Aron G. Nusbaum

Interactions of Methicillin Resistant Staphylococcus aureus USA300 and Pseudomonas aeruginosa in Polymicrobial Wound Infection

Understanding the pathology resulting from Staphylococcus aureus and Pseudomonas aeruginosa polymicrobial wound infections is of great importance due to their ubiquitous nature, increasing prevalence, growing resistance to antimicrobial agents, and ability to delay healing. Methicillin-resistant S. aureus USA300 is the leading cause of community-associated bacterial infections resulting in increased morbidity and mortality. We utilized a well-established porcine partial thickness wound healing model to study the synergistic effects of USA300 and P. aeruginosa on wound healing. Wound re-epithelialization was significantly delayed by mixed-species biofilms through suppression of keratinocyte growth factor 1. Pseudomonas showed an inhibitory effect on USA300 growth in vitro while both species co-existed in cutaneous wounds in vivo. Polymicrobial wound infection in the presence of P. aeruginosa resulted in induced expression of USA300 virulence factors Panton-Valentine leukocidin and α-hemolysin. These results provide evidence for the interaction of bacterial species within mixed-species biofilms in vivo and for the first time, the contribution of virulence factors to the severity of polymicrobial wound infections.

Effective Method to Remove Wound Bacteria: Comparison of Various Debridement Modalities in an In Vivo Porcine Model

BACKGROUND Debridement is one of the crucial steps for successful wound care. In addition to removing necrotic tissue, debridement has been shown to reduce wound-associated bacteria that delay healing. Using an in vivo porcine model, we compared the effects of various methods of debridement, including hydrosurgery and plasma-mediated bipolar radiofrequency ablation (PBRA), on bacterial removal and wound healing. METHODS One hundred thirty-five deep dermal wounds were inoculated with methicillin resistant Staphylococcus aureus (MRSA) and covered with a polyurethane dressing for 48 h to allow for biofilm formation. Wounds were then treated with either PBRA (at two settings), hydrosurgery, sharp debridement, or no debridement. Biopsies were collected for microbiology and histologic assessment on d 0, 2, 9, and 21 post-treatment. RESULTS All treatment groups showed a statistically significant reduction in MRSA counts relative to no debridement at all times points (P < 0.05). PBRA at a maximum setting had the lowest MRSA counts at all recovery times and, compared with all other treatment groups, a statistically significant difference was observed on d 21 (P < 0.05). No detrimental effects on the healing process were noted with any of the debridement methods. CONCLUSION While sharp debridement has been established as the traditional gold standard for rapid removal of necrotic, infected tissue, our results suggest that novel debridement modalities show clinical promise for the treatment of chronic ulcers and burn wounds, especially when bacteria are present.

Frontal fibrosing alopecia in a man: results of follicular unit test grafting.

Frontal fibrosing alopecia (FFA) is characterized by scarring alopecia of the frontotemporal hairline that may occasionally extend as far as the mid-scalp. The affected areas show pale discoloration of the skin, with loss of follicular orifices and variable degrees of perifollicular erythema and scaling. Thinning of the eyebrows accompanies the frontotemporal recession. Although the histologic features of FFA are comparable with those of lichen planopilaris (LPP), clinically, multifocal areas of scarring alopecia as seen in LPP are absent. Recommended therapies include topical corticosteroids and tacrolimus, intralesional triamcinolone, oral antimalarials, and finasteride. Although Kossard originally described FFA in postmenopausal women in 1994 and termed it ‘‘postmenopausal frontal fibrosing alopecia,’’ it has subsequently been reported in premenopausal women. To our knowledge, this is the fourth male case reported in the literature and the first reported attempt at hair transplantation in a patient with this disease.

