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Background Diffuse large B cell lymphoma (DLBCL) is an aggressive disease. The first-line treatment is well defined in young patients, however in oldest old patients treatment remains unclear. Objectives To investigate the impact of therapeutics management and geriatric evaluation on survival in aged patients with DLBCL. Methods We performed a systematic review of PUBMED and COCHRANE databases of published report on elderly patients (median age 80 and above) with DLBCL, from January 2002 to January 2020. Results We included 32 studies (6 prospective and 26 retrospective). Patients treated with anthracyclines-containing chemoimmunotherapy had a two-years overall survival (OS) of 59% to 74.3% in prospective studies, and 48.1 to 64.6% in retrospective studies. With less intensive treatment without anthracyclines, two-years OS was 28% to 53%. Without specific treatment, median OS was two months. History of falls and severe comorbidities were associated with a decrease survival. Conclusions Chemoimmunotherapy with anthracyclines increase survival in selected very elderly patients in compared to less intensive regimen. Geriatric assessment, in particular altered mobility disorders and severe comorbidities, are predictive of survival and should be associated to the therapeutic decision. More comparative studies are needed to guide the management of frailer patients.

Background Pazopanib is a tyrosine kinase inhibitor given at the approved dose of 800 mg orally once daily (OD), but often requiring individual dose adjustment due to toxicity. Limited data is available to guide prescription in older patients especially the unfit according to geriatric assessment. Patients and methods VOTRAGE is a 3 + 3 dose-escalation, open-label phase I trial of continuous OD oral administration of pazopanib to evaluate safety, PK and PD data in unfit older patients with advanced solid tumors. The primary objective was to determine the maximum tolerated dose (MTD). PK data were compared with those obtained in younger adult patients in a population PK analysis. Results Eighteen patients with a median age of 82.5 years (range 75–91) were included in three dosing cohorts (400, 600, and 800 mg daily). Three dose-limiting toxicities (DLT) were observed in five patients at 800 mg and one DLT at 600 mg in six evaluable patients. MTD was defined as level 2 dose (600 mg). Individual oral clearance was not correlated with age. A relationship was observed between the occurrence of DLT and pazopanib plasma exposure. Decreased oral bioavailability of pazopanib when given with proton-pump inhibitors was confirmed in this group of patients. Conclusion We recommend performing geriatric assessment in patients older than 75 and starting pazopanib at 600 mg per day in unfit older patients. Therapeutic drug monitoring appears very helpful in this population.

Objective Hematological treatment decisions in older adults with hematological malignancies are complex. Our objective is to study the impact of a comprehensive geriatric assessment on hematological treatment decision in older patients and the factors associated with change in treatment plan. Methods We conducted a cross-sectional analysis of patients aged 65 years and above with hematological malignancies, hospitalized between 2008 and 2019 at the University Cancer Institute of Toulouse. They were assessed by a geriatrician/nurse team using a comprehensive geriatric assessment (CGA). A penalized logistic regression model with elastic net regularization was used to identify factors associated with change in hematological treatment plan. Results A total of 424 patients were included. Main hematological malignancies were lymphoma (36.1 %), acute myeloid leukemia (26.9 %) and myelodysplastic syndrome (19.8%). Change in hematological treatment plan was suggested after CGA for 92 patients (21.7%). Factors associated with change in treatment plan were functional impairment according to ADL and IADL scale, mobility impairment, the presence of comorbidity defined by the Charlson score > 1 and increasing age. Conclusion A CGA has a significant impact on hematological treatment decision in older patients. Functional and mobility impairment, comorbidities and age are predictive factors of change in treatment plan.

The implementation of cross-functional measures along the care pathway of cancer patients in France is globally lower in the elderly. However, age is not a criterion for excluding curative treatment, and the evaluation of physical, psychological and social resources and comorbidities is particularly significant in this population. Identifying needs in terms of support care which influences the patient's quality of life as well as the efficacy of treatments is also essential. The objective of geriatric oncology coordination is to offer elderly cancer patients global treatment, curative or otherwise, through the putting in place of a personalised care programme.

Recent European Society of Parenteral and Enteral Nutrition guidelines highlighted the interest of prevention, diagnosis and treatment of malnutrition in the management of coronavirus disease 19 (COVID-19) patients. The aim of our study was to evaluate the prevalence of malnutrition in patients hospitalised for COVID-19. In a prospective observational cohort study malnutrition was diagnosed according to the Global Leadership Initiative on Malnutrition (GLIM) two-step approach. Patients were divided into two groups according to the diagnosis of malnutrition. Covariate selection for the multivariate analysis was based on P n 46, 57·5 %) was similar in the two groups. Three patients who died (3·75 %) were malnourished. Multivariate analysis exhibited that low BMI (OR 0·83, 95 % CI 0·73, 0·96, P = 0·0083), dyslipidaemia (OR 29·45, 95 % CI 3·12, 277·73, P = 0·0031), oral intake reduction P = 0·0422) and glomerular filtration rate (Chronic Kidney Disease Epidemiology Collaboration; CKD-EPI) at admission (OR 0·979, 95 % CI 0·96, 0·998, P = 0·0297) were associated with the occurrence of malnutrition. We demonstrate the existence of a high prevalence of malnutrition in a general cohort of COVID-19 inpatients according to GLIM criteria. Nutritional support in COVID-19 care seems an essential element.

Background The effects of SARS-CoV-2 (COVID-19) on the myocardium and their role in the clinical course of infected patients are still unknown. The severity of SARS-CoV-2 is driven by hyperinflammation, and the effects of SARS-CoV-2 on the myocardium may be significant. This study proposes to use bedside observations and biomarkers to characterize the association of COVID-19 with myocardial injury. Objective The aim of the study is to describe the myocardial function and its evolution over time in patients infected with SARS-CoV-2 and to investigate the link between inflammation and cardiac injury. Methods This prospective, monocentric, observational study enrolled 150 patients with suspected or confirmed SARS-CoV-2 infection at Toulouse University Hospital, Toulouse, France. Patients admitted to the intensive care unit (ICU), regular cardiologic ward, and geriatric ward of our tertiary university hospital were included during the pandemic period. Blood sampling, electrocardiography, echocardiography, and morphometric and demographic data were prospectively collected. Results A total of 100 patients were included. The final enrolment day was March 31, 2020, with first report of results at the end of the first quarter of 2021. The first echocardiographic results at admission of 31 patients of the COCARDE-ICU substudy population show that biological myocardial injury in COVID-19 has low functional impact on left ventricular systolic function. Conclusions A better understanding of the effects of COVID-19 on myocardial function and its link with inflammation would improve patient follow-up and care. Trial Registration Clinicaltrials.gov NCT04358952; https://clinicaltrials.gov/ct2/show/NCT04358952 International Registered Report Identifier (IRRID) DERR1-10.2196/24931

(1) Background: COVID-19 has become a global pandemic and older patients present higher mortality rates. However, studies on the characteristics of this population set are limited. The objective of this study is to describe clinical characteristics and outcomes of older patients hospitalized with COVID-19. (2) Methods: This retrospective cohort study was conducted from March to May 2020 and took place in three acute geriatric wards in France. Older patients hospitalized for COVID-19 infections were included. We collected clinical, radiological, and laboratory outcomes. (3) Results: Ninety-four patients were hospitalized and included in the final analysis. Mean age was 85.5 years and 55% were female. Sixty-four (68%) patients were confirmed COVID-19 cases and 30 (32%) were probable. A majority of patients were dependent (77%), 45% were malnourished, and the mean number of comorbidities was high in accordance with the CIRS-G score (12.3 &plusmn, 25.6). The leading causes of hospitalization were fever (30%), dyspnea (28%), and geriatric syndromes (falls, delirium, malaise) (18%). Upon follow-up, 32% presented acute respiratory failure and 30% a geriatric complication. Frailty and geriatric characteristics were not correlated with mortality. Acute respiratory failure (p = 0.03) and lymphopenia (p = 0.02) were significantly associated with mortality. (4) Conclusions: Among older patients hospitalized with COVID-19, clinical presentations were frequently atypical and complications occurred frequently. Frailty and geriatric characteristics were not correlated with mortality.

