ARTERIAL INSUFFICIENCIES: Hyperbaric Oxygen Therapy for Selected Problem Wounds.

The use of hyperbaric oxygen (HBO2) for the treatment of selected problem wounds has focused almost entirely on the diabetic foot ulcer (DFU) in recent years. The prevalence of DFUs in today's patient population and the reimbursement available for the treatment of DFUs have given it priority status in discussions about problem wounds, but there are sound fundamental reasons why additional oxygen may have benefits in the treatment of non-DFU wounds.

Larval Therapy for Chronic Cutaneous Ulcers: Historical Review and Future Perspectives.

Cutaneous ulcers tend to become chronic and have a profound impact on quality of life. These wounds may become infected and lead to greater morbidity and even mortality. In the past, larvae (ie, maggots) of certain common flies (Lucilia sericata and Lucilia cuprina) were considered useful in ulcer management because they only remove necrotic tissue while promoting healthy tissue in the wound bed, thus helping wounds heal faster. Recently, maggots from several other fly species (Calliphora vicina, Calliphora vomitoria, Phormia regina, Chrysomya albiceps, Sarcophaga carnaria, and Hermetia illucens) have been shown in vitro to possess characteristics (ie, debridement efficacy and putative antimicrobial potentialities) that make them suitable candidates for possible use in clinical practice. This review presents a historical analysis of larval debridement and speculates future directions based on the literature presented.

Bitter Melon Extract Promotes Granulation Tissue Growth and Angiogenesis in the Diabetic Wound.

OBJECTIVE: Bitter melon is a plant fruit that has been shown to exert a hypoglycemic effect when used systemically in patients with diabetes. This study was designed to investigate the topical effect of bitter melon on diabetic wounds using the wound chamber model in rats. DESIGN: Two bilateral wound chambers were implanted subcutaneously in the thoracic-lumbar region of male Sprague-Dawley rats. Diabetes was induced with streptozotocin 7 days after implantation of wound chambers. After 24 hours of induction of diabetes, aqueous extract of bitter melon was injected into 1 wound chamber, and saline (0.9% sodium chloride solution) was injected into the contralateral chamber once daily for 3 days. Wound fluid was collected on day 4 for analysis, following which rats were euthanized. The granulation tissue encapsulating the wound chamber was removed and processed for histology. Controls included diabetic rats with wound chambers injected with saline (instead of bitter melon) and nondiabetic rats with wound chambers injected with bitter melon. RESULTS: In rats with diabetes, wound granulation tissue treated with bitter melon was well formed, with distinct cellular layers, whereas the saline-treated granulation tissue showed a severe loss of tissue organization and blood vessels. Moreover, the bitter melon treatment increased angiogenesis in the diabetic granulation tissue, marked by abundant microvessels and large blood vessels. In nondiabetic rats, no differences in wound granulation tissues were observed between saline- and bitter melon-treated groups. Bitter melon treatment had no effect on systemic blood glucose levels or insulin receptor substrate 1, suggesting that its stimulatory effect on diabetic granulation tissue was not due to alteration of systemic blood glucose levels. CONCLUSIONS: When applied locally to diabetic wounds, bitter melon extract prevents regression of granulation tissue and blood vessels, thus accelerating and improving wound healing.

Multiple Scrotal Ulcers in an Infant Due to a Traditional Child Care Practice: Salting.

Application of salt to the newborn's skin is a common traditional child care custom in Turkey. We present an infant with multiple ulcerating scrotal lesions due to prolonged salt exposure in the diaper area. Scrotal ulcers associated with salting have not been described previously.

[Effects of Qizhi Jiangtang capsule on dermal ulcer in type 2 diabetic rats].

