CD68-positive tumour associated macrophages, PD-L1 expression, and EBV latent infection in a high HIV-prevalent South African cohort of Hodgkin lymphoma patients.

A higher proportion of CD68-positive tumour associated macrophages (TAMs) has been associated with poorer outcomes in HIV-negative patients with Hodgkin lymphoma (HL), but whether this is true in HIV-positive patients with HL is not known. In this study, we investigated the number of CD68-positive TAMs and expression of programmed cell death-ligand 1 (PD-L1) in lymph node specimens from HL patients and correlated expression with clinical features (HIV status, disease severity and survival) and histopathological features (EBV latent positivity and subtype of HL). We stained archived lymph node specimens from 77 patients diagnosed with HL for CD68 and PD-L1. Stains were graded as: CD68 low (≤25%), CD68 high (>25%), PD-L1 low (≤50%), and PD-L1 high (>50%). Expression levels were correlated with the clinical and histopathological features using bivariate and multivariate analyses. Survival was analysed by overall and progression-free survival. Thirty-four of the 77 included patients (44%) were HIV-positive. EBV latency was detected in 97% of HIV-positive HL patients and in 14% of HIV-negative HL patients. A high CD68 score was associated with lower median haemoglobin levels (9.4 vs 11.4 g/dL; p=0.02), platelet numbers (262 vs 424 cells ×109/L; p=0.01), and lymphocyte numbers (0.99 vs 1.70 cells ×109/L, p=0.01) and a trend towards advanced disease (international prognostic score ≥4; hazard ratio 2.4; confidence interval 0.89-6.47; p=0.08). HIV status did not affect CD68 or PD-L1 expression. A higher proportion of CD68-positive TAMs was found in samples that were EBV-positive. HIV positivity and EBV negativity correlated with poorer survival. CD68 and PD-L1 expression were not predictive of survival. High CD68 expression was associated with EBV positivity but not HIV positivity and did not predict adverse outcomes. PD-L1 expression was unaffected by HIV status or EBV positivity and did predict adverse outcomes.

Determinants of hair cortisol concentration in children: A systematic review.

BACKGROUND: Several factors are known contribute to hair cortisol concentration (HCC) in adults. However, there is less research on determinants of HCC in children and adolescents. HCC is a valuable tool for medical research pertaining to the hypothalamic-pituitary-adrenal (HPA) axis. This review aims to assess the extent to which established determinants of HCC in adults have been consistently reported in children (birth - 18 years) and to identify determinants of HCC specific to this age group. METHODS: Eligible studies were identified, selected and appraised as per PRISMA-P guidelines and as detailed in our systematic review protocol, registered on PROSPERO (registration number CRD42017056220). In view of contrasting methods and measures, a meta-analysis could not be done but a qualitative synthesis was performed. RESULTS: Thirty-six studies were included in the analysis. Higher HCC is associated with male sex and anthropometry, particularly increased body mass index and waist circumference. There is preliminary evidence to suggest that socio-economic status is inversely related to child HCC, particularly with reference to caregiver education and income. Of note, most of the studies analysing socio-economic variables were performed in relatively equal societies. Hair wash frequency and use of hair products and treatments do not affect HCC when proximal segments of hair are used. There is conflicting evidence regarding the relationship between HCC and age in children and adolescents. Further investigation is required to better delineate if and how the following are associated with HCC in children: hair colour, hair type, exposure to trauma and stressors, psychiatric illness, atopic illness, steroid use (including topical and inhaled steroids) and perinatal variables. CONCLUSIONS: Sex and anthropometry are potential confounders and should be considered for adjustment in hair cortisol research. Hair wash frequency and use of hair products and treatments are not important confounders when proximal hair segments are used. A better understanding of HCC in children in relation to exposure to trauma and stressors is required before it can be used as a biomarker, particularly in terms of vulnerable developmental stages, definition and measurement of stress, and temporal relationship to stressors. Age, SES and other correlates also warrant further investigation.