International audience; Frailty is known to predict dementia. However, its link with neurodegenerative alterations of the central nervous system(CNS) is not well understood at present. We investigated the association between the biomechanical response of the CNS and frailty in older adults suspected of normal pressure hydrocephalus (NPH) presenting with markers of multiple co-existing pathologies. The biomechanical response of the CNS was characterized by the CNS elastance coefficient inferred from phase contrast magnetic resonance imaging and intracranial pressure monitoring during a lumbar infusion test. Frailty was assessed with an index of health deficit accumulation. We found a significant association between the CNS elastance coefficient and frailty, with an effect size comparable to that between frailty and age, the latter being the strongest known risk factor for frailty. Results were independent of CSF dynamics, showing that they are not specific to the NPH neuropathological condition. The CNS biomechanical characterization may help to understand how frailty is related to neurodegeneration and detect the shift from normal to pathological brain ageing.

Objectives To examine frailty determinants differences in patients with a recent diagnosis of cancer compared to non-cancer patients among older adult. Revealing those differences will allow us to individualize the exact frailty management in those patients diagnosed with cancer. Design This is an observational cross-sectional, monocentric study. Setting Patients were evaluated at the Geriatric Frailty Clinic (GFC), in the Toulouse University Hospital, France, between October 2011 and February 2016. Participants 1996 patients aged 65 and older were included (1578 patients without cancer and 418 patients with solid and hematological cancer recently diagnosed). Measurements Frailty was established according to the frailty phenotype. The frailty phenotype measures five components of frailty: weight loss, exhaustion, low physical activity, weakness and slow gait. Frailty phenotype was categorized as robust, pre-frail and frail. Results In a multinomial logistic regression, cancer, compared to the non-cancer group, is not associated with an increased likelihood of being classified as pre frail (RRR 0.9, 95% CI [0.5; 1.6], p 0.9) or frail (RRR 1.2, 95% CI [0.7; 2.0], p 0.4) rather than robust. When considering each Fried criterion, a significant higher odd of weight loss was observed in older patients with cancer compared to the non-cancer patients (OR 2.3, 95% CI [1.8; 3.0], p Conclusion In this real-life study evaluating elderly patients with and without cancer, we didn’t confirm our hypothesis, in fact we found that cancer was not associated with frailty severity using both a phenotypic model and a deficit accumulation approach. Cancer may contribute, at least additively, to the development of frailty, like any other comorbidity, rather than a global underlying condition of vulnerability.

Background Half of cancer cases occur in patients aged 70 and above. Majority of older patients are eligible for chemotherapy but evidence for treating this population is sparse and severe toxicities affect more than half of them. Determining prognostic biomarkers able to predict poor chemotherapy tolerance remains one of the major issues in geriatric oncology. Ageing is associated with body composition changes (increase of fat mass and loss of lean mass) independently of weight-loss. Previous studies suggest that body composition parameters (particularly muscle mass) may predict poor chemotherapy tolerance. However, studies specifically including older adults on this subject remain sparse and the majority of them study body composition based on computed tomography (CT) scanner (axial L3 section) muscle mass estimation. This method is to date not validated in elderly cancer patients. Methods This trial (Fraction) will evaluate the discriminative ability of appendicular lean mass measured by dual-energy X-ray absorptiometry (DXA) to predict severe toxicity incidence in older cancer-patients treated with first-line chemotherapy. DXA is considered the gold standard in body composition assessment in older adults. Patient’s aged ≥70 diagnosed with solid neoplasms or lymphomas at a locally advanced or metastatic stage treated for first-line chemotherapy were recruited. Patients completed a pre-chemotherapy assessment that recorded socio-demographics, tumor/treatment variables, laboratory test results, geriatric assessment variables (function, comorbidity, cognition, social support and nutritional status), oncological risk scores and body composition with DXA. Appendicular lean mass was standardized using evidence based international criteria. Participants underwent short follow-up geriatric assessments within the first 3 months, 6 months and a year after inclusion. Grade 3 to 5 chemotherapy-related toxicities, as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) were assessed at each chemotherapy cycle. Discussion The finding that body composition is associated with poor tolerance of chemotherapy could lead to consider these parameters as well as improve current decision-making algorithms when treating older adults. Trial registration ClinicalTrials.gov Identifier: NCT02806154 registered on October 2016.

Background Frailty and hemoglobin concentration, above what would be considered clinical anemia, are two common findings in older patients that lead to an increased risk of negative health outcomes. The objective of this study is to evaluate whether hemoglobin concentration is an independent predictor of frailty and investigate possible causal pathways with a focus on the relationship between inflammation or nutrition and hemoglobin concentration. Methods 1829 community-dwelling participants aged 65 years or older who visited the Toulouse frailty day hospital during 2011 and 2016 were included in this analysis. Patients underwent a comprehensive geriatric assessment and had a blood sample taken. A series of multivariate logistic regression models were performed after minimizing potential influence from age, gender, kidney function, inflammation, cognition, nutritional status and certain socio-economic factors. Results Hemoglobin concentration and frailty are significantly associated after minimizing potential influence from other covariates (p p > 0.005). Conclusions Hemoglobin concentration is strongly associated with frailty in older adults. These results can have potentially important implications for prevention policies targeting frailty by identifying potential patients with high risk of adverse outcomes and functional outcomes.

Consequences of inappropriate prescriptions and polymedication in patients suffering from cancer are beginning to be well documented. However, the methods used to evaluate these consequences are often discussed. Few studies evaluate the risk of interaction with anticancer drugs in elderly patients suffering from cancer. To describe the prevalence (i) of polypharmacy, (ii) of potentially inappropriate drug prescriptions and (iii) of drug interactions involving anticancer treatments, using a multiple reference tools. A retrospective, cross-sectional, multicenter study performed from January to December 2012. Patients aged 65 years or older suffering from cancer presented at the oncogeriatric multidisciplinary meeting. Polymedication (>6 drugs), potentially inappropriate prescriptions and drug interactions involving anticancer treatment were analyzed in combination with explicit and implicit criteria within a global approach. Among the 106 patients included in this study, polypharmacy was present in 60.4% of cases, potentially inappropriate drug prescription in 63.1% and drug interactions in 16% of case, of which 47% involved anti-cancer treatments. Twenty-seven major drug interactions were identified and eight interactions involved chemotherapy. Polymedication, inappropriate prescribing and drug interactions involving anti-cancer drugs are common and largely underestimated in elderly cancer patients.

