Thibault Mura

How many dementia cases in France and Europe? Alternative projections and scenarios 2010-2050.

Background and purpose:  The objective of this study is to estimate the number of dementia cases expected to occur in France and Europe over the next few decades until 2050.

Regulatory B10 Cells Are Decreased in Patients With Rheumatoid Arthritis and Are Inversely Correlated With Disease Activity

Regulatory interleukin‐10 (IL‐10)–producing B cells (B10 cells) have been shown to prevent and cure collagen‐induced arthritis in mice. In humans, very little is known about B10 cells in rheumatoid arthritis (RA). Several B cell subsets, such as CD24highCD38high, CD24highCD27+, and CD5+ B cells, were suggested to be precursors of B10 cells. We aimed to analyze these B cell subsets and B10 cells in RA patients and healthy controls.

Peripubertal female athletes in high-impact sports show improved bone mass acquisition and bone geometry.

OBJECTIVE Intensive physical training may have a sport-dependent effect on bone mass acquisition. This cross-sectional study evaluated bone mass acquisition in girls practicing sports that put different mechanical loads on bone. MATERIALS/METHODS Eighty girls from 10.7 to 18.0 years old (mean 13.83 ± 1.97) were recruited: 20 artistic gymnasts (AG; high-impact activity), 20 rhythmic gymnasts (RG; medium-impact activity), 20 swimmers (SW, no-impact activity), and 20 age-matched controls (CON; leisure physical activity <3h/wk). Areal bone mineral density (aBMD) was determined using DEXA. Hip structural analysis applied at the femur evaluated cross-sectional area (CSA, cm(2)), section modulus (Z, cm(3)), and buckling ratio. Bone turnover markers and OPG/RANKL levels were analyzed. RESULTS AG had higher aBMD than SW and CON at all bone sites and higher values than RG in the lumbar spine and radius. RG had higher aBMD than SW and CON only in the femoral region. CSA and mean cortical thickness were significantly higher and the buckling ratio was significantly lower in both gymnast groups compared with SW and CON. In RG only, endocortical diameter and width were reduced, while Z was only increased in AG compared with SW and CON. Reduced bone remodeling was observed in RG compared with AG only when groups were subdivided according to menarcheal status. All groups showed similar OPG concentrations, while RANKL concentrations increased with age and were decreased in SW. CONCLUSION High-impact activity clearly had a favorable effect on aBMD and bone geometry during the growth period, although the bone health benefits seem to be more marked after menarche.

A retrospective analysis of 157 surgical procedures performed without replacement therapy in 83 unrelated factor VII-deficient patients.

Summary.  Background: Inherited factor (F)VII deficiency is the commonest of the rare bleeding disorders, with a wide set of hemorrhagic features. Other than for the severe clinical forms (for which treatment guidelines are well defined), consistent recommendations regarding perioperative replacement management do not exist for mild and asymptomatic FVII‐deficient patients. Objectives: The present study aimed to evaluate the influence of bleeding history, FVII procoagulant activity levels (FVII:C) and the type of surgical procedure on the management of inherited FVII‐deficient patients before surgery. Patients: One hundred and fifty‐seven surgical procedures, performed without replacement therapy, in 83 unrelated FVII‐deficient patients (median FVII:C = 5%, range 0.6%–35%) were analyzed. Results: The overall bleeding rate was 15.3%. We found a significant relationship between previous deep traumatic hematomas and bleeding at surgery, although relationships with previous common epistaxis, easy bruising and menorrhagia were not significant. The receiver‐operating characteristic (ROC) curve analysis performed on the first 83 procedures allowed us to define a cut‐off value of 7% with a sensitivity of 87% (negative predictive value: 94%). To enhance the sensitivity, and to take into account the potential variation resulting from non‐standardized FVII:C measurements, we would suggest applying a threshold of 10%. Conclusion: We have proposed recommendations for the perioperative management of FVII‐deficient patients based on FVII:C levels, a thorough bleeding history and the type of surgery involved. By applying these recommendations, minor procedures that risk only external or controlled hemorrhage can be performed in asymptomatic or mildly affected adults, even those with FVII:C levels below 10%.

