Noninvasive induction of angiogenesis in tissues by external suction: sequential optimization for use in reconstructive surgery.

In reconstructive surgery, tissues are routinely transferred to repair a defect caused by trauma, cancer, chronic diseases, or congenital malformations; surgical transfer intrinsically impairs metabolic supply to tissues placing a risk of ischemia-related complications such as necrosis, impaired healing, or infection. Pre-surgical induction of angiogenesis in tissues (preconditioning) can limit postsurgical ischemic complications and improve outcomes, but very few preconditioning strategies have successfully been translated to clinical practice due to the invasiveness of most proposed approaches, their suboptimal effects, and their challenging regulatory approval. We optimized a method that adopts noninvasive external suction to precondition tissues through the induction of hypoxia-mediated angiogenesis. Using a sequential approach in a rodent model, we determined the parameters of application (frequency, suction levels, duration, and interfaces) that fine-tune the balance of enhanced angiogenesis, attenuation of hypoxic tissue damage, and length of treatment. The optimized repeated short-intermittent applications of intermediate suction induced a 1.7-fold increase in tissue vascular density after only 5 days of treatment (p < 0.05); foam interfaces showed the same effectiveness and caused less complications. In a second separate experiment, our model showed that the optimized technique significantly improves survival of transferred tissues. Here we demonstrate that noninvasive external suction can successfully, safely, and promptly enhance vascularity of soft tissues: these translational principles can help design effective preconditioning strategies, transform best clinical practice in surgery, and improve patient outcomes.

Systematic review of the methodological and reporting quality of case series in surgery.

BACKGROUND: Case series are an important and common study type. No guideline exists for reporting case series and there is evidence of key data being missed from such reports. The first step in the process of developing a methodologically sound reporting guideline is a systematic review of literature relevant to the reporting deficiencies of case series. METHODS: A systematic review of methodological and reporting quality in surgical case series was performed. The electronic search strategy was developed by an information specialist and included MEDLINE, Embase, Cochrane Methods Register, Science Citation Index and Conference Proceedings Citation index, from the start of indexing to 5 November 2014. Independent screening, eligibility assessments and data extraction were performed. Included articles were then analysed for five areas of deficiency: failure to use standardized definitions, missing or selective data (including the omission of whole cases or important variables), transparency or incomplete reporting, whether alternative study designs were considered, and other issues. RESULTS: Database searching identified 2205 records. Through the process of screening and eligibility assessments, 92 articles met inclusion criteria. Frequencies of methodological and reporting issues identified were: failure to use standardized definitions (57 per cent), missing or selective data (66 per cent), transparency or incomplete reporting (70 per cent), whether alternative study designs were considered (11 per cent) and other issues (52 per cent). CONCLUSION: The methodological and reporting quality of surgical case series needs improvement. The data indicate that evidence-based guidelines for the conduct and reporting of case series may be useful.

Systematic review of methodological quality of individual performance measurement in surgery.

BACKGROUND: Calls for greater transparency with improved quality, safety and outcomes have led to performance tracking of individual surgeons. This study evaluated the methodology of studies investigating individual performance in surgery. METHODS: MEDLINE, Embase, PsycINFO, AMED and the Cochrane Database of Systematic Reviews (from their inception to July 2014) were searched. Two authors independently reviewed citations using predetermined inclusion and exclusion criteria; 91 data points per study were extracted. RESULTS: The search strategy yielded 8514 citations; 101 were eligible, comprising 1 006 037 procedures by 14 455 surgeons. Thirty-four studies were prospective and 66 were retrospective. The aim of the studies was either to assess individual performance and describe the learning curve of a procedure, to describe factors influencing performance, or to describe methods for routine performance monitoring. Some 51·5 per cent of the studies investigated 500 or fewer procedures. Most (77 of 101) were single-centre studies. Less than half of the studies (42, 41·6 per cent) employed statistical modelling or stratification to adjust performance measures. Forty studies (39·6 per cent) adjusted outcomes for case mix. Seventeen (16·8 per cent) adjusted metrics for surgeon-specific factors. Thirteen studies (12·9 per cent) considered clustering in their analyses. The most frequent outcome studied was duration of operation (59·4 per cent), followed by complication rate (45·5 per cent) and reoperation rate (29·7 per cent); 15·8 per cent of studies recorded mortality, and 4·0 per cent explored patient satisfaction. Only 48·5 per cent of studies displayed procedural learning curves using a graph. CONCLUSION: There exist substantial shortcomings in methodological quality, outcome measurements and quality improvement evaluation among current studies of individual surgical performance. Methodological guidelines should be established to ensure that assessments are valid.

