Abstract:

The number of individuals with chronic cutaneous wounds has been increasing worldwide due to an aging population, diabetes, obesity, and cardiovascular disease. In the United States, almost seven million Americans have chronic skin ulcers. Many therapeutic approaches have been used. However, the treatment outcomes are not always ideal because of failure to achieve complete wound closure in around 60% of cases, scarring, and high rate of recurrence. Therefore, there is a need for more effective therapies. Stem cells offer promising possibilities. Pre-clinical studies have shown that bone- or adipose tissue-derived mesenchymal stem cells (MSCs) have a competitive advantage over other types of stem cells due to their better defined multipotent differentiating potential, paracrine effects, immunomodulatory properties, and safety. However, large controlled clinical trials are needed to examine the capabilities of MSCs in humans and to assess their safety profile. In this review, we highlight emerging treatments in tissue regeneration and repair and provide some perspectives on how to translate current knowledge about stem cells—both multipotent and pluripotent—into viable clinical approaches for treating patients with difficult to heal wounds.

Authors:

Ayman Grada, MD, Research Fellow, Department of Dermatology, Boston University School of Medicine, Boston, Massachusetts, Vincent Falanga, MD, FACP, Program Director and Vice-Chair of Research, Department of Dermatology and Biochemistry, Boston University School of Medicine, Boston, Massachusetts

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Abstract:

Adipose derived regenerative cells (ADRCs) are a heterogeneous population of cells including multipotent adipose derived stems cells, other progenitor cells, fibroblasts, T-regulatory cells, and macrophages. Preclinical data exist supporting benefits that are predominantly through angiogenesis, modulation of inflammation, and wound remodeling. Such effects are likely paracrine in nature. The application of autologous ADRCs has been investigated across multiple therapeutic areas. While there are numerous publications, there is a relative lack of double-blind, well-controlled, randomized clinical trials in the literature. Nevertheless, a consistency in outcomes and a consistency with preclinical and laboratory studies suggests a true positive effect. The therapeutic areas reported include orthopedics, autoimmune disease, wounds and reconstruction, cardiology, peripheral vascular disease, genitourinary disorders, gastrointestinal fistulas, and neurology. Case reports have documented wound healing in otherwise intractable wounds such as ischemic- and radiation-related cutaneous ulcers and enterocutaneous fistulas. An open label, 12-patient-study indicated substantial improvement in hand manifestations of scleroderma across multiple endpoints. Post-radical prostatectomy urinary incontinence improved in a study of 11 patients with local delivery of ADRCs. Small studies of intramyocardial delivery have been associated with trends towards benefit. The studies also indicate that same day fat harvest through liposuction, cell processing, and cell delivery is feasible and can be performed with an acceptable safety profile. The objective of this review is to highlight the interest, potential, and trends that support the need to continue evaluation and exploration for the role of ADRCs as a therapeutic agent.

Authors:

Steven Kesten, MD, Chief Medical Officer, Cytori Therapeutics, Inc., San Diego, California, John K. Fraser, PhD, Chief Scientist, Cytori Therapeutics, Inc., San Diego, California

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Abstract:

Introduction: This is the first systematic review to explore the evidence on PHMB and determine how effective this topical agent is for the treatment of chronic wounds. Materials and Methods: PubMed, Ovid MEDLINE, CINAHL, Embase, the Cochrane library, and Scopus were searched for relevant articles published from 1946 to February 3, 2014, with no restrictions on publication status. ProQuest was searched for relevant dissertations, editorials, and conference abstracts. Non-indexed journals were searched and companies that manufacture wound care materials containing PHMB were contacted for unpublished data. Only randomized controlled trials available in English were included. Bias was assessed using the CONSORT document for all included studies. After inclusion and exclusion criteria were determined, four reviewers (ET, SK, SG, RD) independently reviewed each title and abstract of the literature search results to determine whether the paper should be included for this review. When disagreements on study inclusion emerged, reviewers resolved them through discussion. Results: Of the 1,725 articles identified in the search, 6 met inclusion criteria. Four studies reported wound healing. Two of these studies evaluated changes in wound surface area and the other two evaluated wound bed evolution with variable results. In five studies, participants randomly assigned to PHMB topical agents showed significant improvement in bacterial control compared to control groups. Five studies reported pain reduction from the use of PHMB agents. Discussion: There were a small number of eligible studies found, but the interventions, outcome measures, and outcome reporting varied greatly, making meta-analysis impossible. PHMB agents were shown to promote healing and reduce pain more effectively than control treatments. Conclusion: The existing evidence shows that topical PHMB may promote healing of chronic stalled wounds, reduce bacterial burden, eliminate methicillin-resistant staphylococcus aureus (MRSA), and alleviate wound-related pain.

