Dermatology Commons^™

Divergence Of Camp Signalling Pathways Mediating Augmented Nucleotide Excision Repair And Pigment Induction In Melanocytes, Erin M. Wolf Horrell, Stuart G. Jarrett, Katharine M. Carter, John A. D'Orazio

Markey Cancer Center Faculty Publications

Loss‐of‐function melanocortin 1 receptor (MC1R) polymorphisms are common in UV‐sensitive fair‐skinned individuals and are associated with blunted cAMP second messenger signalling and higher lifetime risk of melanoma because of diminished ability of melanocytes to cope with UV damage. cAMP signalling positions melanocytes to resist UV injury by upregulating synthesis of UV‐blocking eumelanin pigment and by enhancing the repair of UV‐induced DNA damage. cAMP enhances melanocyte nucleotide excision repair (NER), the genome maintenance pathway responsible for the removal of mutagenic UV photolesions, through cAMP‐activated protein kinase (protein kinase A)‐mediated phosphorylation of the ataxia telangiectasia‐mutated and Rad3‐related (ATR) protein on the S435 …

Pathologists' Diagnosis Of Invasive Melanoma And Melanocytic Proliferations: Observer Accuracy And Reproducibility Study., Joann G Elmore, Raymond L Barnhill, David E Elder, Gary M Longton, Margaret S Pepe, Lisa M Reisch, Patricia A Carney, Linda J Titus, Heidi D Nelson, Tracy Onega, Anna N A Tosteson, Martin A Weinstock, Stevan R Knezevich, Michael W Piepkorn

Articles, Abstracts, and Reports

No abstract provided.

Inhibition Of Age-Related Therapy Resistance In Melanoma By Rosiglitazone-Mediated Induction Of Klotho., Reeti Behera, Amanpreet Kaur, Marie R. Webster, Suyeon Kim, Abibatou Ndoye, Curtis H. Kugel, Gretchen M. Alicea, Joshua Wang, Kanad Ghosh, Phil Cheng, Sofia Lisanti, Katie Marchbank, Vanessa Dang, Mitchell Levesque, Reinhard Dummer, Xiaowei Xu, Meenhard Herlyn, Andrew E. Aplin, Alexander Roesch, Cecilia Caino, Dario C. Altieri, Ashani T. Weeraratna

Department of Cancer Biology Faculty Papers

Purpose: Aging is a poor prognostic factor for melanoma. We have shown that melanoma cells in an aged microenvironment are more resistant to targeted therapy than identical cells in a young microenvironment. This is dependent on age-related secreted factors. Klotho is an age-related protein whose serum levels decrease dramatically by age 40. Most studies on klotho in cancer have focused on the expression of klotho in the tumor cell. We have shown that exogenous klotho inhibits internalization and signaling of Wnt5A, which drives melanoma metastasis and resistance to targeted therapy. We investigate here whether increasing klotho in the aged microenvironment …

Evaluating Cultural Competency And Patient Satisfaction In An Urban Dermatology Clinic., Jordan V. Wang, Nicholas Ross, Matthew Keller

Department of Dermatology and Cutaneous Biology Faculty Papers

Cultural competency continues to gain increased attention in medicine. Not only does it play a significant role in the delivery of health care and patient outcomes, but it also remains a major determinant of patient satisfaction. This study investigated how patients in an urban dermatology clinic rated their satisfaction with cultural competency. Compared to White patients, satisfaction scores were greater for Hispanic or Latino patients and less for Asian patients, while there was no significant difference for Black or African American patients. There were clear differences in patient satisfaction rates of various dimensions of cultural competency. A follow-up study with …

Elevated Dietary Magnesium During Pregnancy And Postnatal Life Prevents Ectopic Mineralization In Enpp1asj Mice, A Model For Generalized Arterial Calcification Of Infancy., Joshua Kingman, Jouni Uitto, Qiaoli Li

