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BackgroundBurns are severe injuries often associated with impaired wound healing. Impaired healing is caused by multiple factors, including dysregulated inflammatory responses at the wound site. Interestingly, montelukast, an antagonist for cysteinyl leukotrienes and U.S. Food and Drug Administration approved for treatment of asthma and allergy, was previously shown to enhance healing in excision wounds and to modulate local inflammation.MethodsIn this study, the authors examined the effect of montelukast on wound healing in a mouse model of scald burn injury. Burn wound tissues isolated from montelukast- and vehicle-treated mice at various times after burn injury were analyzed for wound areas ( n = 34 to 36), reepithelialization ( n = 14), inflammation ( n = 8 to 9), and immune cell infiltration ( n = 3 to 6) and proliferation ( n = 7 to 8).ResultsIn contrast to previously described beneficial effects in excision wounds, this study shows that montelukast delays burn wound healing by impairing the proliferation of keratinocytes and endothelial cells. This occurs largely independently of inflammatory responses at the wound site, suggesting that montelukast impairs specifically the proliferative phase of wound healing in burns. Wound healing rates in mice in which leukotrienes are not produced were not affected by montelukast.ConclusionMontelukast delays wound healing mainly by reducing the proliferation of local cells after burn injury.Clinical relevance statementAlthough additional and clinical studies are necessary, our study suggests that burn patients who are on montelukast may exhibit delayed healing, necessitating extra observation.

Background In 2010, this Journal published my comprehensive review of the literature on hypertrophic scars and keloids. In that article, I presented evidence-based algorithms for the prevention and treatment of these refractory pathologic scars. In the ensuing decade, substantial progress has been made in the field, including many new randomized controlled trials. To reflect this, I have updated my review. Methods All studies were evaluated for methodologic quality. Baseline characteristics of patients were extracted along with the interventions and their outcomes. Systematic reviews, meta-analyses, and comprehensive reviews were included if available. Results Risk factors that promote hypertrophic scar and keloid growth include local factors (tension on the wound/scar), systemic factors (e.g., hypertension), genetic factors (e.g., single-nucleotide polymorphisms), and lifestyle factors. Treatment of hypertrophic scars depends on scar contracture severity: if severe, surgery is the first choice. If not, conservative therapies are indicated. Keloid treatment depends on whether they are small and single or large and multiple. Small and single keloids can be treated radically by surgery with adjuvant therapy (e.g., radiotherapy) or multimodal conservative therapy. For large and multiple keloids, volume- and number-reducing surgery is a choice. Regardless of the treatment(s), patients should be followed up over the long term. Conservative therapies, including gel sheets, tape fixation, topical and injected external agents, oral agents, and makeup therapy, should be administered on a case-by-case basis. Conclusions Randomized controlled trials on pathologic scar management have increased markedly over the past decade. Although these studies suffer from various limitations, they have greatly improved hypertrophic scar and keloid management. Future high-quality trials are likely to improve the current hypertrophic scar and keloid treatment algorithms further.

Tie-over bolster dressing to secure a skin graft is associated with low graft take rates in irregular, high-mobility areas and suboptimal recipient wound beds. Negative-pressure wound therapy has become a well-established method to secure the graft, with a graft take rate of this method reported to be 96.7 percent. However, comparative efficacies between the two methods on irregular, high-mobility areas are yet to be determined.Patients eligible for skin graft were randomly assigned to receive either negative-pressure wound therapy or tie-over bolster dressing between December of 2014 and December of 2015. The primary outcome was determined by the take rate of skin grafts between postoperative days 5 and 7. The secondary outcomes were dressing time and postoperative complications, including hematoma, seroma, infection, displacement, and necrosis.A total of 86 patients were assigned to receive either negative-pressure wound therapy ( n = 43) or tie-over bolster dressing ( n = 43) for skin graft treatment. Negative-pressure wound therapy significantly improved the take rate of grafts as compared with tie-over bolster dressing (97.2 versus 90.2 percent; p = 0.005). The improvements came from the grafts in irregular, high-mobility areas in the respective groups (97.6 versus 81.7 percent; p0.001). Negative-pressure wound therapy reduced skin graft displacement as a postoperative complication as compared with tie-over bolster dressing (one versus nine patients; p = 0.007). Dressing time using negative-pressure wound therapy was significantly shorter compared with tie-over bolster dressing (15.2 ± 4.2 versus 27.4 ± 4.3 minutes; p = 0.001).Negative-pressure wound therapy can improve the take rate of skin grafts in irregular, high-mobility areas and shorten the dressing time.Therapeutic, I.

When first described for breast reconstruction, the presence of acellular dermal matrices was associated with increased seroma formation and infection. However, clinical safety data have gradually improved with surgeon experience to an acceptable outcomes profile of acellular dermal matrix-assisted reconstruction when compared to submuscular implant coverage. In fact, acellular dermal matrix use potentially decreases capsular contracture rates and facilitates expansion for staged prepectoral breast reconstruction. Because of new regulatory requirements, the collection of unbiased, well-powered premarket approval data summarizing long-term clinical outcomes will be essential over the coming years to understand the clinical performance of acellular dermal matrix use in breast reconstruction. Currently, the authors can highlight the physiologic benefits of acellular dermal matrix use in breast reconstruction by evaluating the components of surgical wound healing that are favorably augmented by the implanted collagen substrate. Acellular dermal matrix takes advantage of the wound healing cascade to incorporate into the patient's tissues-a process that requires a coordinated inflammatory infiltrate and angiogenesis. The presence of acellular dermal matrix augments and modulates the wound healing process to its advantage by simultaneously increasing the invasion of appropriate cellular constituents to facilitate expeditious healing and accelerate angiogenesis. In this article, the authors summarize the wound healing literature to demonstrate the mechanisms acellular dermal matrices use to biointegrate and the literature in which cellular constituents and soluble growth factors are up-regulated in the presence of acellular dermal matrix. Lastly, the authors use their experimental observations of acellular dermal matrix incorporation to corroborate the literature.

