Checkpoint-blocker-induced autoimmunity is associated with favourable outcome in metastatic melanoma and distinct T-cell expression profiles

Background Immune checkpoint blockers (ICBs) activate CD8⁺ T cells, eliciting both anti-cancer activity and immune-related adverse events (irAEs). The relationship of irAEs with baseline parameters and clinical outcome is unclear.Methods Retrospective evaluation of irAEs on survival was performed across primary (N = 144) and secondary (N = 211) independent cohorts of patients with metastatic melanoma receiving single agent (pembrolizumab/nivolumab—sICB) or combination (nivolumab and ipilimumab—cICB) checkpoint blockade. RNA from pre-treatment and post-treatment CD8⁺ T cells was sequenced and differential gene expression according to irAE development assessed.Results 58.3% of patients developed early irAEs and this was associated with longer progression-free (PFS) and overall survival (OS) across both cohorts (log-rank test, OS: P < 0.0001). Median survival for patients without irAEs was 16.6 months (95% CI: 10.9–33.4) versus not-reached (P = 2.8 × 10⁻⁶). Pre-treatment monocyte and neutrophil counts, but not BMI, were additional predictors of clinical outcome. Differential expression of numerous gene pathway members was observed in CD8⁺ T cells according to irAE development, and patients not developing irAEs demonstrating upregulated CXCR1 pre- and post-treatment.Conclusions Early irAE development post-ICB is associated with favourable survival in MM. Development of irAEs is coupled to expression of numerous gene pathways, suggesting irAE development in-part reflects baseline immune activation.Subject terms: Immunotherapy, Melanoma     

The primary health care physician and the cancer patient: tips and strategies for managing sexual health

There is a large and growing population of long-term cancer survivors. Primary care physicians (PCPs) are playing an increasingly greater role in the care of these patients across the continuum of cancer survivorship. In this role, PCPs are faced with the responsibility of managing a range of medical and psychosocial late effects of cancer treatment. In particular, the sexual side effects of treatment which are common and have significant impact on quality of life for the cancer survivor, often go unaddressed. This is an area of clinical care and research that has received increasing attention, highlighted by the presentation of this special issue on Cancer and Sexual Health. The aims of this review are 3-fold. First, we seek to overview common presentations of sexual dysfunction related to major cancer diagnoses in order to give the PCP a sense of the medical issues that the survivor may present with. Barriers to communication about sexual health issues between patient/PCPs in order are also described in order to emphasize the importance of PCPs initiating this important conversation. Next, we provide strategies and resources to help guide the PCP in the management of sexual dysfunction in cancer survivors. Finally, we discuss case examples of survivorship sexual health issues and highlight the role that a PCP can play in each of these case examples.     

Investigating the Association Between Internet Health Information Use and Patient Willingness to Communicate with Health Care Providers

ABSTRACT

Communication between health professionals and patients is an intergroup phenomenon where the health professional has the most power and status. Over the past few decades, there has been a steady increase in the availability to patients of information about healthcare and specific diseases on the Internet. In this paper, we ask whether the use of Internet health information assists patients to manage their consultations with health professionals better and whether it alters the intergroup dynamic by providing a more equal status for patients. In this study 370 participants from Australia and Canada completed a survey that included a ‘willingness to communicate with health professionals’ scale. They also commented on their use and trust of Internet health information. Thematic analysis suggests that patients’ use of Internet health information serves as a broker between patients and their health provider in health consultations. We discuss the implications of these findings for health practitioners as they address how easier Internet access influences patient interactions with health professionals. We consider future research directions these finding provide in explaining communication behaviour in this context.     

Nickel Allergy and Our Children's Health: A Review of Indexed Cases and a View of Future Prevention

Nickel is the leading cause of allergic contact dermatitis (ACD) from early childhood through adolescence. Studies have shown that skin piercings and other nickel‐laden exposures can trigger the onset of nickel ACD in those who are susceptible. Nickel ACD causes a vast amount of cutaneous disease in children. Cases of nickel ACD in children have been reported in peer‐reviewed literature from 28 states. Common items that contain inciting nickel include jewelry, coins, zippers, belts, tools, toys, chair studs, cases for cell phones and tablets, and dental appliances. The diagnosis of nickel ACD has been routinely confirmed by patch testing in children older than 6 months suspected of ACD from nickel. Unlike in Europe, there are no mandatory restrictions legislated for nickel exposure in the United States. Denmark has demonstrated that regulation of the nickel content in metals can lower the risk of ACD and the associated health care–related costs that arise from excess nickel exposure. To further awareness, this article reviews the prominent role of nickel in pediatric skin disease in the United States. It discusses the need for a campaign by caretakers to reduce nickel‐related morbidity. Lastly, it promotes the model of European legislation as a successful intervention in the prevention of nickel ACD.