Wound tissue can utilize a polymeric template to synthesize a functional extension of skin.

Prompt and long-term closure of full-thickness skin wounds is guinea pigs and humans is achieved by applying a bilayer polymeric membrane. The membrane comprises a top layer of a silicone elastomer and a bottom layer of a porous cross-linked network of collagen and glycosaminoglycan. The bottom layer can be seeded with a small number of autologous basal cells before grafting. No immunosuppression is used and infection, exudation, and rejection are absent. Host tissue utilizes the sterile membrane as a culture medium to synthesize neoepidermal and neodermal tissue. A functional extension of skin over the entire wound area is formed in about 4 weeks.

Systematic review of therapeutic nipple-sparing versus skin-sparing mastectomy.

Background: The use of nipple-sparing mastectomy (NSM) is increasing, despite unproven oncological safety in the therapeutic setting. The aim of this systematic review was to determine the safety and efficacy of NSM compared with skin-sparing mastectomy (SSM). Methods: A literature search of all original studies including RCTs, cohort studies and case-control studies comparing women undergoing therapeutic NSM or SSM for breast cancer was undertaken. Primary outcomes were oncological outcomes; secondary outcomes were clinical, aesthetic, patient-reported and quality-of-life outcomes. Data analysis was undertaken to explore the relationship between NSM and SSM, and preselected outcomes. Heterogeneity was assessed using the Cochrane tests. Results: A total of 690 articles were identified, of which 14 were included. There was no statistically significant difference in 5-year disease-free survival and mortality for NSM and SSM groups, where data were available. Local recurrence rates were also similar for NSM and SSM (3·9 versus 3·3 per cent respectively; P = 0·45). NSM had a partial or complete nipple necrosis rate of 15·0 per cent, and a higher complication rate than SSM (22·6 versus 14·0 per cent respectively). The higher overall complication rate was due to the rate of nipple necrosis in the NSM group (15·0 per cent). Conclusion: In carefully selected cases, NSM is a viable choice for women with breast cancer who need to have a mastectomy. More research is needed to help further refine which surgical approaches to NSM optimize outcomes.

Impact of frailty on outcomes in surgical patients: A systematic review and meta-analysis.

IMPORTANCE: Age has historically been used to predict negative post-surgical outcomes. The concept of frailty was introduced to explain the discrepancies that exist between patients' chronological and physiological age. The efficacy of the modified frailty index (mFI) to predict surgical risk is not clear. OBJECTIVE: We sought to synthesize the current literature to quantify the impact of frailty as a prognostic indicator across all surgical specialties. DATA SOURCES: Pubmed and Cochrane databases were screened from inception to 1 January 2018. STUDY SELECTION: Studies utilizing the modified Frailty Index (mFI) as a post-operative indicator of any type of surgery. The mFI was selected based on a preliminary search showing it to be the most commonly applied index in surgical cohorts. DATA EXTRACTION AND SYNTHESIS: Articles were selected via a two-stage process undertaken by two reviewers (AP and DS). Statistical analysis was performed in Revman (Review manager V5.3). The random-effects model was used to calculate the Risk Ratios (RR). MAIN OUTCOME(S) AND MEASURE(S): The primary outcomes: post-operative complications, re-admission, re-operation, discharge to a skilled care facility, and mortality. RESULTS: This meta-analysis of 16 studies randomizes 683,487 patients, 444,885 frail, from gastrointestinal, vascular, orthopedic, urogenital, head and neck, emergency, neurological, oncological, cardiothoracic, as well as general surgery cohorts. Frail patients were more likely to experience complications (RR 1.48, 95%CI 1.35-1.61; p < 0.001), major complications (RR 2.03, 95%CI 1.26-3.29; p = 0.004), and wound complications (RR 1.52, 95%CI 1.47-1.57; p < 0.001). Furthermore, frail patients had higher risk of readmission (RR 1.61, 95%CI 1.44-1.80; p < 0.001) and discharge to skilled care (RR 2.15, 95%CI 1.92-2.40; p < 0.001). Notably, the risk of mortality was 4.19 times more likely in frail patients (95% CI 2.96-5.92; p < 0.001). CONCLUSIONS: and Relevance: This study is the first to synthesize the evidence across multiple surgical specialties and demonstrates that the mFI is an underappreciated prognostic indicator that strongly correlates with the risk of post-surgical morbidity and mortality. This supports that formal incorporation of pre-operative frailty assessment improves surgical decision-making.