Metabolic Syndrome, Its Components, and Mortality in the Elderly

CONTEXT AND OBJECTIVE The metabolic syndrome (MetS) has been shown to predict mortality in the middle-aged, but less is known on the impact of MetS and its components on mortality risk in the elderly. Our objectives were 1) to examine the association of MetS with the risk of all-cause and cause-specific mortality in a French elderly community-dweller cohort and 2) to determine the main components driving these associations. PARTICIPANTS AND METHODS Prospective analyses were carried out on 7118 men and women aged 65 yr and over from the Three-City cohort. Association between MetS (defined using the National Cholesterol Education Program Adult Treatment Panel III criteria) and mortality risk over the 7-yr follow-up was assessed using Cox proportional hazards models. RESULTS After adjusting for sociodemographic variables, health behaviors, and health status, a 50% increased risk for all-cause mortality was observed in participants with MetS at baseline compared with those without, with a hazard ratio of 1.54 [95% confidence interval (CI) = 1.24-1.92]. Elevated fasting blood glucose, high triglycerides, and low high-density lipoprotein cholesterol were the major contributors to this association, acting synergistically on mortality risk. For coronary heart disease mortality and cancer mortality, the hazard ratios associated with MetS were 2.21 (95% CI = 1.07-4.55) and 1.49 (95% CI = 1.04-2.14), respectively. CONCLUSIONS By showing that an elevated fasting blood glucose potentiates the excess mortality risk associated with lipid abnormality, our study supports the status of MetS as a risk factor for mortality in the elderly. Our findings emphasize the importance of MetS screening and managing dyslipidemia and hyperglycemia in older persons in general practice.

Measuring cognitive change in subjects with prodromal Alzheimer's disease

Objective To investigate the sensitivity of a large set of neuropsychological tests to detect cognitive changes due to prodromal Alzheimers disease(AD); to compare their metrological properties in order to select a restricted number of these tests for the longitudinal follow-up of subjects with prodromal AD. Participants 212 patients with mild cognitive impairment were tested at baseline by a standardised neuropsychological battery, which included: the Free and Cued Selective Reminding test (FCSRT), the Benton Visual Retention test, the Deno100, verbal fluency, a serial digit learning test, the double task of Baddeley, the Wechsler Adult Intelligence Scale (WAIS) similarities, the Trail-Making Test and the WAIS digit symbol test. Patients were monitored every 6 months for up to 3 years in order to identify those who converted to AD (retrospectively classified as prodromal AD). Statistical analyses were performed using a nonlinear multivariate mixed model involving a latent process. This model assumes that the psychometric tests are nonlinear transformations of a common latent cognitive process, and it captures the metrological properties of tests. Results 57 patients converted to AD. The most sensitive tests in the detection of cognitive changes due to prodromal AD were the FCSRT, the semantic verbal fluency and the Deno100. Some tests exhibited a higher sensitivity to cognitive changes for subjects with high levels of cognition, such as the free recall, delayed free recall scores of the FCSRT and the semantic verbal fluency, whereas others showed a higher sensitivity at low levels of cognition, such as the total recall score of the FCSRT. Conclusions Tests used for the follow-up of prodromal AD subjects should be chosen among those that actually decline in this stage of the disease and should be selected according to the subject’s initial scores.

Response to tocilizumab in rheumatoid arthritis is not influenced by the body mass index of the patient.

Objective. To assess the relationship between the body mass index (BMI) and the efficacy of tocilizumab (TCZ) in patients with rheumatoid arthritis (RA). Methods. We conducted a retrospective study in 222 patients with RA followed by 5 centers. The European League Against Rheumatism response was evaluated at 6 months. Univariate and multivariate logistic regressions were performed. Results. No significant association between the BMI and the response to TCZ at 6 months was found after adjustment for potential confounding factors (adjusted OR 0.45, 95% CI 0.16–1.24, p = 0.13 and OR 1.19, 95% CI 0.31–4.48, p = 0.78 for BMI 25–30 kg/m2 and BMI > 30 kg/m2, respectively, compared to BMI < 25 kg/m2). Conclusion. Response to TCZ in patients with RA is not influenced by the baseline BMI, in contrast to anti-tumor necrosis factor drugs.

Etanercept normalises left ventricular mass in patients with rheumatoid arthritis

