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Item A Case of Metastatic Basal Cell Carcinoma (BCC) With Spinal and Pulmonary Metastases Treated With Vismodegib, Sonedigib, and Radiotherapy(Springer Nature, 2022-03-17) Samia, Arthur M.; Nenow, Joseph M.; Boyer, Philip; Medicine, School of MedicineBasal cell carcinoma (BCC) is the most common malignancy worldwide and has one of the most favorable prognoses due to its tendency to remain local. Clinical presentation with rare distant metastases significantly increases morbidity and mortality. Historically, no effective therapies have existed for locally advanced or metastatic BCC. Recent research highlights the possibility of treating patients with advanced and metastatic BCC with hedgehog pathway inhibitors, such as vismodegib or sonedigib. We present the case of a 62-year-old male with a history of a large left shoulder lesion, which was diagnosed as a nodulocystic BCC following biopsy and histopathologic examination. The primary lesion was managed with surgical excision, and his ensuing metastatic disease was treated with vismodegib, sonedigib, tumor debulking, and radiation therapy. Magnetic resonance imaging and computed tomography of the chest revealed probable metastases to the apical segment of the left upper lobe and thoracic spine, leading to spinal stenosis and probable cause of the patient's ataxia and paresthesias. Due to the ability of BCCs to transform during metastasis, it is impossible to identify the nature of metastatic lesions (i.e., basaloid, squamous, or hybrid) without biopsy. In this case report, we review the etiologies, typical demographics, presentation patterns, and treatment regimens for metastatic BCC and the possibility of metastatic disease transforming to squamous or hybrid variants.Item Cost Minimization Analysis of a Teledermatology Triage System in a Managed Care Setting(American Medical Association, 2021) Zakaria, Adam; Miclau, Theodore A.; Maurer, Toby; Leslie, Kieron S.; Amerson, Erin; Dermatology, School of MedicineImportance: Teledermatology (TD) enables remote triage and management of dermatology patients. Previous analyses of TD systems have demonstrated improved access to care but an inconsistent fiscal impact. Objective: To compare the organizationwide cost of managing newly referred dermatology patients within a TD triage system vs a conventional dermatology care model at the Zuckerberg San Francisco General Hospital and Trauma Center (hereafter referred to as the ZSFG) in California. Design, setting, and participants: A retrospective cost minimization analysis was conducted of 2098 patients referred to the dermatology department at the ZSFG between June 1 and December 31, 2017. Intervention: Implementation of the TD triage system in January 2015. Main outcomes and measures: The main outcome was mean cost to the health care organization to manage newly referred dermatology patients with or without TD triage. To estimate costs, decision-tree models were constructed to characterize possible care paths with TD triage and within a conventional dermatology care model. Costs associated with primary care visits, dermatology visits, and TD visits were then applied to the decision-tree models to estimate the mean cost of managing patients following each care path for 6 months. The mean cost for each visit type incorporated personnel costs, with the mean cost per TD consultation also incorporating software implementation and maintenance costs. Finally, ZSFG patient data were applied within the models to evaluate branch probabilities, enabling calculation of mean cost per patient within each model. Results: The analysis captured 2098 patients (1154 men [55.0%]; mean [SD] age, 53.4 [16.8] years), with 1099 (52.4%) having Medi-Cal insurance and 879 (41.9%) identifying as non-White. In the decision-tree model with TD triage, the mean (SD) cost per patient to the health care organization was $559.84 ($319.29). In the decision-tree model for conventional dermatology care, the mean (SD) cost per patient was $699.96 ($390.24). Therefore, the TD model demonstrated a statistically significant mean (SE) cost savings of $140.12 ($11.01) per patient. Given an annual dermatology referral volume of 3150 patients, the analysis estimates an annual savings of $441 378. Conclusions and relevance: Implementation of a TD triage system within