Background The comprehensive geriatric assessment (CGA) is the gold standard in geriatric oncology to identify patients at high risk of adverse outcomes and optimize cancer and overall management. Many studies have demonstrated that CGA could modify oncologic treatment decision. However, there is little knowledge on which domains of the CGA are associated with this change. Moreover, the impact of frailty and physical performance on change in cancer treatment plan has been rarely assessed. Methods This is a cross-sectional study of older patients with solid or hematologic cancer referred by oncologists for a geriatric evaluation before cancer treatment. A comprehensive geriatric assessment was performed by a multidisciplinary team to provide guidance for treatment decision. We performed a multivariate analysis to identify CGA domains associated with change in cancer treatment plan. Results Four hundred eighteen patients, mean age 82.8 ± 5.5, were included between October 2011 and January 2016, and 384 of them were referred with an initial cancer treatment plan. This initial cancer treatment plan was changed in 64 patients (16.7%). In multivariate analysis, CGA domains associated with change in cancer treatment plan were cognitive impairment according to the MMSE score (p = 0.020), malnutrition according to the MNA score (p = 0.023), and low physical performance according to the Short Physical Performance Battery (p = 0.010). Conclusion Cognition, malnutrition and low physical performance are significantly associated with change in cancer treatment plan in older adults with cancer. More studies are needed to evaluate their association with survival, treatment toxicity and quality of life. The role of physical performance should be specifically explored.

A consensual and operational definition of frailty is necessary in geriatric oncology. While many studies have focused on geriatric syndromes evaluated in the comprehensive geriatric assessment (CGA) to select patients at higher risk of poor outcomes, few have compared CGA data with Fried's phenotype of frailty, the most consensual measurement of frailty in geriatrics. Our objective was to determine a threshold of impaired domains evaluated in CGA associated with Frailty status.A cross-sectional study including all patients with cancer, evaluated from January 2011 to February 2016 at the Geriatric Frailty Clinic, Toulouse. A CGA was performed evaluating seven geriatric domains. Frailty was measured by Fried's phenotype to classify patients into three groups (robust/pre-frail/frail). We plotted a ROC curve to determine the threshold of impaired domains associated with frailty according to Fried.We included 418 patients aged 82.8 years (range 66-100 years). Thirty-three patients (7.9%) were robust, 155 (37.1%) pre-frail and 230 (55%) frail. There was a significant difference in ADL, IADL, nutrition, cognition and polypharmacy between the three groups (p .001 for each domain). Frail patients had more impaired geriatric domains on CGA than pre-frail and robust patients (respectively 4.5 ± 1.5, 2.8 ± 1.6 and 2.1 ± 1.2; p .001). The threshold of 4 impaired geriatric domains associated with Fried's Frailty status was identified (Se 77.39%, Sp 67.55%). Area under the curve was 79.6%.The phenotype of frailty is associated with more impaired geriatric domains and a threshold of 4 altered domains could be used to detect frailty from CGA data.

Background:Making the diagnosis of aortitis may be challenging in the “real life”.18F-FDG PET/CT (PET) has emerged has the gold standard to diagnose aortitis but it is expensive and not always quickly available. Injected CT-scan (CT) can also be used to diagnose aortitis, which is suspected when there is an extended circumferential, non-atherosclerotic increase of the aortic wall thickness (AWT). However, data are lacking on the diagnostic performances of AWT to diagnose aortitis.Objectives:To describe the diagnostic performance of AWT measured by CT to diagnose aortitis in patients over 50 years of age.Methods:We performed a monocentric retrospective study between 2013 and 2018 including 1) all patients over 50 years of age who had performed a PET for inflammation or fever of unknown origin or for suspicion of classical giant cell arteritis (GCA), aortitis or large vessel vasculitis (LVV); 2) with an injected CT-scan performed in the 30 days before or after PET; 3) not diagnosed to have cancer or infection 4) exposed to corticosteroids for less than 3 days at the time of CT and PET. The gold standard for aortitis was PET positivity according to the 2018 European consensus grading criteria (1). AWT was measured at different aortic segments (ascending aorta, descending thoracic aorta and suprarenal abdominal aorta) by a single radiologist unaware of the result of PET and of the previous interpretation of CT-scan.Results:Eighty-nine patients were included (female: 47%; mean age 68.8 (50-93) years; GCA: n=28). Twenty patients had aortitis according to the PET result (GCA: n=16).Mean maximal aortic wall thickening was: 3.25 mm (median: 3.3; range: 2-4.6) in the aortitis group and 2.2 mm (median: 2.1; range 1-3.8) in the negative PET group (p < 0.001).The best ROC curve AUC (85%) was obtained considering the maximal AWT on the thoracic and suprarenal abdominal aorta only. The AUC of the ROC curve at the ascendant thoracic aorta was poor (75%) (Figure).The Youden’s index of the ROC curve was 2.6 mm with a sensitivity of 85 % and specificity of 71 % (Table) for aortitis diagnosis. An AWT ≤ 2.0 mm exclude the diagnosis of aortitis. The 3 mm threshold had a PPV of only 52% and an AWT ≥ 4 mm was fully specific.Conclusion:Aortitis diagnosis using a routine injected CT-scan interpreted by a single radiologist may be certain when showing an AWT ≥ 4 and excluded for an AWT≤ 2.0. The threshold of 3 mm seems not sufficiently specific to diagnose aortitis without a confirmatory PET.References:[1]Riemer H.J.A. Slart et al. FDG-PET/CT(A) imaging in large vessel vasculitis and polymyalgia rheumatica: joint procedural recommendation of the EANM, SNMMI, and the PET Interest Group (PIG), and endorsed by the ASNC. Eur J Nucl Med Mol Imaging. 2018 Jul;45(7):1250–69.Table.Performance of different threshold for maximal thickness of the aortic wall for diagnosis of aortitis using PET positivity as the gold standard*.Thickness (mm)SensitivitySpecificityNPVPPVaccuracy≥ 1.9100 %30.4%100 %29.41 %46 %≥ 2.0100 %31.88 %100 %29.85 %47 %≥ 2.295 %53.62 %97.36 %37.25 %63 %≥ 2.685 %71.01 %94.23 %45.94 %74 %≥ 3.060 %84.05 %87.88 %52.17 %78 %≥ 3.360 %92.75 %88.89 %70.59 %85 %≥ 3.535 %95.65 %83.54 %70 %82 %≥ 3.825 %98.55 %81.92 %83.33 %82 %≥ 4.020 %100 %81.17 %100 %82 %*Made with ROC curve in descendant thoracic and suprarenal segment of the aorta; PET:18F-FDG PET/CT; NPV: negative predictive value; PPV: positive predictive value.Figure.ROC curve of aortic wall thickness, in descendant thoracic and suprarenal abdominal segments for the diagnosis of aortitis.Disclosure of Interests:None declared