Department of Dermatology and Cutaneous Biology Faculty Papers

Generalized arterial calcification of infancy (GACI) is an autosomal recessive disorder caused by mutations in the ENPP1 gene. It is characterized by mineralization of the arterial blood vessels, often diagnosed prenatally, and associated with death in early childhood. There is no effective treatment for this devastating disorder. We previously characterized the Enpp1asjmutant mouse as a model of GACI, and we have now explored the effect of elevated dietary magnesium (five-fold) in pregnant mothers and continuing for the first 14 weeks of postnatal life. The mothers were kept on either control diet or experimental diet supplemented with magnesium. Upon weaning at …

Completion Dissection Or Observation For Sentinel-Node Metastasis In Melanoma., Mark Faries, John F Thompson, Alistair J Cochran, Robert H Andtbacka, Nicola Mozzillo, Jonathan S Zager, Tiina Jahkola, Tawnya L Bowles, Alessandro Testori, Peter D Beitsch, Harald J Hoekstra, Marc Moncrieff, Christian Ingvar, Michel W J M Wouters, Michael S Sabel, Edward A Levine, Doreen Agnese, Michael Henderson, Reinhard Dummer, Carlo R Rossi, Rogerio I Neves, Steven D Trocha, Frances Wright, David R Byrd, Maurice Matter, Eddy Hsueh, Alastair Mackenzie-Ross, Douglas B Johnson, Patrick Terheyden, Adam C Berger, Tara L Huston, Jeffrey D Wayne, B Mark Smithers, Heather B Neuman, Schlomo Schneebaum, Jeffrey E Gershenwald, Charlotte E Ariyan, Darius C Desai, Lisa Jacobs, Kelly M Mcmasters, Anja Gesierich, Peter Hersey, Steven D Bines, John M Kane, Richard J Barth, Gregory Mckinnon, Jeffrey M Farma, Erwin Schultz, Sergi Vidal-Sicart, Richard A Hoefer, James M Lewis, Randall Scheri, Mark C Kelley, Omgo E Nieweg, R Dirk Noyes, Dave S B Hoon, He-Jing Wang, David A Elashoff, Robert M Elashoff

Articles, Abstracts, and Reports

BACKGROUND: Sentinel-lymph-node biopsy is associated with increased melanoma-specific survival (i.e., survival until death from melanoma) among patients with node-positive intermediate-thickness melanomas (1.2 to 3.5 mm). The value of completion lymph-node dissection for patients with sentinel-node metastases is not clear.

METHODS: In an international trial, we randomly assigned patients with sentinel-node metastases detected by means of standard pathological assessment or a multimarker molecular assay to immediate completion lymph-node dissection (dissection group) or nodal observation with ultrasonography (observation group). The primary end point was melanoma-specific survival. Secondary end points included disease-free survival and the cumulative rate of nonsentinel-node metastasis.

RESULTS: Immediate completion …

Expanding The Genotypic Spectrum Of Bathing Suit Ichthyosis., Nareh V. Marukian, Rong-Hua Hu, Brittany G. Craiglow, Leonard M. Milstone, Jing Zhou, Amy Theos, Hande Kaymakcalan, Deniz A. Akkaya, Jouni J. Uitto, Hassan Vahidnezhad, Leila Youssefian, Susan J. Bayliss, Amy S. Paller, Lynn M. Boyden, Keith A. Choate

Department of Dermatology and Cutaneous Biology Faculty Papers

Importance: Bathing suit ichthyosis (BSI) is a rare congenital disorder of keratinization characterized by restriction of scale to sites of relatively higher temperature such as the trunk, with cooler areas remaining unaffected. Fewer than 40 cases have been reported in the literature. Bathing suit ichthyosis is caused by recessive, temperature-sensitive mutations in the transglutaminase-1 gene (TGM1). Clear genotype-phenotype correlations have been difficult to establish because several of the same TGM1 mutations have been reported in BSI and other forms of congenital ichthyosis. We identify novel and recurrent mutations in 16 participants with BSI.

