines engaged in reviewing and discussing numerous relevant scientific studies, focusing on the role of TOTc in treating chronic ulcers. RESULTS: Continuous transdermal oxygen therapy has proven to be an effective and safe treatment for chronic and/or hard-to-heal ulcers. This therapy directly addresses the wound's oxygen deficiency, providing an environment conducive to healing. Significant benefits were observed, including the acceleration of the healing process, wound size reduction, and an enhancement in patient quality of life. Its efficacy was found across various ulcer etiologies, underscoring its therapeutic versatility. CONCLUSIONS: Continuous transdermal oxygen therapy is effective and safe for treating chronic and hard-to-heal ulcers. It's crucial to address each case individually and through a multidisciplinary approach to maximize this therapy's benefits. Both evidence and clinical experience back its utility across a variety of ulcer etiologies.

RESUMEN: Introducción: El oxígeno es esencial en la cicatrización de heridas. Su ausencia o hipoxia puede retrasar este proceso, especialmente en individuos con comorbilidades, lo que podría resultar en heridas complejas o de difícil cicatrización. La Asociación Colombiana de Diabetes (ACD) y la Asociación Colombiana de Medicina Interna (ACMI) se unieron con un grupo diverso de expertos para brindar recomendaciones sobre la eficacia y práctica de la terapia de oxígeno transdérmico continuo (TOTc) en el cuidado de estas heridas. Método: Se utilizó la técnica Delphi modificada para obtener respuestas y retroalimentación controlada. Expertos de diversas disciplinas participaron en la revisión y discusión de numerosos estudios científicos relevantes, centrados en el papel de la TOTc en el tratamiento de úlceras crónicas. Resultados: El oxígeno transdérmico continuo ha demostrado ser una terapia eficaz y segura en el tratamiento de úlceras crónicas y/o de difícil cicatrización. Esta terapia aborda directamente la deficiencia de oxígeno en la herida, proporcionando un entorno propicio para la curación. Se observaron beneficios significativos, incluyendo aceleración del proceso de cicatrización, reducción del tamaño de la herida y mejora en la calidad de vida del paciente. Se encontró eficacia en diversas etiologías de úlceras, subrayando su versatilidad terapéutica. Conclusiones: La terapia de oxígeno transdérmico continuo es eficaz y segura para tratar úlceras crónicas y de difícil cicatrización. Es vital abordar cada caso de manera individualizada y mediante un enfoque multidisciplinario para maximizar los beneficios de esta terapia. La evidencia y experiencia clínica respaldan su utilidad en diversas etiologías de úlceras. Palabras clave: Terapia de oxígeno transdérmico continuo, Oxígeno, Pie diabético, Cicatrización de heridas, Cuidado de heridas, Úlceras vasculares, Lesiones por presión, Hipoxia, Infección.

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.

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.

Use of a bacterial fluorescence imaging system to target wound debridement and accelerate healing: a pilot study.

OBJECTIVE: Optimal wound-bed preparation consists of regular debridement to remove devitalised tissues, reduce bacterial load, and to establish an environment that promotes healing. However, lack of diagnostic information at point-of-care limits effectiveness of debridement. METHOD: This observational case series investigated use of point-of-care fluorescence imaging to detect bacteria (loads >104CFU/g) and guide wound bed preparation. Lower extremity hard-to-heal wounds were imaged over a 12-week period for bacterial fluorescence and wound area. RESULTS: A total of 11 wounds were included in the study. Bacterial fluorescence was present in 10 wounds and persisted, on average, for 3.7 weeks over the course of the study. The presence of red or cyan fluorescent signatures from bacteria correlated with an average increase in wound area of 6.5% per week, indicating stalled or delayed wound healing. Fluorescence imaging information assisted in determining the location and extent of wound debridement, and the selection of dressings and/or antimicrobials. Elimination of bacterial fluorescence signature with targeted debridement and other treatments correlated with an average reduction in wound area of 27.7% per week (p<0.05), indicative of a healing trajectory. CONCLUSION: These results demonstrate that use of fluorescence imaging as part of routine wound care enhances assessment and treatment selection, thus facilitating improved wound healing.

Achilles Tendon Augmented Repair Using Human Acellular Dermal Matrix: A Case Series.

Achilles tendon ruptures are common in the general population, especially among members of the older demographic occasionally active in sports. Operative treatments provide a lower incidence of rerupture than do nonoperative treatments, although surgical complications remain a concern. The use of a human acellular dermal matrix to augment Achilles tendon repair might reduce the incidence of complications. In the present case series, we describe the outcomes of 9 patients who underwent Achilles tendon repair with acellular dermal matrix augmentation. Functional outcomes were evaluated using the Foot Function Index-Revised long form, and the clinical results were recorded. After a mean average follow-up period of 14.4 (range 12.0 to 20.0) months, the mean Foot Function Index-Revised long form score was 33.0% ± 4.2%. No cases of rerupture or complications that required additional treatment occurred during the observation period. The outcomes we have presented support further evaluation beyond this case series for using a human acellular dermal matrix to augment Achilles tendon repairs.