BACKGROUND: Infected wounds extend healing time and are associated with higher treatment costs than noninfected wounds. Several observational studies indicate that negative-pressure wound therapy with instillation can effectively reduce bacterial bioburden and improve wound healing. Only a few randomized trials with small sample sizes have been published, and a meta-analysis directly comparing negative-pressure wound therapy with instillation to current standard care is lacking. It is therefore uncertain whether negative-pressure wound therapy with instillation actually improves wound healing. The authors performed a systematic review and hypothesized that negative-pressure wound therapy with instillation reduces wound closure time. METHODS: The PubMed, Embase, and CENTRAL databases were searched up to December of 2020 for English studies that compare negative-pressure wound therapy with instillation-to either negative-pressure wound therapy without instillation or to other types of wound care-for the treatment of acute or chronically infected wounds. Time to wound closure was analyzed using a random effects meta-analysis in predefined subgroups according to study design and comparative wound care. RESULTS: The authors identified 14 studies describing 1053 patients. Meta-analysis of three randomized trials shows no significant difference in time to wound closure between negative-pressure wound therapy with instillation and that without (mean difference, 0.48 day; 95 percent CI, -0.70 to 1.65; I ² = 0 percent). Data from eleven observational studies indicate that negative-pressure wound therapy with instillation reduces wound closure time (from 1.6 to 16.8 days; no pooled data). Because of imprecision and risk of bias, the available evidence provides only low-level certainty. CONCLUSIONS: There is currently insufficient evidence to support or discard the use of negative-pressure wound therapy with instillation for infected wounds. More randomized trials are needed to determine whether a beneficial effect can be substantiated.

The creation of dead space in rhinoplasty creates a welcoming environment for erratic soft -tissue contraction. If rhinoplasty surgeons can control and reliably predict skin contraction and wound healing, rhinoplasty results will undoubtedly improve. Obliteration of dead space is a key component in rhinoplasty as it minimizes soft-tissue contraction, resulting in a more predictable outcome. In this article, the authors present a systematic five-step dead space closure surgical plan.

SUMMARY One of the most versatile soft-tissue flaps available for elbow coverage that is reliable, quick, and easy to perform, with minimal donor defect and without the sacrifice of a major blood vessel, is the antegrade posterior interosseous artery flap. A large amount of vascularized fascia can be dissected with the flap, and it can be useful in lining the elbow joint or any exposed implant(s). After flap harvest, the donor site is often amenable to primary closure or requires a simple skin graft for closure. This article explains the technique for harvesting an antegrade posterior interosseous artery flap and describes 10 cases in which the flap was used for complex soft-tissue defects of the elbow not amenable to local wound care or skin grafting.

Background Surgical reconstruction options of soft-tissue defects often include random pattern skin flaps. Flap survival depends on flap size and rotation arc and can be challenging regarding flap perfusion, leading to wound healing complications, insufficient wound coverage, and even flap loss. Therefore, novel approaches that promote skin flap survival are required. Bone marrow-derived mesenchymal stem cells intravenous infusion is therapeutically effective in various experimental disease models by means of multimodal and orchestrated mechanisms including anti-inflammatory and immunomodulatory effects, and by means of microvasculature reestablishment. Methods A modified McFarlane-type rodent skin flap model was used. After skin flap surgery, intravenous infusion of mesenchymal stem cells or vehicle was performed. In vivo optical near-infrared imaging using indocyanine green was performed, followed by histologic analysis, including hematoxylin and eosin and Masson trichrome staining, and gene expression analysis. Results The flap survival area was greater in the mesenchymal stem cell group. In vivo optical near-infrared perfusion imaging analysis suggested that skin blood perfusion was greater in the mesenchymal stem cell group. Ex vivo histologic analysis demonstrated that the skin structure was more clearly observed in the mesenchymal stem cell group. The dermal thickness was greater in the mesenchymal stem cell group, according to the Masson trichrome staining results. The authors observed a higher expression of fibroblast growth factor 2 mRNA in the tissues of the mesenchymal stem cell group using quantitative reverse-transcription polymerase chain reaction. Conclusion These results suggest that intravenous infusion of bone marrow-derived mesenchymal stem cells promotes skin survival of random pattern flaps, which is associated with increased blood perfusion and higher expression of fibroblast growth factor 2.

Flap reconstruction is recommended for select patients undergoing abdominoperineal resection to mitigate complications. However, the clinical effectiveness and financial implications of flap reconstruction remain unknown. The authors aim to compare the costs and complications for patients undergoing abdominoperineal resection with and without flap reconstruction.The Truven MarketScan Databases (2009 to 2016) were used to perform retrospective population-based analysis of colorectal carcinoma patients who underwent abdominoperineal resection with and without flap reconstruction. Univariate and multivariable logistic regressions were used to study effective cost (cumulative cost/number of healthy days) and complications.Of 2557 total abdominoperineal resection patients, 194 patients underwent flap reconstruction. Patients undergoing flap reconstruction had a higher Elixhauser Comorbidity Index (p = 0.004) and were more likely to have local invasion (p0.001). At 6 months postoperatively, there were no differences in complications between the two groups (p = 0.116). Flap reconstruction was protective against intraabdominal infections (OR, 0.4; 95 percent CI, 0.2 to 0.9; p = 0.033) but conferred an increased risk of wound complications (OR, 1.5; 95 percent CI, 1.0 to 2.3; p = 0.039). Total median cost of care was similar (abdominoperineal resection alone, $40,050; abdominoperineal resection with flap, $41,380; p = 0.456). Effective cost was greater for abdominoperineal resection alone ($259/healthy day) than abdominoperineal resection with flap ($186/healthy day) but was not statistically significant (p = 0.17).Patients with flap reconstruction displayed a higher comorbidity score and more extensive disease, but these unfavorable factors did not result in a higher complication rate, total cost, or effective cost. Therefore, flap reconstruction for complex perineal defects confers a benefit in select patients and is a judicious use of health care resources.Therapeutic, III.

