[Show abstract][Hide abstract] ABSTRACT: Regulatory T cells (Tregs), which are characterized by expression of the transcription factor Foxp3, are a dynamic and heterogeneous population of cells that control immune responses and prevent autoimmunity. We recently identified a subset of Tregs in murine skin with properties typical of memory cells and defined this population as memory Tregs (mTregs). Due to the importance of these cells in regulating tissue inflammation in mice, we analyzed this cell population in humans and found that almost all Tregs in normal skin had an activated memory phenotype. Compared with mTregs in peripheral blood, cutaneous mTregs had unique cell surface marker expression and cytokine production. In normal human skin, mTregs preferentially localized to hair follicles and were more abundant in skin with high hair density. Sequence comparison of TCRs from conventional memory T helper cells and mTregs isolated from skin revealed little homology between the two cell populations, suggesting that they recognize different antigens. Under steady-state conditions, mTregs were nonmigratory and relatively unresponsive; however, in inflamed skin from psoriasis patients, mTregs expanded, were highly proliferative, and produced low levels of IL-17. Taken together, these results identify a subset of Tregs that stably resides in human skin and suggest that these cells are qualitatively defective in inflammatory skin disease.
The Journal of clinical investigation 02/2014; · 15.39 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Many patients obtain medical information from the Internet. Inaccurate information affects patient care and perceptions.
To assess the accuracy and completeness of information regarding Mohs micrographic surgery (MMS) on the Internet.
Prospective cross-sectional Internet-based study reviewing 30 consecutive organic results from three U.S. urban areas on "Mohs surgery" using Google. Text was assessed using a consensus-derived rating scale that quantified necessary and additional or supplementary information about MMS, as well as wrong information. Websites were classified according to type of sponsor.
Ninety-one percent of sites conveyed basic information about MMS. There was variation in the mean amount of additional information items (range 0-9) according to website type: 8.4, medical societies; 6.7, academic practices; 5.9, web-based medical information resources; 4.7, private practices; and 4.4, other (p < .001). Cumulatively, academic practices and professional societies (mean 7.42) provided more additional information than private practices and web-based sources (mean 5.11, p < .001). There were no differences based on geographic location. Wrong items included misspelling Mohs (10%), indicating that only plastic surgeons could reconstruct (7%), and noting MMS was never cost-effective (7%).
High-ranking websites provide basic information about MMS. Academic practice and professional society sites provide more-comprehensive information, but private practice sites and web-based medical information sources also provide additional information.
Dermatologic Surgery 10/2013; · 1.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Cigarette smoking is the leading cause of preventable death and a major public health concern. Numerous clinical and experimental studies have examined the effect of nicotine on wound healing and surgical procedures, but there are limited published reports in the dermatologic surgery literature. OBJECTIVE: This article seeks to develop evidence-based recommendations regarding the effect of tobacco use in patients undergoing dermatologic surgery procedures. METHODS: This article reviews the existing published English-language literature pertaining to the effects of tobacco on wound healing and surgical complications. RESULTS: Tobacco use is associated with a higher incidence of postoperative complications including wound dehiscence, flap or graft necrosis, prolonged healing time, and infections. LIMITATIONS: This review article only summarizes past reports and studies. CONCLUSION: Recommendations for smoking cessation before dermatologic surgery are provided based on the available data.
Journal of the American Academy of Dermatology 10/2012; · 5.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To critically review the body of clinical trials that report the rates of skin cancer in patients on a biologic therapy, in order to discern whether this therapy is associated with any increase risk of skin cancer.
Review of MEDLINE database and the Cochrane library database was conducted, to identify randomized controlled trials and meta-analyses that evaluated the safety of biologic therapies, and specifically reported rates of skin cancer in patients on biologic therapies.
Two reviewers independently evaluated eligibility and collected the data. Studies selected were large randomized controlled trials and meta-analyses with large number of patient populations from clinical trials and post-marketing surveillance data that reported specifically the rate of skin cancer while on a biologic therapy.