Background Cardiovascular mortality is increased in patients with rheumatoid arthritis (RA). RA is associated with an increased left ventricular mass index (LVMI), a strong marker of cardiovascular mortality, and vessel abnormalities. Experimental studies have suggested that tumour necrosis factor α (TNFα) may induce LV hypertrophy. Objective To study the effect of medium-term (3- and 6-months) treatment with the TNFα inhibitor etanercept (ETN) and synthetic disease-modifying antirheumatic drugs (sDMARDs) on LV morphological features and arterial stiffness in patients with RA. Methods Consecutive female patients with active RA requiring treatment with ETN (n=28) or sDMARDs (n=20) were included. Clinical and biological monitoring, echocardiography and pulse wave velocity (PWV) assessment were performed at inclusion and at 3 and 6 months after the start of treatment. Paired t tests and multivariate linear regression analysis were used. Results Mean LVMI tended to be higher at baseline in the ETN group than in the sDMARD group (96.5±19.8 vs 84.3±26.8 g/m2; p=0.11 for the ETN and sDMARD groups, respectively). In patients with ETN treatment, mean LVMI was significantly decreased at 3 and 6 months (−6.3±7.6 and −14.2±9.3 g/m2; p<0.001), with no change from baseline for patients with sDMARD treatment (−2.2±10.9 and −2.7±10.2 g/m2, respectively). Blood pressure (BP) and aortic PWV were not changed by either treatment. Conclusions ETN induced a significant decrease in LVMI with medium-term treatment with no change in BP or PWV. TNFα may be an important factor of LV hypertrophy, which may explain the benefit of TNF inhibitors on cardiovascular morbidity and mortality in RA. These results need to be confirmed by larger studies and with other TNF inhibitors.

Bone mineral density acquisition in peripubertal female rhythmic gymnasts is directly associated with plasma IGF1/IGF-binding protein 3 ratio

OBJECTIVES Intense physical activity in peripubertal girls may delay menarche and cause menstrual disorders and estrogen deficiency, particularly in sport disciplines that require strict weight control. It may also have a deleterious effect on bone mass acquisition. The aim of this study was to determine the time-course of bone mass accretion in peripubertal elite female rhythmic gymnasts (FRGs) over a 1-year period, as well as the anthropometric and hormone parameters that could be helpful for predicting bone mineral density (BMD) gain. METHODS AND DESIGN We conducted a 1-year follow-up study in 29 FRGs (10.7-16.1 years old). Whole body composition and BMD of the whole body, proximal femur, lumbar spine, mid-radius, and skull were measured by dual energy X-ray absorptiometry (DXA). Moreover, baseline growth- and bone metabolism-related hormones such as IGF1, IGF-binding protein 3 (IGFBP3), leptin, and bone markers were measured. RESULTS BMD increased significantly at all bone sites throughout puberty, particularly between Tanner stages II and IV-V (P=0.025 to P<0.001). The IGF1 level, IGF1/IGFBP3 ratio, and leptin level were higher in late pubertal stages (i.e. IV-V) compared with early stage (i.e. I). In simple and multivariate analyses, only the IGF1/IGFBP3 ratio was strongly correlated with the BMD change at all bone sites (r=0.49, P=0.02 to r=0.77, P<0.0001). CONCLUSION This 1-year follow-up study of peripubertal FRGs showed that BMD gain was maximal around Tanner stage III. The plasma IGF1/IGFBP3 ratio was associated with bone mass acquisition in this period, and it may thus serve as a surrogate marker of bone mass gain in this population.

Specific Bone Mass Acquisition in Elite Female Athletes

CONTEXT Cross-sectional studies have demonstrated that physical activity can improve bone mass acquisition. However, this design is not adequate to describe the specific kinetics of bone mass gain during pubertal development. OBJECTIVE To compare the kinetics of bone mass acquisition in female adolescent athletes of sports that impose different mechanical loads and untrained controls throughout puberty. STUDY PARTICIPANTS A total of 72 girls with ages ranging from 10.8 to 18.0 years were recruited: 24 rhythmic gymnasts (RG, impact activity group), 24 swimmers (SW, no-impact activity), and 24 age-matched controls (CON). MAIN OUTCOME MEASURES Areal bone mineral density (aBMD) was determined using dual-energy x-ray absorptiometry and bone turnover markers were analyzed. All the investigations were performed at baseline and after 1 year. RESULTS At baseline and after 1 year of follow-up, RG presented significantly greater aBMD adjusted for age, fat-free soft tissue, and fat mass compared with CON and SW, only at the femoral region. When aBMD variation throughout the pubertal period was modeled for each group from individual values, the aBMD at the femoral region was significantly higher in RG compared with the other 2 groups from 12.5 to 14 years, and this difference lasted up to 18 years. Moreover, the mean annual aBMD gain tended to be higher in RG compared with SW and CON only at the femoral region and this gain lasted longer in RG. Bone remodeling markers decreased similarly with age in the 3 groups. CONCLUSIONS This study, which was based on linear mixed models for longitudinal data, demonstrated that the osteogenic effect of gymnastics is characterized by greater bone mass gain localized at mechanically loaded bone (ie, the proximal femur) principally around the menarcheal period. Moreover, the bone mass gain lasts longer in gymnasts, which may be explained by the delay in sexual maturation.