Hallmarks of cancer in patients with heart failure: data from BIOSTAT-CHF.

BACKGROUND: Within cardio-oncology, emerging epidemiologic studies have demonstrated a bi-directional relationship between heart failure (HF) and cancer. In the current study, we aimed to further explore this relationship and investigate the underlying pathophysiological pathways that connect these two disease entities. METHODS: We conducted a post-hoc analysis in which we identified 24 Gene Ontology (GO) processes associated with the hallmarks of cancer based on 92 biomarkers in 1960 patients with HF. We performed Spearman's correlations and Cox-regression analyses to evaluate associations with HF biomarkers, severity and all-cause mortality. RESULTS: Out of a total of 24 GO processes, 9 biological processes were significantly associated with adverse clinical outcome. Positive regulation of mononuclear cell proliferation demonstrated the highest hazard for reaching the clinical endpoint, even after adjusting for confounders: all-cause mortality HR 2.00 (95% CI 1.17-3.42), p = 0.012. In contrast, negative regulation of apoptotic process was consistently associated with a lower hazard of reaching the clinical outcome, even after adjusting for confounders: all-cause mortality HR 0.74 (95% CI 0.59-0.95), p = 0.016. All processes significantly correlated with HF biomarkers, renal function and HF severity. CONCLUSIONS: In patients with HF, GO processes associated with hallmarks of cancer are associated with HF biomarkers, severity and all-cause mortality.

Cortico-striatal white-matter connectivity underlies the ability to exert goal-directed control.

The balance between goal-directed and habitual control has been proposed to determine the flexibility of instrumental behaviour, in both humans and animals. This view is supported by neuroscientific studies that have implicated dissociable neural pathways in the ability to flexibly adjust behaviour when outcome values change. A previous Diffusion Tensor Imaging study provided preliminary evidence that flexible instrumental performance depends on the strength of parallel cortico-striatal white-matter pathways previously implicated in goal-directed and habitual control. Specifically, estimated white-matter strength between caudate and ventromedial prefrontal cortex correlated positively with behavioural flexibility, and posterior putamen-premotor cortex connectivity correlated negatively, in line with the notion that these pathways compete for control. However, the sample size of the original study was limited, and so far, there have been no attempts to replicate these findings. In the present study, we aimed to conceptually replicate these findings by testing a large sample of 205 young adults to relate cortico-striatal connectivity to performance on the slips-of-action task. In short, we found only positive neural correlates of goal-directed performance, including striatal connectivity (caudate and anterior putamen) with the dorsolateral prefrontal cortex. However, we failed to provide converging evidence for the existence of a neural habit system that puts limits on the capacity for flexible, goal-directed action. We discuss the implications of our findings for dual-process theories of instrumental action.

Clinical characteristics of women with HIV in the RESPOND cohort: A descriptive analysis and comparison to men.

BACKGROUND: Women with HIV are globally underrepresented in clinical research. Existing studies often focus on reproductive outcomes, seldom focus on older women, and are often underpowered to assess sex/gender differences. We describe CD4, HIV viral load (VL), clinical characteristics, comorbidity burden, and use of antiretroviral therapy (ART) among women with HIV in the RESPOND study and compare them with those of the men in RESPOND. METHODS: RESPOND is a prospective, multi-cohort collaboration including over 34 000 people with HIV from across Europe and Australia. Demographic and clinical characteristics, including CD4/VL, comorbidity burden, and ART are presented at baseline, defined as the latter of 1 January 2012 or enrolment into the local cohort, stratified by age and sex/gender. We further stratify men by reported mode of HIV acquisition, men who have sex with men (MSM) and non-MSM. RESULTS: Women account for 26.0% (n = 9019) of the cohort, with a median age of 42.2 years (interquartile range [IQR] 34.7-49.1). The majority (59.3%) of women were white, followed by 30.3% Black. Most women (75.8%) had acquired HIV heterosexually and 15.9% via injecting drug use. Nearly half (44.8%) were receiving a boosted protease inhibitor, 31.4% a non-nucleoside reverse transcriptase inhibitor, and 7.8% an integrase strand transfer inhibitor. The baseline year was 2012 for 73.2% of women and >2019 for 4.2%. Median CD4 was 523 (IQR 350-722) cells/µl, and 73.6% of women had a VL <200 copies/mL. Among the ART-naïve population, women were more likely than MSM but less likely than non-MSM (p < 0.001) to have CD4 <200 cells/µL and less likely than both MSM and non-MSM (p < 0.001) to have VL ≥100 000 copies/mL. Women were also more likely to be free of comorbidity than were both MSM and non-MSM (p < 0.0001). CONCLUSION: RESPOND women are diverse in age, ethnicity/race, CD4/VL, and comorbidity burden, with important differences relative to men. This work highlights the importance of stratification by sex/gender for future research that may help improve screening and management guidelines specifically for women with HIV.