Effects on mortality of a nutritional intervention for malnourished HIV-infected adults referred for antiretroviral therapy: a randomised controlled trial.

Malnourished HIV-infected African adults are at high risk of early mortality after starting antiretroviral therapy (ART). We hypothesized that short-course, high-dose vitamin and mineral supplementation in lipid nutritional supplements would decrease mortality

Mercury in the Black Sea:New Insights From Measurements and Numerical Modeling

Redox conditions and organic matter control marine methylmercury (MeHg) production. The Black Sea is the world's largest and deepest anoxic basin and is thus ideal to study Hg species along the extended redox gradient. Here we present new dissolved Hg and MeHg data from the 2013 GEOTRACES MEDBlack cruise (GN04_leg2) that we integrated into a numerical 1-D model, to track the fate and dynamics of Hg and MeHg. Contrary to a previous study, our new data show highest MeHg concentrations in the permanently anoxic waters. Observed MeHg/Hg percentage (range 9-57%) in the anoxic waters is comparable to other subsurface maxima in oxic open-ocean waters. With the modeling we tested for various Hg methylation and demethylation scenarios along the redox gradient. The results show that Hg methylation must occur in the anoxic waters. The model was then used to simulate the time evolution (1850-2050) of Hg species in the Black Sea. Our findings quantify (1) inputs and outputs of Hg-T (similar to 31 and similar to 28 kmol yr(-1)) and MeHgT (similar to 5 and similar to 4 kmol yr(-1)) to the basin, (2) the extent of net demethylation occurring in oxic (similar to 1 kmol yr(-1)) and suboxic water (similar to 6 kmol yr(-1)), (3) and the net Hg methylation in the anoxic waters of the Black Sea (similar to 11 kmol yr(-1)). The model was also used to estimate the amount of anthropogenic Hg (85-93%) in the Black Sea

Circulating proteins as predictors of cardiovascular mortality in endstage renal disease

Introduction: Proteomic profiling of end-stage renal disease (ESRD) patients could lead to improved risk prediction and novel insights into cardiovascular disease mechanisms. Plasma levels of 92 cardiovascular disease-associated proteins were assessed by proximity extension assay (Proseek Multiplex CVD-1, Olink Bioscience, Uppsala, Sweden) in a discovery cohort of dialysis patients, the Mapping of Inflammatory Markers in Chronic Kidney disease cohort [MIMICK; n = 183, 55% women, mean age 63 years, 46 cardiovascular deaths during follow-up (mean 43 months)]. Significant results were replicated in the incident and prevalent hemodialysis arm of the Salford Kidney Study [SKS dialysis study, n = 186, 73% women, mean age 62 years, 45 cardiovascular deaths during follow-up (mean 12 months)], and in the CKD5-LD-RTxcohort with assessments of coronary artery calcium (CAC)-score by cardiac computed tomography (n = 89, 37% women, mean age 46 years). Results: In age and sex-adjusted Cox regression in MIMICK, 11 plasma proteins were nominally associated with cardiovascular mortality (in order of significance: Kidney injury molecule-1 (KIM-1), Matrix metalloproteinase-7, Tumour necrosis factor receptor 2, Interleukin-6, Matrix metalloproteinase-1, Brain-natriuretic peptide, ST2 protein, Hepatocyte growth factor, TNF-related apoptosis inducing ligand receptor-2, Spondin-1, and Fibroblast growth factor 25). Only plasma KIM-1 was associated with cardiovascular mortality after correction for multiple testing, but also after adjustment for dialysis vintage, cardiovascular risk factors and inflammation (hazard ratio) per standard deviation (SD) increase 1.84, 95% CI 1.26–2.69, p = 0.002. Addition of KIM-1, or nine of the most informative proteins to an established risk-score (modified AROii CVM-score) improved discrimination of cardiovascular mortality risk from C = 0.777 to C = 0.799 and C = 0.823, respectively. In the SKS dialysis study, KIM-1 predicted cardiovascular mortality in age and sex adjusted models (hazard ratio per SD increase 1.45, 95% CI 1.03–2.05, p = 0.034) and higher KIM-1 was associated with higher CACscores in the CKD5-LD-RTx-cohort. Conclusions Our proteomics approach identified plasma KIM-1 as a risk marker for cardiovascular mortality and coronary artery calcification in three independent ESRD-cohorts. The improved risk prediction for cardiovascular mortality by plasma proteomics merit further studies.Swedish Research CouncilSwedish Heart–Lung foundationEuropean Union Horizon 2020 (Grant number 634869)Dalarna UniversityUppsala UniversitySwedish Medical Research CouncilNjurfondenEuropean Union’s Horizon 2020 research and innovation programme, Marie Sklodowska-Curie Grant Agreement no. 722609Publishe

