La glycation est un processus physiologique accru par l’hyperglycémie chronique. En cas de diabète, la glycation et l’oxydation induisent la formation de produits de la glycation avancée (Advanced Glycation End-products, AGEs), délétères pour les tissus. Du fait de leurs propriétés optiques, il est possible de mesurer l’autofluorescence cutanée (AF), corrélée aux concentrations tissulaires des AGEs. Cette mesure est de réalisation facile, et non invasive. L’AF est un marqueur de la mémoire métabolique, associé aux valeurs anciennes de l’HbA1c. Cependant, l’âge, la fonction rénale et l’hérédité influencent les valeurs d’AF. Elle est associée aux complications micro- et macroangiopathiques du diabète quel que soit leur type. En définitive, l’AF pourrait être utilisée comme marqueur prédictif précoce des complications du diabète. Même si son interprétation reste délicate, l’utilisation de l’AF en pratique courante serait possible afin d’optimiser la prise en charge du patient vers une médecine personnalisée.

Advanced glycation end-products play a role in diabetic vascular complications. Their optical properties allow to estimate their accumulation in tissues by measuring the skin autofluorescence (SAF). We searched for an association between SAF and major adverse cardiovascular events (MACE) incidence in subjects with Type 1 Diabetes (T1D) during a 7 year follow-up.

Background & aims: Eating habits may influence the life span and the quality of ageing process by modulating inflammation. The RISTOMED project was developed to provide a personalized and balanced diet, enriched with or without nutraceutical compounds, to decrease and prevent inflammageing, oxidative stress and gut microbiota alteration in healthy elderly people. This paper focused on the effect on inflammation and metabolism markers after 56 days of RISTOMED diet alone or supplementation with three nutraceutical compounds.Methods: A cohort of 125 healthy elderly subjects was recruited and randomized into 4 arms (Arm A, RISTOMED diet; Arm B, RISTOMED diet plus VSL#3 probiotic blend; Arm C, RISTOMED diet plus AISA d-Limonene; Arm D, RISTOMED diet plus Argan oil). Inflammatory and metabolism parameters as well as the ratio between Clostridium cluster IV and Bifidobacteria (CL/B) were collected before and after 56 days of dietary intervention, and their evolution compared among the arms. Moreover, participants were subdivided according to their baseline inflammatory parameters (erythrocytes sedimentation rate (ESR), C-Reactive Protein, fibrinogen, Tumor Necrosis Factor-alfa (TNF-alpha), and Interleukin 6) in two clusters with low or medium-high level of inflammation. The evolution of the measured parameters was then examined separately in each cluster.Results: Overall, RISTOMED diet alone or with each nutraceutical supplementation significantly decreased ESR. RISTOMED diet supplemented with d-Limonene resulted in a decrease in fibrinogen, glucose, insulin levels and HOMA-IR. The most beneficial effects were observed in subjects with a medium-high inflammatory status who received RISTOMED diet with AISA d-Limonene supplementation. Moreover, RISTOMED diet associated with VSL#3 probiotic blend induced a decrease in the CL/B ratio.Conclusions: Overall, this study emphasizes the beneficial anti-inflammageing effect of RISTOMED diet supplemented with nutraceuticals to control the inflammatory status of elderly individuals. (C) 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

POSTERSwas performed on whole blood specimens by a PCR-based restriction fragment length polymorphism assay, as previously described (Tanabe KK et al., JAMA 2008).Results: At presentation, BCLC stage and Child class were A (N = 51), B (N = 29), C (N = 18), D (N = 4), and A (N = 72), B (N = 26), and C (N = 4), respectively.The median number of tumor nodules was 1, and the largest median nodule size was 3.2 cm.The population was in Hardy-Weinberg equilibrium for rs4444903 (A/A: N = 34, A/G: N = 50, G/G: N = 18, variant allele frequency = 0.42).The age at diagnosis was younger in carriers of the variant allele, either analyzed genotypically (A/A vs. A/G vs. G/G, 74 vs. 69 vs. 67 years, p = 0.029) or by a dominant model (A/A vs. G/*, 74 vs. 69 years, p = 0.021).Gender, aetiology, presentation modality, follow-up duration, BCLC stage, Child class, nodule number, major nodule size, and serum alpha-fetoprotein had no association with rs4444903.At the end of follow-up, 38 patients had died (median survival time =48 months).At univariate analysis, survival probabilities were related to BCLC stage, major nodule size, Child class, and portal vein thrombosis presence and but not to rs4444903 alleles.The only independent predictors of survival at presentation were tumor size and number of tumor nodules.Conclusions: Carriers of the variant G allele at the rs4444903 SNP present with HCC on average five years earlier than carriers of the wild-type allele, suggesting that G carriers might benefit from entering a surveillance program at younger age.