Cleft lip results in disruption of the nasal foundation and collapse of tip structures. Most approaches to primary rhinoplasty focus on correction of lower lateral cartilages; however, recurrent deformity is common, and secondary revision is frequently required. The authors describe an alternate approach that focuses on the foundation to "upright the nose," without any nasal tip dissection. This study assessed changes with surgery and with growth. Secondary goals were to compare methods of sidewall reconstruction and septoplasty and to identify predictors of relapse.Consecutive patients undergoing repair (n = 102) were assessed. Images were captured preoperatively, postoperatively, and at 5 years of age (when available) using three-dimensional stereophotogrammetry. Standard anthropometric and contemporary shape-based analysis (volume ratio, dorsal deviation, and alar-cheek definition) was performed to assess longitudinal changes. Images of age-matched normal control subjects were used for comparison.Significant changes in anthropometric and morphometric measurements occurred following surgery. Postoperative form was similar to controls immediately after surgery and at 5 years. Nasal corrections were satisfactory, and only two patients have elected to undergo revision. When subjects were grouped according to cleft type, we found the same trends. When comparing different methods of nasal sidewall reconstruction or septoplasty, we found no differences. Alveolar cleft width was a significant predictor of worse preoperative and postoperative form.Significant nasal correction can be achieved by means of reconstruction of nasal foundation, without nasal tip dissection. Preservation of tissue planes may allow for easier secondary revision, if necessary.Therapeutic, IV.

Botulinum toxin type A (BTxA) injection is effective for surgical scar prevention. Although some studies have aimed to confirm the efficacy of BTxA injection at different time points, none has been conducted to determine the most appropriate timing of injection for scar management. The authors predicted that the injection of BTxA at different times during the wound healing process would cause differing scar quality improvement and clarify unknown molecular mechanisms.The study included adults who underwent thyroidectomy. All patients received paralesional BTxA injections on the day of the surgery on either the right or left side of the operative site. The same dose was injected on the noninjected side by means of the same method after 2 weeks. At 2, 4, 12, and 24 weeks postoperatively, the modified Stony Brook Scar Evaluation Scale, visual analogue scale, and erythema index were used for objective, subjective, and quantitative evaluations of the scar. At week 24 postoperatively, a quantitative scar assessment was performed with respect to the erythema index, skin elasticity, melanin index, and friction.On objective evaluation of the scar and patient satisfaction at 24 weeks postoperatively, the operation-day injection side showed better outcomes than the 2-week-postoperative injection side. These differences were significant from postoperative week 4. In the final quantitative scar assessment at postoperative week 24, significant improvements were observed in the erythema index and skin elasticity.These results suggest that immediate postoperative BTxA injection is more effective for thyroidectomy scar management in terms of erythema, skin elasticity, and patient satisfaction.Therapeutic, II.

Minced skin grafting is a procedure that involves mincing of the harvested skin and grafting it back onto the wounds. The authors aimed to investigate whether minced skin grafting reduces the healing time and improves the sequential postoperative appearance of donor sites.A single-center, two-treatment, half-side comparative study was performed. The split-thickness skin remaining after grafting was minced until pasty. The small pasty graft mass was uniformly spread on half of the entire donor site. Minced skin grafting was not performed on the other side. The data from 30 patients were used for analysis.The average time to complete healing of the donor sites in the minced skin grafting and control groups was 9.4 ± 2.5 and 12.4 ± 3.6 days, respectively. The difference in the healing time between the two groups was statistically significant (p0.001). Three blinded surgeons used a scale to grade photographs according to the degree of conspicuous donor sites in comparison with the normal skin around the donor sites. All observers reported that the differences in donor-site appearance between the minced skin grafting and control groups were statistically significant at postoperative months 1 and 2, and two observers reported that the differences in donor-site appearance were significant at months 4, 6, and 12. The differences in the number of patients with donor-site dyspigmentation between the minced skin grafting and control groups at 12 months were statistically significant (p0.05).This prospective half-side comparative trial demonstrates that minced skin grafting promotes wound healing and improves donor-site appearance after split-thickness skin grafting.Therapeutic, II.

Background When analyzing cleft lip repair techniques, the modified rotation-advancement repair is most widely used; however, the anatomical subunit approach is gaining popularity. The purpose of this study was to compare the outcomes of these two surgical techniques performed by the same surgeon. Methods Anthropometric measurements were performed on postoperative photographs of cleft lip repairs performed by a single surgeon. As described by Rossell-Perry, four parameters were measured: lip height, lip width, vermilion height, and alar base width. An aesthetic ratio of cleft to noncleft sides for each measurement was used as a quantitative measure of outcome. Qualitative analysis of cleft lip repair was evaluated using the Steffensen criteria. Results TWELVE: modified rotation-advancement repairs and 10 anatomical subunit repairs were analyzed. A one-sample t test was used to assess the difference of each aesthetic ratio from the perfect ratio of 1.00. For repairs involving an incomplete cleft lip, statistically significant asymmetry was detected in vermilion height for the rotation-advancement repair and no measurements in the anatomical subunit approach. For repairs involving a complete cleft lip, statistically significant asymmetry was detected in lip height, vermilion height, and alar base for the rotation-advancement repair and in lip height for the anatomical subunit approach. Conclusions THE AUTHORS': findings show that when separating the complete and incomplete cleft lips, the rotation-advancement technique seemed to have asymmetry in more parameters than the anatomical subunit approach. This seems to suggest that the outcomes of the anatomical subunit technique are less dependent on cleft lip severity. Clinical question/level of evidence Therapeutic, III.

