Effect of betaine, C-phycocyanin or physical activity on tumour growth of lung cancer in rats

SESSION 2 - NUTRITIONAL CARE AND PHYSICAL ACTIVITY FOR CANCER PATIENTOxidative stress seems to play a crucial role as a secondary messenger in the regulation of several cellular processes such as apoptosis, survival and proliferation, and could be involved in all steps of the lung carcinogenesis (i.e.initiation, promotion and progression). Physical activity and nutrition are two factors able to modulate oxidative stress and associated mechanisms. Betaine and C-phycocyanin are two known micronutrients having antioxidant, anti-inflammatoryand anti-proliferative effects. Previously, our team showed that betaine and/or C-phycocyanin treatment decreased the viability of A549 cells in vitro (pulmonary adenocarcinoma cell line).The main objective of this work was to evaluate the effect of nutritional factors (betaine, C-phycocyanin or physical activity) on growth of implanted A549 cells in Nude rats and to determine underlying mechanisms. Firstly, we showed that these two micronutrients, whether associated or supplied separately, slowed down the lung tumour growth through similar mechanisms (NF-B activation and increase of lipid peroxidation and expression of proinflammatory cytokines (IL-1, Cox-2 et TNF-) in tumour). Also, some mechanisms were specific for each micronutrient or their combination. C-phycocyanin induced a decrease of phosphorylated AKT / total AKT ratio, and an increase of phosphorylated p38 / total p38 ratio, both mechanisms promoting apoptosis and autophagy. On the other hand, betaine associated with C-phycocyanin increased caspase-3 / pro-caspase-3 ratio. Secondly, we studied the effect of voluntary physical activity on growth of implanted A549 cells in Nude rats. We showed that voluntary physical activity slowed down the lung tumour growth, without significant difference if animals were supplied with betaine or/and C-phycocyanin. It seems that the increase of lipid peroxidation, NF-B and p38 activation, and AKT inhibition, all having a role in promotion of a cell death, are responsible for the tumour growth slowdown followingthe physical activity. Diet enriched with betaine or/and C-phycocyanin slows down the growth of pulmonary adenocarcinoma cells implanted in rats, suggesting their interest in anti-cancer activity. Physical activity seems to act on similar mechanisms as these micronutrients. Our results have to be confirmed with further studies, but are already suggesting a potential application in lung cancer patient

Effect of early postextubation high-flow nasal cannula vs conventional oxygen therapy on hypoxaemia in patients after major abdominal surgery: a French multicentre randomised controlled trial (OPERA)

International audienc

Three Versus 6 Months of Oxaliplatin-Based Adjuvant Chemotherapy for Patients With Stage III Colon Cancer: Disease-Free Survival Results From a Randomized, Open-Label, International Duration Evaluation of Adjuvant (IDEA) France, Phase III Trial

IF 26.303 (2017)International audiencePurpose : Reduction of adjuvant treatment duration may decrease toxicities without loss of efficacy in stage III colon cancer. This could offer clear advantages to patients and health care providers. Methods : In International Duration Evaluation of Adjuvant Chemotherapy (IDEA) France, as part of the IDEA international collaboration, patient with colon cancer patients were randomly assigned to 3 and 6 months of modified FOLFOX6 (mFOLFOX6: infusional fluorouracil, leucovorin, and oxaliplatin) or capecitabine plus oxaliplatin (CAPOX) by physician choice. The primary end point was disease-free survival (DFS), and analyses were descriptive. Results : A total of 2,010 eligible patients received either 3 or 6 months of chemotherapy (modified intention-to-treat population); 2,000 (99%) had stage III colon cancer (N1: 75%, N2: 25%); 1,809 (90%) received mFOLFOX6, and 201 (10%) received CAPOX. The median age was 64 years, and the median follow-up time was 4.3 years. Overall, 94% (3 months) and 78% (6 months) of patients completed treatment (fluoropyrimidines ± oxaliplatin). Maximal grade 2 and 3 neuropathy rates were 28% and 8% in the 3-month arm and 41% and 25% in the 6-month arm ( P < .001). Final rates of residual neuropathy greater than grade 1 were 3% in the 3-month arm and 7% in the 6-month arm ( P < .001). There were 578 DFS events: 314 and 264 in the 3- and 6-month arms, respectively. The 3-year DFS rates were 72% and 76% in the 3- and 6-month arms, respectively (hazard ratio [HR], 1.24; 95% CI, 1.05 to 1.46; P = .0112). In the 3 and 6-month arms, respectively, for patients who received mFOLFOX6, the 3-year DFS rates were 72% and 76% (HR, 1.27; 95% CI, 1.07 to 1.51); for the T4 and/or N2 population, they were 58% and 66% (HR, 1.44; 95% CI, 1.14 to 1.82); and for the T1-3N1 population, they were 81% and 83% (HR, 1.15; 95% CI, 0.89 to 1.49). Conclusion : IDEA France, in which 90% of patients received mFOLFOX6, shows superiority of 6 months of adjuvant chemotherapy compared with 3 months, especially in the T4 and/or N2 subgroups. These results should be considered alongside the international IDEA collaboration data