POSTERSfor HCC are available only for patients with early stage tumors, so it is necessary to discover a precise method for detecting early stage HCC.MicroRNAs (miRNAs) play important roles in gene regulatory networks, and aberrant miRNA expression has been observed in human hepatocarcinogenesis.This study compared the expression of miRNA in surgically resected HCC tissues and surrounding nontumor tissue from 23 patients with early stage HCC.We also compared the expression of miRNA in serial stages of HCC in a mouse HCC model.This study looked for miRNAs that can be used as biomarkers of HCC.Methods: miRNAs were isolated from mouse liver tissues, surgically resected HCC tissues, and surrounding non-tumor tissues from 23 HCC patients and used to synthesize cDNA.We designed primers for 50 miRNAs, which were selected based on published microarray studies.We used SYBR Green quantitative RT-PCR (qRT-PCR) assays to compare the expression of miRNAs in HCC and surrounding non-HCC tissues in humans and in the mouse HCC model.Results: Six miRNAs were highly up-regulated in early stage HCC; miR-17-5p, 24, 25, 107, 221, and 222 were significantly up-regulated in 65, 61, 74, 65, 83, and 78% of the HCC samples, respectively.In more than 90% of the HCC samples (21 of 23 samples), at least one of miR-221 and miR-25 was up-regulated, as compared with adjacent non-tumor tissues.miR-17-5p, 24, 25, 221, and 222 were also significantly up-regulated in the mouse HCC model.In addition, miR-222 was progressively up-regulated with the stage of HCC in this model.Conclusions: We identified miRNAs that are significantly upregulated in early HCC.More than 90% of the patients with an early stage HCC had elevated expression of either miR-221 or miR-25, suggesting that the combination of these the two microRNAs might be an effective biomarker for detecting early HCC.In addition, miR-222 is suitable for determining the stage of HCC.

and were similar among older and younger adults (all p N 0.05). The subscales with the greatest improvement were social function and role function. Although 2MWT improved by 64% and 68% among younger and older patients (p = 0.69), improvements in grip strength and timed chair stands were much smaller (24% and 39% in younger adults, 15% and 18% in older adults, respectively). Patterns of recovery in physical performance were similar among older and younger adults (all p N 0.05). Results were similar when missing data were imputed. Conclusion: Survivors of AML after successful intensive chemotherapy achieve significant improvements in QOL, fatigue, and physical function by one year after diagnosis. The course of recovery is remarkably similar in younger and older AML patients, although significant attrition in older adults is a noteworthy limitation and fatigue improved less in older adults than younger adults. These data suggest that appropriately selected older patients generally recover as well as younger adults following IC for AML.

Le conseil diététique dans l’étude interventionnelle randomisée INOGAD reposait sur l’utilisation de fiches de conseil expliquées au patient lors d’entretien en face-à-face au cours des cures successives de chimiothérapie. L’objectif de cette étude ancillaire était d’en évaluer l’observance.