Biological incorporation of human acellular dermal matrix used in Achilles tendon repair.

Human acellular dermal matrices (ADMs) are used successfully in a variety of procedures, including sports medicine related, wound repair, and breast reconstructions, but the mechanism of repair is still not fully understood. An opportunity to explore this mechanism presented itself when a patient experienced a rerupture of the native tendon due to a fall that occurred 2 months after undergoing an Achilles tendon repair using Matracell treated ADM. The ADM was removed and an extensive histology analysis was performed on the tissue. Additionally, a literature review was conducted to determine the mechanism of ADM integration into the tendon structure and explore if differences in this mechanism exist for different types of human ADMS. The histology analysis demonstrated that the healing process during a tendon reconstruction procedure is similar to that of wound healing. Furthermore, the literature review showed that differences exist in the mechanism for integration among various human ADMs and that these differences may be due to variances in the methods and technologies that manufactures use to process human ADMs.

Monitoring the effect of continuous topical oxygen therapy with near-infrared spectroscopy: a pilot case series in wound healing.

BACKGROUND: Sufficient oxygen is critical for multiple processes in wound healing. Nonhealing wounds have low tissue oxygen levels due to damaged microvasculature and comorbidities limiting tissue perfusion. Hypoxia may be reversed using continuous topical oxygen therapy (cTOT). Objective measures to identify and track hypoxic wounds and their response to adjunctive oxygen are key. OBJECTIVE: To understand the effect of cTOT on recalcitrant wounds by tracking wound area and changes in tissue oxygenation using a near-infrared spectroscopy (NIRS) device. MATERIALS AND METHODS: Five patients with nonhealing wounds received treatment with cTOT over 5 weeks. Routine wound measures and tissue oxygenation were recorded over that period. RESULTS: Reductions in wound area and improvements in tissue oxygenation were seen in all 5 patients, with 3 patients healing within 5 weeks despite the previous long duration of their wounds. Trends in tissue oxygenation and relative wound surface area over the treatment period demonstrated a reduction in wound area as tissue oxygenation improved. CONCLUSION: This case series reinforces previous studies that cTOT is an effective, noninvasive treatment as a key adjunct to standard care in nonhealing wounds. Moreover, point-of-care tools such as the NIRS imaging device provided objective information concerning tissue oxygenation improvements, thus giving useful insights to the clinician.

A single-center pilot study investigating the effects of a native cross-linked extracellular matrix with polyhexamethylene biguanide to manage chronic lower extremity wounds exhibiting bacterial contamination.

BACKGROUND: Elevated bacterial bioburden and biofilm formation are common causes for delayed wound healing. Biofilm is an assemblage of surface-associated microbes enclosed in a self-produced matrix. Identifying and managing biofilm is a crucial component of successful wound care protocols. PURPOSE: To determine the effects of a native cross-linked extra cellular matrix with polyhexamethylene biguanide (PHMP; PHMP antimicrobial [PCMP]), in conjunction with next-generation DNA sequencing (NGS) and targeted debridement by fluorescence imaging, on managing bacterial bioburden to support wound healing. METHODS: Over 6 weeks, fluorescence images were captured to assess bacterial contamination as were standard images with measurements. Tissue swabs were obtained and analyzed using NGS to quantify bacterial bioburden. PCMP was applied at each treatment visit. RESULTS: Baseline wound duration was 23.0 ± 6.7 weeks, and baseline size was 7.9 ± 7.1 cm2. Two out of 5 wounds healed by week 4. The mean percentage area reduction of all wounds was 59.7% by week 4 and 78.1% by week 6. All wounds were fluorescence positive on week 1 and fluorescence negative by Week 4. CONCLUSION: PCMP, as an antimicrobial barrier, combined with use of a real-time method of bacterial detection, may be beneficial in managing the wound healing environment.

Management of late radiation tissue injury ulcers with continuous topical oxygen therapy supports wound healing in patients of advanced age following Mohs surgery: a case series.

BACKGROUND: The long-term chronic effect of radiotherapy is commonly referred to as LRTI. Clinical complications such as skin atrophy, tissue fibrosis, endothelial damage, ulcer formation, and compromised wound healing are common sequela. Despite advances in medicine over the past decade, there remains a need for effective treatments for LRTI skin necrosis and ulcerations. MATERIALS AND METHODS: This case series discusses cTOT in 3 patients of advanced age with LRTI wounds having undergone Mohs surgery. All wounds had been recalcitrant to multiple wound care treatments. All patients suffered with significant wound pain as well. RESULTS: cTOT resulted in complete wound healing in all 3 patient cases. Additionally, all 3 patients reported a significant reduction in wound pain during the course of therapy. CONCLUSIONS: The positive outcomes exhibited in this case series suggest that cTOT is an effective treatment in the management of Mohs surgery patients with compromised wound healing due to radiation, advanced age, and comorbidities.