Introduction:There are discrepancies across recommendations about the indication of bone marrow smear in adults diagnosed for immune thrombocytopenia (ITP). The 2011 American Society of Hematology guidelines do not recommend bone marrow smear in case of typical ITP. In contrast, the 2010 international consensus and the 2017 French guidelines recommend systematic bone marrow smear in adults aged >60 years even in case of typical ITP to detect a blood cancer, particularly myelodysplastic syndrome. This recommendation is driven from expert consensus. Data are lacking about the positivity rate of this examination in older patients with typical ITP. The aim of this study was to assess the positivity rate of bone marrow smear at ITP diagnosis in >60-year-old patients with no other clinical or biological sign of hematological malignancy. Methods:Data source was theCARMEN (Cytopénies Auto-immunes : Registre Midi-PyréneEN) registry. All adult patients with an incident diagnosis of ITP in the French Midi-Pyrénées region (South of France, 3 million inhabitants) are prospectively enrolled since June 2013 in the multicenter CARMEN registry. ITP is defined by international guidelines (platelet count 60 years; absence of clinical signs of hematological malignancy (lymphadenopathy, hepatomegaly, splenomegaly); isolated thrombocytopenia on blood count; bone marrow smear performed at ITP diagnosis. We described patients with abnormal bone marrow smear and implications for ITP management. Results:We identified 114patients (66 men and 48 women) satisfying all inclusion criteria. Mean age at ITP diagnosis was 76 years (standard deviation - SD: 9 years). Platelet count at diagnosis was 32.7 x 109/L (SD: 27.7 x 109/L) and 58 patients presented with bleeding: skin bleeding only (n=33), oral bleeding (n=17), epistaxis (n=10) and hematuria (n=3). Only one patient had an abnormal bone marrow smear corresponding to a characterized hematological disease: a myelodysplastic syndrome. It was a 62-year-old man without medical history who presented in 2014 with extensive skin bleeding, and isolated thrombocytopenia (6 x 109/L). Other blood count parameters were: hemoglobin: 15.2 g/dL; MCV: 83 fL; leukocytes: 5.3 x 109/L; polynuclear neutrophils: 3.5 x 109/L; lymphocytes: 1.0 x 109/L; monocytes: 0,3 x 109/L . Bone marrow smear revealed normal cellularity. The megakaryocytic lineage was normally represented with significant number of megakaryocytes with multiple separated nuclei. Significant dysgranulopoiesis was also observed with pseudo-Pelger-Huët anomaly and cytoplasmic hypogranulation. Some erythroblasts with defective haemoglobination or cytoplasmic vacuolation were present. This aspect was compatible with the diagnosis of myelodysplastic syndrome with multilineage dysplasia (MDS-MLD). Karyotype was normal. The patient was initially treated for ITP with steroids and intravenous immunoglobulins (with partial response), then with danazol (complete response), eltrombopag (after loss of response to danazol and ocular bleeding, resulting in complete response) and more recently romiplostim (after loss of response to eltrombopag, resulting in complete response). He was treated in 2019 by rituximab to spare exposure to thrombopoietin receptor agonists, without efficacy. Before Rituximab, another bone marrow smear was performed (4 years after the first one) with the same cytologic and cytogenetic features (MLD-MDS with normal caryotype). Conclusions:Diagnosis of hematological malignancy is very uncommon in >60 year-old patients who present with typical ITP. Myelodysplastic syndrome was found in 1 (0.8%) patient in this series, and did not impact the management or the evolution of the patient with a five-year follow-up. Overall, this study sustains guidelines that does not recommend systematic testing for bone marrow examination in >60 year-old patients with typical ITP. Disclosures Comont: BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees. Recher:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sunesis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Honoraria; Macrogenics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Jazz: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Beyne-Rauzy:Novartis: Research Funding; Cellgene: Research Funding. Moulis:CSL Behring: Research Funding; Amgen pharma: Research Funding, Speakers Bureau; Novartis pharma: Research Funding, Speakers Bureau.

International audience; Objective: The aim of our study was to assess major cardiovascular event incidence, predictors, and mortality in ANCA-associated vasculitis (AAV).Methods: We conducted a retrospective cohort study of all GPA or MPA, according to Chapel Hill Consensus Conference classification criteria, diagnosed between 1981 and 2015. Major cardiovascular event was defined as acute coronary artery disease, or ischemic stroke, or peripheral vascular disease requiring a revascularization procedure. We calculated the comparative morbidity/mortality figure (CMF) and we used Cox proportional hazards regression models to assess the risk of coronary artery disease, ischemic stroke associated with AAV, after adjusting for covariates.Results: 125 patients, 99 GPA (79,2%) and 26 MPA (20,8%), were followed 88.4 ± 78.3 months. Ischemic stroke incidence was four times higher than in the general population (CMF 4,65; 95% CI 4,06-5,31). Coronary artery disease incidence was four times higher than in the general population (CMF 4,22; 95% CI 1,52-11,68). Smoking habits and history of coronary artery disease were strongly associated with coronary artery disease occurrence (adjusted HR 8.8; 95% CI 2.12-36.56, and adjusted HR 10.3; 95% CI 1.02-104.5, respectively). ENT flare-up was an independent protective factor for coronary artery disease occurrence. We did not identify factors significantly associated with stroke occurrence. The age-adjusted mortality rate was 22.5 per 1000 person-years. Mortality in AAV was 1.5 times higher than in the general population (CMF 1.56; 95% CI 1.34-1.83).Conclusion: AAV have a significantly increased risk of mortality, ischemic stroke, and coronary artery disease.

Introduction: Cancer in the elderly is a major public issue. However, older patients have long been debarred from clinical trials. There is a high unmet medical need for specific trials addressing oncology strategies adapted to older patients' conditions. While randomised phase III trials remain the gold standard, they usually require large numbers of patients. In this perspective, late single-arm phase II trials assessing treatment feasibility might prove a good alternative. However, it is essential to take into account the heterogeneity in an ageing population characterised by frailty. Standard parallel phase II studies in defined frail and non-frail populations also require a high number of patients. Used in molecular subtyping and treatment effect heterogeneity, stratified adaptive designs can improve statistical performance, but they have never been used in geriatric oncology. This report describes their potential benefits and useful applications as compared with standard designs. Methods: In a heterogeneous population, stratified adaptive designs allowed us to select subgroups of interest in two stages. Operational characteristics were evaluated through simulations of clinical trials under different scenarios. Results: Simulations showed that the use of stratified adaptive designs can efficiently minimise both the number of patients to be included and accrual duration with competitive statistical power and high heterogeneity detection rate at interim analysis. Conclusion: Compared with classical phase II designs, stratified adaptive phase II trial methodology offers a promising approach to improve clinical research in geriatric oncology. These designs may also be efficient in other populations such as children or adolescents and young adults. (C) 2018 Elsevier Ltd. All rights reserved.

Objectives: Arterial hypertension is among the leading risks for mortality. This burden requires in hypertensive patients the use of single, double or more antihypertensive drugs. The relationship between intracranial pressure (ICP) and arterial blood pressure is complex and still under debate. The impact of antihypertensive drugs on ICP is unknown. We wanted to understand whether the use of antihypertensive drugs has a significant influence on ICP and cerebrospinal fluid (CSF)/brain related parameters.

Introduction A comprehensive geriatric assessment (CGA) evaluating several domains of health is recommended for elderly patients with cancer. Effects of altered domains on the risk of death in this population need to be clarified. The aim of this study was to estimate the independent association of each CGA domain to overall survival (OS). Method Patients included in the ONCODAGE cohort completed a CGA at baseline. Cox models (one per domain) estimated the hazard ratio (HR) of death for each CGA domain. Directed Acyclic Graphs (DAGs) selected specific sets of adjustment factors for each model. Results The analysis included 1264 patients (mean age: 78 years, women: 70%). Median follow-up was 5.2 years, and 446 patients died. Each altered domain had a detrimental effect on survival, sometimes dependent on gender, age, education or time from inclusion. Nutritional status had a time-varying effect, with higher mortality rates if altered only within the first 3 years of follow-up. In case of altered mobility, the risk of death was higher only for the youngest patients and, in case of altered autonomy, only for the youngest women. An altered neurological state led to higher mortality rates; this effect increased with the level of education. Patients with altered psychological status or more than four comorbidities at baseline had also higher mortality rates. Conclusions Patients with an altered CGA domain have a higher risk of death than those without any alteration. The effect of some alterations is different in some subgroups or at a given time of the treatments.

