Evolution of CD4 T-Cell count with age in a cohort of young people growing up with perinatally acquired HIV

Background: Recent studies have shown a decrease in CD4 count during adolescence in young people with perinatally acquired HIV (PHIV). We examine changes and predictors of CD4 over time in PHIV in the UK and compare to published CD4 data in the general population.// Methods: PHIV followed in the Collaborative HIV Paediatric Study who started antiretroviral therapy (ART) from 2000 onwards were included. Follow-up data from the UK Collaborative HIV Cohort Study were also used. Changes in CD4 count over time from age 10 to 20 years were analysed using mixed effects models. Potential predictors included demographics, age at ART start, nadir CD4 z-score (age-adjusted) in childhood and time-updated viral load.// Results: Of 1,258 PHIV included, 669 (53%) were female, median [IQR] age at ART initiation was 8.3 years [3.5, 12.1] and nadir CD4 z-score was -4.0 [-5.9, -2.5]. In multivariable analysis, mean CD4 count was higher in PHIV who started ART before age 10 and had a nadir CD4 z-score ≥-4 in childhood; these PHIV had a decline in CD4 count after age 10 which was comparable to the general population. Mean CD4 count was lower in PHIV who had started ART before age 10 and had a nadir CD4 z-score <-4 in childhood; for this group the decline in CD4 count after age 10 was steeper over time.// Conclusions: In children, as well as starting ART at an early age, optimising ART to maintain a higher CD4 z-score during childhood may be important to maximize immune reconstitution later in life

Pressure Load: The Main Factor for Altered Gene Expression in Right Ventricular Hypertrophy in Chronic Hypoxic Rats

BACKGROUND: The present study investigated whether changes in gene expression in the right ventricle following pulmonary hypertension can be attributed to hypoxia or pressure loading. METHODOLOGY/PRINCIPAL FINDINGS: To distinguish hypoxia from pressure-induced alterations, a group of rats underwent banding of the pulmonary trunk (PTB), sham operation, or the rats were exposed to normoxia or chronic, hypobaric hypoxia. Pressure measurements were performed and the right ventricle was analyzed by Affymetrix GeneChip, and selected genes were confirmed by quantitative PCR and immunoblotting. Right ventricular systolic blood pressure and right ventricle to body weight ratio were elevated in the PTB and the hypoxic rats. Expression of the same 172 genes was altered in the chronic hypoxic and PTB rats. Thus, gene expression of enzymes participating in fatty acid oxidation and the glycerol channel were downregulated. mRNA expression of aquaporin 7 was downregulated, but this was not the case for the protein expression. In contrast, monoamine oxidase A and tissue transglutaminase were upregulated both at gene and protein levels. 11 genes (e.g. insulin-like growth factor binding protein) were upregulated in the PTB experiment and downregulated in the hypoxic experiment, and 3 genes (e.g. c-kit tyrosine kinase) were downregulated in the PTB and upregulated in the hypoxic experiment. CONCLUSION/SIGNIFICANCE: Pressure load of the right ventricle induces a marked shift in the gene expression, which in case of the metabolic genes appears compensated at the protein level, while both expression of genes and proteins of importance for myocardial function and remodelling are altered by the increased pressure load of the right ventricle. These findings imply that treatment of pulmonary hypertension should also aim at reducing right ventricular pressure

Multicentre prospective observational study evaluating recommendations for mastectomy by multidisciplinary teams

Background Recommendations for mastectomy by multidisciplinary teams (MDTs) may contribute to variation in mastectomy rates. The primary aim of this multicentre prospective observational study was to describe current practice in MDT decision‐making for recommending mastectomy. A secondary aim was to determine factors contributing to variation in mastectomy rates. Methods Consecutive patients undergoing mastectomy between 1 June 2015 and 29 February 2016 at participating units across the UK were recruited. Details of neoadjuvant systemic treatment (NST), operative and oncological data, and rationale for recommending mastectomy by MDTs were collected. Results Overall, 1776 women with breast cancer underwent 1823 mastectomies at 68 units. Mastectomy was advised by MDTs for 1402 (76·9 per cent) of these lesions. The most common reasons for advising mastectomy were large tumour to breast size ratio (530 women, 29·1 per cent) and multicentric disease (372, 20·4 per cent). In total, 202 postmenopausal women with oestrogen receptor‐positive (ER+) unifocal tumours were advised mastectomy and not offered NST, owing to large tumour to breast size ratio in 173 women (85·6 per cent). Seventy‐five women aged less than 70 years with human epidermal growth factor receptor 2‐positive (HER2+) tumours were advised mastectomy and not offered NST, owing to large tumour to breast size ratio in 45 women (60 per cent). Conclusion Most mastectomies are advised for large tumour to breast size ratio, but there is an inconsistency in the use of NST to downsize tumours in patients with large ER+ or HER2+ cancers. The application of standardized recommendations for NST could reduce the number of mastectomies advised by MDTs