BACKGROUND This study investigated whether a hyaluronic acid-povidone-iodine compound can enhance diabetic wound healing. METHODS A dorsal skin defect (6 × 5 cm) in a streptozotocin-induced diabetes rodent model was used. Seventy male Wistar rats were divided into seven groups: I, normal control; II, diabetic control, no treatment; III, diabetic rats, lower molecular weight (100 kDa) hyaluronic acid; IV, rats, higher molecular weight (1000 kDa) hyaluronic acid; V, rats, 0.1% povidone-iodine; VI, rats, lower molecular weight hyaluronic acid plus povidone-iodine; and VII, rats, higher molecular weight hyaluronic acid plus povidone-iodine. Histologic examination was performed with hematoxylin and eosin staining. CD45, Ki-67, prolyl 4-hydroxylase, and vascular endothelial growth factor were evaluated with immunohistochemical staining. RESULTS Compared with the control, higher molecular weight hyaluronic acid plus povidone-iodine-treated rats had significantly reduced wound area (p < 0.001). Higher molecular weight hyaluronic acid plus povidone-iodine increased wound healing time when compared with higher molecular weight hyaluronic acid, povidone-iodine, or lower molecular weight hyaluronic acid plus povidone-iodine. Histology revealed significantly increased neovessels and suppressed inflammatory response in the higher molecular weight hyaluronic acid plus povidone-iodine group when compared with the control group. Immunohistochemical staining revealed significantly increased Ki67, prolyl 4-hydroxylase, and vascular endothelial growth factor expression, and suppressed CD45 expression in the higher molecular weight hyaluronic acid plus povidone-iodine group when compared with the other groups. CONCLUSION Higher molecular weight hyaluronic acid plus povidone-iodine complex dressing significantly facilitated diabetic wound healing via increasing neovascularization and tissue regeneration and suppressing a proinflammatory response.

BACKGROUND In the diabetic foot, the skin may crack and develop fissures, potentially increasing vulnerability to ulceration and infection. Therefore, maintaining adequate skin hydration may be crucial for diabetic wound healing. However, no clinical study has addressed this issue. This study aimed to determine and compare the effect of the skin hydration level on diabetic wound healing with that of the tissue oxygenation level, which is recognized as the most reliable parameter in predicting diabetic wound healing. METHODS This retrospective study included 263 diabetic patients with forefoot ulcers. Skin hydration and transcutaneous oxygen pressure data collected before and after percutaneous transluminal angioplasty were analyzed. Skin hydration and tissue oxygenation were graded as poor, moderate, or acceptable. Wound healing outcomes were graded as healed without amputation, minor amputation, or major amputation. Wound healing outcomes were compared using four parameters: skin hydration at baseline, transcutaneous oxygen pressure at baseline, post-percutaneous transluminal angioplasty skin hydration, and post-percutaneous transluminal angioplasty transcutaneous oxygen pressure. RESULTS Each of the four parameters exhibited statistically significant correlations with wound healing outcomes. In the concurrent analysis of both skin hydration and transcutaneous oxygen pressure, skin hydration was a dominant parameter (p = 0.0018) at baseline, whereas transcutaneous oxygen pressure was a dominant parameter (p < 0.0001) following percutaneous transluminal angioplasty. CONCLUSIONS Skin hydration level might be a useful predictor for diabetic wound healing. In particular, the skin hydration level before recanalization was found to be superior to transcutaneous oxygen pressure in predicting wound healing. CLINICAL QUESTION/LEVEL OF EVIDENCE Risk, III.

Limb salvage for chronic lower extremity wounds requires long-term care best delivered by specialized multidisciplinary centers. This optimizes function, reduces amputation rates, and improves mortality. These centers may be limited to urban/academic settings, making access and appropriate follow-up challenging. Therefore, the authors hypothesize that both system- and patient-related factors put this population at exceedingly high risk for loss to follow-up.Records were reviewed retrospectively for 200 new patients seen at the Georgetown Center for Wound Healing in 2013. The primary outcome was loss to follow-up, defined as three consecutive missed appointments despite explicit documentation indicating the need for return visits. Demographic, clinical, and geographic data were compared. Multivariate logistic regression analysis for loss to follow-up status controlled for variables found significant in the bivariate analysis. Spatial dependency was evaluated using variograms.Over a 6.5-year-period, 49.5 percent of patients followed were lost to follow-up. Male sex and increased driving distance to the limb salvage center were risk factors for loss to follow-up. Wound-specific characteristics including ankle and knee/thigh location were also associated with higher rates of loss to follow-up. There was no spatial dependency or discrete clustering of at-risk patients.This study is the first of its kind to investigate the demographic and clinical characteristics that predispose chronic lower extremity wound patients to loss to follow-up. These findings inform stakeholders of the high rates of loss to follow-up and support decentralized specialty care, in the form of telemedicine, satellite facilities, and/or dedicated case managers. Future work will focus on targeting vulnerable populations through focused interventions to reduce patient and system burden.Risk, III.