Objective: To expand the genotypic spectrum of …

Laboratory Tests In Patients Treated With Isotretinoin: Occurrence Of Liver And Muscle Abnormalities And Failure Of Ast And Alt To Predict Liver Abnormality., Guy F. Webster, Timothy G. Webster, Lorraine R. Grimes

Department of Dermatology and Cutaneous Biology Faculty Papers

Current laboratory monitoring may not be optimal. A retrospective chart review was performed on thelaboratory results of 246 patients who were treated with isotretinoin for acne over a 9-year period. Tests obtained were CBC, lipid panel, AST, ALT, CK, GGT,and C-reactive protein. Thirty-five patients had an elevated AST and 35 of these had an elevated CK; 32 had an elevated ALT and 11 of these had an elevated CK. Thirteen patients had an elevated GGT; in 5 this was the only abnormality, whereas 8 had a GGT elevation accompanied by an elevated AST or ALT. Two had an elevated GGT …

The Skin Cancer Health Crisis And Recommended Intervention Methods, Blaire Brooks

Senior Theses

Despite the increasing research connecting UVR exposures to skin cancer, rates of skin cancer are rising. Skin cancer is now the most common form of cancer and there are significant health care costs associated with treating the cases (Balk et al., 2013). As a result, the United States needs greater initiatives to increase educational programs, physician counseling, and political action regarding ultraviolet exposure and incidence of skin cancer. Evaluation of the types of skin cancer, perceptions of tanning, and current regulations and recommendations are required in order to form the initiatives to combat the growth of skin cancer.

Systematic Analysis Of Whole Exome Sequencing Determines Ret G691s Polymorphism As Germline Variant In Melanoma, Brent J. Smith Jr, Jennifer D. Hintzsche, Carol M. Amato, Aik-Choon Tan, Keith R. Wells, Allison J. Applegate, Rita T. Gonzalez, Jodie R. Barr, William A. Robinson

Marshall Journal of Medicine

Abstract

The RET proto-oncogene encodes a receptor tyrosine kinase that is activated by glial cell derived neutrotrophic factor (GDNF). Previous studies have found that a single nucleotide polymorphism (SNP), RETp (G691S), in the juxtamembrane domain enhances the signaling pathway and promotes tumor growth by GDNF in pancreatic and thyroid cancer in addition to melanoma. It is uncertain however whether this SNP is a germline variant or somatic mutation. A prior study reported that the RETp variant was a germline SNP in desmoplastic and non-desmoplastic melanomas. In the present study, we examined both melanoma tissue samples and matching peripheral blood DNA …

Interprofessional Collaboration To Prevent Hospital-Acquired Pneumonia (Hap), Jessica Cooper, Amber Manning, Morgan Miller, Megan Mustard, Haleigh Pike, Suzi White

Celebration of Student Scholarship Poster Sessions Archive

No abstract provided.

Considerations For The Use Of Medical Devices In Dermatology., Jordan Wang, Dorota Z. Korta, Christopher B. Zachary

Department of Dermatology and Cutaneous Biology Faculty Papers

This manuscript addresses the significant considerations concerning the development and use of medical devices in dermatology. With the rapidly growing demand and booming market for medical devices, especially lasers, it is crucial that dermatologists become familiar with the nuances associated with supporting clinical studies, consumer-driven marketing strategies, and the complex relationships that exist between physicians, industry, and consumers. An examination of these relationships includes an overview of the potential biases pertaining to advisory panels and treating clinicians. The aim of this paper is to serve as an introduction to the background of medical devices and to offer dermatologists important information …

Fungus Amungus -- A Common Disease State That Is Commonly Missed: A Survey Based Study, Ramsin Yadgar, Adam Friedman, Neal Bhatia

GW Research Days 2016 - 2020

Background: Dermatophyte infections involving the skin, hair, or nails affect an estimated 25% of the world's population, and accounted for 51 million outpatient visits over a ten-year period (1995-2004) in the United States alone. Dermatomycosis is routinely managed by dermatologists, though given the diversity of clinical presentations, is sometimes misdiagnosed, which can result in inappropriate therapy, worsening of symptoms, and even result in additional skin and soft tissue infections.

Methods: An interactive survey of board-certified dermatologists was conducted at the 2016 Orlando Dermatology Aesthetic & Clinical Conference, during a seminar on superficial mycotic infections. The structure of the survey entailed …

Thin Melanoma With Nodal Involvement: Analysis Of Demographic, Pathologic, And Treatment Factors With Regard To Prognosis., Giorgos Karakousis, Phyllis A Gimotty, Edmund K Bartlett, Myung-Shin Sim, Madalyn G Neuwirth, Douglas Fraker, Brian J Czerniecki, Mark B Faries

Articles, Abstracts, and Reports

BACKGROUND: Although only a small proportion of thin melanomas result in lymph node metastasis, the abundance of these lesions results in a relatively large absolute number of patients with a diagnosis of nodal metastases, determined by either sentinel lymph node (SLN) biopsy or clinical nodal recurrence (CNR).