Topical autologous blood clot therapy: consensus panel recommendations to guide use in the treatment of complex wound types.

The etiology of acute and chronic wounds goes beyond those often reported in the literature, including those with exposed structures, those in which the entire wound bed cannot be visualized, and patients who are not candidates for typical standard of care. Treatment options for these patients may be limited. TABCT is a viable option for these complex wound types and is not hindered by logistical, procedural, or patient factors. A consensus panel of providers with extensive experience in treatment of these wound types was convened to develop consensus recommendations on the use of TABCT in specific complex wound types. Four consensus statements were defined for TABCT use in patients who cannot undergo sharp or extensive debridement, as a protective barrier to prevent further bacterial ingress, in patients with wounds in which the entire wound bed cannot be safely visualized, and in wounds with exposed tendon and/or bone. Consensus panel recommendations show that TABCT application assists in maintenance of a moist wound healing environment, autolytic debridement, recruitment and delivery of factors essential for wound healing, prevention of pathogen entry, and ability to completely fill wound voids that cannot be fully visualized. Additional advantages of TABCT use are its cost-effectiveness, ease of access, minimal related complications, and proven clinical efficacy.

Use of a Novel Adhesive Suture Retention Device in Non-traumatic Diabetic Lower Extremity Amputations: A Multicenter Case Review.

Background: Amputations in the diabetic foot are commonly associated with complications, including delayed wound healing, surgical site dehiscence, and the need for additional amputations. Use of a novel adhesive suture retention device (ASRD) has been previously shown to support improved linear closure outcomes. The purpose of this retrospective case review was to determine if the adoption of the ASRD in 5 podiatric surgical practices would reduce postoperative complications in patients with diabetes undergoing foot amputations including surgical site dehiscence and the need for additional amputation. Methods: A 5-center retrospective chart review was performed to assess the difference in postoperative surgical site dehiscence and reamputation rates for patients with diabetes undergoing minor and major lower extremity amputations before and after adopting the use of the ARSD. Results: Adoption of the adhesive retention suture device was associated with an overall decrease in wound dehiscence of 81% (P < .01). Additionally, there was an 89% reduction in progression to higher level amputation in the ARSD cohort (P = .015). Conclusions: Utilization of the ARSD decreased the incidence of postoperative wound dehiscence and reamputation in this patient cohort, thus lessening patient morbidity and decreasing the overall cost of care.

A Proposed Algorithm to Diagnose and Treat Lower Extremity Hematomas.

BACKGROUND: Pretibial injury is common. Although the mechanism of injury may be minor, in a specific patient population, misdiagnosis and delay in appropriate treatment can lead to dire consequences. The ability to identify and properly treat these patients early has the potential to reduce the need for surgical intervention, hospitalization, and prolonged care. METHODS: A literature review was performed to develop the Lower Extremity Hematoma Algorithm (LEHA) to aid in identifying and managing these injuries in the patient population at greatest risk. RESULTS: A case example is provided to demonstrate how implementation of the LEHA may have led to early diagnosis and treatment, avoiding expensive advanced and prolonged care. CONCLUSION: Implementation of the LEHA may expedite the identification of patients at risk for deep dissecting hematomas, enabling faster implementation of appropriate treatment and thereby helping to contain health care costs through avoiding surgical intervention.

Topical autologous blood clot therapy: an introduction and development of consensus panel to guide use in the treatment of complex wound types.

Complex or hard-to-heal wounds can be acute or chronic; the complexity is based on patient-specific local, systemic, and psychosocial factors. Use of autologous tissue can be a significant adjunct to wound closure. Grafts and flaps are the most common autologous tissue used in wound reconstruction. However, patient factors, wound size, and exposed structures may preclude using these methods as primary or even secondary closure techniques. Alternative autologous tissue therapies include those derived from adipose, epidermis or dermis, bone marrow, and blood. Limitations of these treatment modalities include access-related difficulty, cost, creation of a secondary donor site, use of singular or limited cell types, and sparse or contradictory evidence basis of their efficacy of use. A panel of providers experienced in wound care and surgical wound management was convened to create a series of publications on the use of topical autologous blood clot therapy (TABCT) in the treatment of complex wounds. This publication, the first in a series, provides an evidence basis of the gap between definition and treatment of complex wounds, an overview of the use of autologous therapies in these wounds, and the science behind TABCT. The development of a consensus panel for decision pathways and recommendations for TABCT use in specific complex wound types are also discussed. Subsequent articles will provide consensus recommendations on the use of TABCT in full-thickness wounds with exposed tendon and/or bone and undermining or tunneling wounds, in wounds in patients who are nonsurgical candidates, in those who cannot undergo sharp debridement, in patients with arterial wounds who have been maximally revascularized, and in those with transsphincteric anal fistula. This article provides a foundation of knowledge and describes the plan for consensus panel decision pathways and recommendation development of use of TABCT in the treatment of specific complex wound types.