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Documentation of 7051 chronic wounds using a new computerized system within a network of wound care centers.

HYPOTHESIS: Wound care can be prospectively recorded on a large scale if a standardized wound documentation system is established. Based on such a documentation system, a network of specialized wound care centers can generate a large and valid database of wound characteristics, wound-healing dynamics, and wound care. DESIGN: A clinical prospective analysis. SETTING: Ten German specialized surgical wound care centers. PATIENTS AND METHODS: In a 2-year pilot phase, 4175 patients with 7051 chronic nonhealing wounds were documented using a new computerized system and treated following defined standards. RESULTS: A total of 1761 diabetic, 1349 venous, 1146 ischemic, 1079 pressure, and 759 postoperative nonhealing wounds and 957 ulcers with other causes were prospectively documented. Chronicity of ulceration was shown by the long wound duration of 433 days (range, 14-1867 days). Wound documentation was well integrated into daily practice, as shown by a mean +/- SD documentation time of 5.7 +/- 2.2 minutes per visit. A multivariate analysis of factors known to interfere with wound healing revealed significant effects of patient compliance, grading of wound depth, and patient age (P<.001 for all). CONCLUSIONS: The German Wound Net achieved, for the first time, centralized and prospective documentation of more than 7000 chronic wounds treated according to defined guidelines. This new concept of a network of specialized wound care centers working with standardized treatment plans and prospective documentation of chronic wounds may open a new dimension for wound-healing studies and may represent an optimal platform for multicenter trials.

Chronic Disease↗

Influence of wound shape on wound contraction in horses.

Three sets of paired circular and square full-thickness skin wounds were made on the dorsum of the metacarpus (n = 48) of 8 horses. Each wound was 6.25 cm2 in area. The wounds were treated topically with an ointment, nonadherent dressing, and bandaged with a snug elastic wrap. Wounds were photographed every other day until healing was complete. Wound areas were measured and exponential and linear wound healing models were applied to the wound healing data generated. Wound healing variables measured for each wound were: number of days to healing, maximal size attained, rate of wound contraction (calculated by use of first-order and linear models), final wound size, and percentage of wound that healed by contraction. The exponential model fit the data significantly better than the linear model. The maximal size attained by circular wounds was significantly smaller than the maximal size attained by square wounds. Wound shape did not influence the rate of wound healing. On the basis of our findings, conversion of circular defects to square defects would not speed wound healing.

Animals↗

Wound cleaning versus wound disinfection: a challenging dilemma.

Our experience with this resident has had a significant impact on our approach to wound management. We no longer accept normal saline as the only option for wound cleansing. Instead, we approach wound cleansing systematically using the wound cleansing model outlined in Figure 1. If healing is not apparent, we critically review the situation and consider the bacterial status of the wound, the phase of wound healing, and the effects of wound cleansing versus wound disinfection on both the bacteria and the cells responsible for wound repair. In infected wounds or those colonized with a high bacterial count, careful attention is given to eradicating bacterial contamination. We carefully weigh the benefits of wound disinfection (eradication of bacterial contamination) against wound cleansing and the potential harm to the resident (delayed wound healing and unnecessary discomfort). If the benefits of wound disinfection outweigh the potential harm to the resident, we choose wound disinfection and monitor its effectiveness on a daily basis. When bacterial contamination has been eradicated and the wound is clean, we resume wound cleansing with normal saline.

Acetic Acid↗

Molecular and mechanistic validation of delayed healing rat wounds as a model for human chronic wounds.