The effect of Qizhi Jiangtang vapsule (QJC) on degree of dermal ulcer cicatrization in 2 type diabetic rats was studied. Except the rats for blank group, other male Wistar rats were used to establish type 2 diabetic model by feeding with high sugar and high fat diet for four weeks and intraperitonally injecting with 30 mg•kg⁻¹ streptozotocin (STZ). After that, the rats were divided into balanced groups according to blood sugar, and received corresponding drugs for treatment for 8 weeks. At the end of week 8, 2 cm diameter circular incision was done on the back of rats. After that, the rats were administered continuously for10 days. Area of ulcer surface was detected every two days. After the last administration, wound granulation tissues were cut down to conduct pathological examination and detect the expression of VEGF, PI3K, p-ERK protein in wound tissues. The results showed that compared with the model group, after application of Qizhi Jiangtang capsule (2.24 g•kg⁻¹), the wound was significantly reduced on day 6 and day 10 of wound formation; inflammation reaction on ulcer surface was significantly reduce; Qizhi Jiangtang capsule can increase VEGF expression in the wound tissues of diabetic rats, and inhibit ERK phosphorylation. It can be concluded that Qizhi Jiangtang capsule can promote skin ulcer healing for diabetes rats, and its mechanism may be related to regulating the expression of VEGA and p-ERK proteins.

Organic light emitting diode improves diabetic cutaneous wound healing in rats.

A major complication for diabetic patients is chronic wounds due to impaired wound healing. It is well documented that visible red wavelengths can accelerate wound healing in diabetic animal models and patients. In vitro and in vivo diabetic models were used to investigate the effects of organic light emitting diode (OLED) irradiation on cellular function and cutaneous wound healing. Human dermal fibroblasts were cultured in hyperglycemic medium (glucose concentration 180 mM) and irradiated with an OLED (623 nm wavelength peak, range from 560 to 770 nm, power density 7 or 10 mW/cm2 at 0.2, 1, or 5 J/cm2). The OLED significantly increased total adenosine triphosphate concentration, metabolic activity, and cell proliferation compared with untreated controls in most parameters tested. For the in vivo experiment, OLED and laser (635 ± 5 nm wavelength) treatments (10 mW/cm2 , 5 J/cm2 daily for a total of seven consecutive days) for cutaneous wound healing were compared using a genetic, diabetic rat model. Both treatments had significantly higher percentage of wound closure on day 6 postinjury and higher total histological scores on day 13 postinjury compared with control. No statistical difference was found between the two treatments. OLED irradiation significantly increased fibroblast growth factor-2 expression at 36-hour postinjury and enhanced macrophage activation during initial stages of wound healing. In conclusion, the OLED and laser had comparative effects on enhancing diabetic wound healing.

Systemic wound care: a meta-review of cochrane systematic reviews.

Wound care is a classic example of a surgical realm with a great variation in care. The diversity in wounds and wound treatments, the limited amount of convincing evidence, and the diverging opinions among doctors and nurses involved in wound care contribute to this undesirable variation in care. For chronic wounds, such as arterial or venous ulcers, pressure sores, and diabetic foot ulcers, but also for acute wounds after surgery or trauma, international and national guidelines provide recommendations on diagnostic procedures and treatment options, but rely mostly on expert opinion. We present the available evidence from Cochrane systematic reviews for the systemic treatment (i.e., not prevention) of patients with wounds, as opposed to topical wound treatments. This evidence shows: - Venous ulcers: High-compression therapy is the classic and evidence-based treatment for treating venous ulcers. Oral pentoxifylline promotes ulcer healing with and without compression therapy. Oral zinc is not effective to heal venous ulcers. - Acute wounds: Recombinant human growth hormone accelerates healing of large burn wounds and donor sites, while high-carbohydrate feeding might reduce the risk of pneumonia. Linezolid is more effective than vancomycin for treating skin and soft tissue infections. Hyperbaric oxygen may help heal crush wounds and skin grafts. Therapeutic touch does not heal acute wounds. - Pressure sores: Air-fluidized and some low-tech devices appear effective for treating existing pressure ulcers. Oral zinc, protein, or vitamin C supplements seem ineffective. Also, evidence is lacking on the effectiveness of repositioning regimes as a treatment option. - Diabetic ulcers: Hyperbaric oxygen therapy and pressure-relieving devices may improve healing rates. - Arterial ulcers: Prostanoids and spinal cord stimulation may be effective in healing ischemic ulcers. Thus, fortunately, some high-level evidence exists for various local and systemic interventions in wound care. Caregivers should be aware of, and apply, the strongest evidence available. Only when all stakeholders (patients, physicians, wound care nurses, but also manufacturers and buyers) implement this available evidence will optimum quality of care for patients with wounds be ensured.