Impact of the PROCESS guideline on the reporting of surgical case series: A before and after study.

INTRODUCTION: The PROCESS guideline was developed in 2016 through expert Delphi consensus. It aimed to improve the quality of reporting of surgical case series. This study assessed the impact of the introduction of the PROCESS guideline on reporting for surgical case series submitted to three journals. METHODS: 20 case series published in the International Journal of Surgery Case Reports (IJSCR), the International Journal of Surgery (IJS) or the Annals of Medicine and Surgery (AMS) in September to December 2016, prior to the introduction of the PROCESS guideline (the pre-PROCESS period), were randomly identified and scored against the PROCESS criteria. Two authors independently scored each article a total score out of 29, the 'PROCESS score' (expressed as a percentage). Scores for the two researchers were compared and consensus was reached to achieve a final score set. The process was repeated for the January 2017 to April 2017 issues of the three journals, post PROCESS implementation (the post-PROCESS period). RESULTS: The mean PROCESS score was 80% (range 66-90%) for the pre-PROCESS period and 84% (range 72-95%) for the post-PROCESS period, a 4% relative increase [STATS]. The Cohen's Kappa score between researchers was 0.907 implying very substantial agreement. CONCLUSION: Implementation of the PROCESS guideline resulted in a 5% improvement in the reporting quality of surgical case series published in three journals. Further research is needed to identify and successfully navigate existing barriers to greater compliance. Authors, reviewers and editors should adhere to the guidelines to boost reporting quality. Journals should develop their policies and guide for authors to incorporate the guideline and mandate compliance.

Impact of the SCARE guideline on the reporting of surgical case reports: A before and after study.

INTRODUCTION: The SCARE guideline was developed in 2016 through an expert Delphi consensus exercise. It aimed to improve the quality of reporting of surgical case reports. The aim of this study was to assess the impact of introducing the SCARE guideline for surgical on reporting of case reports submitted to a single journal. METHODS: A total of 20 case reports published in the International Journal of Surgery Case Reports (IJSCR) and Annals of Medicine and Surgery (AMS) in July and August 2016, prior to the introduction of the SCARE guideline (the pre-SCARE period), were randomly identified and scored against the SCARE criteria. Two independent teams performed the scoring giving a total score out of a theoretical maximum of 34 for each case report, the 'SCARE score' (expressed as a percentage). The scores for the two teams were then compared and consensus was reached to achieve a final sore set. This process was repeated for the January and February 2017 issues of the journal, post implementation of the guideline (the post-SCARE period). SCARE scores were compared between the pre- and post-SCARE periods. RESULTS: The mean pre-SCARE score was 75.0% (standard deviation ± 6.29, Range 62-84), and the mean post-SCARE score was 82.6% (standard deviation ± 8.02, range 66-99), a 10% relative increase in compliance which was statistically significant (P < 0.001). The Cohen's Kappa score between teams A and B was 0.871, implying very substantial agreement. CONCLUSION: Implementation of the SCARE guideline resulted in a 10% improvement in the reporting quality of surgical case reports published in a single journal. Adherence to SCARE reporting guidelines by authors, reviewers and editors should be improved to boost reporting quality. Journals should develop their policies, submission processes and guide for authors to incorporate the guideline.

The relative thermal stability of tissue macromolecules and cellular structure in burn injury.

When tissue is subjected to higher than physiological temperatures, protein and cell organelle structures can be altered resulting in cell death and subsequent tissue necrosis. A burn injury can be stratified into three main zones, coagulation, stasis and edema, which correlate with the extent of heat exposure and thermal properties of the tissue. While there has been considerable effort to characterize the time-temperature dependence of the injury, relatively little attention has been paid to the other important variable, the thermal susceptibility of the tissue. In the present study, we employ a standard physical chemistry approach to predict the level of denaturation at supraphysiological temperatures of 12 vital proteins as well as RNA, DNA and cell membrane components. Melting temperatures and unfolding enthalpies of the cellular components are used as input experimental parameters. This approach allows us to establish a relation between the level of denaturation of critical cellular components and clinical manifestations of the burn through the characteristic zones of the injury. Specifically, we evaluate the degree of molecular alteration for characteristic temperature profiles at two different depths (Mid-Dermis and Dermis-Fat interface) of 80 degrees C; 20s contact burn. The results of this investigation suggest that the thermal alteration of the plasma membrane is likely the most significant cause of the tissue necrosis. The lipid bilayer and membrane-bound ATPases show a high probability of thermal damage (almost 100% for the former and 85% for the latter) for short heat exposure times. These results suggest that strategies to minimize the damage in a burn injury might focus on the stabilization of the cellular membrane and membrane-bound ATPases. Further work will be required to validate these predictions in an in vivo model.