Background Atropinic drugs can increase the risk of falls, cognitive impairment, and mortality in older patients; however, whether exposure to atropinic drugs is associated with frailty status remains unknown. Our aim was to assess the association between frailty status and exposure to atropinic drugs in a geriatric day hospital population. Methods We carried out a cross-sectional study that included all the patients consulting for the first time at the Geriatric Frailty Clinic for Assessment of Frailty and Prevention of Disability in Toulouse, France, from January 2013 to October 2013. Frailty was defined by 3 or more of Fried et al's criteria. Atropinic drugs were those with clinical antimuscarinic effect from the Anticholinergic Drug Scale (excluding drugs weighted 1 point and not listed by Duran et al) and from Laroche et al list (to include drugs marketed in France not present in the Anticholinergic Drug Scale). To explore a dose-effect relationship, we calculated the atropinic burden using the Anticholinergic Drug Scale weights. We performed logistic regression models adjusted for age, gender, comorbidities, being community dwelling or not, cognitive status, educational level, and polypharmacy (≥6 drugs). Results We included 437 patients (227 frail and 210 robust or prefrail). Exposure to at least one atropinic drug was associated with frailty (odds ratio 1.97, 95% confidence interval 1.10–3.53, P = .02). Due to a statistically significant interaction between age and atropinic burden, a dose-effect relationship for atropinic burden was explored in patients younger than 85 years, showing a significant association between atropinic burden score and frailty ( P = .01). The Odds ratio for an atropinic burden greater than or equal to 3 versus 0 was 3.84, 95% confidence interval 1.43–10.34 ( P Conclusions In a geriatric day hospital, population frailty is associated with a high atropinic burden.

International audience

Therapeutic patient education (TPE) has largely demonstrated its efficiency in the care of patients suffering from chronic conditions, as defined by the World Health Organization (WHO). At the same time TPE has been implemented in Oncology, particularly in the field of pain management but not only, considering cancer as a ‘chronic condition’. Moreover, in the early 2000s, Geriatric Oncology has begun to emerge as a discipline. Indeed, as the incidence of cancer regularly increases during the life, cancerous pathologies are prevalent in subjects over 65 years, and the care of these subjects is raising very different issues and challenges from those of younger patients (polypathology and co-morbidity, iatrogenesis, cognitive disorders and dementia, sensory deficits, role of caregivers...).TPE has secondary followed this development in getting adjusted to the specific needs of this population. Because of its global, multidimensional and holistic character, TPE now appears as an interesting tool in Geriatric Oncology. Some educational programs have been created, implemented and evaluated but only a few are specifically addressed to the geriatric population. This communication is a brief review of Therapeutic Education Programs designed for geriatric patients suffering from cancer and hematological conditions.

As the incidence of invasive breast cancer will increase with age, the number of elderly patients with a diagnosis metastatic breast cancer will also rise. But the use of cytotoxic drugs in elderly metastatic breast cancer patients is not systematic and is dreaded by medical oncologists. The need for prospective oncologic data from this population seems increasingly obvious. The main objective of this review is to investigate design and characteristics of phase II trials that assess activity and feasibility of chemotherapies in elderly advanced/metastatic breast cancer patients. An electronic search in PUBMED allowed us to retrieve articles published in English language on phase II trials in elderly metastatic breast cancer between January 2002 and May 2016. Sixteen publications were finally included in this review. The primary endpoint was a simple, a composite, and a co-primary endpoints in 11, three, and two studies, respectively. Efficacy was the primary objective in 15 studies: simple (n = 10), composite (n = 3), co-primary endpoints (n = 2). Composite or co-primary endpoints combined efficacy and toxicity. Thirteen studies used multistage designs. Only five studies evaluated the feasibility, i.e., to jointly assess efficacy and tolerance to treatment (toxicity, quality of life, etc) as primary endpoint. Development of elderly specific phase III clinical trials might be challenging, it therefore seems essential to conduct phase II clinical trials evaluating jointly efficacy and toxicity in a well-defined geriatric population. Use of multistage designs that take into account heterogeneity would allow to identify a subpopulation at interim analysis and to reduce the number of patients exposed to an inefficient or a toxic treatment regimen. It is crucial to evaluate new therapies (targeted therapies, immunotherapies) using adequate methodologies (Study design, endpoint).

To evaluate visual performance and factors associated with abnormal vision in patients screened for frailty at the Geriatric Frailty Clinic (GFC) for Assessment of Frailty and Prevention of Disability at Toulouse University Hospital. Retrospective, observational cross-sectional, single-centre study. Institutional practice. Patients were screened for frailty during a single-day hospital stay between October 2011 and October 2014 (n = 1648). Collected medical records included sociodemographic data (including living environment and educational level), anthropometric data, and clinical data. The general evaluation included the patient’s functional status using the Activities of Daily Living (ADL) scale and the Instrumental Activity of Daily Living (IADL) scale, the Mini-Mental State Examination (MMSE) for cognition testing, and the Short Physical Performance Battery (SPPB) for physical performance. We also examined Body Mass Index (BMI), the Mini-Nutritional Assessment (MNA), and the Hearing Handicap Inventory for the Elderly Screening (HHIE-S) tool. The ophthalmologic evaluation included assessing visual acuity using the Snellen decimal chart for distant vision, and the Parinaud chart for near vision. Patients were divided into groups based on normal distant/near vision (NDV and NNV groups) and abnormal distant/near vision (ADV and ANV groups). Abnormal distant or near vision was defined as visual acuity inferior to 20/40 or superior to a Parinaud score of 2, in at least one eye. Associations with frailty-associated factors were evaluated in both groups. The mean age of the population was 82.6 ± 6.2 years. The gender distribution was 1,061 females (64.4%) and 587 males (35.6%). According to the Fried criteria, 619 patients (41.1%) were pre-frail and 771 (51.1%) were frail. Distant and near vision data were available for 1425 and 1426 patients, respectively. Distant vision was abnormal for 437 patients (30.7%). Near vision was abnormal for 199 patients (14%). Multiple regression analysis showed that abnormal distant vision as well as abnormal near vision were independently associated with greater age (P < 0.01), lower educational level (P < 0.05), lower performance on the MMSE (P < 0.001), and lower autonomy (P < 0.02), after controlling for age, gender, educational level, Fried criteria, and MMSE score. The high prevalence of visual disorders observed in the study population and their association with lower autonomy and cognitive impairment emphasises the need for systematic screening of visual impairments in the elderly. Frailty was not found to be independently associated with abnormal vision.