the dermatology department at the ZSFG was associated with cost savings, suggesting that managed health care settings may experience significant cost savings from using TD to triage and manage patients.Item Data-driven imaging of tissue inflammation using RGB-based hyperspectral reconstruction toward personal monitoring of dermatologic health(Optical Society of America, 2017-10-26) Kim, Taehoon; Visbal-Onufrak, Michelle A.; Konger, Raymond L.; Kim, Young L.; Pathology and Laboratory Medicine, School of MedicineSensitive and accurate assessment of dermatologic inflammatory hyperemia in otherwise grossly normal-appearing skin conditions is beneficial to laypeople for monitoring their own skin health on a regular basis, to patients for looking for timely clinical examination, and to primary care physicians or dermatologists for delivering effective treatments. We propose that mathematical hyperspectral reconstruction from RGB images in a simple imaging setup can provide reliable visualization of hemoglobin content in a large skin area. Without relying on a complicated, expensive, and slow hyperspectral imaging system, we demonstrate the feasibility of determining heterogeneous or multifocal areas of inflammatory hyperemia associated with experimental photocarcinogenesis in mice. We envision that RGB-based reconstructed hyperspectral imaging of subclinical inflammatory hyperemic foci could potentially be integrated with the built-in camera (RGB sensor) of a smartphone to develop a simple imaging device that could offer affordable monitoring of dermatologic health.Item Evidence-Based Utility of Adjunct Antioxidant Supplementation for the Prevention and Treatment of Dermatologic Diseases: A Comprehensive Systematic Review(MDPI, 2023-07-27) Tran, Jasmine Thuy; Diaz, Michael Joseph; Rodriguez, Daphnee; Kleinberg, Giona; Aflatooni, Shaliz; Palreddy, Siri; Abdi, Parsa; Taneja, Kamil; Batchu, Sai; Forouzandeh, Mahtab; Medicine, School of MedicineSkin conditions are a significant cause of fatal and nonfatal disease burdens globally, ranging from mild irritations to debilitating diseases. Oxidative stress, which is an imbalance between reactive oxygen species and the cells' ability to repair damage, is implicated in various skin diseases. Antioxidants have been studied for their potential benefits in dermatologic health, but the evidence is limited and conflicting. Herein, we conducted a systematic review of controlled trials, meta-analyses, and Cochrane review articles to evaluate the current evidence on the utility of antioxidant supplementation for adjunct prevention and treatment of skin disease and to provide a comprehensive assessment of their role in promoting dermatologic health. The Cochrane Library, PubMed, EMBASE, and Epistemonikos databases were queried. Eligibility criteria included (1) primary focus on nanoparticle utility for skin cancer; (2) includes measurable outcomes data with robust comparators; (3) includes a number of human subjects or cell-line types, where applicable; (4) English language; and (5) archived as full-text journal articles. A total of 55 articles met the eligibility criteria for the present review. Qualitative analysis revealed that topical and oral antioxidant supplementation has demonstrated preliminary efficacy in reducing sunburns, depigmentation, and photoaging. Dietary exogenous antioxidants (namely vitamins A, C, and E) have shown chemopreventive effects against skin cancer. Antioxidant supplementation has also shown efficacy in treating non-cancer dermatoses, including rosacea, psoriasis, atopic dermatitis, and acne vulgaris. While further studies are needed to validate these findings on a larger scale, antioxidant supplementation holds promise for improving skin health and preventing skin diseases.Item Four year efficacy of prophylactic human papillomavirus quadrivalent vaccine against low grade cervical, vulvar, and vaginal intraepithelial neoplasia and anogenital warts: randomised controlled trial(BMJ Publishing Group, 2010-07-20) The FUTURE I/II Study Group; Dillner, Joakim; Kjaer, Susanne K.; Wheeler, Cosette M.; Sigurdsson, Kristján; Iversen, Ole-Erik; Hernandez-Avila, Mauricio; Perez, Gonzalo; Brown, Darron R.; Koutsky, Laura A.; Tay, Eng Hseon; García, Patricia; Ault, Kevin A.; Garland, Suzanne M.; Leodolter, Sepp; Olsson, Sven-Eric; Tang, Grace W.K.; Ferris, Daron