Secukinumab in adult patients with lichen planus: Efficacy and safety results from the randomised, placebo-controlled, proof-of-concept PRELUDE study.

BACKGROUND: Patients with lichen planus (LP) refractory to available therapies often experience a high disease burden; representing a population with a clear unmet need for new treatments. OBJECTIVES: To evaluate the efficacy and safety of secukinumab 300 mg over 32 weeks in adult patients with biopsy-proven cutaneous LP (CLP), mucosal LP (MLP) or lichen planopilaris (LPP), inadequately controlled by topical corticosteroids. METHODS: PRELUDE was a, randomised, double-blind, placebo-controlled, Phase 2 proof-of-concept study that enrolled patients with CLP, MLP or LPP. Eligible patients were randomised to eithersecukinumab 300 mg every 4 weeks for 32 weeks (SECQ4W), or placebo for 16 weeks followed by secukinumab 300 mg every 2 weeks (SECQ2W) for 16 weeks. The primary endpoint was achievement of the newly designed Investigator's Global Assessment (IGA) score ≤2 at Week 16. RESULTS: Overall, 111 patients were randomised (n=37 each) to CLP, MLP and LPP cohorts. As the proof-of-concept criteria were not met for any of the 3 cohorts, the primary objective was not met. A numerically higher proportion of patients achieved IGA ≤2 response at Week 16 with SECQ4W vs. placebo in the MLP (37.5% [95% credibility interval (Crl): 20.3-57.2] vs. 23.1% [95% Crl: 6.5-49.2]) and LPP cohorts (37.5% [95% Crl: 20.2-57.3] vs. 30.8% [95% Crl: 10.8-57.6]). In the LPP cohort, a sustained response for IGA ≤2 from Week 16 to Week 32 was achieved with SECQ4W (Week 16: 37.5%; Week 32: 45.8%), and a substantial improvement was observed in IGA ≤2 response in patients of this cohort switching from placebo (Week 16: 30.8%) to SECQ2W after Week 16 (Week 32: 63.6%). The safety profile was consistent with the known profile of secukinumab and showed no new or unexpected signals. CONCLUSIONS: PRELUDE is the first randomised controlled basket trial evaluating interleukin-17A inhibition with secukinumab across 3 subtypes of LP. Secukinumab was well-tolerated and safe, showing different response rates across the 3 subtypes, with numerical IGA improvements in MLP and LPP, and no response in CLP. The study raises the question of a differential role of interleukin-17A across LP subtypes. The novel IGA score showed significant correlation with patient as well as physician reported outcome measurements. TRIAL REGISTRATION NUMBER: NCT04300296.

Accuracy assessment of remotely sensed data to analyze lake water balance in semi-arid region.

Lake water level fluctuation is a function of hydro-meteorological components, namely input, and output to the system. The combination of these components from in-situ and remote sensing sources has been used in this study to define multiple scenarios, which are the major explanatory pathways to assess lake water levels. The goal is to analyze each scenario through the application of the water balance equation to simulate lake water levels. The largest lake in Iran, Lake Urmia, has been selected in this study as it needs a great deal of attention in terms of water management issues. We ran a monthly water balance simulation of nineteen scenarios for Lake Urmia from 2003 to 2007 by applying different combinations of data, including observed and remotely sensed water level, flow, evaporation, and rainfall. We used readily available water level data from Hydrosat, Hydroweb, and DAHITI platforms; evapotranspiration from MODIS and rainfall from TRMM. The analysis suggests that the consideration of field data in the algorithm as the initial water level can reproduce the fluctuation of Lake Urmia water level in the best way. The scenario that combines in-situ meteorological components is the closest match to the observed water level of Lake Urmia. Almost all scenarios showed good dynamics with the field water level, but we found that nine out of nineteen scenarios did not vary significantly in terms of dynamics. The results also reveal that, even without any field data, the proposed scenario, which consists entirely of remote sensing components, is capable of estimating water level fluctuation in a lake. The analysis also explains the necessity of using proper data sources to act on water regulations and managerial decisions to understand the temporal phenomenon not only for Lake Urmia but also for other lakes in semi-arid regions.

Exploration of Mistreatment and Burnout Among Resident Physicians: a Cross-Specialty Observational Study.