Authors:

Eliot To, MClSc-WH, DCH, Chiropodist, St. Joseph's Health Centre, Toronto, Ontario, Rebecca Dyck, RN, MClSc-WH, St. Catharines, Ontario, Stephanie Gerber, RN, MClSc-WH, Chronic Disease Manager, Fort Frances Family Health Team, Fort Frances, Ontario, Shauna Kadavil, MClSc-WH, BScOT(C), Occupational Therapist, South Health Campus, Calgary, Alberta, Kevin Y. Woo, PhD, RN, FAPWCA, Assistant Professor, School of Nursing, Faculty of Health Sciences, Queen's University, Kingston, Ontario

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Abstract:

Melanoma is characterized by a high degree of chromosome instability (CIN), the loss or gain of entire chromosomes or pieces of chromosomes. Also, CIN is likely to drive the progression of benign melanocytic lesions to malignant tumors, although very little is known about the acquisition of the mechanisms that promote CIN along this progression. Here, we describe the development of a model system to study the progression of melanomagenesis starting with normal human melanocytes followed by inactivation of the p53 and pRb tumor suppressors by addition of the E6/E7 proteins. The cells were then transduced with a growth-promoting, constitutionally-active mutant NRAS. The addition of E6/E7 and E6/E7 NRAS was found to give a growth advantage to the cells compared to normal melanocytes and a statistically significant gain of aneuploidy; aneuploidy was 24.7% in primary melanocytes, 33.8% in E6/E7 melanocytes, and 70.5% in E6/E7 NRAS melanocytes. Further, we found an increase in tetraploid cells in the cell model which was statistically significant between primary melanocytes and E6/E7, NRAS melanocytes. We also observed an increase in aneuploid cells between three population doublings in primary melanocytes, whereas this increase was not seen in the E6/E7 melanocytes. Together, these data demonstrate that this model system utilizing stepwise addition of genetic mutations driving melanomagenesis is a useful tool to study CIN and could even be used to study the mechanisms responsible for these alterations in genetic makeup.

Authors:

Julia Escandon, MD, PhD Candidate, Sheila and David Fuente Cancer Biology Graduate Program, Sylvester Comprehensive Cancer Center, Department of Dermatology and Cutaneous Surgery, University of Miami – Miller School of Medicine, Miami, Florida, Lauren King, MS, Field Application Specialist, Cellay, Inc., Cambridge, Massachusetts, Reuven Blobstein, BS, Medical Student, Department of Dermatology and Cutaneous Surgery, University of Miami – Miller School of Medicine, Miami, Florida, Mark S. Eller, PhD, Senior Scientist, Sheila and David Fuente Cancer Biology, Graduate Program, Sylvester Comprehensive Cancer Center, University of Miami – Miller School of Medicine, Miami, Florida, Joan Aurich-Costa, PhD, Chief Scientific Officer, Cellay, Inc., Cambridge, Massachusetts

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Abstract:

Introduction: Hyperbaric oxygen therapy (HBOT) is defined as breathing 100% oxygen at a pressure ≥1.4 atmospheres absolute (ATA). Adjunct HBOT is one modality used for treatment of certain complex wounds. The resulting increase in oxygen delivery to wounded tissue has been associated with reduced edema, reduced inflammation, improved infection control, increased collagen deposition, and increased angiogenesis. However, there remains a relative paucity of evidence supporting the use of HBOT in the treatment of certain acute and chronic, non-healing wounds. This feasibility study was undertaken to evaluate the ability of fluorescence angiography to provide real-time visualization and objective assessment of changes in local tissue perfusion over a standard course of HBOT. Materials and Methods: This single-center, prospective, feasibility study included a total of 34 subjects with wounds of various etiologies deemed eligible for treatment with adjunct HBOT. Fluorescence angiography was performed pre- and post-HBOT sessions 1, 5, 10, 15, and 20. The imaging sequences were analyzed to determine the effects of HBOT on local tissue perfusion to the wounds. Results: A total of 22 subjects received a minimum of 10 HBO sessions with associated pre- and post-fluorescence angiography performed and analyzed. Fluorescence angiography was able to provide both real-time visualization and objective assessment of changes in tissue perfusion over the course of adjunct HBOT. Conclusion: The results of this feasibility study suggest that serial fluorescence angiography can detect short- and long-term changes in wound area tissue perfusion associated with HBOT. These findings may assist in the selection and monitoring of patients undergoing HBOT.