e19532 Background: Number of elderly people is growing and with them the possibility to develop cancer. Specific cares and particularly chemotherapy must allow to maintain their quality of life. Methods: From 2003 to 2006, cohort of 364 patients older than 70 years with cancer was evaluated by oncologist and geriatrician before chemotherapy in public and private hospitals in south-west of France. Quality of life of patients was appreciated by QLQ-C30 completion. Standard geriatric evaluation occurred and oncologic endpoints were collected . Global quality of life, functions and symptoms items were calculated according to Aaronson (JNCI 1993) using EORTC SAS Program provided. Results: Median age was 77.5 years [range 70-99.4] and sex ratio was 214/150 (M/F). Most of patients had metastatic status 65.6% (n = 231) among several cancer location. Creatinine clearance was <50ml/min in 42% (n = 153) and 29.9% presented one comorbidity grade 3-4 and 8.3% at least 2 comorbidities. Global quality of life was not related to age, cancer location and metastatic status. Global quality of life was associated with sex (p = 0.014), toxicities during treatment (0.014), weight loss (p<10-3), performance status (p<10-3) and death within 6 months of treatment beginning. Except for comorbidities, all elements from geriatric standard evaluation were linked significantly to global quality of life. All functions (physical, role, cognitive, emotional and social) were stronghtly associated with weight loss (<5%, 5 to 10%, >10%) (p<10-3) and MNA (≤23.5 vs >23.5) (p<10-3) as well as performance status (0-1 vs. >1) (p<10-3) and IADL (≤7 vs. >7) omitting emotion (p = 10-3). Most of symptoms were related to weight loss and MNA (excepted financial impact and dyspnea) (p = 10-3) and in majority (fatigue, pain, appetite loss) they were linked to poor performance status (p<10-3) and low IADL score (p = 10-3). Conclusions: Poor Global quality of life was correlated to poor scores of standard geriatric evaluation and early death. Altered functions and presence of symptoms were related to malnutrition status (weight loss, poor MNA) and loss of autonomy (poor performance status and low IADL). No significant financial relationships to disclose.

Au diagnostic, l'état nutritionnel des patients âgés peut avoir des conséquences sur l'évolution de la maladie cancéreuse et la tolérance au traitement. Nous avons souhaité évaluer l'impact de l'intervention nutritionnelle sur le pronostic des patients âgés cancéreux traités par chimiothérapie et à risque de dénutrition. Un essai randomisé en ouvert compare les soins usuels versus une intervention nutritionnelle comportant une consultation diététique basée sur le conseil à chaque cycle de traitement pendant 4 mois. Dix-neuf centres publics et privés du Grand Sud-Ouest doivent inclure 820 patients de plus de 70 ans. A cette étape de l'étude, 121 (46,3 %) avaient un cancer digestif : côlon 57,0 %, pancréas 28,1 %, estomac 10,7 % et primitif inconnu 4,1 %, selon le questionnaire MNA, 76 patients 62,7 % étaient à risque de dénutrition. L'âge moyen était de 77,9 ans, la proportion H/F était de 0,57. Le score OMS (0-1) était bon pour 70,2 %. Le taux moyen d'albumine était 35,8 g/l. Parmi eux, 54,4 % prenaient 4 médicaments ou plus. La moyenne de perte de poids était de 8,6 kg ou 13,0 %. Le stade de la maladie était avancé pour 66,1 %. La majorité des patients, 77,7 % recevaient une 1ère ligne de chimiothérapie. A chaque cycle des patients à risque, les prises alimentaires sur 24 heures ont été enregistrées. La diététicienne a rencontré tous les patients du bras intervention et les a contactés par téléphone si l'intercure était plus de 14 jours. Ces patients ont reçu une évaluation gérontologique testant la mémoire, la dépendance, le moral, la qualité de vie, les caractéristiques socio-démographiques au début et à la fin de l'étude. La réponse et la toxicité du traitement ont été enregistrées. La moyenne du score de screening du MNA (max 12) était de 8,2 pour tous les patients et 7,4 pour les patients à risque. Le score global (max 18) était de 12,9 et 12,5, le score total (max 30) 21,0 et 19,9 respectivement. Les enquêtes alimentaires ont été effectuées avant traitement, après 1 cycle et après 2 cycles pour 55,9 %. Initialement, la consommation en protéine était de 0,91 g/kg/J pour augmenter de 26,4 % et les prises totales étaient de 20,7 Kcal/kg/J augmentant de 22,2 % à la 2e évaluation. Le nombre de repas par jour augmentait de 3,7 à 4,3. La supplémentation orale était prise par 9 % des patients avant traitement et par 26,5 % au 2e enregistrement. Dans le groupe intervention nutritionnelle, la diététicienne a pu rencontrer 80,6 % des patients, 80,0 % et 84,4 % à la 1ère, 2ème et 3ème visite. Pour les patients concernés, le contact téléphonique a été effectif pour 58,3 % d'entre eux, 65,2 % et 61,9 % à la 1ère, 2ème et 3ème intercure. Près des deux-tiers des patients avec un cancer digestif traités par chimiothérapie étaient à risque de dénutrition selon le questionnaire du MNA. Le score de screening du MNA semble être un bon marqueur pour les identifier. Avant traitement, les prises alimentaires étaient en dessous des recommandations mais ont augmenté de plus de 20 % au cours du traitement. L'intervention diététique précoce peut potentialiser ces résultats et aider au management des toxicités induites par le traitement. Ce travail est financé par un PHRC, l'InCa, la ligue nationale contre le cancer.

