Patterns in metabolite profile are associated with risk of more aggressive prostate cancer: A prospective study of 3,057 matched case–control sets from EPIC

Metabolomics may reveal novel insights into the etiology of prostate cancer, for which few risk factors are established. We investigated the association between patterns in baseline plasma metabolite profile and subsequent prostate cancer risk, using data from 3,057 matched case–control sets from the European Prospective Investigation into Cancer and Nutrition (EPIC). We measured 119 metabolite concentrations in plasma samples, collected on average 9.4 years before diagnosis, by mass spectrometry (AbsoluteIDQ p180 Kit, Biocrates Life Sciences AG). Metabolite patterns were identified using treelet transform, a statistical method for identification of groups of correlated metabolites. Associations of metabolite patterns with prostate cancer risk (OR_1SD) were estimated by conditional logistic regression. Supplementary analyses were conducted for metabolite patterns derived using principal component analysis and for individual metabolites. Men with metabolite profiles characterized by higher concentrations of either phosphatidylcholines or hydroxysphingomyelins (OR_1SD = 0.77, 95% confidence interval 0.66–0.89), acylcarnitines C18:1 and C18:2, glutamate, ornithine and taurine (OR_1SD = 0.72, 0.57–0.90), or lysophosphatidylcholines (OR_1SD = 0.81, 0.69–0.95) had lower risk of advanced stage prostate cancer at diagnosis, with no evidence of heterogeneity by follow-up time. Similar associations were observed for the two former patterns with aggressive disease risk (the more aggressive subset of advanced stage), while the latter pattern was inversely related to risk of prostate cancer death (OR_1SD = 0.77, 0.61–0.96). No associations were observed for prostate cancer overall or less aggressive tumor subtypes. In conclusion, metabolite patterns may be related to lower risk of more aggressive prostate tumors and prostate cancer death, and might be relevant to etiology of advanced stage prostate cancer.     

The impact of poverty on educational outcomes for children

Over the past decade, the unfortunate reality is that the income gap has widened between Canadian families. Educational outcomes are one of the key areas influenced by family incomes. Children from low-income families often start school already behind their peers who come from more affluent families, as shown in measures of school readiness. The incidence, depth, duration and timing of poverty all influence a child’s educational attainment, along with community characteristics and social networks. However, both Canadian and international interventions have shown that the effects of poverty can be reduced using sustainable interventions. Paediatricians and family doctors have many opportunities to influence readiness for school and educational success in primary care settings.     

Reliability of the acetabular teardrop as a landmark

Summary This study investigated the effect of tilt and observer reliability on radiographic measurements of the position of a prosthetic acetabular cup in seven dry bone pelves using the teardrop as a landmark. Coronal or sagittal tilt of more than five degrees was easily recognisable and there was effectively no observer variation in the measurements up to this limit. In addition, 90 out of 100 randomly selected antero-posterior pelvic radiographs from an outpatient department were not significantly rotated and 93 demonstrated a clearly defined teardrop. Measurements about the teardrop on routine radiographs are therefore sufficiently accurate to allow assessment of prosthetic position.

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La valeur du sourcil cotyloidien comme repère d'analyse radiologique

Résumé Cette étude, conduite sur 7 bassins secs, apprécie l'effet de l'inclinaison du bassin sur la qualité de l'analyse radiographique de la position d'une cupule prothétique de hanche en utilisant le sourcil cotyloïdien comme repère. Une inclinaison du bassin dans les plans coronal et sagittal est aisément détectable et il n'existe pas de variation d'analyse entre les différents observateurs en dessous de 5° d'inclinaison. De plus, sur 100 radiographies antéro-postérieures de bassin choisies au hasard dans les dossiers de consultation, 90 avaient été réalisées sans incidence particulièrement adaptée et l'on pouvait repérer facilement le sourcil sur 93% d'entre elles. Les mesures faites sur des radios de routine sont donc suffisamment précises pour permettre l'évaluation de la position d'une prothèse à partir du sourcil cotyloïdien.

     

银屑病和日光性角化病皮损应用氨基-γ-酮戊酸荧光染色后肉眼荧光强度与原卟啉Ⅸ含量的相互关系

应用5-氨基-γ-酮戊酸（ALA）诱导的卟啉荧光诊断（FDAP）中，肉眼可观察到原卟啉IX（PpIX）沉积。因操作重复性低，且涉及PpIX肿瘤选择的机制知之甚少，所以解释荧光数据仍有些困难。本研究中，作者要研究FDAP后银屑病和日光性角化病（AK）患者皮损的PpIX沉积情况。基于此目的，将患者脱屑区皮损和无皮损正常皮肤用20％ALA油孵育3h，进行FDAP，取强荧光区皮损和无皮损处皮肤活检。从活检标本中提取PpIX、蛋白质和双链DNA行荧光分光光度法定量，用图像分析软件分析由FDAP获得的数字图像。     

