Reducing our environmental footprint and improving our health : Greenhouse gas emission and land use of usual diet and mortality in EPIC-NL: A prospective cohort study

Background: Food choices influence health status, but also have a great impact on the environment. The production of animal-derived foods has a high environmental burden, whereas the burden of refined carbohydrates, vegetables and fruit is low. The aim of this study was to investigate the associations of greenhouse gas emission (GHGE) and land use of usual diet with mortality risk, and to estimate the effect of a modelled meat substitution scenario on health and the environment. Methods: The usual diet of 40011 subjects in the EPIC-NL cohort was assessed using a food frequency questionnaire. GHGE and land use of food products were based on life cycle analysis. Cox proportional hazard ratios (HR) were calculated to determine relative mortality risk. In the modelled meat-substitution scenario, one-Third (35 gram) of the usual daily meat intake (105 gram) was substituted by other foods. Results: During a follow-up of 15.9 years, 2563 deaths were registered. GHGE and land use of the usual diet were not associated with all-cause or with cause-specific mortality. Highest vs. lowest quartile of GHGE and land use adjusted hazard ratios for all-cause mortality were respectively 1.00 (95% CI: 0.86-1.17) and 1.05 (95% CI: 0.89-1.23). Modelled substitution of 35 g/d of meat with vegetables, fruit-nuts-seeds, pasta-rice-couscous, or fish significantly increased survival rates (6-19%), reduced GHGE (4-11%), and land use (10-12%). Conclusions: There were no significant associations observed between dietary-derived GHGE and land use and mortality in this Dutch cohort. However, the scenario-study showed that substitution of meat with other major food groups was associated with a lower mortality risk and a reduced environmental burden. Especially when vegetables, fruit-nuts-seeds, fish, or pasta-rice-couscous replaced meat

Pretransplant Mobilization With Granulocyte Colony-Stimulating Factor Improves B-Cell Reconstitution by Lentiviral Vector Gene Therapy In Scid-X1 Mice

Hematopoietic stem cell (HSC) gene therapy is a demonstrated effective treatment for X-linked severe combined immunodeficiency (SCID-X1), but B-cell reconstitution and function has been deficient in many of the gene therapy treated patients. Cytoreductive preconditioning is known to improve HSC engraftment, but in general it is not considered for SCID-X1 since the poor health of most of these patients at diagnosis and the risk of toxicity preclude the conditioning used in standard bone marrow stem cell transplantation. We hypothesized that mobilization of HSC by granulocyte colony-stimulating factor (G-CSF) should create temporary space in bone marrow niches to improve engraftment and thereby B-cell reconstitution. In the present pilot study supplementing our earlier preclinical evaluation (Huston et al., 2011), Il2rg(-/-) mice pretreated with G-CSF were transplanted with wild-type lineage negative (Lin(-)) cells or Il2rg(-/-) Lin(-) cells transduced with therapeutic IL2RG lentiviral vectors. Mice were monitored for reconstitution of lymphocyte populations, level of donor cell chimerism, and antibody responses as compared to 2 Gy total body irradiation (TBI), previously found effective in promoting B-cell reconstitution. The results demonstrate that G-CSF promotes B-cell reconstitution similar to low-dose TBI and provides proof of principle for an alternative approach to improve efficacy of gene therapy in SCID patients without adverse effects associated with cytoreductive conditioning.Wo

Induction chemoradiation in stage IIIA/N2 non-small-cell lung cancer: a phase 3 randomised trial.

BACKGROUND: One of the standard options in the treatment of stage IIIA/N2 non-small-cell lung cancer is neoadjuvant chemotherapy and surgery. We did a randomised trial to investigate whether the addition of neoadjuvant radiotherapy improves outcomes. METHODS: We enrolled patients in 23 centres in Switzerland, Germany and Serbia. Eligible patients had pathologically proven, stage IIIA/N2 non-small-cell lung cancer and were randomly assigned to treatment groups in a 1:1 ratio. Those in the chemoradiotherapy group received three cycles of neoadjuvant chemotherapy (100 mg/m(2) cisplatin and 85 mg/m(2) docetaxel) followed by radiotherapy with 44 Gy in 22 fractions over 3 weeks, and those in the control group received neoadjuvant chemotherapy alone. All patients were scheduled to undergo surgery. Randomisation was stratified by centre, mediastinal bulk (less than 5 cm vs 5 cm or more), and weight loss (5% or more vs less than 5% in the previous 6 months). The primary endpoint was event-free survival. Analyses were done by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00030771. FINDINGS: From 2001 to 2012, 232 patients were enrolled, of whom 117 were allocated to the chemoradiotherapy group and 115 to the chemotherapy group. Median event-free survival was similar in the two groups at 12·8 months (95% CI 9·7-22·9) in the chemoradiotherapy group and 11·6 months (8·4-15·2) in the chemotherapy group (p=0·67). Median overall survival was 37·1 months (95% CI 22·6-50·0) with radiotherapy, compared with 26·2 months (19·9-52·1) in the control group. Chemotherapy-related toxic effects were reported in most patients, but 91% of patients completed three cycles of chemotherapy. Radiotherapy-induced grade 3 dysphagia was seen in seven (7%) patients. Three patients died in the control group within 30 days after surgery. INTERPRETATION: Radiotherapy did not add any benefit to induction chemotherapy followed by surgery. We suggest that one definitive local treatment modality combined with neoadjuvant chemotherapy is adequate to treat resectable stage IIIA/N2 non-small-cell lung cancer. FUNDING: Swiss State Secretariat for Education, Research and Innovation (SERI), Swiss Cancer League, and Sanofi