These findings provide estimates of cancer risk based on BRCA1 and BRCA2 mutation carrier status using prospective data collection and demonstrate the potential importance of family history and mutation location in risk assessment.

In various subsets of critically ill patients, arterial hyperoxia was associated with poor hospital outcome. Considering the substantial heterogeneity of included studies and the lack of a clinical definition, more evidence is needed to provide optimal oxygen targets to critical care physicians.

IntroductionArterial concentrations of carbon dioxide (PaCO2) and oxygen (PaO2) during admission to the intensive care unit (ICU) may substantially affect organ perfusion and outcome after cardiac arrest. Our aim was to investigate the independent and synergistic effects of both parameters on hospital mortality.MethodsThis was a cohort study using data from mechanically ventilated cardiac arrest patients in the Dutch National Intensive Care Evaluation (NICE) registry between 2007 and 2012. PaCO2 and PaO2 levels from arterial blood gas analyses corresponding to the worst oxygenation in the first 24 h of ICU stay were retrieved for analyses. Logistic regression analyses were performed to assess the relationship between hospital mortality and both categorized groups and a spline-based transformation of the continuous values of PaCO2 and PaO2.ResultsIn total, 5,258 cardiac arrest patients admitted to 82 ICUs in the Netherlands were included. In the first 24 h of ICU admission, hypocapnia was encountered in 22 %, and hypercapnia in 35 % of included cases. Hypoxia and hyperoxia were observed in 8 % and 3 % of the patients, respectively. Both PaCO2 and PaO2 had an independent U-shaped relationship with hospital mortality and after adjustment for confounders, hypocapnia and hypoxia were significant predictors of hospital mortality: OR 1.37 (95 % CI 1.17–1.61) and OR 1.34 (95 % CI 1.08–1.66). A synergistic effect of concurrent derangements of PaCO2 and PaO2 was not observed (P = 0.75).ConclusionsThe effects of aberrant arterial carbon dioxide and arterial oxygen concentrations were independently but not synergistically associated with hospital mortality after cardiac arrest.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-015-1067-6) contains supplementary material, which is available to authorized users.

Background: The effect of risk-reducing salpingo-oophorectomy (RRSO) on breast cancer risk for BRCA1 and BRCA2 mutation carriers is uncertain. Retrospective analyses have suggested a protective effect but may be substantially biased. Prospective studies have had limited power, particularly for BRCA2 mutation carriers. Further, previous studies have not considered the effect of RRSO in the context of natural menopause.Methods: A multi-centre prospective cohort of 2272 BRCA1 and 1605 BRCA2 mutation carriers was followed for a mean of 5.4 and 4.9 years, respectively; 426 women developed incident breast cancer. RRSO was modelled as a time-dependent covariate in Cox regression, and its effect assessed in premenopausal and postmenopausal women. Results: There was no association between RRSO and breast cancer for BRCA1 (HR = 1.23; 95% CI 0.94-1.61) or BRCA2 (HR = 0.88; 95% CI 0.62-1.24) mutation carriers. For BRCA2 mutation carriers, HRs were 0.68 (95% CI 0.40-1.15) and 1.07 (95% CI 0.69-1.64) for RRSO carried out before or after age 45 years, respectively. The HR for BRCA2 mutation carriers decreased with increasing time since RRSO (HR = 0.51; 95% CI 0.26-0.99 for 5 years or longer after RRSO). Estimates for premenopausal women were similar.