Diabetic hand infections and hyperbaric oxygen therapy.

OBJECTIVE: The aim of this study was to discuss the clinical characteristics and results of hand infections in diabetic patients treated with hyperbaric oxygen therapy (HBOT). METHODS: This retrospective study included 10 patients with diabetes mellitus who underwent HBOT due to hand infections between January 2006 and February 2011. RESULTS: Amputation was performed at the level of the right hand index finger proximal interphalangeal joint in 1 patient and at the level of the distal phalanx of the left hand middle finger in 1 due to necrotizing soft tissue infection. Ulcers of 8 patients healed completely without amputation. CONCLUSION: The addition of HBOT to the standard treatment may contribute to the healing of hand ulcers in diabetics by increasing the tissue oxygenation and correcting the process of disturbed wound healing.

Influence of a specific, biorhythmically defined physical stimulus on deficient vasomotion in small-caliber arterioles in the subcutis in patients with diabetic polyneuropathy.

As part of a placebo-controlled study series on a random sample of patients with diabetic polyneuropathy and trophic skin lesions on the edge of the foot, functional characteristics of the local microcirculation and immune system were measured to check the complementary-therapy success of biorhythmically defined vasomotion stimulation. Over a 30-day treatment period, complementary-therapy success was demonstrated for an additional physical vasomotion stimulation to increase the therapeutic success of established treatment concepts.

[Effect of mild moxibustion on macrophage number and collagen expression of raw surface tissue in chronic refractory skin ulcer rats].

OBJECTIVE: To observe the effect of mild moxibustion on the number of macrophages and contents of collagen I and III in the raw surface tissue in chronic skin ulcer rats so as to study its mechanism underlying promoting scar formation. METHODS: Eighty male SD rats were randomly divided into normal (n = 8), model (n = 24), TDP (n = 24) and moxibustion (n = 24) groups. Chronic refractory skin ulcer was established by making an open wound at the back and local intramuscular injection of hydrocortisone sodium succinate. For rats of the TDP and moxibustion groups, TDP irradiation or mild moxibustion was applied to the raw surface, bilateral "Shenshu" (BL 23) and "Zusanli" (ST 36) for 15 min, once daily for 7, 10 and 14 days, respectively. The number of macrophages in the raw surface tissue was counted under light microscope after H. E. staining and col- lagen I and III expressions of the raw surface tissue were detected by immunohistochemistry. RESULTS: In comparison with the normal group, the numbers of macrophages in the raw surface tissue were increased significantly in the model group on day 7, 10 and 14 (P < 0.05); while compared with the model group, the numbers of macrophages were increased further obviously in the moxibustion group on day 7 and 10 and in the TDP group on day 10 after the treatment (P < 0.05). Compared with the model group, the numbers of macrophages in both TDP and moxibustion groups were down-regulated obviously (P < 0. 05). In regard to collagen I and III expression of the raw surface tissue, compared with the normal group, the collagen I protein expression level was down-regulated markedly in the model group on the 7th day (P < 0.01); whereas in comparison with the model group, the expression levels of collagen I and III were increased considerably in the TDP and moxibustion groups on day 7 and 14 after the treatment (P < 0.05, P < 0.01). The ratios of collagen I/III expression were remarkably higher in the model group than in the normal group on day 7 and 14 (P < 0.05), and significantly lower in the TDP group on day 7 and 14 and in the moxibustion group on day 14 than in the model group (P < 0.05, P < 0.01). The effects of moxibustion were obviously superior to those of TDP in up-regulating macrophage number on day 10, up-regulating collagen I and III expressions on day 14, and down-regulating macrophage number on day 14 after the treatment (P < 0.05, P < 0.01). No significant differences were found between the TDP and moxibustion groups in up-regulating macrophage number, and collagen I and III protein expressions, and in down-regulating the ratios of collagen I/III expression on day 7 after the treatment (P > 0.05). CONCLUSION: Mild moxibustion can regulate the number of macrophages and strengthen the expression of collagen proteins in the raw surface tissue in the chronic skin ulcer rats, which may contribute to its effect in promoting wound healing and reducing scar formation.

