Khang T. Nguyen

Bacteriophage therapy for Staphylococcus aureus biofilm-infected wounds: a new approach to chronic wound care.

Background: Bacterial biofilms, which are critical mediators of chronic wounds, remain difficult to treat with traditional methods. Bacteriophage therapy against biofilm has not been rigorously studied in vivo. The authors evaluate the efficacy of a species-specific bacteriophage against Staphylococcus aureus biofilm–infected wounds using a validated, quantitative, rabbit ear model. Methods: Six-millimeter dermal punch wounds in New Zealand rabbit ears were inoculated with wild-type or mutant, biofilm-deficient S. aureus. In vivo biofilm was established and maintained using procedures from our previously published wound biofilm model. Wounds were left untreated, or treated every other day with topical S. aureus–specific bacteriophage, sharp débridement, or both. Histologic wound healing and viable bacterial count measurements, and scanning electron microscopy were performed following harvest. Results: Wild-type S. aureus biofilm wounds demonstrated no differences in healing or viable bacteria following bacteriophage application or sharp débridement alone. However, the combination of both treatments significantly improved all measured wound healing parameters (p < 0.05) and reduced bacteria counts (p = 0.03), which was confirmed by scanning electron microscopy. Bacteriophage treatment of biofilm-deficient S. aureus mutant wounds alone also resulted in similar trends for both endpoints (p < 0.05). Conclusions: Bacteriophages can be an effective topical therapy against S. aureus biofilm–infected wounds in the setting of a deficient (mutant) or disrupted (débridement) biofilm structure. Combination treatment aimed at disturbing the extracellular biofilm matrix, allowing for increased penetration of species-specific bacteriophages, represents a new and potentially effective approach to chronic wound care. These results establish principles for biofilm therapy that may be applied to several different clinical and surgical problems.

Deficient cytokine expression and neutrophil oxidative burst contribute to impaired cutaneous wound healing in diabetic, biofilm-containing chronic wounds.

Diabetic patients exhibit dysregulated inflammatory and immune responses that predispose them to chronic wound infections and the threat of limb loss. The molecular underpinnings responsible for this have not been well elucidated, particularly in the setting of wound biofilms. This study evaluates host responses in biofilm‐impaired wounds using the TallyHo mouse, a clinically relevant polygenic model of type 2 diabetes. No differences in cytokine or Toll‐like receptor (TLR) expression were noted in unwounded skin or noninoculated wounds of diabetic and wild‐type mice. However, diabetic biofilm‐containing wounds had significantly less TLR 2, TLR 4, interleukin‐1β, and tumor necrosis factor‐α expression than wild‐type wounds with biofilm (all p < 0.001). Both groups had similar bacterial burden and neutrophil infiltration after development of biofilms at 3 days postwounding, but diabetic wounds had significantly less neutrophil oxidative burst activity. This translated into a log‐fold greater bacterial burden and significant delay of wound epithelization for biofilm‐impaired diabetic wounds at 10 days postwounding. These results suggest that impaired recognition of bacterial infection via the TLR pathway leading to inadequate cytokine stimulation of antimicrobial host responses may represent a potential mechanism underlying diabetic susceptibility to wound infection and ulceration.

Predictors of readmission after breast reconstruction: a multi-institutional analysis of 5012 patients.

BackgroundRecent health care legislation institutes penalties for surgical readmissions secondary to complications. There is a paucity of evidence describing risk factors for readmission after breast reconstruction procedures. MethodsPatients undergoing breast reconstruction in 2011 were identified in the National Surgical Quality Improvement Program database. Patients were grouped as purely immediate implant/tissue-expander reconstructions or purely autologous reconstruction for analysis. Reconstructions involving multiple types of procedures were excluded due to difficulty with classification. Perioperative variables were analyzed using &khgr;2 and Student t test as appropriate. Multivariate regression modeling was used to identify risk factors for readmission. ResultsOf 5012 patients meeting inclusion criteria, 3960 and 1052 underwent implant/expander and autologous reconstructions, respectively. Implant/expander and autologous cohorts experienced similar readmission rates (4.34% vs 5.32%, respectively; P = 0.18). However, autologous reconstructions experienced a higher rate of overall complications than implant/expander reconstructions (19.96% vs 5.86%, respectively; P < 0.05), as well as higher rates of reoperation (9.7% vs 6.5%, respectively; P < 0.05). Common predictors of readmission for implant/expander and autologous cohorts included operative time, American Society of Anesthesiologist class 3 and 4, and superficial surgical site infection. Smoking, sepsis, deep wound infection, organ space infection, and wound disruption were predictive of readmission for implant/expander reconstruction only, whereas hypertension was predictive of readmission after autologous reconstruction only. ConclusionsThis is the first study of readmission rates after breast reconstruction. Knowledge of specific risk factors for readmission may improve patient outcomes, steer strategies for optimizing reconstructive outcomes, and minimize readmissions.

