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This analysis of surveillance data details the spectrum of travel-related dermatological conditions among returning Canadian travellers in this cohort, and provides an epidemiologic framework for Canadian physicians encountering these patients.

Activation of the hypothalamic-pituitary-adrenal (HPA) axis of fetal sheep during late gestation is associated with increases in plasma concentrations of adrenocorticotropic hormone (ACTH) and cortisol, and ultimately results in parturition. However, the mechanisms contributing to the concurrent increases in ACTH and cortisol are unclear. Plasma estradiol-17 beta (E2) concentrations increase progressively in the prepartum ovine fetus, and we hypothesized that E2 may influence HPA activity by affecting either basal and/or hypoxemia-stimulated ACTH release. We examined potential mechanisms, including altered expression of pro-opiomelanocortin (POMC) in fetal pituitary corticotrophs, and changes in corticosteroid binding globulin (CBG) and/or the enzymes 11 beta hydroxy steroid dehydrogenase (11 beta HSD)-1 or 11 beta HSD-2 in liver and placenta, that could alter negative feedback control. We infused fetal sheep at 127 d of gestation with either E2 (100 micrograms/24 h) or saline for 100 h. Fetal arterial blood samples were collected at 8 h intervals during the infusion of E2 or saline (n = 4), for measurement of basal plasma ACTH and cortisol concentrations, as well as plasma corticosteroid binding capacity (CBC). Placenta and fetal liver samples were collected at 100 h for measurement of placental 11 beta HSD-1 and 11 beta HSD-2 mRNA and hepatic CBG and 11 beta HSD-1 mRNA, by Northern blotting. Fetal pituitary samples were collected for measurement of POMC mRNA by in situ hybridization. In a separate experiment, fetuses were exposed to 2 h of hypoxemia at 75 h of E2 or saline infusion (n = 4), and fetal arterial blood samples were collected during the period of hypoxemia for measurement of plasma ACTH and cortisol concentrations. E2 infusion had no effect on basal plasma concentrations of ACTH or total cortisol, or on the stimulated levels of ACTH or total cortisol achieved in response to hypoxemia. Basal fetal pituitary POMC mRNA also did not change significantly with E2 infusion. No significant increases were observed in plasma CBC during E2 administration. However, hepatic CBG and 11 beta HSD-1 mRNA were significantly elevated in the livers of E2-treated fetuses. Placental 11 beta HSD-1 mRNA; but not 11 beta HSD-2 mRNA was increased by E2 treatment. These data do not support a direct effect of exogenous E2 at the level of basal or hypoxemia-stimulated ACTH output, but suggest that elevated E2 concentrations may alter the expression of genes encoding proteins implicated in tonic regulation of fetal HPA function.

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specimen from the patient's cutaneous SCC lesions was strongly positive for PD-L1 (Figure 2), suggesting that blockade of the PD-1/PD-L1 pathway might be a therapeutic option. After considering several factors-adaptive immunotherapy in the form of PD-1 inhibitors had recently been approved by the FDA for metastatic melanoma and was now commercially available; early data in head and neck squamous cells showed potential efficacy 5,6 ; and no good treatment options were available that would preserve quality of life-the patient decided to pursue an off-label trial of pembrolizumab (intravenous infusions, 2 mg/kg every 3 weeks). He tolerated the treatment with adverse effects of mild fatigue, chills, malaise, arthralgias, and weight loss. After 2 cycles, dramatic tumor response was observed (Figure 2). After 6 cycles, the patient was still progression free. Discussion | A recent retrospective study of patients with unresectable cutaneous SCC showed that only 30% responded to therapy of any kind, and overall survival of such patients was only 10.9 months. 1,3 Hence, unresectable cutaneous SCCs represent an unmet medical need. This case highlights the potential for immunotherapy in the form of PD-1/PD-L1 inhibition to address this need, a finding that requires further investigation through clinical trials.

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