The estimation of the risk of poor tolerance and overdose of antineoplastic agents protocols represents a major challenge in oncology, particularly in older patients. We hypothesize that age-related modifications of body composition (i.e. increased fat mass and decreased lean mass) may significantly affect tolerance to chemotherapy. We conducted a systematic review for the last 25 years (between 1990 and 2015), using US National library of Medicine Medline electronic bibliographic database and Embase database of cohorts or clinical trials exploring (i) the interactions of body composition (assessed by Dual X-ray Absorptiometry, Bioelectrical Impedance Analyses, or Computerized Tomography) with pharmacokinetics parameters, (ii) the tolerance to chemotherapy, and (iii) the consequences of chemotherapies or targeted therapies on body composition. Our search identified 1504 articles. After a selection (using pre-established criteria) on titles and abstract, 24 original articles were selected with 3 domains of interest: impact of body composition on pharmacokinetics (7 articles), relationship between body composition and chemotoxicity (14 articles), and effect of anti-cancer chemotherapy on body composition (11 articles). The selected studies suggested that pharmacokinetic was influenced by lean mass, that lower lean mass could be correlated with toxicity, and that sarcopenic patients experienced more toxicities that non-sarcopenic patients. Regarding fat mass, results were less conclusive. No studies specifically explored the topic of body composition in older cancer patients. Plausible pathophysiological pathways linking body composition, toxicity, and pharmacokinetics are sustained by the actual review. However, despite the growing number of older cancer patients, our review highlighted the lack of specific studies in the field of anti-neoplastic agents toxicity regarding body composition conducted in elderly.

BACKGROUND Cancer care in people over 75 years of age is particularly complex and requires collaboration between oncologists, geriatricians, GPs and other professional and family carers. To improve the care pathways for elderly people living with cancer, the French health authorities have created a network of oncologists and geriatricians; however, GPs experience difficulties in establishing their place in this network. OBJECTIVE This study aimed to analyse the impressions of French GPs involved in the care of elderly patients with cancer, including their feelings regarding their relationships with their oncologist and geriatrician colleagues. METHODS A qualitative approach using focus groups was employed. The proceedings of these focus groups were recorded, retranscribed and subjected to thematic analysis. RESULTS Although heavily involved in the care of their elderly patients living with cancer, the GPs who participated reported feeling isolated in their role at each step during the course of the disease. The principal themes addressed were screening and diagnosis, therapeutic decisions, multidisciplinary consultation meetings, the announcement of the diagnosis and monitoring at home. Their relationships with their oncologist colleagues showed much room for improvement, and they were unaware of the oncogeriatric network. CONCLUSIONS Improving the communication between GPs, oncologists and geriatric medicine seems to be one response to the isolation that GPs feel when caring for older people with cancer. At the primary care level, integration of GPs into the oncogeriatric network and the creation of a cancer care communication system in collaboration with the relevant hospital teams may be effective solutions.

La Presse Medicale - In Press.Proof corrected by the author Available online since lundi 29 avril 2013

Objective To describe the cognitive, functional, and nutritional features of patients admitted to a Special Acute Care Unit (SACU) for elderly patients with Alzheimer's disease (AD). Methods One-year observational study of patients with AD and other related disorders hospitalized in the SACU, Department of Geriatrics, Toulouse university Hospital during 2005. A comprehensive neurocognitive and non-cognitive geriatric assessment was performed. Data on full clinical evaluation, nutritional status, activities of daily living (ADL), gait and balance disturbance, behavioural and psychological symptoms (BPSD), and sociodemographics were recorded. Results Four-hundred and ninety-two patients were assessed. Their mean age was 81.1 ± 7.7, the mean length of stay was 10.7 ± 6.3 days, 62% were female, 63.9% were admitted from their own home and 30.4% from a nursing home. Eighty percent of patients had probable Alzheimer's disease or mixed dementia, less than 20% had other causes of dementia. Results of their comprehensive assessment showed a mean mini-mental state examination of 14.5 ± 7.4; a mean total ADL score of 3.7 ± 1.7. Seventy-seven percent had gait or balance disturbances; 90% of patients presented an unsatisfactory nutritional status. The most common reason for admission was BPSD. Conclusion AD complications are responsible for many acute admissions. Elderly patients suffering from dementia represent a population with unique clinical characteristics. Further randomised clinical trials are needed to evaluate the effectiveness of Special Acute Care Units for patients with AD and other related disorders. Copyright © 2007 John Wiley & Sons, Ltd.

Resume Introduction Une pathologie thymique, benigne ou maligne, peut accompagner les pathologies auto-immunes. Si elle est plus frequente en cas de myasthenie, de neuromyotonie ou encore d’erythroblastopenie, elle peut se rencontrer dans presque toutes les maladies auto-immunes. Observation Nous rapportons la premiere description, a notre connaissance, d’une association entre un thymome malin et un syndrome de Reynolds (definie par la presence d’une cirrhose biliaire primitive et d’une sclerodermie). Conclusion L’hypothese physiopathologique avancee est un echappement thymique de lymphocytes T autoreactifs a l’origine de la pathologie auto-immune dans ce contexte de syndrome auto-immun multiple.

Resume Propos. La majorite des etudes de la maladie d'Alzheimer concerne les stades legers a moderes de la pathologie. Les quelques etudes realisees dans les stades evolues de la maladie concernent des patients en institution. Le but de notre travail a ete d'etudier les diverses caracteristiques des patients atteints d'une maladie d'Alzheimer a un stade moderement severe au sein d'une population francaise vivant a domicile et de decrire les facteurs associes a la severite de la maladie. Methodes. Nous avons compare les donnees initiales des patients participant a la cohorte REAL.FR (Reseau sur la maladied'Alzheimer francais) en fonction du stade de la maladie evalue par le score au Mini Mental Status (stade leger a modere defini par un score ≥ 15 et stade moderement severe defini par un score Resultats. Apres prise en compte de l'ensemble des facteurs associes au seuil du Mini Mental Status (≥ ou Conclusions. Les stades evolues de la demence representent un probleme majeur tant sur le plan medical que socio-economique. Une meilleure connaissance de l'histoire naturelle de la maladie pourrait apporter certains elements de reflexion quant aux diverses possibilites de prise en charge.

Background Cryofibrinogenemia is frequently associated with cryoglobulinemia. The aim of this study was to determine the characteristics associated with the presence of cryofibrinogenemia in patients with cryoglobulinemic vasculitis. Methods This was a single-center retrospective study that included patients with cryoglobulinemic vasculitis who were tested for cryofibrinogen at a tertiary referral center between January 1, 2011 and December 31, 2012. Twenty-nine patients fulfilled the CryoVas (cryoglobulinemic vasculitis) Survey criteria for cryoglobulinemic vasculitis. Eighteen patients had a detectable cryofibrinogen (CF-positive) and 11 had no detectable cryofibrinogen (CF-negative). Median cryoglobulin levels were 89 ± 129 mg/L in the CF-positive group and 68 ± 82 mg/L in the CF-negative group ( P = .32). Median cryofibrinogen level was 70 ± 174 mg/L. Clinical manifestations were similar in both groups. Cancers and hematological disorders were more frequent among CF-positive patients (39% vs 0%, P = .026). Levels of alpha-1 and alpha-2 globulinemia were higher in the CF-positive group. Cryofibrinogenemia ≥ 100 mg/L was associated with cryoglobulinemic vasculitis (odds ratio [OR] 2.86; 95% confidence interval [CI], 1.06-7.73) in cryoglobulinemic patients. Presence of cryofibrinogenemia was associated with use of corticosteroids, immunosuppressants, or plasmapheresis in cryoglobulinemic vasculitis patients (OR 22.7; 95% CI, 2.02-256.44). Conclusions Our results strongly suggest that presence of cryofibrinogenemia is associated with a more severe phenotype among patients with cryoglobulinemic vasculitis.