Authors:

Jonathan F. Arnold, MD, ABPM-UHM, CWS-P, Medical Director, Great River Wound and Hyperbaric Medicine Clinic, Great River Medical Center, West Burlington, Iowa, Melissa Roscum, RN, BSN, CHT, CWCA, Staff Nurse, Great River Wound and Hyperbaric Medicine Clinic, Great River Medical Center, West Burlington, Iowa

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Abstract:

Surgical site infections (SSIs) are a drain on the healthcare economy. A recent development for the primary prevention of wound infections is the use of negative pressure wound therapy (NPWT) on closed wounds. The Prevena™ Incision Management System (KCI USA, Inc., San Antonio, TX) is a new NPWT designed for application on closed surgical incisions in order to prevent potential wound-related complications. We evaluated the use of this new technology on large abdominal incisions following complex ventral hernia repairs with abdominal wall reconstruction in patients with risk factors for developing wound complications and conducted a review of the current literature pertaining to the use of NPWT on closed incisions.

Authors:

Sala Abdalla, BSc, MBBS, MRCS, Specialist Registrar, Department of General Surgery, Queen Elizabeth Hospital, Woolwich, London, Rachel Rolph, MBBS, MRCS, Specialist Registrar, Department of General Surgery, Queen Elizabeth Hospital, Woolwich, London, Anjali Rampersad, MBBS, Foundation Year 1 Doctor, Department of General Surgery, Queen Elizabeth Hospital, Woolwich, London, Grisma Patel, MBBS, Foundation Year 1 Doctor, Department of General Surgery, Queen Elizabeth Hospital, Woolwich, London, Tayo Oke, MBBS, M.Med.Sci, FRCS (Gen), FRCS (Ed), Consultant/Colorectal Surgeon, Department of General Surgery, Queen Elizabeth Hospital, Woolwich, London, UK

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Abstract:

Introduction: The application of 0.1% polyhexanide-betaine gel and irrigating solution was used in place of saline during standard of care wound treatment for 70 chronic wounds of various etiologies. Our goal in this study sample was to investigate the number of days to wound closure, change in absolute wound size, and antimicrobial initiation from baseline visit, following application of polyhexanide-betaine in standard of care wound treatment. Results suggested a benefit of Prontosan® (Polyhexanide-betaine, B. Braun Medical Inc., Allentown, Pennsylvania), with very few patients being administered supplemental antibiotic treatment. Materials and Methods: A retrospective chart analysis evaluated 0.1% polyhexanide-betaine as an adjuvant in the management of chronic non-healing wounds. Over a two-year period at a single wound center, 0.1% polyhexanide-betaine gel and irrigating solution were applied in place of saline during standard of care wound treatment for 70 chronic wounds of various etiologies. Standard weekly wound protocols and debridement were performed. All wounds were evaluated for days to closure, change in wound dimensions, and number of patients requiring antibiotic therapy after initial consultation at the study site. Results: A case series of 49 patients presented 70 wounds for analysis. Antimicrobial therapy was initiated in five of 49 patients. Days to wound closure revealed that venous wounds showed the shortest number of days to closure (29 days) with diabetic ulcers the longest (92 days). Significant comorbid conditions and concomitant medications were present in all groups and did not appear associated with closure rates. Conclusions: The use of 0.1% polyhexanide-betaine gel and solution in treating chronic non-healing wounds provided a moist wound healing environment facilitating closure. Of particular note was the fact that with polyhexanide-betaine, antimicrobial therapy was not initiated in nearly 90% of patients. It is theorized that the antimicrobial effect of 0.1% polyhexanide-betaine gel and solution inhibited bacterial colonization and reduced the need for antimicrobial usage. A prospective controlled and randomized study is warranted to further explore this theory.

Authors:

Michael Moore, MD, FACS, FACCWS, Medical Director, Wound Institute and Research Center, Dunmore, Pennsylvania, Nanci Dobson, RN, CCRP, CWCA, Clinical Research Coordinator, Wound Institute and, Research Center, Dunmore, Pennsylvania, Wes Cetnarowski, MD, Senior Vice President Scientific Affairs and Chief Medical Officer, B. Braun Medical Inc., Allentown, Pennsylvania

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