Body mass index as a continuous predictor of outcomes after expander-implant breast reconstruction.

BackgroundStudies show that obesity is a risk factor for complications after expander/implant breast reconstructions. However, reports vary on the precise threshold of body mass index (BMI) as a predictor of heightened risk. We endeavored to link BMI as a continuous variable to overall complications in a single-surgeon series of expander-implant reconstructions. MethodsFrom 399 patients undergoing expander-implant reconstruction, 551 breasts were stratified to normal weight, overweight, and obese groups for analysis and comparison with previous studies. Logistic regression was performed to predict changes to risk profile per increment of BMI. ResultsComplication rates for obese and overweight patients were significantly greater than for normal weight patients, that is, 21.1% and 24.0% versus 10.4%, respectively (P < 0.005). A unit increase in BMI predicted a 5.9% increase in the odds of a complication occurring, and 7.9% increase in the odds of reconstruction ending in failure. ConclusionsBy expanding the analysis of BMI to include patients who do not meet the traditional definition of obesity (BMI ≥ 30 kg/m2), we demonstrated that simply overweight patients (25 ⩽ BMI < 30 kg/m2) had an elevated complication rate. Moreover, through regression analysis, we established that BMI as a continuous variable predicts outcomes from expander-based breast reconstruction.

Impact of a novel, antimicrobial dressing on in vivo, Pseudomonas aeruginosa wound biofilm: Quantitative comparative analysis using a rabbit ear model

The importance of bacterial biofilms to chronic wound pathogenesis is well established. Different treatment modalities, including topical dressings, have yet to show consistent efficacy against wound biofilm. This study evaluates the impact of a novel, antimicrobial Test Dressing on Pseudomonas aeruginosa biofilm‐infected wounds. Six‐mm dermal punch wounds in rabbit ears were inoculated with 106 colony‐forming units of P. aeruginosa. Biofilm was established in vivo using our published model. Dressing changes were performed every other day with either Active Control or Test Dressings. Treated and untreated wounds were harvested for several quantitative endpoints. Confirmatory studies were performed to measure treatment impact on in vitro P. aeruginosa and in vivo polybacterial wounds containing P. aeruginosa and Staphylococcus aureus. The Test Dressing consistently decreased P. aeruginosa bacterial counts, and improved wound healing relative to Inactive Vehicle and Active Control wounds (p < 0.05). In vitro bacterial counts were also significantly reduced following Test Dressing therapy (p < 0.05). Similarly, improvements in bacterial burden and wound healing were also achieved in polybacterial wounds (p < 0.05). This study represents the first quantifiable and consistent in vivo evidence of a topical antimicrobial dressings impact against established wound biofilm. The development of clinically applicable therapies against biofilm such as this is critical to improving chronic wound care.

A Novel Approach to Keloid Reconstruction with Bilaminar Dermal Substitute and Epidermal Skin Grafting.

BACKGROUND Keloids represent a challenging problem. Surgical excision remains the definitive treatment for immediate lesion debulking, but recurrence rates are reported to be 45 to 100 percent. The authors present a staged reconstructive approach using a dermal regeneration substrate and epidermal grafting to minimize recurrence and donor-site morbidity. METHODS Keloids were completely excised down to normal subcutaneous tissue or perichondrium. A bilaminar dermal regeneration matrix was approximated to the entire wound, with the silicone lamina oriented superficially. Reconstruction was delayed for at least 21 days to allow for neodermal ingrowth. The silicone lamina was then removed, and an epidermal skin graft was harvested from the thigh and secured to the neodermis with nonocclusive dressing. Reconstructed defects and donor sites were assessed for recurrence of keloids and scar appearance. RESULTS Five patients underwent treatment; two had keloids involving the superior helix of the ear (average area, 2.6 cm), two had keloids involving the chest (average area, 28 cm), and one had a keloid in the pubic region (area, 10 cm). All had failed at least one previous treatment with direct excision and steroid injections. Mean follow-up was 48.8 weeks (range, 38 to 60 weeks). Average time to complete wound epithelialization was 5.5 weeks. There were no infections or cellulitis. All reconstructed defects were aesthetically acceptable and remained flat without significant widening. There were no long-term complaints of pruritus or pain and there was no evidence of donor-site scarring. CONCLUSIONS Epidermal grafting provides significant advantages when used with a dermal regeneration matrix. This approach obviates reliance on skin creep and flap undermining to achieve primary closure. Exclusion of dermis and significant extracellular matrix components limits contracture, further facilitating tension-free wound healing. Scarring response within the donor site and graft is also minimized. CLINICAL QUESTION/LEVEL OF EVIDENCE Therapeutic, IV.

