Topical timolol may improve overall scar cosmesis in acute surgical wounds.

Acute wounds created by dermatologists following the removal of nonmelanoma skin cancers are closed either by primary or secondary intention, and the best cosmetic outcome is preferentially desired. One parameter that determines the overall cosmesis of the healed wound is its vascularity. Vascular tone results from a complex interplay of a variety of chemokines in the body and their interaction with receptors located on endothelial cell surfaces. In this study, our aim was to determine if topical timolol could improve the overall cosmesis of acute surgical wounds. We determined that patients who treated their acute surgical wounds with topical timolol had improved cosmesis compared to control.

Coagulation disorders and their cutaneous presentations: Pathophysiology.

Hypercoagulable states are inherited or acquired predispositions to venous or arterial thromboses that are best understood in the context of the coagulation cascade. Dermatologists can play a critical role in diagnosing and treating patients with hypercoagulable states because cutaneous symptoms may be a presenting manifestation, thereby reducing morbidity and mortality related to these conditions. This review focuses on the epidemiology and pathophysiology of hypercoagulable states, while the accompanying article iterates the basic clinical features, diagnostic testing, and management of patients who have these conditions.

Coagulation disorders and their cutaneous presentations: Diagnostic work-up and treatment.

Both inherited and acquired hypercoagulable states can present with nonspecific clinical manifestations, such as petechiae, purpura, livedo reticularis, and ulcerations. A good history and physical examination are crucial to diagnoses of these conditions. Inherited conditions tend to present either in neonatal period or later in life, while acquired conditions typically occur later in life. Diagnostic studies are performed to identify the coagulation cascade deficiency or defect. Treatment primarily hinges on anticoagulation and wound care. In this article, we provide an in-depth analysis of the clinical manifestations, diagnostic considerations, and management options of patients in hypercoagulable states.

Serratia marcescens Bullous Cellulitis in a Splenectomized Patient: A Case Report and Review of the Literature.

Serratia marcescens is a Gram-negative bacillus belonging to the Enterobacteriaceae family. Cutaneous infection with Serratia is rare, and usually occurs in immunocompromised individuals. Primary cutaneous infections are uncommon, but they are typically severe and are associated with significant morbidity and mortality. The pathogenetic factors leading to S. marcescens infection are not fully understood, but contributing virulence factors include proteases, secreted exotoxins, and the formation of biofilm. We report a case of cellulitis occurring in a splenectomized patient, which led to multiple wound debridements and a transmetatarsal amputation. This dramatic case led us to review the published literature on soft tissue infections caused by S. marcescens.

Choosing a Wound Dressing Based on Common Wound Characteristics.

Significance: Chronic wounds are a major healthcare burden.The practitioner should have an appropriate understanding of both the etiology of the wound as well as the optimal type of dressings to use. Fundamental wound characteristics may be used to guide the practitioner's choice of dressings. The identification of optimal dressings to use for a particular wound type is an important element in facilitating wound healing. Recent Advances: Researchers have sought to design wound dressings that aim to optimize each stage in the healing process. In addition, dressings have been designed to target and kill infection-causing bacteria, with the incorporation of antimicrobial agents. Critical Issues: Chronic wounds are frequently dynamic in presentation, and the numerous wound dressings available make dressing selection challenging for the practitioner. Choosing the correct dressing decreases time to healing, provides cost-effective care, and improves patient quality of life. Future Directions: Research into the mechanisms of wound healing has enhanced our ability to heal chronic wounds at a faster rate through the use of moisture-retentive dressings. Newer dressings are incorporating the use of nanotechnology by incorporating miniature electrical sensors into the dressing. These dressings are engineered to detect changes in a wound environment and alert the patient or practitioner by altering the color of the dressing or sending a message to a smartphone. Additional investigations are underway that incorporate biologic material such as stem cells into dressings.

Patient Satisfaction After Mohs Surgery is not Dependent on Seeing Post-Mohs Defect Prior to Repair.

BACKGROUND: Optimizing patient satisfaction and scar outcomes is important for the practicing Mohs surgeon. OBJECTIVE: To evaluate whether showing or not showing patients their post-Mohs defect prior to repair influences scar satisfaction. MATERIALS AND METHODS: Fifty patients with a nonmelanoma skin cancer on their head or neck requiring Mohs micrographic surgery were randomized to either see or not see their post-Mohs defect in the mirror prior to repair. Patients evaluated their scar at Week 1 and Week 4 using the patient scar assessment questionnaire. RESULTS: There was no statistically significant difference in the primary (scar satisfaction) or secondary outcomes (wound care compliance and complication rates) between the two groups. CONCLUSION: There is no difference in patient scar satisfaction whether patients see or do not see their post-Mohs defect prior to repair.

Low-grade elastic compression regimen for venous leg ulcers--an effective compromise for patients requiring daily dressing changes.