METHODS: Independent cohorts with thin melanoma and either SLN metastasis or CNR were identified at two melanoma referral centers. At both centers, SLN metastasis patients were included. At center 1, the CNR cohort included patients with initial negative clinical nodal evaluation followed by CNR. At center 2, the CNR cohort was restricted to …

Review Article: Pathogenesis And Clinical Manifestations Of Gastrointestinal Involvement In Systemic Sclerosis., Sumit Kumar, Jagmohan Singh, Satish Rattan, Anthony J. Dimarino, Sidney Cohen, Sergio A. Jimenez

Department of Dermatology and Cutaneous Biology Faculty Papers

BACKGROUND: Gastrointestinal tract (GIT) involvement is a common cause of debilitating symptoms in patients with systemic sclerosis (SSc). There are no disease modifying therapies for this condition and the treatment remains symptomatic, largely owing to the lack of a clear understanding of its pathogenesis.

AIMS: To investigate novel aspects of the pathogenesis of gastrointestinal involvement in SSc. To summarise existing knowledge regarding the cardinal clinical gastrointestinal manifestations of SSc and its pathogenesis, emphasising recent investigations that may be valuable in identifying potentially novel therapeutic targets.

METHODS: Electronic (PubMed/Medline) and manual Google search.

RESULTS: The GIT is the most common internal …

Adverse Reactions Of Biological Therapies In Patients With Psoriasis, Maria I. Sârbu, Mircea Tampa, Mădălina I. Mitran, Cristina I. Mitran, Alexandra M. Limbău, Simona R. Georgescu

Journal of Mind and Medical Sciences

Psoriasis is a chronic, immune-mediated disorder characterized by well demarcated, erythematous plaques covered by thick, silvery-white scales, most often located on the knees, elbows, sacral area and scalp. It has a significant impact on the patient's quality of life.

Biological therapies revolutionized the treatment of psoriasis vulgaris but there has been concern regarding the use of those agents due to severe adverse reactions reported in patients receiving TNF-α inhibitors for various inflammatory diseases.

The aim of this paper is to review the most important adverse reactions reported in patients receiving biological treatments. The most common and severe side effects associated …

Pleomorphic Fibroma., Huyenlan Dinh Do, Cynthia L. Bartus Md, Nektarios I. Lountzis Md, Stephen M. Purcell Do

Department of Medicine

No abstract provided.

Atr Mutations Promote The Growth Of Melanoma Tumors By Modulating The Immune Microenvironment., Chi-Fen Chen, Rolando Ruiz-Vega, Priya Vasudeva, Francisco Espitia, Tatiana B Krasieva, Sebastien De Feraudy, Bruce J Tromberg, Sharon Huang, Chad P Garner, Jie Wu, Dave S B Hoon, Anand K Ganesan

Articles, Abstracts, and Reports

Melanomas accumulate a high burden of mutations that could potentially generate neoantigens, yet somehow suppress the immune response to facilitate continued growth. In this study, we identify a subset of human melanomas that have loss-of-function mutations in ATR, a kinase that recognizes and repairs UV-induced DNA damage and is required for cellular proliferation. ATR mutant tumors exhibit both the accumulation of multiple mutations and the altered expression of inflammatory genes, resulting in decreased T cell recruitment and increased recruitment of macrophages known to spur tumor invasion. Taken together, these studies identify a mechanism by which melanoma cells modulate the immune …

The Efficacy And Safety Of Apremilast, Etanercept And Placebo In Patients With Moderate-To-Severe Plaque Psoriasis: 52-Week Results From A Phase Iiib, Randomized, Placebo-Controlled Trial (Liberate)., K Reich, M Gooderham, L Green, A Bewley, Z Zhang, I Khanskaya, R M Day, J Goncalves, K Shah, V Piguet, J Soung

Dermatology Faculty Publications

BACKGROUND: Apremilast, an oral, small-molecule phosphodiesterase 4 inhibitor, has demonstrated efficacy in patients with moderate-to-severe psoriasis.