Le but d'un essai clinique est d'évaluer un aspect particulier de l'effet d'un traitement, par exemple l'efficacité, en répondant à une question précise. La question posée ou objectif de l'étude est essentielle et son intérêt (clinique et en termes de santé publique) doit être certain. Elle doit être posée de façon précise, les précisions portant sur les modalités d'administration du médicament, les caractéristiques de la pathologie, le critère d'évaluation de l'efficacité, etc. On distingue différents types d'essais correspondant à différents objectifs que sont la détermination de paramètres pharmacocinétiques, l'évaluation de l'efficacité thérapeutique comparée, l'évaluation d'une forme galénique particulière, l'évaluation de la tolérance et l'évaluation d'effets indésirables rares. Les essais portant sur l'évaluation de l'efficacité d'un médicament comparativement à un placebo ou un médicament de référence sont les plus connus des cliniciens. Ces essais recouvrent globalement les différentes phases de développement d'un médicament, telles qu'elles sont définies et appliquées de façon réglementaire par les acteurs de l'industrie pharmaceutique. Nous rappelons ici les grandes caractéristiques de ces quatre phases en insistant sur quelques points pratiques. La méthodologie qui est commune à tous les types d'essais fait l'objet de développements ultérieurs.

La prévalence du surpoids et de l’obésité est en augmentation dans le monde depuis plusieurs décennies, chez les hommes comme chez les femmes. En France, la prévalence du surpoids chez les adultes atteint 49 % en 2015 (54 % des hommes et 44 % des femmes), dont 17 % d’obèses. D’après la dernière évaluation réalisée par le CIRC en 2017, le surpoids et l’obésité sont des facteurs de risque établis pour 13 localisations de cancers avec un risque de cancer chez les obèses variant fortement en fonction des localisations cancéreuses. En 2015 en France, on estime que 5,4 % des cancers étaient attribuables à l’excès de poids soit 18 600 cas, dont 3400 cancers du côlon, 2600 cancers du rein, 4500 cancers du sein et 2500 cancers de l’endomètre. L’obésité est aussi associée à un moins bon pronostic pour certains cancers, en particulier les cancers du sein et du côlon. L’obésité chez les enfants et les adolescents, en augmentation dans de nombreux pays, a également été associée à une augmentation du risque de cancer à l’âge adulte. L’obésité a pour origine principale un déséquilibre de la balance énergétique et est favorisée par un régime alimentaire riche en produits transformés, viande rouge, acides gras trans et saturés, boissons et aliments sucrés et pauvres en fruits et légumes, légumineuses et céréales complètes. Les principales recommandations nationales et internationales en matière de réduction de la prévalence de l’obésité préconisent donc de pratiquer une activité physique et d’avoir une alimentation équilibrée.In the past decades, obesity and overweight prevalence has been rising worldwide, in both men and women. In France, the prevalence of overweight in adults was 49% in 2015 (54% among men and 44% among women), including 17% of obese adults. According to the last evaluation performed by IARC in 2017, overweight and obesity are established risk factors for 13 cancer sites with risk estimates per 5 kg/m2 varying largely depending on the cancer site. In 2015 in France, 5.4% of cancer cases could be attributed to excess weight, corresponding to 18,600 cases, including 3400 colon cancers, 2600 kidney cancers, 4500 breast cancers and 2500 endometrial cancers. Obesity is also related to worse prognosis for some cancers, in particular breast and colon cancers. Obesity in children and adolescents, also rising in many countries, has also been associated to an increase in adult cancer risk. A major cause of obesity is a disequilibrium in energy balance favoured by a diet rich in processed food, red meat, trans and saturated fatty acids, sweetened foods and beverages and poor in fruits and vegetables, legumes and whole grains. Main national and international recommendations to reduce the prevalence of obesity are to have a balanced diet and regular physical activity.