Longitudinal serum bicarbonate and mortality risk in older patients with advanced chronic kidney disease: Analyses from the EQUAL cohort

Background. We aimed to explore the relationship between serum bicarbonate (SBC) and mortality in advanced chronic kidney disease (CKD) during three distinct treatment periods: during the pre-kidney replacement therapy (KRT) period, during the transition phase surrounding the start of KRT (transition-CKD) and during KRT. Methods. Using the European QUALity Study on treatment in advanced CKD (EQUAL) cohort, which includes patients aged ≥65 years and estimated glomerular filtration rate (eGFR) ≤20 mL/min/1.73 m2 from six European countries, we explored the association between longitudinal SBC and all-cause mortality in three separate CKD populations: pre-KRT, transition-CKD and in the KRT populations, using multivariable time-dependent Cox regression models. We evaluated effect modification by pre-specified variables on the relationship between SBC and mortality Results. We included 1485 patients with a median follow-up of 2.9 (interquartile range 2.7) years, during which 529 (35.6%) patients died. A U-shaped relationship between SBC levels and all-cause mortality was observed in the pre-KRT population (P = .03). Low cumulative exposure, defined as the area under the SBC trajectory before KRT initiation, was associated with increased mortality risk after transitioning to KRT (P = .01). Similarly, in the KRT population, low SBC levels showed a trend towards increased mortality risk (P = .13). We observed effect modification by subjective global assessment category (P-value for interaction = .02) and KRT (P-value for interaction = .02). Conclusions. A U-shaped relationship describes the association between SBC and mortality in the advanced CKD pre-KRT population, whereas in the KRT population a trend towards an increased mortality risk was observed for low SBC levels

A longitudinal study of systemic inflammation and recovery of lean body mass among malnourished HIV-infected adults starting antiretroviral therapy in Tanzania and Zambia

BACKGROUND/OBJECTIVES: The effects of inflammation on nutritional rehabilitation after starting antiretroviral therapy (ART) are not well understood. We assessed the relationship between inflammation and body composition among patients enrolled in the Nutritional Support for African Adults Starting Antiretroviral therapy (NUSTART) trial in Tanzania and Zambia from 2011 to 2013. SUBJECTS/METHODS: HIV-infected, ART-eligible adults with body mass index (BMI) of <18.5 kg/m(2) enrolled in the NUSTART trial were eligible for this study. Anthropometric and body composition data were collected at recruitment and 6 and 12 weeks post ART and C-reactive protein (CRP) was measured at recruitment and 6 weeks. The relationships between CRP and body composition were assessed using multiple regression. RESULTS: Of the 1815 trial participants, 838 (46%) had baseline and 6-week CRP measurements. Median age was 36 years, 55% were females and median CD4 count was 135 cells/μl. A one-log reduction in CRP at 6 weeks was associated with increased mid-upper arm circumference (0.45 cm; 95% CI: 0.30, 0.61), calf circumference (0.38 cm; 0.23, 0.54), waist circumference (0.98 cm; 0.59, 1.37), BMI (0.37 kg/m(2); 0.24, 0.50) and fat-free mass (0.58 kg; 0.26, 0.91), but not with fat mass (0.09 kg; -0.17, 0.34). Fat-free mass gains persisted at 12 weeks and were more closely associated with 6-week CRP values than with baseline values. CONCLUSIONS: Reduction in CRP shortly after ART initiation was associated with higher fat-free mass gains. Further studies are warranted to determine whether interventions to reduce systemic inflammation will enhance gains in fat-free mass