Organized skin structure is regenerated in vivo from collagen-GAG matrices seeded with autologous keratinocytes.

A well-characterized collagen-glycosaminoglycan matrix (CGM) that has been shown to function as a dermal analog was seeded with freshly disaggregated autologous keratinocytes and applied to full-thickness wounds in a porcine model. CGM were impregnated with 50,000 keratinocytes per cm2, a seeding density that produces a confluent epidermis within 19 d post-grafting and affords a 60-fold surface expansion of the donor epidermis. In this study, the temporal sequence of events in epidermal and neodermal formation was analyzed histopathologically and immunohistochemically from 4 to 35 d post-grafting. The epidermis was observed to form from clonal growth of individual keratinocytes into epithelial cords and islands that gradually enlarged, coalesced, differentiated to form large horn cysts, and finally reorganized at the graft surface to form a fully differentiated, normally oriented epidermis with rete ridges. Simultaneously, a neodermis formed from migration of endothelial cells, fibroblasts, and macrophages into the CGM from the underlying wound bed, resulting in formation of blood vessels, the production of abundant extracellular matrix, and the degradation of the CGM fibers, respectively. Gradually, the stromal cellularity of the CGM decreased and collagen deposition and remodeling increased to form a neodermal connective tissue matrix beneath the newly formed epidermis. Complete dissolution of the CGM occurred, partly as a result of degradation by an ongoing foreign-body giant cell reaction that peaked at 8-12 d post-grafting, but neither acute inflammation nor evidence of immune stimulation were observed. Within 1 mo, many structural components of normal skin were reconstituted.

Functional reconstruction following electrical injury.

Worldwide, high voltage electrical injury continues to cause significant morbidity, disability, and mortality despite improvements in electrical safety. Joule heating and cell membrane disruption are two mechanisms important in understanding the pathophysiology of electrical injury. The degree of tissue damage is often more extensive than initially perceived on clinical exam. Using modern reconstructive techniques, the functional outcome of electrical injury victims can be improved. The type of reconstruction selected for each injury can be selected from a number of options from the reconstructive ladder. Donor site considerations, risks of the surgery, team experience, and patient preference are important factors in this selection.

The use of collagen-GAG membranes in reconstructive surgery.

Porous collagen-glycosaminoglycan (PCG) membranes with a porous silicone elastomer coating have been useful as a scaffold for dermal replacement in burn victims. Critical physicochemical parameters of these membranes include pore size, cross-link density, the percentage of glycosaminoglycan, and the degree of banding of the collagen. These factors govern the immunobiological response. Optimizing these parameters can reduce inflammation, scarring, and contraction of wounds grafted with PCG membranes. PCG membranes are currently commercially manufactured (Integra, Integra Life Sciences, New Jersey) and available for clinical use. Because clinical outcomes have improved using these membranes for burn wound coverage, other skin reconstruction problems including scar resurfacing, keloids, treatment of donor sites, and treatment of chronic wounds can be considered as potential applications. This manuscript illustrates our early experience using Integra as a CG membrane for dermal replacement in reconstructive surgery. Our results indicate that CG membranes can lead to improved compliance and appearance compared to a meshed graft and may be sequentially placed in multiple layers to correct contour deformities. Also, in one case, we observed that, if placed on a wound bed with embedded skin epithelial cells, the PCG promotes epithelialization through the PCG matrix. The use of this material results in a supple integument with many similarities to normal skin.

Tropical pyomyositis presenting in the upper extremity.

Tropical pyomyositis is a staphylococcal infection, usually of a single large muscle, most commonly seen in young men in tropical regions. The following presents a case of tropical pyomyositis in a 62-year-old man that affected all four extremities, including the muscles of the forearms. Computed tomography was a useful guide for directing surgical explorations. To decrease the degree of disability from the multiple operative sites, we successfully used limited longitudinal incisions and conservative débridements.

The anticatabolic and wound healing effects of the testosterone analog oxandrolone after severe burn injury.

