Characterizing the role of dermatologists in developing artificial intelligence for assessment of skin cancer.

BACKGROUND: The use of artificial intelligence (AI) for skin cancer assessment has been an emerging topic in dermatology. Leadership of dermatologists is necessary in defining how these technologies fit into clinical practice. OBJECTIVE: To characterize the evolution of AI in skin cancer assessment and characterize the involvement of dermatologists in developing these technologies. METHODS: An electronic literature search was performed using PubMed by searching machine learning or artificial intelligence combined with skin cancer or melanoma. Articles were included if they used AI for screening and diagnosis of skin cancer using data sets consisting of dermoscopic images or photographs of gross lesions. RESULTS: Fifty-one articles were included, and 41% of these had dermatologists included as authors. Articles that included dermatologists described algorithms built with more images versus articles that did not include dermatologists (mean, 12,111 vs 660 images, respectively). In terms of underlying technology, AI used for skin cancer assessment has followed trends in the field of image recognition. LIMITATIONS: This review focused on models described in the medical literature and did not account for those described elsewhere. CONCLUSIONS: Greater involvement of dermatologists is needed in thinking through issues in data collection, data set biases, and applications of technology. Dermatologists can provide access to large, diverse data sets that are increasingly important for building these models.

Sexual dysfunction in men taking systemic dermatologic medication: A systematic review.

BACKGROUND: Prescription medications are among the most common causes of sexual dysfunction, and patients are often hesitant to seek help when experiencing these symptoms. OBJECTIVE: In this review, we identify the available evidence of sexual adverse effects in men using systemic dermatologic medications and suggest screening protocols and actions that may improve a patient's symptoms where possible. METHODS: A systematic review was conducted of all articles in the PubMed database published from the time of inception to May 2018 to identify studies evaluating the use of systemic dermatologic medications in men with evidence of sexual adverse effects. Subsequently, a secondary in-depth literature review was performed for each individual medication. RESULTS: There were 5497 articles reviewed in the primary systematic review, and 59 articles covering 11 systemic dermatologic medications met inclusion criteria. We identified level 1 evidence for sexual adverse effects as a primary outcome in patients taking finasteride. LIMITATIONS: Many included studies were limited by sample size and methodology. CONCLUSION: The information in this review may serve as a reference of adverse effects when deciding on a therapeutic agent and a guide to help identify patients to screen for sexual dysfunction.

Infertility and teratogenicity after paternal exposure to systemic dermatologic medications: A systematic review.

BACKGROUND: This systematic review assesses effects of paternal exposure to dermatologic medications by using the former US Food and Drug Administration (FDA) pregnancy categories as a benchmark. OBJECTIVE: To assess whether systemic dermatologic medications can cause infertility and teratogenicity when taken by men. METHODS: Categories D and X dermatologic medications were identified; a systematic review of the literature and reviews of the FDA Adverse Events Reporting System and prescribing information were performed to identify the effects of these medications on male fertility and teratogenicity. A secondary search was performed to assess for other systemic dermatologic medications causing teratogenicity or infertility following paternal exposure. RESULTS: A total of 13 medications met the inclusion criteria. Of 1,032 studies identified, 19 were included after a systematic review of the literature. Studies evaluating medication effects with paternal exposure were identified for 10 of the 13 evaluated medications, and evidence of a negative effect was identified for 6 medications. LIMITATIONS: We did not encounter any studies for 3 medications that met the inclusion criteria. Information submitted to the FDA Adverse Events Reporting System may not reflect the incidence of side effects. CONCLUSIONS: Many former pregnancy category D and X systemic dermatologic medications also have effects on male fertility. More research and better-quality studies are required in this area, particularly studies assessing potential teratogenicity.

Analysis of spin in the reporting of studies of topical treatments of photoaged skin.

BACKGROUND: Spin-reporting that distorts the interpretation of results-is not unusual within scientific literature. OBJECTIVE: To appraise strategies of spin among placebo-controlled double-blind clinical trials of topical treatments for photoaged skin. METHODS: A systematic review of the literature was performed to identify placebo-controlled double-blind clinical trials of topical treatments for photoaged skin. A survey of spin strategies was developed and applied to the cohort of identified studies. RESULTS: The systematic review led to the identification of 20 studies in which various types of spin strategies, broadly classified as either inappropriate statistical analyses or inappropriate interpretation of results, were used. The most commonly used strategies included use of multiple primary outcomes (95%), inappropriate extrapolation of results from specific outcomes to global improvements (95%), focus on within-group comparisons (75%), and focus on interim analyses to give more weight to nonsignificant findings (65%). LIMITATIONS: Classification of spin strategies was subjective and might not encompass all the methods used in the published literature. CONCLUSION: Findings in this study inform efforts to reduce spin in the dermatologic literature.

Psoriasis and suicidality: A review of the literature.

Psoriasis is a chronic systemic inflammatory skin disease, which has been associated with an increased risk of numerous medical and psychiatric comorbidities, including suicidality. Suicidality, which can be divided into the categories of suicidal ideation, suicide attempt, and completed suicide, is highly prevalent in the psoriasis population, and multiple studies have been published on the subject of psoriasis and suicidal ideation and behavior (SIB), including two recent meta-analyses. However, the available literature is limited and inconsistent, and the association between the two remains incompletely understood. The present review aims to cohesively synthesize and summarize the available evidence, while making a clinically relevant distinction between the sub-categories of suicidality, by examining not only the epidemiology of the association but also the plausible molecular mechanisms and the potential influence of biologic therapies. Additionally, this review aims to critically examine and understand the potential contribution of depression in the psoriasis and suicidality relationship. This will allow us to better understand the complex and multi-faceted relationship between psoriasis and suicidality, to identify those who may be most at risk for SIB, to make evidence-based clinical decisions regarding treatment and management, and to more completely address the needs of psoriasis patients.