Venous leg ulcers (VLUs) affect millions of patients worldwide and are a tremendous financial burden on our health care system. The hallmark of venous disease of the lower extremities is venous hypertension, and compression is the current mainstay of treatment. However, many patients are non-compliant, partly because of the complexity of the dressings and the difficulties with application and removal. The aim of our study was to test an effective compression dressing regimen for patients with VLUs who require changing the ulcer primary dressing twice daily. We used two layers of a latex-free tubular elastic bandage for compression. The primary endpoint of our study was increased wound-healing rate and our secondary endpoint was complete wound closure. All active study subjects had positive healing rates at week 4 and week 8. Two subjects achieved complete wound closure by week 8. We conclude that compression with a latex-free tubular elastic bandage can be safely used in patients with VLUs requiring frequent dressing changes. This type of compression allows for daily inspection of wounds, dressing changes at home, flexibility in the context of clinical trials, and is a compromise for patients who are intolerant to compression dressings.

The emerging use of bone marrow-derived mesenchymal stem cells in the treatment of human chronic wounds.

INTRODUCTION: Close to 5 million people in the USA are affected by chronic wounds, and billions of dollars are spent annually for their treatment. Despite advances in chronic wound management over the past decades, many patients afflicted with chronic wounds fail to heal or their ulcers recur. There is emerging evidence that the use of bone marrow-derived mesenchymal stem cells (BM-MSCs) can offset this situation of impaired healing. AREAS COVERED: This article provides a review of the use of BM-MSC for the treatment of chronic wounds, the current development of stem cell delivery to chronic wounds and related challenges are also described in this manuscript. EXPERT OPINION: Numerous animal studies and a few pilot studies in human wounds have shown that BM-MSC can augment wound closure. Still, the primary contribution of mesenchymal stem cells (MSCs) to cutaneous regeneration and the long-term systemic effects of MSCs are yet to be established. In addition, we need to determine whether other types of stem/progenitor cells will be more effective. Therefore, more randomized controlled clinical trials need to be undertaken. It is of importance to remember that even with the most advanced and sophisticated therapeutic approaches, proper wound care and adherence to basic principles remain critical.

Connective tissue ulcers.

Connective tissue disorders (CTD), which are often also termed collagen vascular diseases, include a number of related inflammatory conditions. Some of these diseases include rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis (scleroderma), localized scleroderma (morphea variants localized to the skin), Sjogren's syndrome, dermatomyositis, polymyositis, and mixed connective tissue disease. In addition to the systemic manifestations of these diseases, there are a number of cutaneous features that make these conditions recognizable on physical exam. Lower extremity ulcers and digital ulcers are an infrequent but disabling complication of long-standing connective tissue disease. The exact frequency with which these ulcers occur is not known, and the cause of the ulcerations is often multifactorial. Moreover, a challenging component of CTD ulcerations is that there are still no established guidelines for their diagnosis and treatment. The morbidity associated with these ulcerations and their underlying conditions is very substantial. Indeed, these less common but intractable ulcers represent a major medical and economic problem for patients, physicians and nurses, and even well organized multidisciplinary wound healing centers.

The immunopathobiology of syphilis: the manifestations and course of syphilis are determined by the level of delayed-type hypersensitivity.

Syphilis has plagued mankind for centuries and is currently resurgent in the Western hemisphere. Although there has been a significant reduction of tertiary disease and recognition of facilitative interactions with human immunodeficiency virus infection, the natural history of syphilis has remained largely unchanged; thus, new strategies are required to more effectively combat this pathogen. The immunopathologic features of experimental syphilis in the rabbit; the course, stages, and pathology of human syphilis; and a comparison of human syphilis with leprosy suggest that the clinical course of syphilis and its tissue manifestations are determined by the balance between delayed-type hypersensitivity (DTH) and humoral immunity to the causative agent, Treponema pallidum. A strong DTH response is associated with clearance of the infecting organisms in a well-developed chancre, whereas a cytotoxic T-cell response or strong humoral antibody response is associated with prolonged infection and progression to tertiary disease. Many of the protean symptoms/appearances of secondary and tertiary human syphilis are manifestations of immune reactions that fail to clear the organism, due to a lack of recruitment and, more importantly, activation of macrophages by sensitized CD4 T cells. The Bacillus Calmette-Guerin vaccination can enhance DTH and has been shown to produce a low, but measurable, beneficial effect in the prevention of leprosy, a disease that shows a disease spectrum with characteristics in common with syphilis. In the prevention of syphilis, a potential vaccine protective against syphilis should be designed to augment the DTH response.

Hic-5 promotes the hypertrophic scar myofibroblast phenotype by regulating the TGF-beta1 autocrine loop.

Following severe traumatic or thermal injury to the dermis, hypertrophic scars (HTSs) often develop in humans. These scar fibroblasts (hypertrophic scar fibroblasts (HTSFs)) retain the myofibroblast phenotype persistently, rather than transiently as in acute wounds. These pathogenic myofibroblasts constitutively express smooth-muscle cell alpha-actin (SMAA), deposit an excessive amount of extracellular matrix (ECM) proteins, are highly contractile, and stably display large focal adhesions. Increasing evidence supports a mechanism in which autocrine production and activation of transforming growth factor-beta1 (TGF-beta1) are required to maintain the pathogenic myofibroblast phenotype. We recently reported that Hic-5, a focal adhesion protein that is upregulated by TGF-beta1, is expressed persistently in HTSF compared to normal adult fibroblasts (NADFs). We now find that Hic-5 is an important regulator of the constitutive myofibroblast phenotype in HTSFs. Silencing the expression of Hic-5 in HTSFs with specific siRNAs dramatically reduces TGF-beta1 production, decreases the generation of supermature focal adhesions reduces expression of SMAA and decreases collagen contraction and ECM synthesis. Our findings demonstrate that Hic-5 is an essential component of the mechanism regulating autocrine production of TGF-beta1 and the resulting pathogenic myofibroblast phenotype.

