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.     

Validation of a Complementary Food Frequency Questionnaire to assess infant nutrient intake

Dietary assessment in infants is challenging but necessary to understand the relationship between nutrition and growth and development. Currently no simple, validated methods exist to assess nutrient intake in New Zealand (NZ) infants. Therefore, this study aimed to assess the relative validity and reproducibility of a Complementary Food Frequency Questionnaire (CFFQ) to determine nutrient intakes of NZ infants. Ninety‐five parent–infant pairs (infant age 10 ± 1 months) completed the CFFQ twice (CFFQ‐1 and CFFQ‐2), 4 weeks apart (to assess reproducibility). A 4‐day weighed food record (4dWFR) was collected between CFFQ administrations (to assess validity). Validity and reproducibility were assessed for intakes of energy and 18 nutrients using Bland–Altman analysis, Pearson's correlation coefficients, cross‐classification, and weighted Kappa (κ). The CFFQ showed acceptable validity: Nutrients from the CFFQ were comparable with the 4dWFR (bias, 9–28%), correlation between methods ranged from r = .18 (saturated fat) to r = .81 (iron; mean r = .52), 54% (mean) of participants were correctly classified (range 39% to 67%), and 7.1% (mean) misclassified into opposite tertiles (range 2.1% to 14.7%). There was acceptable agreement between the CFFQ and 4dWFR (κ = 0.20–0.60). The CFFQ showed good reproducibility: Correlations ranged from r = .34 (folate) to r = .80 (zinc); for 16 nutrients, >50% of participants were correctly classified, and for all nutrients, <10% of participants were grossly misclassified. All nutrients showed acceptable to good agreement (κ > 0.20). The CFFQ has acceptable relative validity and good reproducibility for assessing nutrient intake in NZ infants aged 9–12 months, making it a useful tool for use in future research.     

Retrograde inspection vs standard forward view for the detection of colorectal adenomas during colonoscopy: A back-to-back randomized clinical trial

BACKGROUND The adenoma detection rate(ADR) is inversely associated with the incidence of interval colorectal cancer and serves as a benchmark quality criterion during screening colonoscopy. However, adenoma miss rates reach up to 26% and studies have shown that a second inspection of the right colon in retroflected view(RFV) can increase ADR.AIM To assess whether inspection of the whole colon in RFV compared to standard forward view(SFV) can increase ADR.METHODS Patients presenting for screening or surveillance colonoscopy were invited to participate in this randomized controlled trial and randomized into two arms. In RFV arm colonoscopy was initially performed with SFV, followed by a second inspection of the whole colon in RFV. In the SFV arm first withdrawal was performed with SFV, followed by a second inspection of the whole colon again with SFV. Number, size and morphology of polyps found during first and second inspection in each colonic segment were recorded and all polyps were removed and sent for histopathology in separate containers.RESULTS Two hundred and five patients were randomly assigned to the RFV(n = 101) and SFV(n = 104) arm. In the RFV arm, both polyp detection rate(PDR) and ADR were increased under second inspection in RFV(PDR 1~(st) SFV: 39.8%, PDR 2~(nd)RFV: 46.6%; ADR 1~(st) SFV: 35.2%, ADR 2~(nd) RFV: 42%). Likewise, in the SFV arm,PDR and ADR were increased under second inspection(PDR 1~(st) SFV: 37.5%, PDR 2~(nd) SFV: 46.6%; ADR 1~(st) SFV: 34.1%, ADR 2~(nd)SFV: 44.3%) with no significant differences in ADR and PDR between the SFV and RFV arm. Mean number of adenomas per patient(APP) was increased in the RFV and SFV(APP RFV arm: 1~(st) SFV: 1.71; 2~(nd) RFV: 2.38; APP SFV arm: 1~(st) SFV: 1.83, 2~(nd)SFV:2.2). The majority of adenomas additionally found during second inspection in RFV or in SFV were located in the transverse and left-sided colon and were 5 mm in size.CONCLUSION Second inspection of the whole colon leads to increased adenoma detection with no differences between SFV and RFV. Hence, increased detection is most likely a feature of the second inspection itself but not of the inspection mode.     

Family correlates of daughter's and son's locus of control expectancies during childhood

Children who expect they can bring about good outcomes and avoid bad outcomes tend to experience more personal successes. Little is known about factors that contribute to these ‘control expectancies’. The purpose of the present study was to determine whether children's internal control expectancies occur in the context of parents’ internal control expectancies, low family strain, and high family cohesiveness and whether these factors are more strongly related to daughters’ than sons’ control expectancies. A community sample of 85 children aged 9–11 years and their parents (85 mothers; 63 fathers) completed rating scales. Fathers’ more internal control expectancies and mothers’ reports of fewer family strains were associated with daughters’ but not sons’ greater internal control expectancies, and greater family cohesiveness was related to both daughters’ and sons’ internal control orientations. These findings suggest that family factors may contribute to children's, particularly daughters’, development of internal control expectancies.     

Defining metronidazole-induced encephalopathy

Journal of Neurology -     

Safety of repeated hyperpolarized helium 3 magnetic resonance imaging in pediatric asthma patients

Background

Hyperpolarized helium 3 magnetic resonance imaging (³He MRI) is useful for investigating pulmonary physiology of pediatric asthma, but a detailed assessment of the safety profile of this agent has not been performed in children.

Objective

To evaluate the safety of ³He MRI in children and adolescents with asthma.

Materials and methods

This was a retrospective observational study. ³He MRI was performed in 66 pediatric patients (mean age 12.9 years, range 8–18 years, 38 male, 28 female) between 2007 and 2017. Fifty-five patients received a single repeated examination and five received two repeated examinations. We assessed a total of 127 ³He MRI exams. Heart rate, respiratory rate and pulse oximetry measured oxygen saturation (SpO₂) were recorded before, during (2 min and 5 min after gas inhalation) and 1 h after MRI. Blood pressure was obtained before and after MRI. Any subjective symptoms were also noted. Changes in vital signs were tested for significance during the exam and divided into three subject age groups (8–12 years, 13–15 years, 16–18 years) using linear mixed-effects models.

Results

There were no serious adverse events, but three minor adverse events (2.3%; headache, dizziness and mild hypoxia) were reported. We found statistically significant increases in heart rate and SpO₂ after ³He MRI. The youngest age group (8–12 years) had an increased heart rate and a decreased respiratory rate at 2 min and 5 min after ³H inhalation, and an increased SpO₂ post MRI.

Conclusion

The use of ³He MRI is safe in children and adolescents with asthma.