BACKGROUND: Treating chronic osteomyelitis of the lower extremities is challenging. The treatment of acute lower limb trauma by orthoplastic teams has shown good results over the past few decades. This study aimed to characterize surgical outcomes of leg and heel chronic osteomyelitis by an orthoplastic team. METHODS: The cases of 113 consecutive leg and heel chronic osteomyelitis patients undergoing soft-tissue reconstruction with an orthopedic procedure were reviewed in this retrospective single-center observational study. The main objective was to assess surgical outcomes of skin healing and gait recovery at the 1-year follow-up. The secondary objective was to evaluate the global success rate at the last follow-up. RESULTS: The median follow-up was 19.7 months. A free flap was performed for 33 patients (29.2 percent) and a locoregional flap was used in 79 patients (69.9 percent). Seventy-two patients (63.7 percent) had chronic osteomyelitis on continuous bone. The others had a septic pseudarthrosis with a mean bone defect length of 42.9 mm. Forty-four patients (38.9 percent) underwent curettage only, eight (7.1 percent) underwent curettage and cement, 20 (17.7 percent) underwent curettage and bone fixation, and 39 (34.5 percent) underwent the Masquelet technique. At the 1-year follow-up, 72 patients (63.7 percent) had achieved skin healing and had recovered their gait. The success rate at all follow-up time points was 82.3 percent. The median time to achieve skin healing was 6.5 months and that to bone union in cases of septic pseudarthrosis was 7.9 months. CONCLUSION: Orthoplastic management of leg and heel chronic osteomyelitis patients with combined soft-tissue reconstruction using an orthopedic procedure was a viable strategy that offered good results even though the time to complete healing was long. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Background The role of nutritional intervention in wound care has been a topic of controversy. Although the efficacy of macronutrient supplementation has been well described, there is a paucity of evidence and no official recommendation regarding the use of vitamins and minerals to optimize wound healing. This is the first review of vitamin and mineral wound intervention that systematically summarizes the literature using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and distills the evidence by wound type. Methods In this comprehensive review, the authors outline the nutrients and delivery methods used in the identified studies, analyze reported treatment outcomes, summarize nutrient effectiveness, and propose evidence-based conclusions to improve wound healing outcomes and enhance the consistency of nutritional intervention in wound care. Results Thirty-six studies with a combined total of 2339 patients investigated the use of oral, topical, or intravenous vitamin and/or mineral supplementation for treatment of the following wound types: burn wounds (n = 3), pressure ulcers (n = 7), diabetic ulcers (n = 4), venous ulcers (n = 7), digital ulcers (n = 1), skin incisions (n = 9), hypertrophic scars (n = 4), and sinonasal wounds (n = 1). Improved outcomes were reported in patients with burn wounds receiving vitamins A, B1, B6, B12, D, and E and zinc, calcium, copper, magnesium, selenium, and zinc; patients with pressure ulcers receiving vitamin C and zinc; patients with diabetic ulcers receiving vitamin A, B9, D, and E; patients with venous ulcers receiving zinc; and patients with hypertrophic scars receiving vitamin E. Conclusions Based on the high-level data provided in this review, the use of specific nutritional interventions may improve the outcome of certain wound types. Further investigation is warranted to draw definitive conclusions.

BACKGROUND Negative-pressure wound therapy (NPWT) with instillation is a novel wound therapy. The optimal solution is still being investigated. Tetrachlorodecaoxygen-anion complex (TCDO) causes increased phagocytosis and oxygenation. The authors' objective was to investigate the efficacy of NPWT with TCDO instillation (NPWTi) and to compare the results with NPWT alone. METHODS A randomized controlled trial was conducted. Inclusion criteria were wound size greater than 4 cm2 and depth greater than 10 mm. Exclusion criteria were malignancy, immunocompromise, and allergy to TCDO. Patients were randomized into NPWT and NPWTi groups. Outcome measurements consisted of wound surface area, depth, volume, tissue culture, and pathologic evaluation. RESULTS A total of 24 patients in each group were enrolled. The percentages of wound surface area reduction of NPWTi and NPWT groups were 24.1 ± 6.8 and 28.2 ± 7.6 on day 12, and 19.0 ± 6.6 and 22.7 ± 7.8 on day 15, respectively (p < 0.05). The percentages of wound depth reduction were 16.4 ± 5.3 and 22.5 ± 10.5 on day 12, and 12.0 ± 6.7 and 14.1 ± 8.0 on day 15, respectively (p < 0.05). The percentages of wound volume reduction were 17.9 ± 4.6 and 21.6 ± 5.8 on day 12, and 14.7 ± 6.0 and 17.1 ± 6.6 on day 15, respectively (p < 0.05). No statistically significant difference in microbial reduction was found between the groups. Histopathologic examination showed that more angiogenesis was observed in the NPWTi group than in the NPWT group. CONCLUSIONS NPWT with TCDO instillation statistically significantly accelerated wound healing, but it did not show significant microbial reduction. The authors' results suggest that TCDO instillation may be an adjunctive treatment in NPWT. CLINICAL QUESTION/LEVEL OF EVIDENCE Therapeutic, II.

Background All common negative-pressure wound therapy systems include a material, usually foam or gauze, at the wound/device interface. In this preclinical study, the authors have compared the effects on different wound healing parameters in the three most common negative-pressure wound therapy systems (i.e., V.A.C.VIA, PREVENA, and PICO) with a new device without foam or gauze (i.e., Platform Wound Dressing). A strong effort was made to avoid bias. The study was conducted under good laboratory practice conditions, with the presence of an independent observer. Methods In pigs, three types of wounds were studied: full-thickness excisions, open incisions, and sutured closed incisions. Several macroscopic and microscopic parameters were studied. The pigs were euthanized on day 9 and all wounds were processed for histology and excisions for immunohistochemistry. Results In general, the devices produced similar results, with only a few significant differences. In the excisions, the Platform Wound Dressing reduced wound area more than the V.A.C.VIA and the PICO. In the excisional wounds, reepithelialization was the same. In open incisions, PREVENA was better than the Platform Wound Dressing. Histologic examination showed that, in open incisions, there was less inflammation in the PREVENA-treated in comparison with the Platform Wound Dressing- and the PICO-treated wounds. Immunohistochemical analyses showed that the Platform Wound Dressing-treated excisions had significantly more blood vessels (von Willebrand factor) than the V.A.C.VIA-treated ones and that the PICO caused less T-cell activation (CD3) than the other two. Conclusion The devices-with foam, with gauze, or without either and just an embossed membrane-performed equally in general.

SUMMARY The multidisciplinary approach to lower extremity function preservation is well established and is globally considered the standard of care. Every member of the team contributes their unique skills and knowledge to patient care. The effective integration of negative-pressure wound therapy with instillation (NPWTi) has fundamentally changed the approach to the infected or contaminated wound. Initially, in conjunction with excisional debridement, NPWTi has demonstrated its utility of expediting wound bed preparation for closure or coverage. With the introduction of a novel foam design, the effectiveness has increased and provided an option in cases where surgical intervention is not available or recommended. The successful implementation and continued monitoring of NPWTi provides an efficient tool to expedite ultimate wound healing and involves all members of the team.