Introduction . In France as in many other countries, first-line treatment of adult immune thrombocytopenia (ITP) is based on conventional dose (1 mg/kg/d) oral steroids (CDOS) during 3 weeks. Intravenous polyvalent immunoglobulin (IVIg) is added in case of severe bleeding. However, conventional dose (1 mg/kg/d) intravenous methylprednisolone (CDMP) is often used as a first-line treatment during a few days before continuation with oral prednisone. Indeed, CDMP may induce earlier response in comparison with CDOS due to the absence of intestinal absorption and of hepatic metabolism to be converted in the active substance. No study has assessed the benefits and the safety of this strategy in comparison with CDOS. This was the aim of this study. Methods. This study was conducted within the CARMEN registry. It is the cohort of all newly diagnosed ITP adults (≥ 18 years) recorded in the Midi-Pyrénées region, South of France, from June 2013 (still ongoing). For the present study, we selected all ITP adults included in the CARMEN registry between 05/01/2013 and 12/31/2015 with platelet count 30 x 109/L twice 7 days apart). Secondary outcomes were: the time to complete response, defined as the time between treatment initiation and complete response (no bleeding and platelet count >100 x 109/L twice 7 days apart); the rates of response and of complete response; and the occurrence of adverse drug reactions (ADRs) due to corticosteroids, analyzed by a pharmacologist and an internal medicine physician using the WHO causality scale. The primary outcome and the time to complete response were assessed using Kaplan-Meier curves. The index date was the date of start of treatment. Follow-up was censored in case of occurrence of the outcome, date of start of second-line treatment, death or date of last follow-up, whichever occurred first. All analyzes were adjusted using a propensity score (PS) assessing the probability of being exposed to CDMP vs. CDOS as well as for concurrent IVIg use. The PS included the following variables: age, gender, comorbidity Charlson score, bleeding score, platelet count before treatment and secondary vs. primary ITP. Log-rank tests were used to compare the 2 groups. Hazard ratios (HRs) were calculated using Cox models. Results. The study included 87 patients (24 in the CDMP group and 63 in the CDOS group). Mean age was 67 years (± 22) and 48% were females. ITP was primary in 84% of patients. Mean platelet count was 9.7 x 109/L (± 8.2). Thirty-four patients were also exposed to IVIg. CDMP was prescribed for 3 days in median (range: 1-10). Mean follow-up was 9.4 months (± 8.5). The overall response and complete response rates were 88.5% and 67%, respectively. The median time to response was 3 days in the CDMP group and 4 days in the CDOS group. It was 6.5 and 17 days for complete response, respectively. Response and complete response occurred earlier in the CDMP group (Figure 1A and 1B). However, only a statistical trend was observed for the time to response (adjusted HR: 1.35, 95% confidence interval - CI: 0.76 - 2.41, p Conclusions. CDMP resulted in an earlier response and complete response than CDOS. Only a trend was observed for the time to response probably due to lack of power to detect smaller variations in platelet counts. In hospitalized patients at ITP onset, initiating CDMP may reduce hospital stay duration. A. Kaplan-Meier curve assessing the probability of response in the CDMP group (full line) and the CDOS group (dotted line); log-rank test: p Disclosures Beyne-Rauzy: Celgene, Novartis: Honoraria.

I ntroduction:The frequency ofimmune thrombocytopenia (ITP)-associated diseases detected at ITP onset is not well known. The positivity rates of tests performed at ITP onset in order to detect these diseases are discussed or unknown, leading to discrepancies among recommendations. The aim of this study was to compare the positivity rates of tests used at ITP diagnosis to detect ITP-associated diseases in the overall ITP population, in the presence of signs evocative of these diseases and in the absence of these signs. Methods:We studied all patients included between June 2013 and May 2016 in the CARMEN (CytopéniesAuto-immunes : Registre Midi-PyréneEN) registry. This multicenter registry is aimed at the prospective follow-up of all incident ITP adults in the French Midi-Pyrénées region (South of France, 3 million inhabitants). Each investigator prospectively follows every patient newly diagnosed for ITP in routine visit or hospital stay. ITP is defined in accordance with French guidelines: platelet count Results:We included 218patients. Median age was 66 years (range: 18-96), 47.3% were female, 34 (15.8%) had a secondary ITP, 104 (48.2%) had bleeding signs, median platelet count was 18 x109/L (range: 1-135) and 144 (66.1%) were treated for ITP within the month following the diagnosis. Bone marrow examination was performed in 167patients. Fivemyelodysplastic syndromes (MDS) were found (3 refractory cytopenia with unilineage dysplasia and 2 with multilineage dysplasia). These 5 ITP patients had platelet count 60 years, these rates were 8.3% and 1.5%, respectively. Antinuclear antibodies (ANAs) were tested in 170 patients without known connective tissue disease and were positive (titer³1/160) in 73 (42.9%). The positivity rates were 40.0% incase of clinical signs of connective tissue disease and 41.8% otherwise. Antiphospholipid antibodies were positive in 7 patients (73 tested). The positivity rates were 11.1%in case of history of thrombosis or fetal loss and 9.4% in the absence of evocative context. The positivity rates ofdirectantiglobulintest (tested in 64 patients) were 30.4% in case of anemia or lowhaptoglobinlevel, and 7.3% otherwise. Serum protein electrophoresis was performed in 158 patients. None had a history of repeated or severe infections.Hypogammaglobulinemia( HCV, HBV and HIV were tested in respectively 143, 140 and 159 patients. No new infection was detected. Nine patients were tested for Helicobacter pylori infection and 3 were positive. One patient had symptoms evocative of gastritis and was positive for Helicobacter. Among the 7 patients without symptoms of gastritis, 2 were positive (28.6%). Thyroid stimulating hormone (TSH) was tested in 112 patients without history of thyroid dysfunction. The positivity rates were 50.0% in case of symptoms evocative of thyroid dysfunction and 7.3% otherwise. Conclusions: Except for ANAs (whose presence may lead to hydroxychloroquine prescription) andhypogammaglobulinemia, the positivity rates were at least three-fold higher in case of evocative context, discussing the systematic use of these tests. HIV, HCV and HBV infections revealed by ITP seem very rare in France. Disclosures Beyne-Rauzy: Celgene, Novartis: Honoraria.

Background: Basal cell carcinoma (BCC), the most prevalent form of cancer worldwide, is a malignant skin neoplasm. It is locally invasive, with an exceptional incidence of reported metastasis. It can also be part of the Gorlin-Goltz syndrome, an autosomal dominant genetic disorder with high penetrance and variable expressivity, which is principally characterized by cutaneous BCC, odontogenic keratocysts, palmar and/or plantar pits, and falx cerebri calcification. Observation: We report the exceptional clinical observation of a 54-year-old man presenting bone metastasis from BCC in Gorlin-Goltz syndrome. Conclusion: Less than 300 cases of metastatic BCC have been reported in the literature. The present case is the second associated with Gorlin-Goltz syndrome.