TGF-beta1 slows the growth of pathogenic myofibroblasts through a mechanism requiring the focal adhesion protein, Hic-5.

Pathogenic scarring is a devastating disorder that impairs normal tissue function after injury. Differentiated myofibroblasts deposit and organize scars over a continuum, from normal to pathogenic, and yet the mechanisms regulating their appearance and disappearance from tissues are enigmatic. We reported previously that key functions of myofibroblasts derived from hypertrophic scars (HTSF) are constitutively activated by an autocrine loop involving transforming growth factor-beta1 (TGF-beta1). We now report that this autocrine induction of TGF-beta1 results in a constitutively high level of Hic-5, which markedly reduces HTSF proliferation relative to normal adult human dermal fibroblasts (NADF) without changing apoptosis. Cyclin D1 and A levels are constitutively lower in HTSF compared to NADF, and the cyclin-dependent kinase inhibitor p21(cip1) is upregulated in HTSF and located in the nucleus. Inhibition of autocrine TGF-beta1 production in HTSF reverses this process, lowering Hic-5 and p21(cip1) levels and increasing replication. Moreover, Hic-5 is partially localized in the nucleus of HTSF, and knocking down Hic-5 with specific siRNAs in these cells results in decreased p21(cip1) levels and a concomitant increase in proliferation. Our findings show that autocrine production of TGF-beta1 upregulates the expression of Hic-5, which is essential for perpetuating the decreased proliferation seen in this pathogenic myofibroblast.

Manganese superoxide dismutase enhances the invasive and migratory activity of tumor cells.

Clinically significant elevations in the expression of manganese superoxide dismutase (Sod2) are associated with an increased frequency of tumor invasion and metastasis in certain cancers. The aim of this study was to examine whether increases in Sod2 activity modulate the migratory potential of tumor cells, contributing to their enhanced metastatic behavior. Overexpression of Sod2 in HT-1080 fibrosarcoma cells significantly enhanced their migration 2-fold in a wound healing assay and their invasive potential 3-fold in a transwell invasion assay. Severity of invasion was directly correlated to Sod2 expression levels and this invasive phenotype was similarly observed in 253J bladder tumor cells, in which Sod expression resulted in a 3-fold increase in invasion compared with controls. Further, migration and invasion of the Sod2-expressing cells was inhibited following overexpression of catalase, indicating that the promigratory/invasive phenotype of Sod2-expressing cells is H(2)O(2) dependent. Sod2 overexpression was associated with a loss of vinculin-positive focal adhesions that were recovered in cells coexpressing catalase. Tail vein injections of Sod2-GFP-expressing HT-1080 cells in NCR nude mice led to the development of pulmonary metastatic nodules displaying high Sod2-GFP expression. Isolated tumors were shown to retain high Sod2 activity in culture and elevated levels of the matrix degrading protein matrix metalloproteinase-1, and a promigratory phenotype was observed in a population of cells growing out from the tumor nodule. These findings suggest that the association between increased Sod2 activity and poor prognosis in cancer can be attributed to alterations in their migratory and invasive capacity.

A TGF-beta1-dependent autocrine loop regulates the structure of focal adhesions in hypertrophic scar fibroblasts.

Following injury, fibroblasts migrate into wounds and differentiate into alpha smooth muscle cell actin (SMCA)-positive cells, termed myofibroblasts, that assemble and remodel the scar. Cultured myofibroblasts assemble larger focal adhesions than do normal dermal fibroblasts and these focal adhesions attach to alpha SMCA-rich stress fibers. Following severe traumatic or thermal injury to the dermis, hypertrophic scars (HTSs) often develop and these scar fibroblasts (HTSFs) express alpha SMCA persistently. We now report that HTSFs stably display large focal adhesions as a consequence of both the autocrine production and activation of transforming growth factor beta1 (TGF-beta1). We also observe that myofibroblasts elaborating larger focal adhesions adhere more tightly to fibronectin. Conditioned medium from HTSFs induces focal adhesion growth in normal fibroblasts and this is blocked by pre-incubation with a soluble TGF-beta1 receptor mimetic. Human foreskin fibroblasts transduced with a retrovirus encoding active TGF-beta1 elaborate large focal adhesions, whereas fibroblasts overexpressing normal, latent TGF-beta1 do not. We conclude that the large focal adhesions found in pathogenic myofibroblasts arise through an autocrine loop involving the production and activation of TGF-beta1; these adhesions likely mediate both tighter adhesion to wound matrix and the exuberant wound contraction observed in pathogenic scars.