SUMMARY The use of negative-pressure wound therapy (NPWT) has become an established therapy for wound management. There have been many advancements in the technology of NPWT including NPWT with instillation and dwell (NPWTi-d). NPWTi-d promotes wound healing by wound cleansing, irrigation, and nonexcisional debridement. NPWTi-d has been shown in comparative clinical studies to decrease the time to definitive wound healing and length of hospitalization. NPWTi-d-using a reticulated open-cell foam dressing with "through" holes (ROCF-CC)-has been postulated to facilitate solubilization, detachment, and elimination of infectious materials, such as slough and thick exudate, before or after operative debridement, and in cases where surgical debridement is not an option. The authors provide an overview on the use of NPWTi-d by reviewing the components of the system, proposed mechanism of action, clinical outcomes, and current consensus guidelines for its utilization.

SUMMARY Negative-pressure wound therapy with instillation and dwell (NPWTi-d) is an option for management of wounds with exposed orthopedic fixation hardware. The mechanical effect of the negative-pressure therapy works to contract the wound edges, and the instillation of solution and its subsequent removal help remove infectious material. NPWTi-d also promotes robust granulation tissue formation. In this article, we discuss the science behind NPWTi-d and its role in the treatment of wounds with indwelling orthopedic fixation hardware.

Background The addition of topical fluid instillation, a programmable "dwell" time and a novel foam-wound interface to the established wound healing benefits of negative-pressure wound therapy (NPWT) works synergistically to benefit patients with complex wounds. This engineering breakthrough for wound care has been termed NPWT with instillation and dwell (NPWTi-d), and the new foam dressings are reticulated open cell foam dressings specifically designed for use with NPWTi-d. This combined technology has shown promise in chronic, complex wounds and has potential for the management of sacral and ischial pressure wounds. Methods A qualitative comprehensive review was performed analyzing articles from PubMed and Medline that reported on the use of NPWTi-d in sacral or ischial pressure ulcers. Case series and case reports were predominant, and results of cases specific to sacral and ischial pressure wounds were extracted from larger studies and summarized for presentation. Results Compared with conventional NPWT alone, NPWTi-d has been shown to help irrigate the wound, remove fibrinous debris, and promote granulation tissue formation. This is associated with a decreased number of operative debridements and decreased hospital length of stay. Conclusions This technology is rapidly demonstrating expanded utilization in hospitalized patients with chronic sacral and ischial pressure ulcers. When used correctly, NPWTi-d serves as an effective "bridge to defined endpoint": whether that is a flap reconstruction, skin grafting, or discharge home with a stable chronic wound and simplified wound care.

Background Pathologic scarring including keloid and hypertrophic scar causes aesthetic and physical problems, and there are clinical difficulties (e.g., posttreatment recurrence) in dealing with pathologic scarring. Understanding the mechanisms that underlie scar control in wound healing will help prevent and treat pathologic scarring. The authors focused on CD206+ macrophages in the wound-healing process, and hypothesized that CD206+ macrophages have antifibrotic effects on fibroblasts. Methods The authors established a co-culture system for CD206+ macrophages and fibroblasts (cell ratio, 1:1). The authors examined the CD206+ macrophages' antifibrotic effects on fibroblasts after a 72-hour culture, focusing on fibrosis-related genes. To identify key factor(s) in the interaction between CD206+ macrophages and fibroblasts, the authors analyzed cytokines in a conditioned medium of the co-culture system. Results Under co-culture with CD206+ macrophages, expression of the following in the fibroblasts was significantly down-regulated: type 1 (fold change, 0.38) and type 3 collagen (0.45), alpha smooth muscle actin (0.24), connective tissue growth factor (0.40), and transforming growth factor-beta (0.66); the expression of matrix metalloproteinase 1 was significantly up-regulated (1.92). Conditioned medium in the co-culture showed a high interleukin (IL)-6 concentration (419 ± 88 pg/ml). When IL-6 was added to fibroblasts, antifibrotic changes in gene expression (as observed under the co-culture) occurred in the fibroblasts. Conclusions The authors' in vitro results revealed that CD206+ macrophages have antifibrotic effects on fibroblasts by means of a paracrine mechanism involving IL-6. Understanding these effects, especially in vivo, will help elucidate the mechanism of scar control in wound healing and contribute to the development of new scar treatments.

BACKGROUND Deep dermal suturing is critical for scar quality outcomes. The authors evaluated a new, fast medical device for dermal suturing, with the hypothesis of noninferiority with regard to clinical scar and cost-effectiveness. METHODS A prospective, patient-blind, randomized, multicenter noninferiority study in 26 French hospitals was conducted. Patients were randomized 1:1 to suturing with conventional thread or a semiautomatic stapler. The Patient Scar Assessment Scale was rated at 3 months for primary endpoint effectiveness. Secondary endpoints were cost-effectiveness of the two suturing methods, prevalence of complications, suturing/operating time, Observer Scar Assessment Scale and Patient Scar Assessment Scale score, scar aesthetic quality 18 months after surgery, and occupational exposure to blood during surgery. RESULTS Six hundred sixty-four patients were enrolled, 660 were randomized, and 649 constituted the full analysis (stapler arm, n = 324; needle arm, n = 325). Primary endpoint Patient Scar Assessment Scale score in the stapler arm was not inferior to that in the needle arm at 3 months or after 18 months. The mean operating time was 180 minutes in the stapler arm and 179 minutes in the needle arm (p = not significant). The mean suturing time was significantly lower in the stapler arm (p < 0.001). There were seven occupational exposures to blood in the needle arm and one in the stapler arm. The two arms did not differ significantly in terms of complications (p = 0.41). The additional cost of using the device was O51.57 for the complete-case population. CONCLUSION Wound healing outcome was no worse than with conventional suturing using a semiautomatic stapler and associated with less occupational exposure to blood. CLINICAL QUESTION/LEVEL OF EVIDENCE Therapeutic, I.