La Presse Medicale - In Press.Proof corrected by the author Available online since jeudi 4 juin 2015

Background: The clinical epidemiology of immune thrombocytopenia (ITP) is not well known. Some issues (bleeding events at diagnosis, association to other autoimmune diseases, rate of infection prior to ITP onset) are not well described in adults. Little is known as regards first-line treatment choice in the real-life practice. Aim: The aims of this study were to assess i) the clinical epidemiology of incident ITP adults; ii) the use of first-line treatments in this population; and iii) the factors associated with the initial use of intravenous (IV) corticosteroids (CS) and of intravenous immunoglobulin (IVIg) in a real-life setting. This study was carried out on behalf of the French national center for autoimmune cytopenia and the French national center for rare diseases in immunohematology. Methods: Study population was the patients included between June 2013 and December 2014 in the CARMEN (Cytopénies Auto-immunes : Registre Midi-PyréneEN) multicenter registry. This multicenter registry is carried out on behalf of the French national center for autoimmune cytopenia and the French national center for rare diseases in immunohematology. The originalities of this registry are: the prospective follow-up of newly diagnosed ITPs, aimed at completeness of recording in the French Midi-Pyrénées region, South of France (3 million inhabitants), and the detailed recording of ITP treatment exposures. All the physicians in charge of ITP patients in the region, belonging to the netwotk of the regional center for autoimmune cytopenia, prospectively follow every patient newly diagnosed for ITP during routine visit or hospital stay. ITP is defined in accordance with French guidelines: platelet count Results: Out of 121 newly diagnosed ITP, 113 patients were followed in the region and gave informed consent. Median age was 65 years (range: 18-95). Half of the patients were female, 24 (21.3%) had a secondary ITP, 57 (50.4%) had a Charlson's score ≥1, median platelet count was 17 x109/L (range: 1-126); 57 (50.9%) had bleeding symptoms, including 2 severe gastro-intestinal tract and 1 intracranial bleeding. Median Khellaf's bleeding score was 5 (range: 0-35). Twenty-five (21.4%) patients had another autoimmune disease (mostly: Hashimoto's thyroiditis, n=6, Sjögren syndrome, n=5, Evans syndrome, n=3) and 23 (20.3%) experienced an infection within the six weeks before ITP onset (including 8 influenza-like and 3 gastro-enteritis like syndromes, the others being various bacterial infections). Sixty-eight (60.2%) patients were treated during the week following the diagnosis. Among them, 66 (98.5%) received CS (median dose: 0.99 mg/kg/d), including 21 (31.3%) IV CS, 29 (43.3%) IVIg, 8 (11,9%) platelet transfusion, 2 romiplostim and 1 rituximab. The factors associated with the use of IV CS were secondary ITP (OR: 5.91; 95% CI: [1.78-19.71]) and Khellaf's bleeding score >8 (OR: 4.09; 95% CI [0.96-17.35]). Those associated with the use of IVIg were Khellaf's bleeding score >8 (OR: 7.30; 95% CI [1.36-32.27]) and platelet count Conclusions: This prospective cohort of newly diagnosed ITP adults confirms that severe bleeding is rare at ITP onset. Associated autoimmune diseases and recent infections are frequent. IVIg and IV CS were frequently used, particularly in case of severe bleeding. Disclosures Godeau: Roche: Research Funding; Amgen: Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Adoue:LFB: Other: Symposium presentations ; OCTAPHARMA: Other: Symposium presentations ; ACTELION: Other: Symposium presentations ; PFIZER: Other: Symposium presentations ; AMGEN: Other: Symposium presentations ; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; GSK: Other: Symposium presentations.

Background: The incidence ofadverse drug reactions (ADRs) related to immune thrombocytopenia (ITP) drugs is not well known in the real-life practice. Aim: The principal aim of this study was to assess the incidence of ADRs related to ITP drugs. The secondary aims were to compare the incidence of ADRs depending on the drugs, and to assess the factors associated to corticosteroids-related ADR occurrence. Methods: Study population was the patients included between June 2013 and December 2014 in the CARMEN (Cytopénies Auto-immunes: Registre Midi-PyréneEN) registry. This multicenter registry is carried out on behalf of the French national center for autoimmune cytopenia and the French national center for rare diseases in immunohematology. It is aimed at the prospective follow-up of all newly diagnosed ITP adults in the French Midi-Pyrénées region (3 million inhabitants). Each investigator prospectively follows every patient newly diagnosed for ITP in routine visit or hospital stay, providing informed consent was received. ITP is defined in accordance with French guidelines: platelet count Results: Out of 116 patients, 81 were exposed to at least one ITP drug and had at least one follow-up visit. At diagnosis, median age was 64 years (range: 18-95), 48.1% were female, 74.1% had primary ITP, 69.1% had bleeding symptoms and median platelet count was 7 x109/L. Eighty patients (98.8%) of the patients were exposed to corticosteroids, 46 (56.8%) to intravenous immunoglobulin (IVIg), 11 (13.6%) to thrombopoietin receptor agonists (TPO-RA), 7 (8.6%) to danazol and 7 to dapsone, 6 (7.4%) to rituximab. Thirty-nine patients (48.1%) experienced at least one significant ADR (58 ADRs in total). The most frequent ADRs were infections (25.0%) and endocrinal diseases (18.5%). Twenty-two (37.9%) ADRs were serious (leading to hospitalization, necessitating a new drug) and 2 were lethal. The overall incidence of ADRs related to ITP drugs was 4.2/100 persons-weeks (95% confidence interval - 95% CI: 3.2-5.2). Corticosteroids showed the highest incidence of ADR (5.2/100 persons-weeks; 95% CI: 3.6-6.8). In multivariate analysis, the 2 remaining variables associated with corticosteroids-related ADR occurrence were an age >60 years (hazard ratio - HR: 1.79, 95% CI: 0.77-4.15) and diabetes mellitus (HR: 2.73, 95% CI: 1.08-6.87). Conclusion: This first study assessing the incidence of ADRs related to ITP drugs in a real-life setting showed that they are frequent. Corticosteroids were the first drug responsible for ADRs, stressing the need of second-line treatments, particularly in older and diabetic patients. Disclosures Godeau: Roche: Research Funding; Amgen: Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Adoue:AMGEN: Other: Symposium presentations; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; GSK: Other: Symposium presentations; OCTAPHARMA: Other: Symposium presentations; PFIZER: Other: Symposium presentations; LFB: Other: Symposium presentations; ACTELION: Other: Symposium presentations.

TPS9635 Background: Efficacy and toxicity of targeted therapies don’t seem to vary considerably with age, but the impact of side effects in elderly patients is a major concern for clinicians. Our s...

Mr. B. was hospitalized for repeated falls and a painful syndrome of his right leg evolving since several weeks. The symptoms began with paroxysmal painful contractures in the lower back and in the right leg. Progressively, a hypertonia of the lower limb has settled, leading to falls, loss of independence and use of a rolling chair. On the clinical examination, we noticed a global contraction of the right leg, with an ankle in equinovarus and a quasi-irreducible flexion at 20 degrees of the knee. Muscle spasms were very painful, triggered by muscle contractions and by emotion. An electrophysiological study was performed. The needle electromyography objectived abnormal muscular activities at rest with a continue muscle activity on the right adductor, quadriceps, anterior tibialis and on muscles of the feet (Fig. 1). Motor and sensory nerve conduction variables, including: motor nerve conduction velocities, distal latencies and amplitudes were within normal. Analysis of the cerebro-spinal fluid was normal. On the immunological findings, anti-nuclear antibodies, anti-neutrophil cytoplasmic antibodies and onco-neural antibodies were negative. Glutamic Acid Decarboxylase antibodies (GAD) were positive at 111 U/ml (N: 0–1). The clinical examination, electrophysiological and immunological findings led to the diagnosis of a limited form of Stiff-man syndrome: a Stiff-leg syndrome.