PURPOSE: Severe burn injury leads to marked catabolism and decreased lean mass, which can impair healing. Anabolic agents can attenuate net catabolism. Our purpose was to determine whether the testosterone analog, oxandrolone, given during the acute post burn period decreased the degree of nitrogen loss and loss of body weight while also increasing the healing rate of a skin donor site. MATERIALS AND METHODS: Patients with burns between 40% and 70% of body surface were studied. A randomized double-blinded placebo-controlled study design was used. Patients were given oxandrolone 20 mg/day (n = 11) or a placebo 20 mg/day (n = 9) beginning between days 2 and 3 post burn. Net nitrogen balance and the healing time of a standardized donor site were measured. Patients were monitored until transferred to a burn rehabilitation facility, an average time period of 33 +/- 9 days. RESULTS: Mean burn size was 49 +/- 8% for placebo and 53 +/- 9% of total body surface for the oxandrolone group. Smoke inhalation was present in approximately 50% of patients in both groups. All patients survived the burn injury. Net weight loss was 8 +/- 3.1 kg in the placebo group compared with 3 +/- 1.9 kg in the oxandrolone group, a statistically significant decrease. Net daily nitrogen loss over a 3-week period (days 7 to 28) was 13 +/- 4 g in placebo treated compared with 4 +/- 1.9 g for the oxandrolone group, a statistically significant decrease. The healing time of a standardized donor site, decreased from the placebo group value of 13 +/- 3 days to 9 +/- 2 days for oxandrolone treated patients, a significant improvement. No major liver dysfunction, or other complication attributable to an anabolic steroid was seen in either group. CONCLUSION: We found the anabolic agent, oxandrolone, significantly decreased weight loss and net nitrogen loss and increased donor site wound healing compared with placebo controls. We noted no complications with the use of oxandrolone.

Management of a patient with advanced AIDS and toxic epidermal necrolysis using human growth hormone and G-CSF.

Toxic epidermal necrolysis (TEN) is a serious drug reaction that is occurring with increased frequency among those affected with HIV and AIDS. It carries a grave prognosis for those with advanced AIDS and massive skin involvement. We report a severe case of TEN treated with wound care, intravenous nutrition, human growth hormone (hgh), and granulocyte colony-stimulating factor (G-CSF).

Flap prefabrication in the head and neck: a 10-year experience.

Tissue neovascularized by implanting a vascular pedicle can be transferred as a "prefabricated flap" based on the blood flow through the implanted pedicle. This technique potentially allows any defined tissue volume to be transferred to any specified recipient site, greatly expanding the armamentarium of reconstructive options. During the past 10 years, 17 flaps were prefabricated and 15 flaps were transferred successfully in 12 patients. Tissue expanders were used as an aid in 11 flaps. Seven flaps were prefabricated at a distant site and later transferred using microsurgical techniques. Ten flaps were prefabricated near the recipient site by either transposition of a local vascular pedicle or the microvascular transfer of a distant vascular pedicle. The prefabricated flaps were subsequently transferred as island pedicle flaps. These local vascular pedicles can be re-used to transfer additional neovascularized tissues. Common pedicles used for neovascularization included the descending branch of the lateral femoral circumflex, superficial temporal, radial, and thoracodorsal pedicles. Most flaps developed transient venous congestion that resolved in 36 to 48 hours. Venous congestion could be reduced by incorporating a native superficial vein into the design of the flap or by extending the prefabrication time from 6 weeks to several months. Placing a Gore-Tex sleeve around the proximal pedicle allowed for much easier pedicle dissection at the time of transfer. Prefabricated flaps allow the transfer of moderate-sized units of thin tissue to recipient sites throughout the body. They have been particularly useful in patients recovering from extensive burn injury on whom thin donor sites are limited.

Flap closure of postpneumonectomy empyema.