OBJECTIVE: Evaluate efficacy and safety of apremilast vs. placebo in biologic-naive patients with moderate-to-severe plaque psoriasis and safety of switching from etanercept to apremilast in a phase IIIb, randomized, double-blind, placebo-controlled study (NCT01690299).

METHODS: Two hundred and fifty patients were randomized to placebo (n = 84), apremilast 30 mg BID (n = 83) or etanercept 50 mg QW (n = 83) through Week 16; thereafter, all patients continued or switched to apremilast through Week 104. The primary efficacy endpoint was achievement of PASI-75 at …

Is Apremilast (Otezla) Effective In Reducing Pruritus In Adults Over 18 Years Old With Plaque Psoriasis?, Stephanie N. Carnes

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not apremilast (Otezla) is effective in reducing pruritus in adults over 18 years old with plaque psoriasis

STUDY DESIGN: This review is based on three randomized controlled trials (RCTs) published in 2012, and 2015.

DATA SOURCES: Three randomized controlled trials comparing the effectiveness of apremilast to a placebo in reducing pruritus in adults over 18 years old with plaque psoriasis, found using PubMed.

OUTCOMES MEASURED: The outcome studied was improvement of the psoriatic plaques based on reduction in pruritus measured by the Pruritus …

Acitretin For The Treatment Of Recalcitrant Plantar Warts, Deep Joshipura, A Goldminz, A Greb, Alice Gottlieb

NYMC Faculty Publications

No abstract provided.

Effect Of Systemic Antioxidant Allopurinol Therapy On Skin Flap Survival, M Ardakani, Kaveh Alizadeh, A Moghadam

NYMC Faculty Publications

No abstract provided.

The Influence Of Tumor Regression, Solar Elastosis, And Patient Age On Pathologists' Interpretation Of Melanocytic Skin Lesions., Linda Titus, Raymond L Barnhill, Jason P Lott, Michael W Piepkorn, David E Elder, Paul D Frederick, Heidi D Nelson, Patricia A Carney, Stevan R Knezevich, Martin A Weinstock, Joann G Elmore

Articles, Abstracts, and Reports

It is not known whether patient age or tumor characteristics such as tumor regression or solar elastosis influence pathologists' interpretation of melanocytic skin lesions (MSLs). We undertook a study to determine the influence of these factors, and to explore pathologist's characteristics associated with the direction of diagnosis. To meet our objective, we designed a cross-sectional survey study of pathologists' clinical practices and perceptions. Pathologists were recruited from diverse practices in 10 states in the United States. We enrolled 207 pathologist participants whose practice included the interpretation of MSLs. Our findings indicated that the majority of pathologists (54.6%) were influenced toward …

Challenges To Smartphone Applications For Melanoma Detection, Jordan V. Wang, Lance W. Chapman, Matthew S. Keller

Department of Dermatology and Cutaneous Biology Faculty Papers

This commentary addresses the emerging market for health-related smartphone applications. Specific to dermatology, there has been a significant increase not only in applications that promote skin cancer awareness and education but also in those meant for detection. With evidence showing that 365 dermatology-related applications were available in 2014--up from 230 in 2012--and that 1 in 5 patients under the age of 50 have used a smartphone to help diagnose a skin problem, there is clearly a large subset of patients participating in this growing trend. Therefore, we are obligated to take a closer look into this phenomenon. Studies have shown …

Ladarixin, A Dual Cxcr1/2 Inhibitor, Attenuates Experimental Melanomas Harboring Different Molecular Defects By Affecting Malignant Cells And Tumor Microenvironment., Daria Marley Kemp, Alyson Pidich, Mary Larijani, Rebecca Jonas, Elizabeth Lash, Takami Sato, Mizue Terai, Maria De Pizzol, Marcello Allegretti, Olga Igoucheva, Vitali Alexeev