French National Retrospective Cohort of Hairy-Cell Leukemias: Risk of Second Malignancies after 10 Years of Follow-up

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Hematopoietic stem cell transplantation in 29 patients hemizygous for hypomorphic IKBKG/NEMO mutations

X-linked recessive ectodermal dysplasia with immunodeficiency is a rare primary immunodeficiency caused by hypomorphic mutations of the IKBKG gene encoding the nuclear factor kappa B essential modulator (NEMO) protein. This condition displays enormous allelic, immunological, and clinical heterogeneity, and therapeutic decisions are difficult because NEMO operates in both hematopoietic and nonhematopoietic cells. Hematopoietic stem cell transplantation (HSCT) is potentially life-saving, but the small number of case reports available suggests it has been reserved for only the most severe cases. Here, we report the health status before HSCT, transplantation outcome, and clinical follow-up for a series of 29 patients from unrelated kindreds from 11 countries. Between them, these patients carry 23 different hypomorphic IKBKG mutations. HSCT was performed from HLA-identical related donors (n = 7), HLA-matched unrelated donors (n = 12), HLA-mismatched unrelated donors (n = 8), and HLA-haploidentical related donors (n = 2). Engraftmentwas documented in 24 patients, and graft-versus-host disease in 13 patients. Up to 7 patients died 0.2 to 12 months after HSCT. The global survival rate after HSCT among NEMO-deficient children was 74% at a median follow-up after HSCT of 57months (range, 4-108 months). Preexisting mycobacterial infection and colitis were associated with poor HSCT outcome. The underlyingmutation does not appear to have any influence, as patients with the same mutation had different outcomes. Transplantation did not appear to cure colitis, possibly as a result of cell-intrinsic disorders of the epithelial barrier. Overall, HSCT can cure most clinical features of patients with a variety of IKBKG mutations.St. Giles FoundationRockefeller UniversityINSERMParis Descartes UniversityCentre de Reference des Deficits Immunitaires Hereditaires (CEREDIH)German Ministry for Education and ResearchNational Institute for Health Research and GOSH Biomedical Research CentreRobert A. Good/Jeffrey Modell FellowshipNecker Hosp Sick Children, AP HP, Study Ctr Immunodeficiencies, Paris, FranceTokyo Med & Dent Univ, Dept Pediat & Dev Biol, Tokyo, JapanNiigata Univ, Grad Sch Med & Dent Sci, Dept Pediat, Niigata, JapanAnn & Robert H Lurie Childrens Hosp Chicago, Div Pediat Dermatol, Chicago, IL 60611 USANorthwestern Univ, Dept Pediat, Feinberg Sch Med, Chicago, IL 60611 USACincinnati Childrens Hosp, Med Ctr, Bone Marrow Transplantat & Immune Deficiency, Cincinnati, OH USAKyoto Univ, Grad Sch Med, Dept Pediat, Kyoto, JapanHirosaki Univ, Grad Sch Med, Dept Pediat, Hirosaki, Aomori, JapanUniv Hosp, Pediat Oncohematoimmunol Unit, Angers, FranceUniv Lyon 1, Sch Med, Genet Unit, Hosp Civils Lyon, Bron, FranceEmory Univ, Dept Pediat, Div Bone Marrow Transplant, Aflac Canc & Blood Disorders Ctr Childrens Hlth, Atlanta, GA 30322 USAUniv Zurich, Univ Childrens Hosp Zurich, Div Stem Cell Transplantat, Zurich, SwitzerlandUniv Hosp, Dept Biochem & Genet, Angers, FranceNatl Inst Pediat, Clin Immunol Dept, Mexico City, DF, MexicoNatl Inst Pediat, Program Hematopoiet Stem Cell Transplantat, Mexico City, DF, MexicoUCL, Great Ormond St Inst Child Hlth, London, EnglandNatl Jewish Hlth, Dept Pediat, Immunodeficiency Diag & Treatment Program, Denver, CO USAOregon Hlth & Sci Univ, Dept Pediat Dermatol, Portland, OR 97201 USAStarship Hosp, Starship Blood & Canc Ctr, Paediat Haematol, Auckland, New ZealandUniv Wales Hosp, Immunodeficiency Ctr Wales, Cardiff, S Glam, WalesUniv Freiburg, Ctr Chron Immunodeficiency, Freiburg, GermanyNewcastle Univ, Inst Cellular Med, Primary Immunodeficiency Grp, Newcastle Upon Tyne, Tyne & Wear, EnglandNewcastle Tyne Hosp NHS Fdn Trust, Great North Childrens Hosp, Paediat Immunol Dept, Newcastle Upon Tyne, Tyne & Wear, EnglandUniv Fed Sao Paulo, Inst Biomed Sci, Dept Pediat, Sao Paulo, BrazilUniv Fed Sao Paulo, Inst Biomed Sci, Dept Immunol, Sao Paulo, BrazilGreat Ormond St Hosp Children NHS Fdn Trust, Blood & Marrow Transplant Unit, London, EnglandNIAID, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USANIH, Dept Lab Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USAParis Descartes Univ, Imagine Inst, Paris, FranceNecker Hosp Sick Children, AP HP, Pediat Hematol Immunol & Rheumatol Unit, Paris, FranceCambridge Biomed Res Ctr, Natl Inst Hlth Res, Cambridge, EnglandOxford Univ Hosp NHS Fdn Trust, Natl Inst Hlth Res, Oxford Biomed Res Ctr, Oxford, EnglandNecker Hosp Sick Children, INSERM, UMR1163, Lab Human Genet Infect Dis,Necker Branch, Paris, FranceRockefeller Univ, St Giles Lab Human Genet Infect Dis, Rockefeller Branch, 1230 York Ave, New York, NY 10021 USAHoward Hughes Med Inst, New York, NY USATexas Childrens Hosp, Baylor Coll Med, Sect Immunol Allergy & Rheumatol, Ctr Human Immunobiol, Houston, TX 77030 USAUniv Fed Sao Paulo, Inst Biomed Sci, Dept Pediat, Sao Paulo, BrazilUniv Fed Sao Paulo, Inst Biomed Sci, Dept Immunol, Sao Paulo, BrazilWeb of Scienc