Nine studies met the eligibility criteria. All studies were of high quality with Strength of Recommendation Taxonomy (SORT) (J Am Board Fam Pract 2004) evidence level of 1. Eight of these trials demonstrated an increased risk of non-melanoma skin cancer (NMSC) while on a biologic therapy. In addition, studies suggested a possible increased risk in patients with history of prior treatments known to also increase risk of skin cancer. Case studies with SORT evidence level 3 are also included in this review for completion; however, these data were not used in the formation of final recommendations.
Biologic medications are highly efficacious and have a relatively good safety profile; however, high-quality evidence suggests that use of biologic therapies may be associated with an increased risk of detection of NMSC. Psoriatic patients may be at an increased risk due to history of treatment with other therapies also known to increase the risk of skin cancer. As such, it may be important to consider biologic therapies as an additional risk factor for development of NMSC and implement regular skin examinations for patients on these therapies.
Journal of Dermatological Treatment 12/2011; 23(4):305-15. · 1.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Squamous cell carcinomas (SCCs) are one of the most frequent forms of human malignancy, but, other than TP53 mutations, few causative somatic aberrations have been identified. We identified NOTCH1 or NOTCH2 mutations in ∼75% of cutaneous SCCs and in a lesser fraction of lung SCCs, defining a spectrum for the most prevalent tumor
suppressor specific to these epithelial malignancies. Notch receptors normally transduce signals in response to ligands on
neighboring cells, regulating metazoan lineage selection and developmental patterning. Our findings therefore illustrate a
central role for disruption of microenvironmental communication in cancer progression. NOTCH aberrations include frameshift and nonsense mutations leading to receptor truncations as well as point substitutions in key
functional domains that abrogate signaling in cell-based assays. Oncogenic gain-of-function mutations in NOTCH1 commonly occur in human T-cell lymphoblastic leukemia/lymphoma and B-cell chronic lymphocytic leukemia. The bifunctional
role of Notch in human cancer thus emphasizes the context dependency of signaling outcomes and suggests that targeted inhibition
of the Notch pathway may induce squamous epithelial malignancies.
Proceedings of the National Academy of Sciences 10/2011; 108(43):17761-17766. · 9.81 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Timely intervention for cancer requires knowledge of its earliest genetic aberrations. Sequencing of tumors and their metastases reveals numerous abnormalities occurring late in progression. A means to temporally order aberrations in a single cancer, rather than inferring them from serially acquired samples, would define changes preceding even clinically evident disease. We integrate DNA sequence and copy number information to reconstruct the order of abnormalities as individual tumors evolve for 2 separate cancer types. We detect vast, unreported expansion of simple mutations sharply demarcated by recombinative loss of the second copy of TP53 in cutaneous squamous cell carcinomas (cSCC) and serous ovarian adenocarcinomas, in the former surpassing 50 mutations per megabase. In cSCCs, we also report diverse secondary mutations in known and novel oncogenic pathways, illustrating how such expanded mutagenesis directly promotes malignant progression. These results reframe paradigms in which TP53 mutation is required later, to bypass senescence induced by driver oncogenes.
Cancer Discovery 07/2011; 1(2):137-43. · 15.93 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Although trichoepitheliomas (TEs) are commonly regarded as benign tumors of follicular origin, the natural history of multiple familial trichoepitheliomas (MFT) and their risk for malignancy has been unclear. We describe a 57-year-old male with numerous skin-colored firm papules and plaques present on the central face since 6 years of age. Recently, some lesions had enlarged and ulcerated. Other family members were similarly affected. Biopsies from multiple lesions showed TEs both alone and associated with basal cell carcinoma (BCC) in the same section, suggesting the secondary development of BCCs within TEs. Many prior reports of BCCs arising within TEs in patients with presumed MFT were likely misdiagnosed cases of nevoid BCC. This report is a compelling example of MFT in which BCCs evolved secondarily. Awareness of the potential for the evolution of carcinoma in patients with MFT is important in the management of these patients.