Deregulation of epidermal stem cell niche contributes to pathogenesis of nonhealing venous ulcers

The epidermis is maintained by epidermal stem cells (ESCs) that reside in distinct niches and contribute to homeostasis and wound closure. Keratinocytes at the nonhealing edges of venous ulcers (VUs) are healing‐incompetent, hyperproliferative, and nonmigratory, suggesting deregulation of ESCs. To date, genes which regulate ESC niches have been studied in mice only. Utilizing microarray analysis of VU nonhealing edges, we identified changes in expression of genes harboring regulation of ESCs and their fate. In a prospective clinical study of 10 VUs, we confirmed suppression of the bone morphogenetic protein receptor (BMPR) and GATA binding protein 3 (GATA3) as well as inhibitors of DNA‐binding proteins 2 and 4 (ID2 and ID4). We also found decreased levels of phosphorylated glycogen synthase kinase 3 (GSK3), nuclear presence of β‐catenin, and overexpression of its transcriptional target, c‐myc, indicating activation of the Wnt pathway. Additionally, we found down‐regulation of leucine‐rich repeats and immunoglobulin‐like domains protein 1 (LRIG1), a gene important for maintaining ESCs in a quiescent state, and absence of keratin 15 (K15), a marker of the basal stem cell compartment suggesting local depletion of ESCs. Our study shows that loss of genes important for regulation of ESCs and their fate along with activation of β‐catenin and c‐myc in the VU may contribute to ESC deprivation and a hyperproliferative, nonmigratory healing incapable wound edge.

Commentary on a Randomized Placebo-Controlled, Double-Blind, Half-Head Study to Assess the Efficacy of Platelet-Rich Plasma on the Treatment of Androgenetic Alopecia.

In this study, Alves andGrimalt present the effects of PRP versus placebo in a half-head paired comparison study of 22 patients with AGA. Patients received a total of 3 treatments at monthly intervals to 2 symmetrical areas on each side of the scalp with injections of either saline or activated PRP (3· concentration). Phototrichogram assessments were obtained at baseline, 3, and 6 months. Compared to baseline, PRP resulted in a significant increase in total hair density and terminal hair density at 6 months; however, only terminal hair density was found to be significantly increased (just below 10%) when PRP was compared with placebo. The authors also analyze the data based on demographics and demonstrate a significant therapeutic response in hair density versus placebo in men, patients#40 years of age, onset of AGA

A Case of Circumscribed Scalp Morphea with Perineural Lymphocytes on Pathology

the age of 25, positive family history, and AGA duration of greater than 10 years. This study is noteworthy as it included equal numbers of men and women, and it used a half-head design comparing symmetrical left and right target areas, which were tattooed for accurate localization of blinded phototrichogram assessments. The demographic analysis is interesting, however, limited by small sample size and seems to indicate thatwomen in this study group did not exhibit a statistically significant improvement with PRP as compared with placebo. Platelet-rich plasma therapy for hair loss consists of injecting concentrated autologous platelets into the scalp, which on activation release growth factors and cytokines such as PDGF, TGF, VEGF, IGF, EGF, and IL-1. This treatment application stems from a clinical study showing enhanced growth of transplanted follicular unit hair grafts. Additionally, in vitro evidence supports a role for PRP in promoting hair growth as PRP applied to dermal papilla cells stimulates their proliferation and upregulates components of the Wnt pathway. The hair promoting effects of PRP are likewise supported by in vivo animal studies demonstrating a faster telogen to anagen transition in mice injected with PRP and also an increase in the number of newly formed follicles and earlier hair formation in grafted murine epidermal and dermal papilla cells exposed to human PRP.

Epithelialization in Wound Healing: A Comprehensive Review

Scalp morphea presents as a scarring alopecia in en coup du sabre pattern. We report an unusual presentation of a round hairless patch of morphea on the occipital scalp present for 15 years. The scalp lesion aligned with 2 other hyperpigmented lesions of biopsy-proven morphea in the lower back. Pathology of horizontal sections from the scalp lesion showed follicular dropout, thickening of the collagen bundles, and preserved eccrine and follicular structures. Marked lymphocytic perineural infiltrate, a reported clue to the diagnosis of scalp morphea, contributed to the diagnosis. This case is unusual due to its rare clinical presentation. It also highlights the importance of recognizing histopathological clues for the diagnosis of uncommon scalp disorders.