Author(s): DeLong, Michael R; Tandon, Vickram J; Da Lio, Andrew L; Deming, Timothy J; Cederna, Paul S | Abstract: BackgroundHost defense peptides are a family of endogenous short peptides that are found in all living beings and play a critical role in innate immunity against infection.MethodsA nonsystematic review of host defense peptides was conducted with specific interest in properties and applications relevant to plastic and reconstructive surgery.ResultsIn addition to their direct antimicrobial actions against pathogens, including multidrug-resistant bacteria, they also demonstrate important functions in immunomodulation, tumor cell lysis, and tissue regeneration. These properties have made them a topic of clinical interest for plastic surgeons because of their potential applications as novel antibiotics, wound healing medications, and cancer therapies. The rising clinical interest has led to a robust body of literature describing host defense peptides in great depth and breadth. Numerous mechanisms have been observed to explain their diverse functions, which rely on specific structural characteristics. However, these peptides remain mostly experimental, with limited translation to clinical practice because of numerous failures to achieve acceptable results in human trials.ConclusionsDespite the broad ranging potential of these peptides for use in the field of plastic and reconstructive surgery, they are rarely discussed in the literature or at scientific meetings. In this review, the authors provide a summary of the background, structure, function, bacterial resistance, and clinical applications of host defense peptides with the goal of stimulating host defense peptide-based innovation within the field of plastic and reconstructive surgery.

BACKGROUND Current rodent models of wound healing and scarring are flawed because of rapid wound contraction and inconspicuous scarring after healing, which is not closely parallel to the physiologic process in humans. This study aimed to establish a novel model of wound healing and scarring in rats. METHODS Excisional wounds were generated in rat tail or dorsal skin and histologic changes and wound contraction were assessed 2, 10, and 16 days after injury. After healing, rat tail scar was investigated for 24 consecutive weeks by histologic and immunohistochemical staining. Finally, a stretched scar model was generated in rat tail with high or low strain after reepithelialization to mimic human hypertrophic scars. The tail hypertrophic scars were analyzed by histology, immunohistochemical staining, and mRNA quantification 0, 2, 6, 12, and 24 weeks after stretching. RESULTS Compared with the dorsal wounds, a larger dermal gap percentage (p < 0.05) and more pronounced granulation were found in rat tail wounds. Tail scars remained conspicuous and underwent maturation over 24 weeks after wound healing. In addition, high mechanical strain induced significantly increased scar area (p < 0.01), scar height (p < 0.05), vessel density (p < 0.01) and hypertrophic scar-related molecule expression, and distorted collagen arrangement in rat tail scars. CONCLUSIONS The rat tail model exhibits minor wound contraction and biological features analogous to both normotrophic and hypertrophic scar in humans when generated with or without stretching, respectively. It is a promising new model for studies of both cutaneous wound healing and scarring.

Background The medial sural artery perforator flap offers thin, pliable tissue with a relatively long pedicle and low donor-site morbidity. This study explores the characteristics and uses of the medial sural artery perforator flap along with postoperative outcomes and complications. Methods A systematic literature review was performed using PubMed, Embase, and Cochrane Central Register of Controlled Trials to identify all cases of medial sural artery perforator flap reconstruction. Descriptive and meta-analyses were performed on pooled outcomes. Multivariate logistic regression identified factors associated with increased complication rates. Results Thirty-five studies encompassing 526 medial sural artery perforator flaps were included for analysis. The most common reasons for surgery were oncologic (47.6 percent) and traumatic injuries (31.8 percent). The oral cavity was the most common recipient location (45.5 percent). Average flap dimensions were 6.0 ± 2.3 cm × 9.8 ± 3.6 cm, with an average pedicle length of 10.1 ± 6.6 cm. Meta-analysis revealed an overall complication rate of 14.3 percent (Q value = 22.16; p = 0.877; I(2)= -39.9). Use of chimeric medial sural artery perforator flaps was associated with significantly higher rates of complications (OR, 3.92; p = 0.039; 95 percent CI, 1.10 to 13.89). The majority of flap donor sites were closed primarily (68 percent) versus 32 percent that were covered with split-thickness skin grafts. A flap width greater than 5.75 cm had an odds ratio of 5.3 (95 percent CI, 1.3 to 21.8; p = 0.014) of having a donor-site complication if closed primarily. Conclusions The medial sural artery perforator flap offers thin, pliable tissue with a relatively long pedicle and has minimal donor-site morbidity when the donor site is managed appropriately. As such, it should be considered a workhorse flap for both head and neck and extremity reconstruction.

BACKGROUND Volumetric muscle loss secondary to traumatic or surgical causes can lead to functional and aesthetic impairments. The authors hypothesize that an implantable muscle-derived stem cell-enriched collagen scaffold could significantly augment muscle regeneration in a murine model of volumetric muscle loss. METHODS Murine muscle-derived stem cells were isolated using a modified preplating technique and seeded onto type 1 collagen scaffolds to create the muscle-derived stem cell-enriched collagen scaffolds. Murine rectus femoris defects of 5 mm were created and randomized to one of three conditions (n = 6 per group): untreated controls, collagen scaffold only, and muscle-derived stem cell-enriched collagen scaffolds. In vivo muscle healing was quantified using micro-computed tomography. Muscle explants were analyzed using standard histology and whole-mount immunofluorescence at 8 weeks. RESULTS In vivo experiments demonstrated significantly greater quadriceps cross-sectional area in the muscle-derived stem cell-enriched collagen scaffold group compared with controls on micro-computed tomography (0.74 ± 0.21 versus 0.55 ± 0.06 versus 0.49 ± 0.04 ratio of experimental to naive quadriceps cross-sectional area; p < 0.05). Muscle explants of the muscle-derived stem cell-enriched collagen scaffold group demonstrated significantly higher cellular density compared with controls (1185 ± 360 versus 359 ± 62 versus 197 ± 68 nuclei/high-power field; p < 0.01). Immunofluorescence for laminin and myosin heavy chain confirmed formation of organized muscle fibers within the defect of the muscle-derived stem cell-enriched collagen scaffold group only. However, appreciable confocal colocalization of myosin heavy chain with green fluorescent protein expression was low. CONCLUSIONS The results of this study indicate that muscle-derived stem cell-enriched scaffolds significantly improved skeletal muscle regeneration in a murine muscle defect model. Based on the low fluorescent colocalization, host progenitor cells appear to contribute significantly to intradefect myogenesis, suggesting that deployment of a viable muscle-derived stem cell-enriched scaffold stimulates a regenerative mitogen response in native tissues.