COVID-19 vaccines show excellent efficacy in clinical trials and effectiveness in real-world data, but some people still become infected with SARS-CoV-2 after vaccination. This study aimed to identify risk factors for post-vaccination SARS-CoV-2 infection and describe the characteristics of post-vaccination illness.This prospective, community-based, nested, case-control study used self-reported data (eg, on demographics, geographical location, health risk factors, and COVID-19 test results, symptoms, and vaccinations) from UK-based, adult (≥18 years) users of the COVID Symptom Study mobile phone app. For the risk factor analysis, cases had received a first or second dose of a COVID-19 vaccine between Dec 8, 2020, and July 4, 2021; had either a positive COVID-19 test at least 14 days after their first vaccination (but before their second; cases 1) or a positive test at least 7 days after their second vaccination (cases 2); and had no positive test before vaccination. Two control groups were selected (who also had not tested positive for SARS-CoV-2 before vaccination): users reporting a negative test at least 14 days after their first vaccination but before their second (controls 1) and users reporting a negative test at least 7 days after their second vaccination (controls 2). Controls 1 and controls 2 were matched (1:1) with cases 1 and cases 2, respectively, by the date of the post-vaccination test, health-care worker status, and sex. In the disease profile analysis, we sub-selected participants from cases 1 and cases 2 who had used the app for at least 14 consecutive days after testing positive for SARS-CoV-2 (cases 3 and cases 4, respectively). Controls 3 and controls 4 were unvaccinated participants reporting a positive SARS-CoV-2 test who had used the app for at least 14 consecutive days after the test, and were matched (1:1) with cases 3 and 4, respectively, by the date of the positive test, health-care worker status, sex, body-mass index (BMI), and age. We used univariate logistic regression models (adjusted for age, BMI, and sex) to analyse the associations between risk factors and post-vaccination infection, and the associations of individual symptoms, overall disease duration, and disease severity with vaccination status.Between Dec 8, 2020, and July 4, 2021, 1 240 009 COVID Symptom Study app users reported a first vaccine dose, of whom 6030 (0·5%) subsequently tested positive for SARS-CoV-2 (cases 1), and 971 504 reported a second dose, of whom 2370 (0·2%) subsequently tested positive for SARS-CoV-2 (cases 2). In the risk factor analysis, frailty was associated with post-vaccination infection in older adults (≥60 years) after their first vaccine dose (odds ratio [OR] 1·93, 95% CI 1·50–2·48; p<0·0001), and individuals living in highly deprived areas had increased odds of post-vaccination infection following their first vaccine dose (OR 1·11, 95% CI 1·01–1·23; p=0·039). Individuals without obesity (BMI <30 kg/m2) had lower odds of infection following their first vaccine dose (OR 0·84, 95% CI 0·75–0·94; p=0·0030). For the disease profile analysis, 3825 users from cases 1 were included in cases 3 and 906 users from cases 2 were included in cases 4. Vaccination (compared with no vaccination) was associated with reduced odds of hospitalisation or having more than five symptoms in the first week of illness following the first or second dose, and long-duration (≥28 days) symptoms following the second dose. Almost all symptoms were reported less frequently in infected vaccinated individuals than in infected unvaccinated individuals, and vaccinated participants were more likely to be completely asymptomatic, especially if they were 60 years or older.To minimise SARS-CoV-2 infection, at-risk populations must be targeted in efforts to boost vaccine effectiveness and infection control measures. Our findings might support caution around relaxing physical distancing and other personal protective measures in the post-vaccination era, particularly around frail older adults and individuals living in more deprived areas, even if these individuals are vaccinated, and might have implications for strategies such as booster vaccinations.ZOE, the UK Government Department of Health and Social Care, the Wellcome Trust, the UK Engineering and Physical Sciences Research Council, UK Research and Innovation London Medical Imaging and Artificial Intelligence Centre for Value Based Healthcare, the UK National Institute for Health Research, the UK Medical Research Council, the British Heart Foundation, and the Alzheimer's Society.