Trends in wound repair: cellular and molecular basis of regenerative therapy using electromagnetic fields.

Chronic ulceration of the leg represents a major, underestimated problem of modern health care, involving physical and cosmetic impairment and social stigma along with high community costs for patients' treatment. The increasing prevalence of chronic ulcers, currently reported to be as much as 0.3% in the general population, should stimulate identification of more efficacious therapeutic approaches to achieve complete healing. The strategies of regenerative medicine based on small molecules, biomimetic scaffolds, gene or cell therapy, and electromagnetic field manipulation represent some of the modern therapeutic alternatives for wound healing. Here we review in an integrated, interdisciplinary approach the modern cellular and molecular mechanistic concepts regarding the involvement of extremely low frequency electromagnetic fields (ELF-EMF) in the complex process of tissue repair, with particular focus on chronic wounds. The data analysis supports three main effects of electromagnetic fields on the wound healing pathways: 1) an antiinflammatory effect, by modulation of cytokine profile that induces the transition of the healing process from a chronic pro-inflammatory to an anti-inflammatory state; 2) a neo-angiogenic effect, by increased endothelial cells proliferation and tubulization and production of fibroblast growth factor (FGF)-2; and 3) a reepithelialization effect, by stimulation of collagen formation. We believe that utilization of ELF-EMF in larger clinical trials designed to optimize these functional parameters would facilitate a better understanding of ELFEMF- induced healing mechanisms and lead to improved therapeutic outcomes for this disabling condition which is often totally resistant to treatment.

Increasing the options for management of large and complex chronic wounds with a scalable, closed-system dressing for maggot therapy.

As reconstructive specialists, burn surgeons are often involved in managing large wounds of various etiologies. Such wounds can pose a management challenge, especially if they are chronic or occur in the setting of critical illness or multiple medical comorbidities. Medical maggots are an effective, selective, and low-risk method for wound debridement. However, their use in large and geometrically complex wounds is limited by the lack of scalability in currently available dressings, which are appropriate for smaller wounds but become cumbersome and ineffective in larger ones. This report describes a novel dressing designed for application of maggot debridement therapy in large and complex wounds. The authors then discuss how use of this dressing may create new management strategies for such wounds by allowing maggots to mechanically debride big, infected wounds. They describe the construction of a maggot containment dressing based on modified components from a negative pressure wound therapy system and provide a case report highlighting its successful clinical use in a large contaminated chronic wound resulting from Fournier's gangrene. In the case described, the novel dressing provided scalability, containment of maggots, control of secretions, and ease of use. The dressing created an environment suitable for maggot survival and allowed effective debridement of a heavily contaminated groin wound. The novel dressing described is shown to function appropriately, allowing controlled use of maggots for effective debridement of large, irregular wounds. Facilitating the use of maggots in such wounds may broaden the algorithm for their management.

[Effect of mild-warm moxibustion on microcirculation in the raw surface tissue of chronic refractory wound in skin ulcer rats].