PURPOSE: Resident physician mistreatment and burnout are widespread issues in medical training, but the association between the two remains unclear. This study examines the prevalence and types of mistreatment among resident physicians in core specialties and its association with burnout syndrome as well as feelings of depression/anxiety. METHODS: A cross-sectional, survey-based observational study of medical residents was conducted at the University of California, Davis Medical Center in 2014. Current residents (PGY2 or higher) in the internal medicine, family medicine, obstetrics/gynecology, surgery, and pediatrics programs completed anonymous questionnaires addressing topics such as workplace mistreatment, feelings of depression/anxiety, and stress management. Burnout was measured using the Maslach Burnout Inventory. RESULTS: Forty-four out of 105 residents (41.9%) witnessed mistreatment of their co-residents while 26 residents (24.8%) disclosed personal accounts of mistreatment. Seventy-one percent of residents met the criteria for burnout. Residents who had been personally mistreated were almost eight times more likely to report burnout (OR 7.6, 95% CI = 1.7-34.4) and almost four times more likely to report symptoms of anxiety and depression (OR 3.8, 95% CI = 1.6-9.1). Public belittlement or humiliation was the most common type of mistreatment. CONCLUSION: Encountering mistreatment was associated with higher rates of burnout, as well as depression/anxiety. While it is uncertain if mistreatment in the workplace has a causative impact on burnout syndrome, the findings reveal the need to address work-related environmental factors that may contribute to both resident physician mistreatment and burnout.

Cushing Syndrome Induced by Topical Corticosteroids for the Treatment of Lichen Sclerosus.

BACKGROUND: Lichen sclerosus is a chronic inflammatory dermatological condition with a predilection for the anogenital area. CASE: We describe a case of iatrogenic Cushing syndrome from the administration of high-potency topical steroids for vulvar lichen sclerosus in a 6-year-old girl. Her symptoms resolved after the cessation of topical steroid treatment. SUMMARY AND CONCLUSION: This case brings attention to iatrogenic Cushing syndrome as a potential complication when using high-potency topical corticosteroids in the anogenital region.

Etiology, evaluation, and management of xerostomia.

Xerostomia is defined as the complaint of oral dryness. It is a condition that primarily affects older adults and can have a significant negative effect on one's quality of life. Patients with xerostomia often do not have objective signs of hyposalivation. The underlying etiology of xerostomia includes a variety of systemic diseases and local factors. Our aim is to provide a comprehensive review of the differential diagnosis, evaluation, and management of xerostomia. Prompt diagnosis and management can alleviate the clinical manifestations of this debilitating condition.

A diagnostic and therapeutic approach to primary burning mouth syndrome.

Primary burning mouth syndrome (BMS) is an oral mucosal disorder that is characterized by a chronic and often debilitating intraoral burning sensation for which no localized or systemic cause can be found. BMS most commonly affects postmenopausal women. The pathophysiology of primary BMS is not well understood. Diagnosing BMS can prove to be challenging. BMS patients can also pose a therapeutic challenge to clinicians who are consulted to evaluate these patients. Most commonly used therapies include tricyclic antidepressants, α-lipoic acid, clonazepam, and cognitive-behavioral therapy. Clinical judgment, patient counseling, and monitoring of pain are important. Further research is required to assess the effectiveness of serotonin and newer serotonin-noradrenalin reuptake inhibitors.

Oral mucosa biology and salivary biomarkers.

Although the surfaces of both the skin and oral mucosa are protected by squamous epithelial cells and fall within the scope of dermatologic practice, the oral cavity contains highly specialized structures and functions distinct from other skin biology and pathologic conditions and are also the purview of clinicians who care for patients with skin and mucosal diseases. We describe the distinct features of the tongue, mucosa, and salivary glands. In particular, we examine the composition and function of the saliva, with special focus on salivary biomarkers. Within the oral cavity, saliva shows great promise as a noninvasive and sensitive marker for many systemic diseases. Biomarkers are being used as diagnostic or monitoring tools for a wide variety of diseases, including systemic lupus erythematosus, Sjögren disease, Behçet disease, and autoimmune blistering disorders, as well as premalignant and malignant lesions of the mouth.

Therapeutic Efficacy of Fresh, Allogeneic Mesenchymal Stem Cells for Severe Refractory Feline Chronic Gingivostomatitis.

