Malnutrition as assessed by nutritional risk index is associated with worse outcome in patients admitted with acute decompensated heart failure: an ACAP-HF data analysis

Malnutrition is common at hospital admission and tends to worsen during hospitalization. This controlled population study aimed to determine if serum albumin or moderate and severe nutritional depletion by Nutritional Risk Index (NRI) at hospital admission are associated with increased length of hospital stay (LOS) in patients admitted with acute decompensated heart failure (ADHF). Serum albumin levels and lymphocyte counts were retrospectively determined at hospital admission in 1740 consecutive patients admitted with primary and secondary diagnosis of ADHF. The Nutrition Risk Score (NRI) developed originally in AIDS and cancer populations was derived from the serum albumin concentration and the ratio of actual to usual weight, as follows: NRI = (1.519 × serum albumin, g/dL) + {41.7 × present weight (kg)/ideal body weight(kg)}. Patients were classified into four groups as no, mild, moderate or severe risk by NRI. Multiple logistic regressions were used to determine the association between nutritional risk category and LOS

Application of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trials

Stromal tumor-infiltrating lymphocytes (sTILs) are a potential predictive biomarker for immunotherapy response in metastatic triple-negative breast cancer (TNBC). To incorporate sTILs into clinical trials and diagnostics, reliable assessment is essential. In this review, we propose a new concept, namely the implementation of a risk-management framework that enables the use of sTILs as a stratification factor in clinical trials. We present the design of a biomarker risk-mitigation workflow that can be applied to any biomarker incorporation in clinical trials. We demonstrate the implementation of this concept using sTILs as an integral biomarker in a single-center phase II immunotherapy trial for metastatic TNBC (TONIC trial, NCT02499367), using this workflow to mitigate risks of suboptimal inclusion of sTILs in this specific trial. In this review, we demonstrate that a web-based scoring platform can mitigate potential risk factors when including sTILs in clinical trials, and we argue that this framework can be applied for any future biomarker-driven clinical trial setting

European paradoxes of coronary heart disease Developing new markers of vitamin E status

SIGLEAvailable from British Library Document Supply Centre-DSC:DXN010028 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Cigarette smokers have decreased lymphocyte and platelet alpha-tocopherol levels and increased excretion of the gamma-tocopherol metabolite gamma-carboxyethyl-hydroxychroman (gamma-CEHC)

Cigarette smoking is associated with increased oxidative stress and increased risk of degenerative disease. As the major lipophilic antioxidant, requirements for vitamin E may be higher in smokers due to increased utilisation. In this observational study we have compared vitamin E status in smokers and non-smokers using a holistic approach by measuring plasma, erythrocyte, lymphocyte and platelet alpha- and gamma-tocopherol, as well as the specific urinary vitamin E metabolites alpha- and gamma-carboxyethylhydroxychroman (CEHC). Fifteen smokers (average age 27 years, smoking time 7.5 years) and non-smokers of comparable age, gender and body mass index (BMI) were recruited. Subjects completed a 7-day food diary and on the final day they provided a 24 h urine collection and a 20 ml blood sample for measurement of urinary vitamin E metabolites and total vitamin E in blood components, respectively. No significant differences were found between plasma and erythrocyte alpha- and gamma-tocopherol in smokers and non-smokers. However, smokers had significantly lower ce-tocopherol (mean +/-SD, 1.34+/-0.31 mumol/g protein compared with 1.94+/-0.54, P = 0.001) and gamma-tocopherol (0.19 +/- 0.04 mumol/g protein compared with 0.26 +/- 0.08, P = 0.026) levels in their lymphocytes, as well as significantly lower (alpha-tocopherol levels in platelets (1.09 +/- 0.49 mumol/g protein compared with 1.60 +/- 0.55, P = 0.014; gamma-tocopherol levels were similar). Interestingly smokers also had significantly higher excretion of the urinary gamma-tocopherol metabolite, gamma-CEHC (0.49 +/- 0.25 mg/g creatinine compared with 0.32 +/- 0.16, P = 0.036) compared to non-smokers, while their (alpha-CEHC (metabolite of a-tocopherol) levels were similar. There was no significant difference between plasma ascorbate, urate and F-2-isoprostane levels. Therefore in this population of cigarette smokers (mean age 27 years, mean smoking duration 7.5 years), alterations to vitamin E status can be observed even without the more characteristic changes to ascorbate and F-2-isoprostanes. We suggest that the measurement of lymphocyte and platelet vitamin E may represent a valuable biomarker of vitamin E status in relation to oxidative stress conditions