Background Prosthetic breast reconstruction is the most common method for treatment of patients undergoing mastectomy. Acellular dermal matrix has become more popular in implant-based breast reconstruction. Methods The authors conducted a retrospective review of all patients undergoing prosthetic breast reconstruction between August of 2002 and December of 2013. Patients were analyzed in terms of demographics, fill volumes, number of expansions, costs, and complications. Results A total of 284 patients underwent mastectomy surgery with 481 implant-based breast reconstructions. Four hundred eight tissue expanders had total muscle coverage, whereas 73 had AlloDerm. The rate of overall complications and major complications was significantly higher in the AlloDerm group: 20.5 percent versus 8.8 percent (p = 0.005), and 13.7 percent versus 5.1 percent (p = 0.0001), respectively. The mean initial fill volume was significantly lower in the total muscle coverage group compared to the acellular dermal matrix group (54 ± 47 versus 167 ± 139; p = 0.00003), resulting in a higher number of expansions (8.1 versus 5.8; p = 0.000051) and longer time to full expansion (60.2 days versus 43.3 days; p = 0.0002). This did not translate into a faster time to expander exchange (162.4 days versus 162.3 days; p = 0.13). Use of AlloDerm added a mean cost of $2217 for each breast. Conclusions Implant-based breast reconstruction has evolved with the advent of acellular dermal matrices. Although the use of acellular dermal matrix allows increased initial fill volumes and fewer total expansions, there is an increased risk of complications and increased costs, especially in patients undergoing bilateral reconstruction. Total muscle coverage remains an excellent option for providing quality breast reconstruction without increased complications. Clinical question/level of evidence Therapeutic, III.

Background The benefits of total transmetatarsal amputation over higher level amputation are well known. However, there are no studies evaluating the effects of first ray- or first two ray-sparing transmetatarsal amputation with flap coverage. The authors evaluated this approach with regard to functional outcome and to identify long-term complications. Methods Retrospective data of 59 patients were evaluated according to their surgical method. Complete transmetatarsal amputation with free flap reconstruction was designated as the transmetatarsal amputation group with 27 patients and first ray- or first two ray-preserving transmetatarsal amputation with free flap reconstruction was designated as the ray group, with 32 patients. Demographics, flap outcomes, additional procedures after initial healing, and functional outcomes were measured and evaluated. Results There was no statistically significant difference in demographic distribution and flap outcomes in either group, except for poor blood glucose control in the ray group. Additional procedures after initial healing showed no statistical difference, but the tendency of minor procedures was higher in the ray group. The maximum achieved ambulatory function was significantly better in the ray group, with an ambulatory function score of 4.4 compared with 3.7 in the transmetatarsal amputation group (p = 0.012). Conclusions The preservation of the first ray or first two rays with free flap reconstruction may functionally benefit the patients despite the higher tendency toward minor procedures after initial healing. Furthermore, the progressive deformity of the preserved first and second toes will inevitably occur, requiring patients to undergo further surgery. Further studies are warranted to evaluate this approach. Clinical question/level of evidence Therapeutic, III.

Use of negative-pressure therapy (NPT) is a well-established therapy for chronic, open, contaminated wounds, promoting formation of granulation tissue and healing. The application of NPT after primary closure (ie, incisional NPT) has also been shown to reduce surgical site infection and surgical site occurrence in high-risk procedures across multiple disciplines. Incisional NPT is believed to decrease edema and shear stress, promote angiogenesis and lymphatic drainage, and increase vascular flow and scar formation. Incisional NPT may be considered when there is a high risk of surgical site occurrence or surgical site infection, particularly in procedures with nonautologous implants, such as hernia mesh or other permanent prosthetics. Here we discuss the proposed physiologic mechanism as demonstrated in animal models and review clinical outcomes across multiple specialties.

In New Zealand, oncoplastic surgery is common, but partial breast reconstruction presents challenges for radiation therapy targeting. Tissue rearrangement creates ambiguity when targeting the tumor bed, with resultant overestimation of treatment volumes. Thus, adoption of advanced methods of radiation therapy have been hindered. This pilot study describes use of a novel three-dimensional implant that provides a scaffolding for tissue ingrowth during partial breast reconstruction and delineates the tumor bed more precisely to assist radiation planning and mammographic surveillance. After informed consent, 15 women were implanted with the three-dimensional bioabsorbable implant. The device was sutured to the tumor bed during lumpectomy, and tissue flaps were mobilized and attached to the implant. Visualization of the marker and radiation treatment volumes were recorded and compared. The implant provided volume replacement and helped to maintain breast contour. Cosmetic outcomes were excellent; no device- or radiation-related complications occurred. One patient had a postoperative hematoma that resolved after percutaneous drainage; there were no postoperative infections. Three-year follow-up shows no tumor recurrences and no untoward effects. When compared to conventional radiation targeting, use of the implant showed that a greater than 50 percent reduction in treatment volume was possible in some cases. Three-year mammograms show no significant artifact, normal tissue ingrowth, and minimal fibrosis. This study describes a method of oncoplastic breast reconstruction using an implantable device that marks the site of tumor excision and provides for volume replacement with tissue ingrowth. Patients tolerated it well, and radiation therapy planning, positioning, and treatment were facilitated.

Much of facial aging can be attributed to volume deflation and tissue laxity. Successful surgical rejuvenation can be achieved through volume restoration with autologous fat grafting of the facial fat compartments. In conjunction with volume restoration, correction of tissue laxity and recontouring of the face and neck can be achieved. Current strategies for surgical correction of the face and neck involve superficial musculoaponeurotic system manipulation, medial platysma plication, and lateral platysma tightening through the lateral platysma window. These combined techniques facilitate optimal results in facial rejuvenation.