Mesenchymal stem cells (MSCs) have potent immunomodulatory functions and are a promising therapy for immune-mediated inflammatory disorders. We previously demonstrated the efficacy of fresh, autologous, adipose-derived MSCs (ASCs) to treat feline chronic gingivostomatitis (FCGS), a chronic oral mucosal inflammatory disease similar to human oral lichen planus. Here, we investigate the use of fresh allogeneic ASCs for treatment of FCGS in seven cats. Radiolabeled ASCs were also tracked systemically. Each cat received two intravenous injections of 20 million ASCs, 1 month apart. Oral inflammation, blood lymphocyte subsets, anti-fetal bovine serum antibody levels, ASC crossmatching and serum proteins and cytokine concentrations were determined. Four of the 7 cats (57%) responded to treatment [complete clinical remission (n = 2) or substantial clinical improvement (n = 2)]. Three cats were nonresponders. Prior to therapy, most cats had increased circulating CD8+ T cells, decreased CD8lo cells, and a decreased CD4/CD8 ratio, however clinical resolution was not associated with normalization of these parameters. Nonresponders showed more severe systemic inflammation (neutrophilia, hyperglobulinemia and increased interferon gamma and tumor necrosis factor alpha concentration) prior to ASC therapy. Clinical remission took up to 20 months and no clinical relapse has occurred. A higher fraction of radiolabeled ASCs were identified in the oral cavity of FCGS affected cats than the control cat. The administration of fresh, allogenic ASCs appeared to have lower clinical efficacy with a delayed response as compared to the fresh, autologous ASCs. In addition, the mechanism(s) of action for autologous and allogenic ASCs may differ in this model of oral inflammation. Stem Cells Translational Medicine 2017;6:1710-1722.

The residency interview is still paramount: results of a retrospective cohort study on concordance of dermatology residency applicant evaluators and influence of the applicant interview.

Application to dermatology residency is a highly competitive process. Although factors associated with successfully matching have been studied, less is known regarding the ability of admissions committees to screen applicants in a uniform manner or the importance of the interview in ranking applicants. Our goal was to retrospectively measure our admission committee evaluators' concordance regarding residency application credentials and interview performance, and ultimately the effects on final applicant ranking.

Human and feline adipose-derived mesenchymal stem cells have comparable phenotype, immunomodulatory functions, and transcriptome.

BACKGROUND: Adipose-derived mesenchymal stem cells (ASCs) are a promising cell therapy to treat inflammatory and immune-mediated diseases. Development of appropriate pre-clinical animal models is critical to determine safety and attain early efficacy data for the most promising therapeutic candidates. Naturally occurring diseases in cats already serve as valuable models to inform human clinical trials in oncologic, cardiovascular, and genetic diseases. The objective of this study was to complete a comprehensive side-by-side comparison of human and feline ASCs, with an emphasis on their immunomodulatory capacity and transcriptome. METHODS: Human and feline ASCs were evaluated for phenotype, immunomodulatory profile, and transcriptome. Additionally, transwells were used to determine the role of cell-cell contact in ASC-mediated inhibition of lymphocyte proliferation in both humans and cats. RESULTS: Similar to human ASCs, feline ASCs were highly proliferative at low passages and fit the minimal criteria of multipotent stem cells including a compatible surface protein phenotype, osteogenic capacity, and normal karyotype. Like ASCs from all species, feline ASCs inhibited mitogen-activated lymphocyte proliferation in vitro, with or without direct ASC-lymphocyte contact. Feline ASCs mimic human ASCs in their mediator secretion pattern, including prostaglandin E2, indoleamine 2,3 dioxygenase, transforming growth factor beta, and interleukin-6, all augmented by interferon gamma secretion by lymphocytes. The transcriptome of three unactivated feline ASC lines were highly similar. Functional analysis of the most highly expressed genes highlighted processes including: 1) the regulation of apoptosis; 2) cell adhesion; 3) response to oxidative stress; and 4) regulation of cell differentiation. Finally, feline ASCs had a similar gene expression profile to noninduced human ASCs. CONCLUSIONS: Findings suggest that feline ASCs modulate lymphocyte proliferation using soluble mediators that mirror the human ASC secretion pattern. Uninduced feline ASCs have similar gene expression profiles to uninduced human ASCs, as revealed by transcriptome analysis. These data will help inform clinical trials using cats with naturally occurring diseases as surrogate models for human clinical trials in the regenerative medicine arena.

Nevoid Basal Cell Carcinoma Syndrome and Hairy Skin Patches.

We report a case of an increasing number of discrete patches of darkly pigmented terminal hair in a patient with nevoid basal cell carcinoma syndrome. This case adds to a small case series of three patients which have previously reported this observation. We report this case to highlight hairy patches as an important clinical feature associated with nevoid basal cell carcinoma syndrome.

Dermatology Medical Education: A Multicenter Survey Study of the Undergraduate Perspective of the Dermatology Clinical Clerkship.