Tabbed Tissue Expanders Improve Breast Symmetry Scores in Breast Reconstruction

Background Achieving symmetry is a key goal in breast reconstruction. Anatomically shaped tabbed expanders are a new tool in the armamentarium of the breast reconstruction surgeon. Suture tabs allow for full control over the expander position and thus inframammary fold position, and, in theory, tabbed expanders mitigate many factors responsible for poor symmetry. The impact of a tabbed expander on breast symmetry, however, has not been formally reported. This study aims to evaluate breast symmetry following expander-implant reconstruction using tabbed and non-tabbed tissue expanders. Methods A chart review was performed of 188 consecutive expander-implant reconstructions that met the inclusion criteria of adequate follow-up data and postoperative photographs. Demographic, oncologic, postoperative complication, and photographic data was obtained for each patient. The photographic data was scored using a 4-point scale assessing breast symmetry by three blinded, independent reviewers. Results Of the 188 patients, 74 underwent reconstruction with tabbed expanders and 114 with non-tabbed expanders. The tabbed cohort had significantly higher symmetry scores than the non-tabbed cohort (2.82/4±0.86 vs. 2.55/4±0.92, P=0.034). Conclusions The use of tabbed tissue expanders improves breast symmetry in tissue expander-implant-based breast reconstruction. Fixation of the expander to the chest wall allows for more precise control over its location and counteracts the day-to-day translational forces that may influence the shape and location of the expander pocket, mitigating many factors responsible for breast asymmetry.

Use of the tabbed expander in latissimus dorsi breast reconstruction

Abstract Latissimus dorsi (LD) myocutaneous flap breast reconstruction with a tissue expander/implant is a post-mastectomy option often used as a salvage procedure for a failed tissue expander (TE). The patient is traditionally placed in the lateral decubitus position for flap dissection and is re-prepped and re-draped in the supine position for placement of the tissue expander. A new generation of anatomically-shaped, tabbed tissue expanders are increasingly being used in place of traditional untabbed expanders. The innovative suture tabs allow for more predictable and controlled expander placement while the patient is in the lateral decubitus position, eliminating the need to reposition the patient intraoperatively. The objective of this study was to evaluate the use of tabbed tissue expanders in latissimus dorsi breast reconstruction, with respect to total operative time, complication rates, and aesthetic outcomes. The outcomes of 34 LD breast reconstruction procedures with tissue expanders were evaluated. Eight patients received tabbed tissue expanders with no position change, while 26 patients underwent an intraoperative position change. Demographic information, total operative time, and follow-up complication data were collected. Aesthetic outcomes were evaluated by three blinded individuals using a validated scoring scale. The mean operative time for procedures with no position change was 107 minutes. The mean operative time for position change cohort was 207 minutes. There was no statistical difference in complication rates or aesthetic outcomes between the two groups. In conclusion, tabbed tissue expanders decrease operative time by eliminating the need for an intraoperative position change without influencing complication rates while maintaining equivalent aesthetic outcomes.

The weave technique for nipple reconstruction.

Abstract Traditional nipple reconstruction relies on local flap techniques. However, there are several problems associated with local flap reconstruction including loss of projection, widening of the base width, and difficulty working around the mastectomy scar. This study presents a variation of traditional local flap nipple reconstruction, which is termed the weave technique. Rather than using two flaps to create base width, the weave technique uses one. By controlling the base width, this may serve to sustain long-term projection. Second, filling the inside of the nipple with the second flap may contribute to longer term projection. Because there is no third flap, it is easier to orient the nipple with respect to the mastectomy scar. To date, the senior author has used this method to reconstruct 55 nipples in 40 patients, with 415 days (range 191–733) mean follow-up time. This includes 45 (82%) nipple reconstructions after tissue expander-implant reconstruction. The use of this technique has produced excellent aesthetic results with nipple projection and site healing. The majority of patients have been satisfied with their nipple reconstruction. Three patients had wound healing difficulties, including two (3.6%) that healed with conservative wound care and one (1.8%) in a radiated patient requiring surgical revision. There were no other revisions necessary and no infections. In summary, the weave technique is a suitable modification to the popular C-V technique that maintains the benefits and simplicity of the aforementioned flap while potentially reducing projection loss, conserving base width, and allowing greater flexibility for nipple placement.