Project description:Studies of animals and plants suggest that nutritional conditions in one generation may affect phenotypic characteristics in subsequent generations. A small number of human studies claim to show that pre-pubertal nutritional experience trigger a sex-specific transgenerational response along the male line. A single historical dataset, the Överkalix cohorts in northern Sweden, is often quoted as evidence. To test this hypothesis on an almost 40 times larger dataset we collect harvest data during the pre-pubertal period of grandparents (G0, n?=?9,039) to examine its potential association with mortality in children (G1, n?=?7,280) and grandchildren (G2, n?=?11,561) in the Uppsala Multigeneration Study. We find support for the main Överkalix finding: paternal grandfather's food access in pre-puberty predicts his male, but not female, grandchildren's all-cause mortality. In our study, cancer mortality contributes strongly to this pattern. We are unable to reproduce previous results for diabetes and cardiovascular mortality.
Project description:BackgroundAcute kidney injury (AKI) is a critical issue in cancer patients because it is not only a morbid complication but also able to interrupt timely diagnostic evaluation or planned optimal treatment. However, the impact of AKI on overall mortality in cancer patients remains unclear.MethodsWe conducted a retrospective cohort study of 67 986 cancer patients, from 2004 to 2013 to evaluate the relationship between AKI and all-cause mortality. We used KDIGO AKI definition and grading system.ResultsDuring 3.9 ± 3.1 years of follow-up, 33.8% of the patients experienced AKI at least once. Among AKI events, stage 1, 2, and 3 was 71.0%, 13.8%, and 15.1%, respectively. AKI incidence was highest in hematologic malignancies, followed by urinary tract cancer, and hepatocellular carcinoma. Male sex, older age, underlying diabetes and hypertension, lower serum albumin and plasma hemoglobin, more frequent radio-contrast exposure, entrance of clinical trials, and receiving chemotherapy were associated with AKI occurrence. AKI development was an independent risk factor for elevated mortality in cancer patients with dose-responsive manner (Stage 1, hazard ratio [HR] 1.183, 95% confidence interval [CI] 1.145-1.221, P < 0.001; Stage 2, HR 1.710, 95% CI 1.629-1.796; Stage 3, HR 2.000, 95% CI 1.910-2.095; No AKI, reference group) even after adjustment. This tendency was reproduced in various cancer types except thyroid cancer and in various treatment modalities, however, not shown in patients with baseline renal dysfunction.ConclusionAKI was an independent risk factor for all-cause mortality in overall cancer patients with dose-responsive manner.
Project description:Medial arterial calcification is accelerated in patients with CKD and strongly associated with increased arterial rigidity and cardiovascular mortality. Recently, a novel in vitro blood test that provides an overall measure of calcification propensity by monitoring the maturation time (T50) of calciprotein particles in serum was described. We used this test to measure serum T50 in a prospective cohort of 184 patients with stages 3 and 4 CKD, with a median of 5.3 years of follow-up. At baseline, the major determinants of serum calcification propensity included higher serum phosphate, ionized calcium, increased bone osteoclastic activity, and lower free fetuin-A, plasma pyrophosphate, and albumin concentrations, which accounted for 49% of the variation in this parameter. Increased serum calcification propensity at baseline independently associated with aortic pulse wave velocity in the complete cohort and progressive aortic stiffening over 30 months in a subgroup of 93 patients. After adjustment for demographic, renal, cardiovascular, and biochemical covariates, including serum phosphate, risk of death among patients in the lowest T50 tertile was more than two times the risk among patients in the highest T50 tertile (adjusted hazard ratio, 2.2; 95% confidence interval, 1.1 to 5.4; P=0.04). This effect was lost, however, after additional adjustment for aortic stiffness, suggesting a shared causal pathway. Longitudinally, serum calcification propensity measurements remained temporally stable (intraclass correlation=0.81). These results suggest that serum T50 may be helpful as a biomarker in designing methods to improve defenses against vascular calcification.
Project description:Following publication of the original paper [1], the authors submitted a new Additional file 5 to replace the one containing formatting issues. The updated Additional file 5 is published in this correction.