[Show abstract][Hide abstract] ABSTRACT: Surgical facelifting procedures remain popular despite the recent introduction of laser, light source, and radiofrequency
devices as facial rejuvenation alternatives. In recent years, facelift surgery has remained one of the most popular cosmetic
procedures in the United States.1 Its popularity persists because of the reproducible surgical rejuvenation with many years duration and minimal risk in experienced
hands. Recent innovations with shorter scars, supra-SMAS (superficial musculoaponeurotic system) dissection, the addition
of liposuction as a concomitant procedure, and less undermining provide comparable surgical outcomes to traditional techniques
with less risk and downtime.2–4 While other specialties have contributed novel ideas,5 cutaneous surgeons have been innovators of a number of less aggressive lifting procedures that can be performed under local
anesthesia and consequently eliminate the complications associated with general anesthesia and minimize the complications
associated with deep plane or composite lifts.6–14 Ongoing innovations in less aggressive techniques will allow facelifting procedures to continue to rise in popularity as
patients seek facial rejuvenation with less risk, scarring, and downtime.
[Show abstract][Hide abstract] ABSTRACT: Although the overall incidence is low, bleeding complications in dermatologic surgery can occur and be the source of significant patient morbidity. In this article, we summarize the key aspects of preoperative assessment of patients at risk for bleeding. A review of current issues and literature regarding safe continuation of anticoagulant and antiplatelet medications in dermatologic surgery patients is also presented. In addition, principles for management of bleeding events, should they occur, are also highlighted.
Seminars in Cutaneous Medicine and Surgery 01/2008; 26(4):189-95. · 2.40 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Injectable hyaluronic acid is a glycosaminoglycan used for soft-tissue augmentation. A number of products that are not Food and Drug Administration (FDA) approved for use in the United States are used commonly in Europe. We report a case of persistent delayed-type hypersensitivity to injected non-animal-stabilized hyaluronic acid. The patient was initially injected in Europe with a non-FDA-approved filler but traveled to the United States for evaluation of this adverse reaction.
A case of adverse reaction to non-animal-stabilized hyaluronic acid is described. An overview of selected hyaluronic acid filler products is provided.
The patient developed persistent facial edema after injection of hyaluronic acid filler to the melolabial folds, glabella, lips, and perioral rhytids.
Injectable hyaluronic acid can be associated with a variety of complications including immediate and delayed-type hypersensitivity reactions. Physicians should be familiar with products used in other countries, as patients may present for evaluation following adverse reaction to fillers obtained abroad or from American physicians using non-FDA-approved products.
Journal of Cosmetic Dermatology 10/2007; 6(3):167-71. · 1.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Individuals of Asian heritage are predisposed to congenital and acquired pigmentary disorders. Cosmetic enhancement is frequently the primary treatment goal for these benign lesions. Accurate diagnosis of the nature of the pigmentary disorder is fundamental for administering safe and effective therapy. Before the advent of modern laser technology, such reported treatments as cryotherapy, dermabrasion, chemical peeling, and surgical excision resulted in unpredictable results. This article focuses on the diagnosis of disorders of pigmentation in Asian patients and reviews laser and light treatment modalities.
Facial Plastic Surgery Clinics of North America 09/2007; 15(3):367-80, vii. · 1.18 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Infection rates in dermatologic surgery are low, ranging on average from 1 to 3%. Studies have shown that many practitioners likely overuse antibiotics, both for prevention of wound infection and in endocarditis prophylaxis. This article discusses patient and environmental risk factors in would infection. Data on wound infection prophylaxis are reviewed, and specific guidelines set forth with regards to appropriate antibiotic usage, drug selection, dosage, and timing. In addition, recommendations surrounding endocarditis and prosthetic joint infection prophylaxis are presented as they apply to dermatologic surgery.
Seminars in Cutaneous Medicine and Surgery 04/2007; 26(1):47-53. · 2.40 Impact Factor