OBJECTIVE: To observe the effects of mild-warm moxibustion on dynamic blood flow, microvessel count (MVC)and vascular endothelial growth factor (VEGF) expression in the wound tissue of the chronic skin ulcer in rats, so as to reveal its underlying mechanism in promoting wound recovery. METHODS: A total of 104 male SD rats with skin injury were randomly divided into control group (n=8), model group (n=32), TDP (far-infrared heating device) group (n=32) and moxibustion group (n=32). Chronic refractory raw surface wound model was established by muscular injection of Hydrocortisone Sodium Succinate. For rats of the TDP and moxibustion groups, TDP irridiation and mild-warm moxibustion were applied to the raw surface, bilateral "Shenshu" (BL 23) and "Zusanli" (ST 36) for 15 min, once daily for 3, 7 and 14 days respectively. The healing rate and the healing time of raw surface of the wound were observed. The blood flow of the raw surface of the wound tissue was measured by laser Doppler flowmeter and the MVC in granulation tissue of chronic skin ulcer was counted under light microscope. VEGF expression was detected by immunohistochemistry. RESULTS: In comparison with the control group, the healing rate of the wound raw surface was significantly lower and the healing time was prolonged in the model group (P < 0.01). Compared with the model group, the healing rates on day 3, 7, 10 and 14 were significantly higher and the healing time was strikingly faster in both TDP and moxibustion groups (P < 0.01, P < 0.05), and the effects of the moxibustion group in increasing the healing rate and shortening the healing time were significantly better than those of TDP group (P < 0.01). In comparison with the model group, the blood flow volume, MVC and VEGF expression levels on day 3 and 7 were upregulated significantly in both TDP and moxibustion groups (P < 0.01, P < 0.05); while the blood flow volume, MVC and VEGF expression level in the moxibustion group and the blood flow volume and VEGF expression level in the TDP group downregulated considerably on day 14 (P < 0.01). No significant difference was found between the TDP and moxibustion groups in the MVC on day 14 after the treatment (P > 0.05). CONCLUSION: Mild-warm moxibustion can promote wound healing, which is closely with its effects in increasing blood flow and MVC, and upregulating VEGF expression in the wound granulation tissue of the chronic skin ulcer.

[Comparative study of the effects of Gypsum Fibrosum and Gypsum Fibrosum Preparatum in promoting granulation].

OBJECTIVE: To investigate the effects of Gypsum Fibrosum and Gypsum Fibrosum Preparatum in promoting granulation. METHODS: The wounds of muscle layer were produced in rats by using surgical operation. Two round wounds, with diameter about 1.5 cm, were cut at the depilatory area of two sides of the back of each rat, with an interval of 2 cm, deep to muscle layer, and the thickness of the knife wound of muscle layer was about 0.15 cm. Forty SD rats with the wounds were randomly divided into 4 groups: untreated group, beifuji-treated group, Gypsum Fibrosum-treated group and Gypsum Fibrosum Preparatum-treated group, with 10 rats in each group. Then the wounds were sprinkled with powders of Gypsum Fibrosum and Gypsum Fibrosum Preparatum, or sprayed with beifuji solution, respectively. The healing state of granulation tissues of the wounds was observed at the eighth and fourteenth day respectively. RESULTS: The number of fibroblasts, the number of capillary tubes and the area of capillary tubes in granulation tissue of wounds in the Gypsum Fibrosum Preparatum-treated group were significantly higher than those in the untreated group and Gypsum Fibrosum-treated group (P<0.01). There were no statistical differences between the Gypsum Fibrosum Preparatum-treated group and the beifuji-treated group. However, Gypsum Fibrosum-treated group showed no obvious differences compared to the untreated group (P>0.05). CONCLUSIONS: Gypsum Fibrosum Preparatum can accelerate the formation of collagenoblast and micrangium in wounds, and the proliferation of granulation tissues, thus promoting the skin wounds to healing. The effect of Gypsum Fibrosum is changed after being calcined, and Gypsum Fibrosum Preparatum has obvious effect in promoting granulation.

[Effects of Wenshen Jianpi Recipe on chronic wound healing in rats].