Dietary intake of total polyphenol and polyphenol classes and the risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

Polyphenols may play a chemopreventive role in colorectal cancer (CRC); however, epidemiological evidence supporting a role for intake of individual polyphenol classes, other than flavonoids is insufficient. We evaluated the association between dietary intakes of total and individual classes and subclasses of polyphenols and CRC risk and its main subsites, colon and rectum, within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. The cohort included 476,160 men and women from 10 European countries. During a mean follow-up of 14 years, there were 5991 incident CRC cases, of which 3897 were in the colon and 2094 were in the rectum. Polyphenol intake was estimated using validated centre/country specific dietary questionnaires and the Phenol-Explorer database. In multivariable-adjusted Cox regression models, a doubling in total dietary polyphenol intake was not associated with CRC risk in women (HR_log2?=?1.06, 95% CI 0.99–1.14) or in men (HR_log2?=?0.97, 95% CI 0.90–1.05), respectively. Phenolic acid intake, highly correlated with coffee consumption, was inversely associated with colon cancer in men (HR_log2?=?0.91, 95% CI 0.85–0.97) and positively associated with rectal cancer in women (HR_log2?=?1.10, 95% CI 1.02–1.19); although associations did not exceed the Bonferroni threshold for significance. Intake of other polyphenol classes was not related to colorectal, colon or rectal cancer risks. Our study suggests a possible inverse association between phenolic acid intake and colon cancer risk in men and positive with rectal cancer risk in women.     

Prospective cost-effectiveness analysis of genomic profiling in breast cancer

BackgroundThe cost-effectiveness of the 70-gene signature (70-GS) (MammaPrint®) has earlier been estimated using retrospective validation data. Based on the prospective 5-year survival data of the microarRAy-prognoSTics-in-breast-cancER (RASTER) study, the aim here was to evaluate the cost-effectiveness reflecting the actual use in clinical practice, including reality-based compliance rates.MethodsCosts and outcomes (quality-adjusted-life-years (QALYs)) were calculated in node-negative (N?) patients included in the RASTER study (n = 427). Sensitivity and specificity of the 70-gene and Adjuvant! Online (AO) were based on 5-year distant-disease-free survival (DDFS). Subgroup analyses were performed for two groups for whom benefit of the 70-gene had earlier been reported: (1) ductal, oestrogen receptor-positive (ER+), tumour diameter 10–30 mm, grade II, age 40–70; (2) ductal, oestrogen receptor-positive, tumour diameter 5–30 mm, grade II/III and age 40–70.ResultsBased on 5-year survival data, the cost-effectiveness of the 70-gene signature versus AO was prospectively confirmed. The total health care costs per patient were €26,786 for the 70-gene and €29,187 for AO. The quality adjusted life years yielded 12.49 and 11.88, respectively. The subgroups retrieved slightly higher life gains and higher costs, but all resulted finally in a favourable position for the 70-gene signature.ConclusionsThe use of the 70-gene signature, as judged appropriate by doctors and patients and supported by a low risk 70-gene signature as an oncological safe choice, was also found to be cost-effective.     

Moderate alcohol consumption is associated with lower chronic disease burden expressed in disability-adjusted life years: a prospective cohort study

The relation of alcohol consumption with disease burden remains debated partly due to opposite associations with cardiovascular disease (CVD) and cancer. The relation of alcohol consumption with disease burden expressed in disability-adjusted life years (DALYs) summarizes opposing associations of alcohol consumption on chronic diseases. This study aimed to investigate the association of alcohol consumption with chronic disease burden expressed in DALYs based on individual-participant data. The study was a prospective study among 33,066 men and women from the EPIC-NL cohort. At baseline, alcohol consumption was assessed with a validated food-frequency questionnaire. Participants were followed for occurrence of and mortality from chronic diseases and DALYs were calculated. After 12.4 years follow-up, 6647 disease incidences and 1482 deaths were documented, resulting in 68,225 healthy years of life lost (6225 DALYs). Moderate drinkers (women 5–14.9 g/day, men 5–29.9 g/day) had a lower chronic disease burden (mean DALYs ?0.27; 95% CI ?0.43; ?0.11) than light drinkers (0–4.9 g/day), driven by a lower disease burden due to CVD (?0.18: ?0.29; ?0.06) but not cancer (?0.05: ?0.16; 0.06). The associations were most pronounced among older participants (≥50 years; ?0.32; ?0.53; ?0.10) and not observed among younger women (?0.08; ?0.43; 0.35), albeit non-significant (p_interaction > 0.14). Substantial drinking (women 15–29.9 g/day, men 30–59.9 g/day) compared to light drinking was not associated with chronic disease burden. Our results show that moderate compared to light alcohol consumption was associated with living approximately 3 months longer in good health. These results were mainly observed among older participants and not seen among younger women.