BACKGROUND/AIMS: Limited data are available regarding the undergraduate dermatology clinical clerkship curriculum in the United States. Our primaryaim is to assess medical students' perspectives of the dermatology clinical clerkship. METHODS: A multicenter survey study was conducted, which included four California dermatology academic programs. A 17-item questionnaire was designed to investigate medical student perception with regard tothe overall educational value of the various teaching aspects of the dermatology clinical clerkship. RESULTS: A total of 152 medical student surveys were completed. Over half of the medical students felt proficient in diagnosing the most commondermatologic conditions. Eighty-seven percent of medical students were very satisfied with the dermatology clerkship. Ninety-one percent of students felt the length of the clerkship was appropriate. CONCLUSIONS: The vast majority of medical students reported a high level of proficiency in the treatment and diagnosis of common skin disorders. In contrast, our findings suggest that medical students may not begaining sufficient hands-on experience in conducting certain dermatologic procedures following the dermatology clerkship. Overall, medical studentperception of the dermatology clinical clerkship was mostly positive.

Effect of a Pre-Treatment Educational Video in Improving Patient Satisfaction with 5-Fluorouracil Treatment for Actinic Keratoses: A Randomized Controlled Trial.

INTRODUCTION: Patient treatment satisfaction and adherence may be affected by the initial understanding of outcomes in the treatment of actinic keratoses with 5-fluorouracil 5% cream (5-FU). Pre-treatment educational videos may optimize this understanding. The objective of this study was to determine whether prospective patient viewing of an educational video delineating treatment effects and expectations improves patient satisfaction and treatment completion rates for the treatment of actinic keratoses with 5-FU. METHODS: Forty-four participants were recruited to the UC Davis Dermatology outpatient clinic. Each participant was randomized to the video (group A) or control group (group B), and topical 5-FU cream treatment was conducted for 2 weeks in both groups. RESULTS: A follow-up questionnaire was performed to assess patient satisfaction and adherence to the treatment regimen. The results of these questions were analyzed using the Mann-Whitney test. One item on the questionnaire asked the patient to rate their overall level of satisfaction on a score of 0-100. The results of this question were analyzed using the unpaired t test. The results of the statistical analysis show no significant difference between the patient group that viewed the video and the patient group that did not view the video. CONCLUSIONS: We speculate that this study may establish a foundation for subsequent studies that may affect the broader medical community and promote development of educational videos.

360-degree Evaluations on Physician Performance as an Effective Tool for Interprofessional Teams: A critical analysis of physician self-assessment as compared to nursing staff and patient evaluations of providers.

ImportanceThe dynamics of the medical care team, including interactions between physicians and nursing staff, has a large role to play in patient care, patient satisfaction, and future possible reimbursement determination. In order to implement changes to improve this dynamic within the medical team, it is imperative that appropriate assessments are completed to determine baseline satisfaction of our patients and nursing staff in addition to provider self-assessment.ObjectiveWe aimed to investigate patient and nursing staff satisfaction with regards to provider quality of care in an outpatient academic dermatology clinic setting. We also sought out to determine provider insight in regards to satisfaction of patient and nursing staff.MethodsOur nursing staff, patients, and providers completed a questionnaire. We then compared nursing satisfaction data and patient satisfaction data with provider self-assessment to determine provider self-awareness.ResultsA total of 23 provider and nurse surveys and 562 patient satisfaction surveys were completed. Paired comparison and descriptive statistics were utilized to compare patient satisfaction, nursing satisfaction, and provider self-assessments.ConclusionsOverall, the results of the surveys demonstrated that the nursing staff and patients had high satisfaction in their interactions with the dermatology physicians. The physicians had appropriate insight into how they were perceived by the nursing staff and patients. Attending physicians as compared to resident physicians and male physicians as compared to female physicians tended to underrate themselves.

Corrigendum to "Cutaneous Plasmacytosis with Perineural Involvement".

[This corrects the article DOI: 10.1155/2014/840845.].

Lupus erythematosus and localized scleroderma coexistent at the same sites: a rare presentation of overlap syndrome of connective-tissue diseases.

Overlap syndromes are known to occur with connective-tissue diseases (CTDs). Rarely, the overlap occurs at the same tissue site. We report the case of a patient with clinical and histopathologic findings consistent with the presence of discoid lupus erythematosus (DLE) and localized scleroderma within the same lesions. Based on our case and other reported cases in the literature, the following features are common in patients with an overlap of lupus erythematosus (LE) and localized scleroderma: predilection for young women, photodistributed lesions, DLE, linear morphology clinically, and positivity along the dermoepidermal junction on direct immunofluorescence. Most patients showed good response to antimalarials, topical steroids, or systemic steroids.

Practical pearls for oral procedures.

We provide an overview of clinically relevant principles of oral surgical procedures required in the workup and management of oral mucosal diseases. An understanding of the fundamental concepts of how to perform safely and effectively minor oral procedures is important to the practicing dermatologist and can minimize the need for patient referrals. This chapter reviews the principles of minor oral procedures, including incisional, excisional, and punch biopsies, as well as minor salivary gland excision. Pre- and postoperative patient care is also discussed.