Les résultats de la chimioembolisation sont décevants dans les études randomisées françaises. L'origine alcoolique fréquente de l'hépatopathie est souvent mise en avant comme explication. Nous avons comparé la survie globale après chimio-embolisation des patients avec consommation excessive d'alcool (> 40 g/j) ou non. 96 malades consécutifs ont reçu une chimioembolisation en première ligne de traitement palliatif dans notre service (2004-2008). Pour chaque patient ont été recueillis prospectivement les paramètres cliniques et biologiques, la consommation journalière d'alcool et le délai de sevrage lors du traitement. L'analyse statistique a utilisé la méthode de Kaplan-Meier, les tests du Khi-2, de log-rank et ANOVA. 96 patients (68 H, 64,6 ans (18-80)) ont reçu une chimioembolisation selective ou hyperselective pour 1 tumeur (49), 2-4 tumeurs (42) ou > 5 (7) de 46,3 cm de taille moyenne. Le score moyen de CHILD était 6,2 (5-11), du MELD 10,38 (4-22) du CLIP 1,5 (0-4) de l'index OMS 0,17 (0-1). Le suivi médian était de 12,2 mois [1,5-44,0]. 28 patients avaient une consommation inférieure à 40 g/j (Groupe A) et 68 > 40 g/j (Groupe B). Les deux groupes ne différaient pas en termes d'âge, sexe, de caractéristiques tumorales (nombre et taille de tumeur, taux d'αFP), de gravité d'hépatopathie sous-jacente (CHILD, MELD), d'état général (index OMS) de score du CLIP et BCLC. Les survies médianes n'étaient pas statistiquement différentes entre le groupe A (12,4 mois) et B (11,6 mois) (p = 0,95). Il n'existait pas non plus de différence de survie globale entre les patients sans consommation d'alcool (24 cas - 12,4 mois) les patients sevrés > 3 mois (40 cas-14,8 mois) et ceux non sevrés (32 cas - 9,6 mois) (p = 0,31). La survie médiane des patients non sevrés (32 cas) était cependant plus faible (9,6 mois contre 13,3 mois pour l'ensemble des autres patients) sans atteindre le seuil de significativité (p = 0,16) et ce malgré des caractéristiques tumorales et des scores de CHILD et MELD comparables au moment du traitement. L'origine alcoolique de la cirrhose n'influe pas sur les résultats de la chimioembolisation dans notre série et ne doit donc pas modifier les indications de traitement. La poursuite de la consommation alcoolique tend cependant à avoir un rôle délétère.

20568 Background: Treatment-related toxicity risk increases with age and may even lead to toxic death. Detailed evaluation of patient's status becomes mandatory. Comprehensive Geriatric assessment (CGA) is an adequate method to evaluate these patients but it is probably not necessary to all patients so that a screening tool should be developed. Methods: In a prospective multicentric cohort, we studied patients older than 70 with cancer and first-line chemotherapy. 364 patients were evaluated with the following CGA tools: MMS, ADL, IADL, MNA, Get up and go, GDS15, CIRSG, QLQ-C30. The data collected allowed us to perform an exploratory study in order to design a screening tool. Results: Analysis of this cohort allowed us to propose a new screening tool (generic name : G8), which included 7 MNA items (A, B, C, E, F, H, P) and age (<80, 80–85, >85), for a total score ranging from 0 (poor score) to 17 (good score). First, geriatrists and oncologists selected these specific items since they were expected to correlate with different dimensions of CGA. Indeed, we observed the following correlations: A (appetite), B (weight loss) and F (BMI) with total MNA score; E (cognition and depression) with MMS; C (motricity) and P (self-related health) with ADL; C with Get up and go; E and P with GDS15; H (medications) with CIRS-G. Next, we applied this new tool to our population of 364 patients. Results suggested that the area under the curve was maximized when the threshold was 14, equivalent to a 90% sensitivity, and a 60% specificity. Conclusions: This exploratory study allowed us to propose the G8 questionnaire as a screening tool for CGA. In collaboration with 15 geriatric French cancer units, we are now conducting a large prospective study (1500 patients) sponsored by the French National Cancer Institute in order to validate the G8 screening tool, as well as the VES-13 questionnaire, using the CGA as the gold- standard. Sponsored by PHRC, sanofi-aventis, AMGEN, Pfizer Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Amgen, Pfizer Oncology, sanofi-aventis