Plasma Thymidine Kinase Activity as a Novel Biomarker in Metastatic Melanoma Patients Treated with Immune Checkpoint Inhibitors.

Background. Immune checkpoint inhibitors (ICI) are effective in fractions of patients with disseminated melanoma. This study is the first to analyze the plasma activity of thymidine kinase (TK), an enzyme involved in DNA synthesis and repair, as a biomarker in melanoma patients. Methods. Plasma samples were collected prior to treatment start in patients with unresectable metastatic cutaneous melanoma, treated with ICI (anti-CTLA-4 and/or anti-PD-1). Plasma TK activity (TKa) levels were determined using the DiviTum TKa ELISA assay. TKa levels were correlated with patients' baseline characteristics, response rate (RR), progression-free survival (PFS), and overall survival (OS). Results. In the 90 study patients, the median TKa level was 42 Du/L (range <20-1787 Du/L). A significantly higher plasma TKa was found in patients with ECOG performance status ≥1 (p = 0.003), M1c-d disease (p = 0.015), and elevated lactate dehydrogenase levels (p < 0.001). The RR was 63.2% and 30.3% in those with low or high TKa, respectively (p = 0.022). The median PFS was 19.9 and 12.6 months in patients with low or high TKa, respectively (hazard ratio (HR) 1.83 (95% CI, 1.08-3.08), p = 0.024). The median OS was >60 months and 18.5 months in patients with low or high TKa, respectively (HR: 2.25 (95% CI, 1.25-4.05), p = 0.011. Conclusions. High pretreatment plasma TKa levels were significantly associated with worse baseline characteristics and poor response and survival in ICI-treated melanoma patients. TKa is hence a novel and interesting plasma biomarker in melanoma and should be further studied to define its role as a prognostic and predictive marker in this disease.

Paediatric approaches to child maltreatment are subject to wide organisational variations across Europe.

AIM: Little is known about the organisation of child maltreatment practice in Europe. We therefore explored medical child protection systems and training across Europe. METHODS: An online survey was completed by physicians working in child maltreatment, identified through professional organisations in 28 member countries of the European Union, Iceland, Norway and Switzerland in 2012-2013. Respondents were questioned regarding management of suspected child maltreatment, mandatory reporting, professional training, patient referral and physician roles in multidisciplinary investigations. Responses underwent a narrative synthesis and descriptive enumerations. RESULTS: The survey was completed by 88 individuals, unevenly distributed in 22 of 31 countries. Physicians were mandated to report child maltreatment in 16 of 22 countries. All of 88 responding physicians described multidisciplinary involvement in the clinical and forensic management of suspected child maltreatment. Practitioners involved in physical examinations included general physicians, paediatricians, forensic medical examiners, gynaecologists and paediatric surgeons. Paediatricians were required to undergo child protection training according to 30 of 86 respondents in 14 of 22 countries. CONCLUSION: This survey demonstrates that there were wide variations in the organisation of child maltreatment paediatrics in Europe. The differing legislative frameworks and models of care are pertinent to consider when comparing epidemiology of maltreatment reported from across European countries.