The purpose of this study was to provide molecular and mechanistic evaluation of an ischemic wound model in rats to determine if it is a valid model for human chronic wounds. Compared to acute wounds, human chronic wounds contain markedly elevated levels of proinflammatory cytokines and matrix metalloproteinases, while matrix metalloproteinase inhibitors and growth factor activity are diminished. Accordingly, tissue from ischemic and normal rat wounds were analyzed for cytokine, proteases and growth factor levels. Dorsal full thickness punch wounds were created in rats using a reproducible template. The ischemic wound group (n = 10) had six uniformly placed wounds within a bipedicled dorsal flap. The control group (n = 10) had the same wounds created without elevation of a flap. On postwound days 3, 6 and 13 wounds were excised and analyzed. Protein levels for tumor necrosis factor-alpha were determined with a rat-specific enzyme-linked immunosorbent assay, while mRNA was determined by RNase protection assay. Matrix metalloproteinases and serine protease detection was done using gelatin and casein zymography, respectively. Significant delay in healing was achieved in the ischemic group: 50% healing for control wounds was at 7 days and 11 days for ischemic wounds (p < 0.001). No significant differences between wound groups were found for interleukin-1beta, and mRNA for tumor necrosis factor-alpha and interleukin-1beta. However, at day 13 ischemic wounds contained significantly more tumor necrosis factor-alpha than controls and normal skin (586 +/- 106 pg/biopsy vs. 79 +/- 7 pg/biopsy vs. 52 +/- 2 pg/biopsy; p < 0. 001). Zymography showed substantially greater quantities of matrix metalloproteinase-2, matrix metalloproteinase-9, and serine proteases in ischemic wounds. This model of delayed healing in rats shares many of the key biochemical, molecular and mechanistic characteristics found in human chronic wounds, namely elevated tumor necrosis factor-alpha and protease levels. As such, this model will likely prove to be useful in chronic wound research, particularly in developing novel therapeutics.

Animals↗

Wound bed score and its correlation with healing of chronic wounds.

Adequate wound bed preparation is essential for healing of leg ulcers, and consists of controlling exudate and edema, decreasing the bacterial burden, promoting healthy granulation tissue, and removing necrotic tissue. Currently, there is no classification system for wound bed preparation that has predictive value. Based on past work and the authors' experience, we have now developed and tested a new classification system that scores the following parameters: healing edges (wound edge effect), presence of eschar, greatest wound depth/granulation tissue, amount of exudate amount, edema, peri-wound dermatitis, peri-wound callus and or fibrosis, and a pink/red wound bed. Each parameter receives a score from 0 (worst score) to 2 (best score), and all the parameter scores are added for a total score. Each wound can have a maximum score of 16 (the best score possible), to a minimum score of 0 (the worst score possible). We used this wound bed score (WBS) system in a study of 177 patients with venous ulcers who had been prospectively treated with and randomized to either conventional therapy (compression alone) or a living bilayered skin construct (BSC). We evaluated serial photographs at baseline to determine whether the results would be predictive of complete wound closure and could validate the WBS. We found that wounds that ultimately achieved full closure had a statistically significant higher WBS than those that did not heal (p = 0.0012). This was also true when separating wounds by treatment modality: standard therapy (p = 0.044) and treatment with a BSC (p = 0.011). When dividing the WBS in the following quartile groups: scores 4-10, 10-12, 12-13, and 13-16, the percentage of healed wounds correlated with the WBS (p = 0.0008). For all wounds, a one unit increase in total WBS resulted on average in a 22.8% increase in odds of healing (OR = 1.228). This WBS seems to have validity in predicting complete wound closure in wounds treated with either standard therapy or advanced modalities, such as BSC. If confirmed and widely adopted in this and other types of wounds, it could be a useful tool in both the clinical and research setting.

Adolescent↗

Cutaneous wound healing in the cat: a macroscopic description and comparison with cutaneous wound healing in the dog.

OBJECTIVE: To describe the macroscopic features of first and second intention cutaneous wound healing in the cat and compare with the dog. STUDY DESIGN: Experimental study. ANIMALS: Domestic shorthaired cats (6) and beagle dogs (6). METHODS: Square, open cutaneous wounds created on the dorsal aspect of the thorax were evaluated for 21 days for temporal and spatial development of granulation tissue, wound contraction, epithelialization, and total healing. To evaluate first intention healing, breaking strength of sutured linear cutaneous wounds was measured at 7 days post-wounding. Laser-Doppler perfusion imaging was used to measure cutaneous perfusion. RESULTS: First intention healing: sutured wounds in cats were only half as strong as those in dogs at day 7 (0.406 versus 0.818 kg breaking strength). Second intention healing: cats produced significantly less granulation tissue than dogs, with a peripheral, rather than central distribution. Wound epithelialization and total wound healing (total reduction in open wound area from contraction and epithelialization) were greater for dogs than for cats over 21 days. Wound contraction on day 7 was greater for dogs, but not on day 14 or 21. Cutaneous perfusion was initially greater for dogs than for cats, but no differences were detected after day 7. CONCLUSIONS: Significant, previously unreported differences in cutaneous wound healing exist between cats and dogs. In general, cutaneous wounds in cats are slower to heal. Cats and dogs also appear to use different mechanisms of second intention healing. In cats wounds close mainly by contraction of the wound edges, whereas in dogs wounds close more from central pull, and epithelialization. CLINICAL RELEVANCE: Surgeons should view the cat as a unique species, which presents its own special challenges in wound healing, and should take this into account when planning treatment of feline wounds, either by primary closure, or by second intention healing.