Human genetic and immunological determinants of critical COVID-19 pneumonia

SARS-CoV-2 infection is benign in most individuals but, in around 10% of cases, it triggers hypoxaemic COVID-19 pneumonia, which leads to critical illness in around 3% of cases. The ensuing risk of death (approximately 1% across age and gender) doubles every five years from childhood onwards and is around 1.5 times greater in men than in women. Here we review the molecular and cellular determinants of critical COVID-19 pneumonia. Inborn errors of type I interferons (IFNs), including autosomal TLR3 and X-chromosome-linked TLR7 deficiencies, are found in around 1-5% of patients with critical pneumonia under 60 years old, and a lower proportion in older patients. Pre-existing auto-antibodies neutralizing IFN alpha, IFN beta and/or IFN omega, which are more common in men than in women, are found in approximately 15-20% of patients with critical pneumonia over 70 years old, and a lower proportion in younger patients. Thus, at least 15% of cases of critical COVID-19 pneumonia can be explained. The TLR3- and TLR7-dependent production of type I IFNs by respiratory epithelial cells and plasmacytoid dendritic cells, respectively, is essential for host defence against SARS-CoV-2. In ways that can depend on age and sex, insufficient type I IFN immunity in the respiratory tract during the first few days of infection may account for the spread of the virus, leading to pulmonary and systemic inflammation

Low incidence of SARS-CoV-2, risk factors of mortality and the course of illness in the French national cohort of dialysis patients

International audienceThe aim of this study was to estimate the incidence of COVID-19 disease in the French national population of dialysis patients, their course of illness and to identify the risk factors associated with mortality. Our study included all patients on dialysis recorded in the French REIN Registry in April 2020. Clinical characteristics at last follow-up and the evolution of COVID-19 illness severity over time were recorded for diagnosed cases (either suspicious clinical symptoms, characteristic signs on the chest scan or a positive reverse transcription polymerase chain reaction) for SARS-CoV-2. A total of 1,621 infected patients were reported on the REIN registry from March 16th, 2020 to May 4th, 2020. Of these, 344 died. The prevalence of COVID-19 patients varied from less than 1% to 10% between regions. The probability of being a case was higher in males, patients with diabetes, those in need of assistance for transfer or treated at a self-care unit. Dialysis at home was associated with a lower probability of being infected as was being a smoker, a former smoker, having an active malignancy, or peripheral vascular disease. Mortality in diagnosed cases (21%) was associated with the same causes as in the general population. Higher age, hypoalbuminemia and the presence of an ischemic heart disease were statistically independently associated with a higher risk of death. Being treated at a selfcare unit was associated with a lower risk. Thus, our study showed a relatively low frequency of COVID-19 among dialysis patients contrary to what might have been assumed