Low oxygen saturation and mortality in an adult cohort; the Tromsø Study

Published version, also available at http://dx.doi.org/10.1186/s12890-015-0003-5Background: Oxygen saturation has been shown in risk score models to predict mortality in emergency medicine. The aim of this study was to determine whether low oxygen saturation measured by a single-point measurement by pulse oximetry (SpO2) is associated with increased mortality in the general adult population. Methods: Pulse oximetry was performed in 5,152 participants in a cross-sectional survey in Tromsø, Norway, in 2001–2002 (“Tromsø 5”). Ten-year follow-up data for all-cause mortality and cause of death were obtained from the National Population and the Cause of Death Registries, respectively. Cause of death was grouped into four categories: cardiovascular disease, cancer except lung cancer, pulmonary disease, and others. SpO2 categories were assessed as predictors for all-cause mortality and death using Cox proportional-hazards regression models after correcting for age, sex, smoking history, body mass index (BMI), C-reactive protein level, self-reported diseases, respiratory symptoms, and spirometry results. Results: The mean age was 65.8 years, and 56% were women. During the follow-up, 1,046 (20.3%) participants died. The age- and sex-adjusted hazard ratios (HRs) (95% confidence intervals) for all-cause mortality were 1.99 (1.33–2.96) for SpO2 ≤ 92% and 1.36 (1.15–1.60) for SpO2 93–95%, compared with SpO2 ≥ 96%. In the multivariable Cox proportional-hazards regression models that included self-reported diseases, respiratory symptoms, smoking history, BMI, and CRP levels as the explanatory variables, SpO2 remained a significant predictor of all-cause mortality. However, after including forced expiratory volume in 1 s percent predicted (FEV1% predicted), this association was no longer significant. Mortality caused by pulmonary diseases was significantly associated with SpO2 even when FEV1% predicted was included in the model. Conclusions: Low oxygen saturation was independently associated with increased all-cause mortality and mortality caused by pulmonary diseases. When FEV1% predicted was included in the analysis, the strength of the association weakened but was still statistically significant for mortality caused by pulmonary diseases

Curcuminoid Binding to Embryonal Carcinoma Cells: Reductive Metabolism, Induction of Apoptosis, Senescence, and Inhibition of Cell Proliferation

Curcumin preparations typically contain a mixture of polyphenols, collectively referred to as curcuminoids. In addition to the primary component curcumin, they also contain smaller amounts of the co-extracted derivatives demethoxycurcumin and bisdemethoxycurcumin. Curcuminoids can be differentially solubilized in serum, which allows for the systematic analysis of concentration-dependent cellular binding, biological effects, and metabolism. Technical grade curcumin was solubilized in fetal calf serum by two alternative methods yielding saturated preparations containing either predominantly curcumin (60%) or bisdemethoxycurcumin (55%). Continual exposure of NT2/D1 cells for 4–6 days to either preparation in cell culture media reduced cell division (1–5 µM), induced senescence (6–7 µM) or comprehensive cell death (8–10 µM) in a concentration-dependent manner. Some of these effects could also be elicited in cells transiently exposed to higher concentrations of curcuminoids (47 µM) for 0.5–4 h. Curcuminoids induced apoptosis by generalized activation of caspases but without nucleosomal fragmentation. The equilibrium binding of serum-solubilized curcuminoids to NT2/D1 cells incubated with increasing amounts of curcuminoid-saturated serum occurred with apparent overall dissociation constants in the 6–10 µM range. However, the presence of excess free serum decreased cellular binding in a hyperbolic manner. Cellular binding was overwhelmingly associated with membrane fractions and bound curcuminoids were metabolized in NT2/D1 cells via a previously unidentified reduction pathway. Both the binding affinities for curcuminoids and their reductive metabolic pathways varied in other cell lines. These results suggest that curcuminoids interact with cellular binding sites, thereby activating signal transduction pathways that initiate a variety of biological responses. The dose-dependent effects of these responses further imply that distinct cellular pathways are sequentially activated and that this activation is dependent on the affinity of curcuminoids for the respective binding sites. Defined serum-solubilized curcuminoids used in cell culture media are thus suitable for further investigating the differential activation of signal transduction pathways

Personalized early detection and prevention of breast cancer: ENVISION consensus statement

Abstract: The European Collaborative on Personalized Early Detection and Prevention of Breast Cancer (ENVISION) brings together several international research consortia working on different aspects of the personalized early detection and prevention of breast cancer. In a consensus conference held in 2019, the members of this network identified research areas requiring development to enable evidence-based personalized interventions that might improve the benefits and reduce the harms of existing breast cancer screening and prevention programmes. The priority areas identified were: 1) breast cancer subtype-specific risk assessment tools applicable to women of all ancestries; 2) intermediate surrogate markers of response to preventive measures; 3) novel non-surgical preventive measures to reduce the incidence of breast cancer of poor prognosis; and 4) hybrid effectiveness–implementation research combined with modelling studies to evaluate the long-term population outcomes of risk-based early detection strategies. The implementation of such programmes would require health-care systems to be open to learning and adapting, the engagement of a diverse range of stakeholders and tailoring to societal norms and values, while also addressing the ethical and legal issues. In this Consensus Statement, we discuss the current state of breast cancer risk prediction, risk-stratified prevention and early detection strategies, and their implementation. Throughout, we highlight priorities for advancing each of these areas

Oxygen desaturation during the six-minute walk test in COPD patients

Objective: To evaluate the behavior of oxygen saturation curves throughout the six-minute walk test (6MWT) in patients with COPD. Methods: We included 85 patients, all of whom underwent spirometry and were classified as having moderate COPD (modCOPD, n = 30) or severe COPD (sevCOPD, n = 55). All of the patients performed a 6MWT, in a 27-m corridor with continuous SpO2 and HR monitoring by telemetry. We studied the SpO2 curves in order to determine the time to a 4% decrease in SpO2, the time to the minimum SpO2 (Tmin), and the post-6MWT time to return to the initial SpO2, the last designated recovery time (RT). For each of those curves, we calculated the slope. Results: The mean age in the modCOPD and sevCOPD groups was 66 ± 10 years and 62 ± 11 years, respectively. At baseline, SpO2 was > 94% in all of the patients; none received supplemental oxygen during the 6MWT; and none of the tests were interrupted. The six-minute walk distance did not differ significantly between the groups. The SpO2 values were lowest in the sevCOPD group. There was no difference between the groups regarding RT. In 71% and 63% of the sevCOPD and modCOPD group patients, respectively, a ≥ 4% decrease in SpO2 occurred within the first minute. We found that FEV1% correlated significantly with the ΔSpO2 (r = −0.398; p < 0.001), Tmin (r = −0.449; p < 0.001), and minimum SpO2 (r = 0.356; p < 0.005). Conclusions: In the sevCOPD group, in comparison with the modCOPD group, SpO2 was lower and the Tmin was greater, suggesting a worse prognosis in the former