Immune checkpoint inhibitors in advanced nasopharyngeal carcinoma: Beyond an era of chemoradiation?

Now is an exciting era of development in immunotherapy checkpoint inhibitors and their effect on the treatment of NPC. While the general prognosis of R/M disease is poor, immunotherapy offers some promise in a malignancy associated with EBV and characterized by a peritumoural immune infiltrate. Our study aims to review past and on-going clinical trials of monoclonal antibody therapies against the checkpoint inhibitors (e.g. PD1 and CTLA-4), in R/M NPC. All randomized and nonrandomized controlled trials involving immune checkpoint inhibitor interventions for treatment of NPC were included in the study. We utilized a validated “risk of bias” tool to assess study quality. Four separate Phase I–II trials report the potential of PD1 inhibitor treatment for patients with NPC. Within the observed groups, camrelizumab combined with chemotherapy achieved an objective response in 91% of patients as first-line treatment for metastatic NPC (PFS 68% at 1-year) but this was associated with a high rate of grade >3 adverse events (87%; CTCAE version 4.03). The remaining three studies focused on recurrent NPC disease in patients who had received at least one line of prior chemotherapy. Within this group, camrelizumab monotherapy achieved an objective response in 34% of patients (PFS 27% at 1-year; range across all three studies 20.5–34%). No NPC trial has yet reported on specific outcomes for non-PD1 checkpoint inhibitors but 11 on-going studies include alternative targets (e.g. PD-L1/CTLA-4) as combination or monotherapy treatments. In considering checkpoint immunotherapies for NPC, initial results show promise for anti-PD1 interventions. Further phase I–III trials are in progress to clarify clinical outcomes, fully determine safety profiles, and optimize drug combinations and administration schedules.     

Annual Research Review: A meta-analytic review of worldwide suicide rates in adolescents

Suicide is a leading cause of death among youth worldwide. The purpose of the current review was to examine recent cross-national trends in suicide mortality rates among 10- to 19-year-olds. This study extracted suicide mortality data from the World Health Organization's (WHO) Mortality Database for the most recent year (since 2010) from any country with available high-quality data (as defined by the WHO's guidelines). Data on access to lethal means (firearms, railways) and measures of economic quality (World Bank Income Group) and inequality (Gini coefficients) were obtained from publicly available data sources. Cross-national suicide mortality rates in youth were heterogeneous. The pooled estimate across all ages, sexes, and countries was 3.77/100,000 people. The highest suicide rates were found in Estonia, New Zealand, and Uzbekistan. Suicide rates were higher among older compared with younger adolescents and higher among males than females. The most common suicide methods were hanging/suffocation and jumping/lying in front of a moving object or jumping from a height. Firearm and railway access were related to suicide deaths by firearms and jumping/lying, respectively. Economic quality and inequality were not related to overall suicide mortality rates. However, economic inequality was correlated with a higher ratio of male:female suicides. This study provides a recent update of cross-national suicide trends in adolescents. Findings replicate prior patterns related to age, sex, geographic region, and common suicide methods. New to this review are findings relating suicide method accessibility to suicide mortality rates and the significant association between income inequality and the ratio of male:female suicide. Future research directions include expanding the worldwide coverage to more low- and middle-income countries, examining demographic groupings beyond binary sex and to race/ethnicity within countries, and clarifying factors that account for cross-national differences in suicide trends.     

The perineal midsagittal view in male fetuses — pivotal for assessing genitourinary disorders

A wide range of genitourinary pathologies can be diagnosed in utero, from a simple vesicoureteral reflux to a more complex disorder of sexual differentiation. The prognosis and neonatal management of these conditions differ significantly. Evaluation of the fetal perineal anatomy is paramount to making the right diagnosis. The aim of this pictorial essay is to show sonographers how to acquire a perineal midsagittal view in a male fetus, and to demonstrate how this specific view allows assessment of the urethra and penis, to differentiate various genitourinary pathologies.

     

The effects of smoking on adolescent trauma patients: a propensity-score-matched analysis

Cigarettes have been demonstrated to be toxic to the pulmonary connective tissue by impairing the lung’s ability to clear debris, resulting in infection and acute respiratory distress syndrome (ARDS). Approximately 8% of adolescents are smokers. We hypothesized that adolescent trauma patients who smoke have a higher rate of ARDS and pneumonia when compared to non-smokers. The Trauma Quality Improvement Program (2014–2016) was queried for adolescent trauma patients aged 13–17 years. Adolescent smokers were 1:2 propensity-score-matched to non-smokers based on age, comorbidities, and injury type. Data were analyzed using chi square for categorical data and Mann–Whitney U test for continuous data. From 32,610 adolescent patients, 997 (3.1%) were smokers. After matching, 459 smokers were compared to 918 non-smokers. There were no differences in matched characteristics. Compared to non-smokers, smokers had an increased rate of pneumonia (3.1% vs. 1.1%, p = 0.01) but not ARDS (0.2% vs. 0%, p = 0.16). Compared to the non-smoking group, the smokers had a longer median total hospital length-of-stay (3 vs. 2 days, p = 0.01) and no difference in overall mortality (1.5% vs. 2.4%, p = 0.29). Smoking is associated with an increased rate of pneumonia in adolescent trauma patients. Future research should target smoking cessation and/or interventions to mitigate the deleterious effects of smoking in this population.