Department of Dermatology and Cutaneous Biology Faculty Papers

CXCR1 and CXCR2 chemokine receptors and their ligands (CXCL1/2/3/7/8) play an important role in tumor progression. Tested to date CXCR1/2 antagonists and chemokine-targeted antibodies were reported to affect malignant cells in vitro and in animal models. Yet, redundancy of chemotactic signals and toxicity hinder further clinical development of these approaches. In this pre-clinical study we investigated the capacity of a novel small molecule dual CXCR1/2 inhibitor, Ladarixin (LDX), to attenuate progression of experimental human melanomas. Our data showed that LDX-mediated inhibition of CXCR1/2 abrogated motility and induced apoptosis in cultured cutaneous and uveal melanoma cells and xenografts independently of the …

Hyaline Fibromatosis Syndrome: A Novel Mutation And Recurrent Founder Mutation In The Cmg2/Antxr2 Gene., Leila Youssefian, Hassan Vahidnezhad, Yahya Aghighi, Vahid Ziaee, Sirous Zeinali, Maryam Abiri, Jouni Uitto

Department of Dermatology and Cutaneous Biology Faculty Papers

No abstract provided.

Review Of Applications Of Microneedling In Dermatology., Christopher Iriarte, Olabola Awosika, Monica Rengifo-Pardo, Alison Ehrlich

Dermatology Faculty Publications

Microneedling (MN) is a novel therapeutic modality in dermatology. Through physical trauma from needle penetration, MN induces a wound healing cascade with minimal damage to the epidermis. This allows for enhancement in the absorption of mainstay topical therapies across the thick stratum corneum. MN has become increasingly utilized over the last several years as it is a relatively simple procedure that is cost-effective, well tolerated, and offers both cosmetic and therapeutic benefits. The ability to treat localized areas of disease has led to numerous studies gauging its potential in focal diseases of inflammation, dyschromia, and photodamage. This review discusses the …

Sustained Nitric Oxide-Releasing Nanoparticles Interfere With Methicillin-Resistant Staphylococcus Aureus Adhesion And Biofilm Formation In A Rat Central Venous Catheter Model., Mircea Radu Mihu, Vitor Cabral, Rodney Pattabhi, Moses T Tar, Kelvin P Davies, Adam J Friedman, Luis R Martinez, Joshua D Nosanchuk

Dermatology Faculty Publications

Staphylococcus aureus is frequently isolated in the setting of infections of indwelling medical devices, which are mediated by the microbe's ability to form biofilms on a variety of surfaces. Biofilm-embedded bacteria are more resistant to antimicrobial agents than their planktonic counterparts and often cause chronic infections and sepsis, particularly in patients with prolonged hospitalizations. In this study, we demonstrate that sustained nitric oxide-releasing nanoparticles (NO-np) interfere with S. aureus adhesion and prevent biofilm formation on a rat central venous catheter (CVC) model of infection. Confocal and scanning electron microscopy showed that NO-np-treated staphylococcal biofilms displayed considerably reduced thicknesses and bacterial …

Systemic Sclerosis: Clinical Manifestations, Anesthetic And Orthopedic Considerations In A Patient, Obada Hasan, Muneeba Jessar, Muhammad Ashar, Shahryar Noordin, Tashfeen Ahmad

Section of Orthopaedic Surgery

Introduction: Systemic sclerosis is a rare and progressive multisystem autoimmune disorder that is characterized pathologically by vascular abnormalities, connective tissue sclerosis and atrophy of skin and various internal organs (e.g., alimentary tract, lungs, heart, kidney, CNS), and autoantibodies. With an unknown etiology, Scleroderma is a complex polygenetic disease. A recent Genome Wide Association Study (GWAS) confirmed a strong association with the Major Histocompatibility Complex (MHC) and autoimmunity. We provide a case scenario along with a review of the systems involved and challenges physicians can face in dealing with this rare disease.
Case Presentation: Our patient, a known case of systemic …

Insights Into Local Tumor Microenvironment Immune Factors Associated With Regression Of Cutaneous Melanoma Metastases By, Junbao Yang, Maris S Jones, Romela Irene Ramos, Alfred A Chan, Agnes F Lee, Leland J Foshag, Peter A Sieling, Mark Faries, Delphine J Lee

Articles, Abstracts, and Reports

No abstract provided.