Animals↗

Comparisons of wound healing among excisional, laser-created, and standard thermal burns in porcine wounds of equal depth.

The present study was designed to characterize similarities and differences among three wounding modalities in partial-thickness porcine wounds. We hypothesized that inherent differences, such as endogenous cytokine delivery into excisional wounds or ablation of eschar during laser vaporization, should accelerate the magnitude and sequence of reparative events above the delayed repair that is frequently observed in patients with burns. A constant mid-dermal depth of injury was created by a Padgett dermatome, a computer-controlled pulsed CO(2) laser, or a temperature-controlled metal template. Wounds were harvested after 5, 10, or 15 days. After 5 days, significant resurfacing differences were apparent with values of 54% in excisions, 29% in lasers, and 12% in standard thermal burns. Sequences of fibroblastic proliferation were measurably different among the three wound modalities. At day 5 the bromodeoxyuridine labeling index for fibroblasts showed laser wound levels greater than excision wound levels, which were greater than burn wound levels; but by day 10, the proliferative profiles indicated that burn wound levels were greater than excision wound levels, which were greater than laser wound levels. Capillary areas (an assessment of angiogenesis) differed among the three wound types throughout the study. Peak values were observed at day 5 in both excisional and laser injuries; however, standard thermal burns did not peak until day 10. Both the magnitude and sequence of expression of three matrix metalloproteinases (-1, -2, and -9) differed among the three types of injuries. Laser wounds showed the earliest peak in matrix metalloproteinase-1 expression, whereas burns showed the least expression at day 5. In conclusion, although the three types of wounds undergo similar reparative processes such as reepithelialization, fibroblastic proliferation, angiogenesis, and expression of matrix metalloproteinases, the magnitude and temporal sequences are measurably altered among the three wound modalities. A greater understanding of specific differences within wound environments may lead to more insightful design of interventional wound therapies.

Journal Article↗

[Wound dressings in chronic wounds].

Hydroactive wound dressings retain exsudate in the wound region or incorporate wound exsudate by gel formation. They create the local environment for moist wound healing which is experimentally and clinically characterized by accelerated reepithelialization, inflammatory reaction and angiogenesis as well as reduced wound pain and wound infection rates. Clinically relevant product groups of hydroactive wound dressings (hydrocolloids and hydropolymers, semipermeable films, calcium alginates) are distinct as to chemical structure, physical properties and functional characteristics in local wound treatment. Between the product groups, there are considerable differences with respect to inflammatory reactions at the wound bottom, absorption of exsudate, occlusion properties, wound edge adherence, adaptability to the wound shape and material integrity of wound dressings. Experimental and clinical results of moist wound treatment by hydroactive wound dressings such as hydrocolloids and hydropolymers, semipermeable films or calcium alginates reveal a wide range of local response on the different types of dressings. They offer the opportunity of therapeutic differentiation. To elucidate the differential indication for different product groups of hydroactive wound dressings in local treatment of chronic wounds, additional experimental and clinical research is required.

Bandages↗

Plastic wound protectors do not affect wound infection rates following laparoscopic-assisted colectomy.

