The advent of personalized medicine has ushered in a new era for cancer therapy with a significant impact on the management of advanced melanoma. Molecular targeted therapies have shown promise in the management of various malignancies, including melanoma, with lower toxicity profiles and better overall survival as compared with conventional therapy. The discovery of BRAF mutations in melanoma led to the development of BRAF inhibitors for the treatment of advanced melanoma. However, growing concerns over drug resistance to molecular targeted therapies including BRAF inhibitors, have spurred efforts to elucidate additional molecular targets for the treatment of advanced melanoma. In this review, we discuss the known molecular aberrations in melanoma, current and novel targeted approaches in its treatment, and drug resistance patterns.

Objective Recent research suggests nicotine metabolism may be influenced by sex hormones. Thus, we hypothesized that circadian smoking patterns would vary by menstrual phase. Methods Healthy female smokers (n = 31) between the ages of 18 and 40 with regular menstrual cycles, and not using hormones or psychotropic medications, were recruited for a randomized clinical study. Subjects recorded the time of each cigarette smoked and their menstrual phase with daily diaries prospectively for one complete menstrual cycle of ad libitum smoking. Analyses included Poisson regression to assess variations in the rate of smoking during waking hours (i.e., 6:00 a.m. and 12:00 midnight) and circadian smoking patterns by menstrual phase. Results Participants were 29.61 ± 5.44 years of age and smoked 16.93 ± 5.37 cigarettes per day. Participants had a lower rate of smoking during waking hours in the follicular phase as compared to the menses phase. There were no significant menstrual phase differences in the circadian smoking patterns. Conclusions These results offer further support for the influence of sex hormones on smoking behavior, but not on circadian patterns of smoking. Additional research is needed to study the direct relationship between nicotine metabolism, sex hormones, menstrual phase, and smoking behavior.

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Introduction: Lichen sclerosus (LS) is a site, gender and age specific disease that affects the vulvar region of menopausal women. The menopausal transition is characterized by physiologic changes that impact basic processes, such as weight, sleep and drug clearance. Our current pharmacopeia includes drugs that target basic metabolic processes such as cholesterol, sex steroidogenesis and the gut microbiome. Introduction of drugs engages complex pathways that govern bile salt metabolism and the provision of sex steroid substrate. We hypothesized that lichen sclerosus in the vulva may represent an off target effect of pharmaceutical alteration of sex steroid substrate in some women. We compared biometric and drug data in women with lichen sclerosus with an age matched control group without disease. Methods: 43 women with lichen sclerosus underwent chart review to determine BMI, Fitzpatrick level, and pharmaceutical burden. This data was compared to 106 randomly selected age matched controls. Logistic regression was adjusted for age, BMI and Fitzpatrick photo typing. The statistical software was R version 3.0.1. Cases were defined as those with diagnosis claims for lichen sclerosus and were obtained from electronic records in a single private practice. Results: Proton pump inhibitors were noted in 12/43 women (28%) cases and 15/106 (14%) controls: p=0.048, (confidence interval CI=-0.01 to 0.287), adjusted p value 0.33; Hormone therapy 5/43 cases (12%), 26/106 (25%) controls: p value 0.078, (CI=-0.25 to 0.002), adjusted p value 0.02. Antihypertensive medications 17/43 (40%) cases, 29/106 (27%) controls, p value 0.14, (CI=-0.047 to 0.29), adjusted p value 0.8. Statins 16/43 cases (37%), 28/106 controls (26%); p=0.19, (CI=-0.05 to 0.27), adjusted p value 0.89. Average age among cases was 63, average age in the control group was 61. Average BMI was 27.5 in the case group, 23.6 in the control group. Logistic regression analysis was adjusted for age, BMI and Fitzpatrick phototyping. Conclusions: Borderline statistical significance was seen with proton pump inhibitors and hormone replacement therapy (HRT). The significance seen with proton pump inhibitors went away with adjustment for Fitzpatrick, age and BMI. The significance seen with HRT withstood adjustment, with the control group featuring more women on hormone replacement therapy than the case group.

Altered mental status is a common presenting complaint in adult medicine with a broad differential diagnosis. When found in the context of chronic medical conditions, less common etiologies can be overlooked. We present a case of acute altered mental status thought to be secondary to acute on chronic hyponatremia in the context of syndrome of inappropriate antidiuretic hormone secretion (SIADH), eventually diagnosed as non-convulsive status epilepticus, partial type. We report the case of a 67-year-old patient with known SIADH of unknown etiology, hypertension, chronic pancreatitis and chronic obstructive pulmonary disease (COPD) who presented with fatigue, myalgia, decreased urine output. On presentation patient also had profound acute on chronic hyponatremia. During sodium correction, the patient developed an acute, progressive decline in mental status. Vital signs remained stable and workup including LP and MRI were negative. Initial electroencephalographic (EEG) showed no definitive seizure activity, but did show bifrontal focal continuous slowing. The patient’s mental status continued to decline and upon further evaluation it was suggested that the EEG findings and the patient’s progressive AMS could be compatible with non-convulsive status epilepticus. The patient received loading doses of IV lorazepam and levetiracetam and within 48 hours after initial treatment was back to baseline. Non-convulsive status epilepticus is a common, but heterogeneous subclass of status epilepticus that is difficult to diagnose. This case demonstrates the difficulty of diagnosing normalized corrected Shannon entropy (NCSE) in the context of other chronic medical conditions and the importance of including it on any differential diagnosis for acute change in mental status.