Empyema continues to be an uncommon, frustrating, and potentially lethal complication of pneumonectomy. Between 1990 and 1994 we treated 16 cases of recalcitrant postpneumonectomy (partial or total) empyema with combinations of pulse lavage, sharp debridement, muscle flaps, myodermal flaps, and thoracoplasty. We performed 11 pectoralis muscle flaps, 6 serratus anterior muscle flaps, 9 latissimus dorsi muscle flaps, 6 rectus abdominis muscle flaps, and 1 trapezius muscle flap for an average of 2.1 muscle flaps per patient. There was 1 omental flap. Of these flaps, 2 were free and the rest pedicled. Ten of the muscle flaps carried deepithelialized cutaneous paddles, and 6 were larger than 150 cm3. Thoracoplasty was done in 11 patients to decrease the volume of the postpneumonectomy empyema cavity. Of 16 patients, 4 failed initially because of persistent bronchopleural fistula or infection but resolved after one additional procedure. There was 1 perioperative death, 3 reoperations for bleeding, 1 patient with upper extremity deep vein thromboses, 1 seroma, and 1 patient with significant postoperative pain syndrome. In order to determine the efficacy of different operative approaches, patients were retrospectively divided into two groups according to the number of operations using flaps needed to resolve their postpneumonectomy empyema. Group A required only one operation using flaps to eliminate the postpneumonectomy empyema. Group B required two operations using flaps to remedy the postpneumonectomy empyema. Group B operations were further classified into B1, for the first operation, and B2, for the second operation. No patient needed more than two operations using flaps. Three significant variables were identified, the number of muscle flaps, the number of ribs in any thoracoplasty, and the preoperative serum albumin level. The A and B2 groups had significantly more muscle flaps transposed (p = 0.006) and ribs resected (p = 0.0002) than the B1 group. These findings suggest that filling the postpneumonectomy empyema space with muscle and collapsing any remaining space by thoracoplasty were the most successful strategy. The B2 group's average albumin level was significantly higher (p = 0.03) than that in either the A or the B1 group, suggesting that improved nutrition may have played a role in the lack of recurrence. Our goals of single-stage closure and decontamination of empyema cavities were best achieved by following these principles: removal of infected and necrotic tissue using sharp debridement and pulsed lavage, repair of bronchopleural fistulas with muscle flaps, and minimization of the dead space with combinations of muscle flaps and thoracoplasty.

Ear replantation without microsurgery.

Reconstitution of the amputated ear remains a challenge to the plastic surgeon. Reattachment as a composite graft of the total or subtotal amputated ear is unreliable. Microsurgical replantation can be performed in a minority of cases; however, difficulty with adequate venous drainage complicates the technical complexity of these cases. To enhance survival of a reattached ear segment, Mladick et al. advocated use of the retroauricular pocket principle. This technique involves deepithelialization of the amputated part, followed by anatomic reattachment to the amputation stump and then burial in a retroauricular pocket. This simple technique increases the surface area of the avulsed segment in contact with surrounding nutrients, maximizing the probability of "take." The relationship between the dermis and cartilage is preserved, thus minimizing the deformity from cartilage warping. The undisturbed dermis on the involved segment can reepithelialize spontaneously, negating the need for a skin graft. We have used this technique successfully in five of six patients.

Effect of keratinocyte seeding of collagen-glycosaminoglycan membranes on the regeneration of skin in a porcine model.

A collagen-glycosaminoglycan matrix, impregnated with autologous keratinocytes, was applied as island grafts onto full-thickness porcine wounds to determine whether complete epidermal coverage could be achieved in a single grafting procedure. Twenty-four grafts with seeding densities ranging from 0 to 3,000,000 cells/cm2 were used to determine the kinetics of epidermal coverage. The time sequence of epidermal formation was then studied between days 14 and 28 using four additional grafts, each seeded with a density of 500,000 cells/cm2. Autologous keratinocytes proliferated as the collagen-glycosaminoglycan matrix was vascularized to form a confluent epidermis by 2 weeks in matrices seeded with at least 100,000 cells/cm2. The epidermal thickness and the number of keratinocyte cysts observed in the neodermis at 2 weeks increased linearly with the logarithm of the seeding density. Sequential analysis of neoepidermis showed the nascent epidermis to be hyperplastic, parakeratotic, and focally lacking in granular layer differentiation at 2 weeks. After 2 weeks, it underwent normal maturation and differentiation. Irrespective of seeding density at 2 weeks the collagen-glycosaminoglycan matrix was well vascularized, contained a dense cellular infiltrate, and was almost completely degraded. These studies demonstrate that seeded keratinocytes proliferate and differentiate to form a confluent epidermis by 2 weeks in matrices seeded with at least 100,000 cells/cm2.

Salvage of externally exposed ventricular assist devices.

Although externally exposed ventricular assist devices are associated with extremely high mortality rates, salvage may be accomplished by early aggressive wound debridement, transposition of a well-perfused autologous tissue (such as omentum), dead space obliteration, and adequate external coverage using vascularized tissue. The temporary suppression rather than the total eradication of the infection should be the goal of these procedures.