BACKGROUND: Wound protectors are plastic sheaths that can be used to line a wound during surgery. Wound protectors can facilitate retraction of an incision without the need for other mechanical retractors and have been proposed as deterrents to wound infection. The purpose of this study was to define the ability of wound protectors to reduce the rate of infection when used in laparoscopic-assisted colectomy. METHODS: We completed a retrospective review of the medical records of patients undergoing nonemergent laparoscopic-assisted colectomy between February 1999 and November 2002. All completely laparoscopic cases were excluded. The wound protector, when used, was applied to the extraction incision during the externalized portion of the procedure (colon and mesentery transection, anastomosis). Outcomes for patients with and without the use of a wound protector were compared. RESULTS: A total of 141 patients underwent laparoscopic-assisted colectomy (98 for benign/malignant tumors, 35 for diverticular disease, and eight for Crohn's disease). There were no differences between the wound protector group ( n = 84) and the no wound protector group ( n = 57) with respect to mean age (55 vs 58 years), average body mass index (27 vs 29 kg/m2), gender, indication for surgery, comorbidities, antibiotics used, or mean operative time (185 vs 173 min). Nine patients in the wound protector group and eight in the no wound protector group developed a wound infection at the colon extraction site ( p = 0.42). Patients undergoing resection for Crohn's disease or diverticulitis had a higher infection rate (18.6%) than patients undergoing resection for polyps or cancer (9.2%; p < 0.05). No wound recurrence of cancer was observed in either group at a mean follow-up of 23 months (range, 3-48). CONCLUSIONS: The wound protector, although useful for mechanical retraction of small wounds, does not significantly diminish the rate of wound infection at the bowel resection/anastomotic site. Patients undergoing elective resection for inflammatory processes have higher infection rates than patients undergoing laparoscopic-assisted colectomy for polyps or cancer.

Adult↗

Wound fluid inhibits wound fibroblast nitric oxide synthesis.

BACKGROUND: Fibroblast-derived nitric oxide (NO) is an autocrine stimulator of collagen synthesis by wound fibroblasts. Little is known about the in vivo regulation of wound fibroblast NO synthesis. We investigated the net effect of wound environment on wound fibroblast NO production and characterized a soluble factor mediating this effect. MATERIALS AND METHODS: Wound fibroblasts and acellular wound fluid (pool of 100 Lewis rats) were isolated from subcutaneously implanted polyvinyl alcohol sponges harvested 10 days post-wounding. Fibroblasts were incubated in the presence of 10% (v/v) wound fluid. Nitrite, an index of NO synthesis, was measured in supernatants by Griess reagent. RESULTS: Wound fibroblasts spontaneously synthesize large amounts of NO. Spontaneous NO synthesis was further increased by LPS + IFN-gamma (P < 0.001). Wound fluid significantly inhibited both spontaneous and LPS plus IFN-gamma-stimulated NO synthesis (by 88 and 55%, respectively; P < 0.01). Wound fluid from 5- to 35-day-old wounds equally suppressed NO synthesis. Separation by Sephadex G-100 gel filtration identified the active factor in wound fluid to have a molecular weight of about 100 kDa. Characterization of this factor showed it to be a heat-resistant (56 degrees C, 30 min), trypsin-sensitive, and neuraminidase-resistant protein (ammonium sulfate precipitation). The isoelectric point appeared to be 7.0, as determined by ion exchange chromatography. Addition of high arginine did not restore the effect of wound fluid on fibroblast NO synthesis, suggesting that substrate is not a limiting factor. CONCLUSION: Our data demonstrate that following postoperative day 5 the wound environment contains a high molecular weight protein that inhibits NO synthesis by wound fibroblasts.

Animals↗

Temporal expression of urokinase plasminogen activator, plasminogen activator inhibitor and gelatinase-B in chronic wound fluid switches from a chronic to acute wound profile with progression to healing.