Severe Oral Mucositis: A Rare Adverse Event of Pembrolizumab.

Treatment of malignancy with anti-programmed cell death 1 (PD-1) immune checkpoint inhibitors can cause mucocutaneous side effects resulting from T cell activation. Due to their recent development, the full side effect profile remains to be fully elucidated, however dermatologic adverse events are most common. The main oral toxicities of these immune checkpoint inhibitors include: xerostomia, dysgeusia, and lichenoid reactions. Oral mucositis occurs more rarely in the setting of PD-1 inhibition, and few other reports of a Grade 3 or higher, severe, stomatitis have been reported in the literature. We present a case of a 78-year-old woman with Grade 3 ulcerative oral mucositis that occurred 13 months after initiation of PD-1 inhibitor, pembrolizumab, for the treatment for lung adenocarcinoma. She was successfully treated with prednisone, and pembrolizumab was temporarily held by her oncologist. Physicians should be aware of the possibility of severe mucositis in the setting of PD-1 inhibitors, as well as the management. J Drugs Dermatol. 2018;17(7):807-809.

Depression and suicidality in psoriasis and clinical studies of brodalumab: a narrative review.

Patients with psoriasis have high rates of depression and may be at increased risk for suicidal ideation and behavior (SIB). Attempted and completed suicides during clinical trials and other studies of psoriasis therapies, including brodalumab, highlight the importance of understanding psychiatric risk factors in patients with psoriasis. Recent meta-analyses, research studies, and published data from brodalumab clinical studies were reviewed. We also summarize research on effects of brodalumab on depression symptoms and occurrences of SIB in brodalumab clinical trials. Psoriasis elevates the risk for depression and possible suicide. Brodalumab has a boxed suicide warning; however, it states that there is no established causal association between treatment with brodalumab and increased risk for SIB. Clinicians are urged to evaluate patients with psoriasis for psychiatric risk factors regardless of their therapy and to consider the package insert and a comprehensive evaluation of relevant literature to make a well-balanced decision.

Psoriasis and the Risk of Depression in the US Population: National Health and Nutrition Examination Survey 2009-2012.

IMPORTANCE: Psoriasis is a risk factor for depression. Depression may also trigger or exacerbate psoriasis. The relationship between psoriasis and depression, however, remains to be fully explored. OBJECTIVE: To investigate the association between psoriasis and major depression in the US population. DESIGN, SETTING, AND PARTICIPANTS: Population-based study using participants in the National Health and Nutrition Examination Survey from 2009 through 2012. MAIN OUTCOMES AND MEASURES: Diagnosis of major depression based on the Patient Health Questionnaire-9. RESULTS: We identified 351 (2.8%) cases of psoriasis and 968 (7.8%) cases of major depression among 12,382 US citizens included in our study. Fifty-eight (16.5%) patients with psoriasis met criteria for a diagnosis of major depression. The mean (SD) Patient Health Questionnaire-9 score was significantly higher among patients with a history of psoriasis than those without psoriasis (4.54 [5.7] vs 3.22 [4.3], P < .001). Psoriasis was significantly associated with major depression, even after adjustment for sex, age, race, body mass index, physical activity, smoking history, alcohol use, history of myocardial infarction (MI), history of stroke, and history of diabetes mellitus (OR, 2.09 [95% CI, 1.41-3.11], P < .001). Interaction term analyses involving patients with a history of both psoriasis and a cardiovascular event, specifically MI or stroke, did not reveal a synergistically increased risk of major depression (psoriasis and MI: OR, 1.09 [95% CI, 0.28-3.60], P = .91; psoriasis and stroke: OR, 0.67 [95% CI, 0.12-3.66], P = .63). In adjusted multivariable models, the risk of major depression was not significantly different between patients with limited vs extensive psoriasis (OR, 0.66 [95% CI, 0.18-2.44], P = .53). CONCLUSIONS AND RELEVANCE: Self-reported history of psoriasis was independently associated with major depression as assessed by a validated screening tool, even when controlling for comorbidities. History of cardiovascular event did not modify the risk of major depression for patients with psoriasis. The severity of psoriasis was unrelated to the risk of major depression. Therefore, all patients with psoriasis, regardless of severity, may be at risk for major depression.

Implications of structures of synaptic tetramers of gamma delta resolvase for the mechanism of recombination.

The structures of two mutants of the site-specific recombinase, gammadelta resolvase, that form activated tetramers have been determined. One, at 3.5-A resolution, forms a synaptic intermediate of resolvase that is covalently linked to two cleaved DNAs, whereas the other is of an unliganded structure determined at 2.1-A resolution. Comparisons of the four known tetrameric resolvase structures show that the subunits interact through the formation of a common core of four helices. The N-terminal halves of these helices superimpose well on each other, whereas the orientations of their C termini are more variable. The catalytic domains of resolvase in the unliganded structure are arranged asymmetrically, demonstrating that their positions can move substantially while preserving the four-helix core that forms the tetramer. These results suggest that the precleavage synaptic tetramer of gammadelta resolvase, whose structure is not known, may be formed by a similar four-helix core, but differ in the relative orientations of its catalytic and DNA-binding domains.