OBJECTIVE: To study the effects of Wenshen Jianpi Recipe (WSJPR, a traditional Chinese medicine for warming kidney and invigorating spleen) on chronic wound healing and the mechanism. METHODS: Ninety-six SD rats were randomly divided into 4 groups, with 24 rats in each group, and back wound was made in the rats. For rats in 3 of the 4 groups, hydrocortisone injection was administered to induce chronic wound. Rats in 2 of the 3 groups were treated with WSJPR and Xinpukang Granules (XPKG) respectively, and the rats in the other group were untreated. The rats in the fourth group were taken as control. The wound healing time and the width of new epidermis were observed, and the histomorphological changes and cell cycle of the granulation tissue, and the protein expressions of epidermal growth factor (EGF), transforming growth factor-beta(1) (TGF-beta(1)) and fibronectin (FN) in the granulation tissue were tested with immunohistochemical technique and flow cytometry. RESULTS: The wound healing time of the WSJPR-treated and XPKG-treated groups was (17.0+/-1.9) and (18.8+/-1.9) d respectively, much shorter than that of the untreated and control groups (P<0.05). On the 14th experiment day, the width of new epidermis of the WSJPR-treated and XPKG-treated groups was (3.73+/-0.19) and (3.21+/-0.15) mm respectively, much wider than that of the untreated and control groups (P<0.05). The numbers of angiogenesis, fibroblasts and cells in the S phase in WSJPR-treated and XPKG-treated groups were much higher than those in the untreated and control groups (P<0.05). Compared with the untreated and control groups, the protein expressions of EGF, TGF-beta(1) and FN in WSJPR-treated and XPKG-treated groups were higher (P<0.05). CONCLUSION: WSJPR can enhance the wound healing. It was likely through accelerating the cell proliferation and up-regulating the expressions of EGF, TGF-beta(1) and FN.

Electrotherapy promotes healing and microcirculation of infrapopliteal ischemic wounds: a prospective pilot study.

OBJECTIVE: To determine if high-voltage pulsed current (HVPC) electrotherapy augments ischemic wound healing and increases periwound microcirculation. DESIGN: A prospective, randomized, single-blinded, sham-controlled clinical trial was conducted on a homogenous subset of quasi-stable ischemic wounds. INTERVENTION: Active HVPC or sham HVPC was applied to wounds for a 14-week period. MAIN OUTCOME MEASURE: Wounds were monitored every 4 weeks, except 2 weeks between weeks 12 and 14, for wound area, wound appearance, and microcirculation, which was measured by transcutaneous oxygen (TcPO2) levels and laser Doppler flow. RESULTS: Ischemic wounds treated with active HVPC decreased in size, contrary to the expected increase in ischemic wound size that was observed in wounds in the control group (P <.05, Student t test; week 4). A trend toward smaller wound area occurred in wounds in the HVPC group compared with wounds in the control group (week 14). Among the HVPC group, an improvement in periwound microcirculation occurred at weeks 8 (P <.05, TcPO2; P <.01, laser Doppler) and 12 (P <.05, laser Doppler). These increases suggest that HVPC promotes arteriolar vasodilation and dermal capillary formation. HVPC was well tolerated. CONCLUSION: The results of this study demonstrate that HVPC decreased the area of ischemic wounds, reversing the expected increase in wound size, and improved microcirculation. The promising results of this pilot study require a larger Phase II study to confirm and generalize these findings. CLINICAL RELEVANCE: Electrotherapy may prove to be a relatively safe and effective complement to surgical revascularization to improve the odds of healing ischemic wounds and promoting limb salvage.

Mind-body techniques in wound healing.

Even the most skilled and resourceful wound care provider encounters stagnation of wound healing from time to time. Patients with chronic, nonhealing wounds often display negative thought patterns and behavioral tendencies that, in turn, hinder biological and emotional healing. An increasing body of research supports the negative effect of stress on wound healing. The impact of deeper, emotion-based "wounds" as complicating factors in conventional wound healing are being further explored. It is theorized that emotions such as lack of self worth, guilt, and anger are strongly correlated to the chronic, nonhealing wound. Mind-body techniques such as affirmations, creative visualization, relaxation, and conscious breathing are suggested for incorporation into the treatment program. These techniques seek to empower and engage the patient by promoting greater personal awareness and assertion in the healing process. Wound care providers are seen as facilitators of the innate healing potential inside each individual. Mind-body techniques are offered as a complement for a more comprehensive wound healing strategy.