The plasminogen activator/plasmin system is known to initiate a proteolytic cascade resulting in the activation of matrix metalloproteinases in vitro leading to the degradation of extracellular matrix. To investigate whether or not this cascade is present during delayed wound healing and contributes to the pathophysiological basis of impaired healing we examined the temporal expression of urokinase plasminogen activator, plasminogen activator inhibitor-1 and gelatinase-B in fluid collected from chronic venous leg ulcers compared to acute surgical mastectomy wounds. Using a chromogenic substrate assay, levels of active urokinase plasminogen activator in chronic wounds were found to be about five fold higher compared to sera and two fold higher compared to mastectomy wounds. Levels of active plasminogen activator inhibitor-1 in chronic wounds were four times higher than those found in sera and two times higher than those found in mastectomy wound fluid. Using a fibrin overlay system and reverse zymography, we found that when the wound was not healing, the expression of urokinase plasminogen activator in chronic wound fluid was initially detected in the active forms (50 and 33 kDa), but that as the wound healed and decreased in size, was detected as an inhibitor- bound urokinase plasminogen activator-plasminogen activator inhibitor-1 complex ( congruent with 80-116 kDa). When the expression of active urokinase plasminogen activator was highest, no plasminogen activator inhibitor-1 was detectable. In contrast, urokinase plasminogen activator was always detected in the inhibitor bound form as a urokinase plasminogen activator-plasminogen activator inhibitor-1 complex in blood- and plasma-derived serum and mastectomy wound fluid. Plasminogen activator inhibitor-1 was detected in blood-derived serum and mastectomy wound fluid but not in plasma derived serum. Expression of matrix metalloproteinase-9 in chronic wound fluids, analyzed by gelatin zymography, showed that when urokinase plasminogen activator was detected in the active forms, matrix metalloproteinase-9 was overexpressed by approximately twice that found in mastectomy wounds and approximately 30 times that detected in blood-derived sera. When urokinase plasminogen activator appeared almost entirely as an enzyme- inhibitor complex, the level of expression of matrix metalloproteinase-9 was similar to that seen in mastectomy wound fluid. We conclude that the switch in urokinase plasminogen activator expression from an active to inhibitor bound form correlates with the decrease seen in matrix metalloproteinase-9 expression suggesting the presence of a proteolytic cascade initiated by the plasminogen activator/plasmin system during wound healing leading to the activation of matrix metalloproteinase-9. In addition, expression of urokinase plasminogen activator and matrix metalloproteinase-9 appear to be useful biomarkers to determine clinical wound healing status.

Adult↗

The wounded dermal equivalent offers a simplified model for studying wound repair in vitro.

Dermal equivalents (DEs), fabricated by seeding fibroblasts into a collagen lattice, may be used as in vitro models for studying wounding and the remodelling processes observed in vivo. We investigated fibroblast responses to a wound stimulus in vitro by making small wounds in DEs. We found that, following wounding, fibroblasts appeared to migrate towards and into the wound defect and appeared to initiate the closure of the wound by bringing together the cut collagen surfaces over a period of 5-11 days. Fibroblast movement into the wound defects was significantly stimulated in the presence of EGF and PDGF (2.8- and 3.5-fold respectively) but not TGF-beta. Cell proliferation in wounded DEs was up to 21% greater than in non-wounded DEs and cell numbers were stimulated further by the addition of TGF-beta, EGF and PDGF (1.5-, 1.7- and 1.8-fold respectively). Wounded DEs also displayed a 2.1-fold increase in latent collagenase production followed by a 1.3-fold increase in active collagenase levels compared to non-wounded DEs. Staining actin fibers within fibroblasts using rhodamine-phalloidin showed that fibroblasts in DEs were under tension, but that this tension was lost upon wounding. Subsequently the stress fibers reappeared concomitantly with the observed "healing" process. Additionally a continuous cell-cell actin cable purse-string developed around the entire wound edge which may be involved in wound closure. The findings suggest that the wounded dermal equivalent offers a valuable model for studying wound healing in vitro.

Actin Cytoskeleton↗

Wound instillation--the next step in negative pressure wound therapy. Lessons learned from initial experiences.

Negative pressure wound therapy uses a reticulated sponge and subatmospheric pressure to facilitate healing of a variety of wounds. The therapy appears to assist wound healing by decreasing wound bacterial burden and edema while facilitating granulation tissue formation. The latest development in negative pressure wound therapy allows clinicians to instill a solution into the wound and is indicated for use when patients receiving negative pressure wound therapy would benefit from the controlled delivery of topical wound treatment solutions and suspensions. A retrospective analysis of five cases was conducted to describe initial experiences with instillation and negative pressure wound therapy (average treatment time on negative pressure wound therapy with instillation 15 days, range 5 to 24 days). In two of the five cases where traditional negative pressure wound therapy was tried, infected wounds improved and culture results became negative following instillation of antibiotics in a saline solution. In all cases where used, instillation of a topical anesthetic appeared to effectively minimize wound pain that is occasionally associated with negative pressure wound therapy. Negative pressure wound therapy with instillation and possibly hyperbaric oxygen therapy may be initiated from the onset of treatment to manage high-risk wounds that appear severely infected and may be limb-threatening if located on an extremity. Controlled clinical studies to ascertain the efficacy and cost-effectiveness of this treatment modality are needed.

Adult↗