Mode de vie et cancer du sein: quels conseils pour la prise en charge de l’après cancer ?

National audienceIt is widely admitted that after adjuvant therapy, about one half of women with localized breast cancer experience a weight gain of 3 kg. It can however reach 8 to 10 kg in numerous cases. Risk factors associated with weight gain are unclear, but women undergoing chemotherapy seem to have an increased risk, especially before the menopause. Retrospective studies suggest that post-treatment weight gain mightincrease the risk of relapse. Furthermore, the only intervention trial in adjuvant breast cancer, though impaired by methodological pitfalls, suggests that limiting weight gain could increase disease free survival. The use of nutritional complements by cancer patients is usually underestimated. Several compounds, such as vitamins C and, E, selenium or carotenoids, have been investigated in clinical trials whose quality is usually poor. Available date nevertheless suggest a deleterious effect of supplementation with anti-oxydants, in particular at supraphysiological doses. The WHEL trial is the only large randomised trial investigating an healthy diet with vegetables, fruits and fiber after localized breast cancer. An effect of survival is observed in the experimental arm only in patients with sufficient level of physical activity. Physical activity, when practiced regularly, improves asthenia, quality of life and even survival, without any detrimental effect. It should however be initiated after an evaluation of patient’s ability and comorbidities, and be realized in specific centers with careful medical follow-up. Its mechanisms of action include regulation of estrogen, insulin, IGF1 and adipokines. Adapted physical activity should be proposed to patients fulfilling precise inclusion criteria.On estime que près de la moitié des femmes traitées pour un cancer du sein localisé sont affectées par un gain de l’ordre de 3 kg, mais des prises de poids de l’ordre de 8 à 10 kg ne sont pas exceptionnelles. Les facteurs de risque ne sont pas clairement individualisés, mais les patientes recevant une chimiothérapie semblent plus concernées, en particulier avant la ménopause. Les études rétrospectives montrent que la prise de poids pourrait être un facteur de risque de rechute, qui plus est, le seules said’ intervention actuellement publié dans le cancer du sein, bien que sujet à des critiques d’ordre méthodologique, suggère un effet positif de la réduction du surpoids sur la survie sans récidive. L’utilisation de compléments nutritionnels par les patients est, quant à elle, largement sous-estimée. De nombreux composés ont fait l’objet d’essais cliniques dont la méthodologie est globalement peu convaincante (vitamines C et E, sélénium, caroténoïdes). Les données disponibles suggèrent un effet négatif de la supplémentation en antioxydants(en particulier à des doses supra-physiologiques) pouvant éventuellement affecter l’efficacité du traitement antitumoral. L’essai WHEL (Women’s Healthy Eating and Living) est le seul grand essai randomisé d’intervention, basé sur une supplémentation en fruits et légumes après traitement d’un cancer du sein localisé : il suggère un effet positif de la supplémentation uniquement si elle est associée à une activité physique suffisante. L’ activité physique régulière lors des soins en cancérologie améliore la qualité de vie, la fatigue, la survie, enparticulier pour les patientes por-teuses de cancer du sein, et ce, sans effet secondaire à condition d’être mise en place après un bilan précis des capacités, des comorbidités, d’être réalisée dans des structures adaptées avec un suivi médical des progrès et des difficultés. Les mécanismes d’action passent par des modifications de sécrétion d’estrogène, d’insuline, d’IGF1 et des adipokines. L’activité physique adaptée en cancérologie doit être proposée aux malades répondant à des critères d’inclusion précis