G.; Paavonen, Jorma; Lehtinen, Matti; Steben, Marc; Bosch, Xavier; Joura, Elmar A.; Majewski, Slawomir; Muñoz, Nubia; Myers, Evan R.; Villa, Luisa L; Taddeo, Frank J.; Roberts, Christine; Tadesse, Amha; Bryan, Janine T.; Maansson, Roger; Lu, Shuang; Vuocolo, Scott; Hesley, Teresa M.; Barr, Eliav; Haupt, Richard; Medicine, School of MedicineObjectives To evaluate the prophylactic efficacy of the human papillomavirus (HPV) quadrivalent vaccine in preventing low grade cervical, vulvar, and vaginal intraepithelial neoplasias and anogenital warts (condyloma acuminata). Design Data from two international, double blind, placebo controlled, randomised efficacy trials of quadrivalent HPV vaccine (protocol 013 (FUTURE I) and protocol 015 (FUTURE II)). The trials were to be 4 years in length, and the results reported are from final study data of 42 months’ follow-up. Setting Primary care centres and university or hospital associated health centres in 24 countries and territories around the world. Participants 17 622 women aged 16-26 years enrolled between December 2001 and May 2003. Major exclusion criteria were lifetime number of sexual partners (>4), history of abnormal cervical smear test results, and pregnancy. Intervention Three doses of quadrivalent HPV vaccine (for serotypes 6, 11, 16, and 18) or placebo at day 1, month 2, and month 6. Main outcome measures Vaccine efficacy against cervical, vulvar, and vaginal intraepithelial neoplasia grade I and condyloma in a per protocol susceptible population that included subjects who received all three vaccine doses, tested negative for the relevant vaccine HPV types at day 1 and remained negative through month 7, and had no major protocol violations. Intention to treat, generally HPV naive, and unrestricted susceptible populations were also studied. Results In the per protocol susceptible population, vaccine efficacy against lesions related to the HPV types in the vaccine was 96% for cervical intraepithelial neoplasia grade I (95% confidence interval 91% to 98%), 100% for both vulvar and vaginal intraepithelial neoplasia grade I (95% CIs 74% to 100%, 64% to 100% respectively), and 99% for condyloma (96% to 100%). Vaccine efficacy against any lesion (regardless of HPV type) in the generally naive population was 30% (17% to 41%), 75% (22% to 94%), and 48% (10% to 71%) for cervical, vulvar, and vaginal intraepithelial neoplasia grade I, respectively, and 83% (74% to 89%) for condyloma. Conclusions Quadrivalent HPV vaccine provided sustained protection against low grade lesions attributable to vaccine HPV types (6, 11, 16, and 18) and a substantial reduction in the burden of these diseases through 42 months of follow-up.Item Genital Self-Image, Sexual Function, and Quality of Life Among Individuals with Vulvar and Non-Vulvar Inflammatory Dermatoses(Springer, 2022) Rivera, Sydney; Flood, Anna; Dykstra, Chandler; Herbenick, Debby; DeMaria, Andrea L.; Medicine, School of MedicineVulvar inflammatory dermatoses (VID; e.g., lichen sclerosus, lichen planus, vulvar dermatitis) can significantly impact sexual function. Both vulvar and non-vulvar inflammatory dermatoses (NVID; i.e., skin conditions not impacting vulvar skin, such as non-genital psoriasis and eczema/dermatitis) have yet to be fully characterized with regard to impact on genital self-image. A 20-min web-based survey was distributed September-November 2020 through social media ads, support groups, and online research recruitment services. Individuals in the USA over age 18 who were assigned female at birth and self-reported having been diagnosed with an inflammatory dermatosis were eligible. The primary outcome was the Female Genital Self-Image Scale (FGSIS). Secondary outcomes included the Female Sexual Function Index (FSFI), the Skindex-16 (a skin-related quality of life measure), the PROMIS Global-10 (assessing global physical/mental health), and sexual behavior histories. Participants (n = 348) reported mean age of 43.1 ± 15.5 (range = 19-81). Nearly one-third (n = 101; 29.0%) reported VID, 173 (50%) had NVID, and 74 (21%) experienced both vulvar and non-vulvar symptoms; they were analyzed as part of the VID group. The mean FGSIS score among participants with VID was 16.9 ± 4.1 and was significantly (p < .01) lower than that of participants with NVID (M = 21.2 ± 4.3), indicating lower genital self-image. Mental health (as measured by PROMIS-Global 10) was also impaired in VID. Rates of sexual dysfunction were high in both groups (> 60%). Findings suggest that in VID, lower genital self-image is correlated with poorer sexual function, quality of life, and global physical and mental health. Additional recommendations for VID management are proposed.Item Genome-wide DNA hypermethylation opposes healing in patients with chronic wounds by impairing epithelial-mesenchymal transition(The American Society for Clinical Investigation, 2022) Singh, Kanhaiya; Rustagi, Yashika; Abouhashem, Ahmed S.; Tabasum, Saba; Verma, Priyanka; Hernandez, Edward; Pal, Durba; Khona, Dolly K.; Mohanty, Sujit K.; Kumar, Manishekhar; Srivastava, Rajneesh; Guda, Poornachander R.; Verma, Sumit S.; Mahajan, Sanskruti; Killian, Jackson A.; Walker, Logan A.; Ghatak, Subhadip; Mathew-Steiner, Shomita S.; Wanczyk, Kristen E.; Liu, Sheng; Wan, Jun; Yan, Pearlly; Bundschuh, Ralf; Khanna, Savita; Gordillo, Gayle M.; Murphy, Michael P.; Roy, Sashwati; Sen, Chandan K.; Surgery, School of MedicineAn extreme chronic wound tissue microenvironment causes epigenetic gene silencing. An unbiased whole-genome methylome was studied in the wound-edge tissue of patients with chronic wounds. A total of 4,689 differentially methylated regions (DMRs) were identified in chronic wound-edge skin compared with unwounded human skin. Hypermethylation was more frequently observed (3,661 DMRs) in the chronic wound-edge tissue compared with hypomethylation (1,028 DMRs). Twenty-six hypermethylated DMRs were involved in epithelial-mesenchymal transition (EMT). Bisulfite sequencing validated hypermethylation of a predicted specific upstream regulator TP53. RNA-Seq analysis was performed to qualify findings from methylome analysis. Analysis of the downregulated genes identified the TP53 signaling pathway as being significantly silenced. Direct comparison of hypermethylation and downregulated genes identified 4 genes, ADAM17, NOTCH, TWIST1, and SMURF1, that functionally represent the EMT pathway. Single-cell RNA-Seq studies revealed that these effects on gene expression were limited to the keratinocyte cell compartment. Experimental murine studies established that tissue ischemia potently induces wound-edge gene methylation and that 5'-azacytidine, inhibitor of methylation, improved wound closure. To specifically address the significance of TP53 methylation, keratinocyte-specific editing of TP53 methylation at the wound edge was achieved by a tissue nanotransfection-based CRISPR/dCas9 approach. This work identified that reversal of methylation-dependent keratinocyte gene silencing represents a productive therapeutic strategy to improve wound closure.Item Healthcare worker knowledge and opinion regarding intimate partner violence screening in an academic dermatology clinic: a survey study(Wolters Kluwer, 2022-08-01) Carr, Christian L.; Rivera, Sydney; Jetelina, Katelyn K.; Mauskar, Melissa; Medicine, School of MedicineItem Identifying Gaps in Global Health Dermatology: A Survey of GLODERM Members(Oxford University Press, 2021) McMahon, Devon E.; Oyesiku, Linda; Amerson, Erin; Beltraminelli, Helmut; Chang, Aileen Y.; Forrestel, Amy; Hay, Roderick; Knapp, Alexia; Kovarik, Carrie; Maurer, Toby; Norton, Scott A.; Rehmus, Wingfield; Van Hees, Colette; Wanat, Karolyn A.; Williams, Victoria L.; Fuller, L. Claire; Freeman, Esther E.; Dermatology, School of MedicineItem Proposed guidelines for appropriate utilization of superficial radiation therapy in management of skin cancers. Zemtsov‐Cognetta criteria(Wiley, 2023) Zemtsov, Alexander; Cognetta, Armand; Marvel, John; Logan, Ann; Dermatology, School of MedicineObjective: To develop appropriate use criteria (AUC) for the treatment of basal cell and squamous cell carcinoma by superficial radiation therapy (SRT) technique. Material and methods: Delphi-type discussion of the experts. Results: Presented in Figure 1. Conclusion: These AUCs are in compliance both with the position statement of the American Academy of Dermatology (AAD) and the ASTRO Clinical Practice Guideline on this subject. It is further recommended that SRT will be only performed by either a dermatologist who is board certified in Mohs surgery (MDS) and who had adequate SRT training or by radiation oncologists. Hopefully, this publication will stimulate further discussion on this topic.