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International audience; The purpose of this multicentric study was to evaluate the prevalence and causes of Elevated Bone Mass (EBM) in patients who underwent DXA scanning over a 10-year period. The prevalence of EBM was 1 in 100. The main causes of EBM were degenerative spine disorders and renal osteodystrophy. Introduction Reports of elevated bone mass (EBM) on routine dual energy X-Ray absorptiometry (DXA) scanning are not infrequent. However, epidemiological studies of EBM are few and definition thresholds are variable. The purpose of this French multicentric study was to evaluate the prevalence and causes of EBM in adult patients who underwent DXA scanning over a 10-year period. Methods This multicentric, retrospective study was conducted in six French regional bone centres. DXA databases were initially searched for individuals with a bone mineral density (BMD) Z-score >= +4 at any site in the lumbar spine or hip from April 1st, 2008 to April 30st, 2018. Results In all, 72,225 patients with at least one DXA scan were identified. Of these, 909 (322 men and 587 women) had a Z-score >= + 4, i.e. a prevalence of 1.26% [1.18-1.34%]. The DXA scan reports and imagery and medical records of the 909 EBM patients were reviewed and 936 causes were found. In 42 patients (4%), no cause could be determined due to unavailability of data. Artefactual causes of EBM were found in 752 patients (80%), in whom the predominant cause was degenerative disease of the spine (613 patients, 65%). Acquired causes of focal EBM-including Paget's disease (n = 7)-were found in 12 patients (1%), and acquired causes of generalized EBM-including renal osteodystrophy (n = 32), haematological disorders (n = 20) and hypoparathyroidism (n = 15)-in 84 patients (9%). Other causes were rare hereditary diseases and unknown EBM in 19 (2%) and 27 (3%) cases respectively. Conclusions The prevalence of EBM was approximately 1 in 100. These findings suggest that degenerative disease of the spine is the main cause of EBM, but that acquired or hereditary diseases are also causal factors.

Context Despite optimization of metabolic balance during pregnancy in type 1 diabetes (T1D), maternal–fetal complications remain higher than in the background population. Objective We examined whether there is an association between glycated hemoglobin (HbA1c) levels and these complications. Methods Retrospective study of pregnancies in 678 T1D subjects at Lille Hospital (1997-2019). The association between variations in HbA1c levels and complications was examined. The composite criterion (CC) was defined as having at least 1 of the following complications: prematurity, pre-eclampsia, large for gestational age (LGA), small for gestational age (SGA), or cesarean section. Results Among the 678 births, median preconception HbA1c was 7.2% (55 mmol/mol), 361 were LGA (56%), 29 were SGA (4.5%), and 504 were births without preterm delivery (76.1%). The CC occurred in 81.8%. Higher HbA1c during the first trimester was associated with the CC (OR 1.04; 95% CI 1.02-1.06 per 0.1% increase; P 6.5% (48 mmol/mol) and a third trimester HbA1c Conclusion Elevated HbA1c is associated with maternal–fetal complications. Despite optimization of metabolic balance during the third trimester, for patients with early glycemic imbalance the risk of LGA persists.

Purpose/introduction A Fracture Liaison Service (FLS) was set up at Lille University Hospital in 2016. The purpose of this study was to assess persistence with osteoporosis treatment in patients from the FLS over a period of 1 year, and to determine predictors of discontinuation. Methods The study population comprised adults of both genders, aged 50 or over, admitted to Lille University Hospital between January 2016 and January 2019 for a low-trauma fracture and managed in our FLS. Outcomes included (1) persistence rate at 1 year after treatment initiation, (2) persistence rate at 2 years after treatment initiation, (3) persistence rate at 1 and 2 years after treatment initiation according to type of treatment, (4) predictors of non-persistence, and (5) reasons for discontinuing treatment over 1 year after initiation. Persistence was determined using the Kaplan–Meier method. Results In all, 1224 patients (≥50 years old) with a recent history of low-trauma fracture (≤12 months) were identified. Of these, 380 patients – 79.2% female; mean (SD) age 76 (11) years – were seen at the FLS. In those 380 patients, 410 fractures were found and 360 of them (87.8%) were major fractures, breaking down as follows: vertebra (44%), hip (19%), proximal humerus (10%), and pelvis (8%). Osteoporosis treatment was prescribed for 367 (96.6%) patients and 275 of them began the prescribed treatment. The following anti-osteoporosis drugs were prescribed: zoledronic acid (n=150, 54.5%), teriparatide (n=63, 22.9%), and denosumab (n=39, 14.2%). Oral bisphosphonates were prescribed for a few patients (n=23, 8.4%). Persistence with osteoporosis medication (any class) was estimated at 84.1% (95% CI: 79.1% to 88.1%) at 12-month follow-up, and dropped to 70.3% (95% CI: 63.7% to 75.9%) at 24 months. When drug-specific analyses were performed using the Kaplan–Meier method, persistence rates at 12 and 24 months were found to be higher with denosumab than with any other treatment. Independent predictors of non-persistence at 12 months were ‘follow-up performed by a general practitioner (GP)’ – Odds Ratio (OR) for GP vs. FLS = 3.68; 95% CI, 1.52 to 8.90, p=0.004 – and ‘treatment with zoledronic acid’ – OR for zoledronic acid vs. denosumab = 3.39; 95% CI, 1.21 to 9.50, p=0.019; OR for zoledronic acid vs. teriparatide = 8.86; 95% CI, 1.15 to 68.10, p=0.035. Conclusions This study provides evidence of the success of our FLS in terms of long-term persistence with osteoporosis treatments. However, osteoporosis treatment initiation still needs to be improved.

The primary objective of this study was to establish sex- and age-specific physical fitness percentiles for French children. The secondary aim was to assess sex, weight status, and age differences for physical fitness levels in French children. A sample of 31 484 children (16 023 boys, 15 461 girls) aged 6-11 years participated in the Diagnoform programme. Cardiorespiratory fitness, muscular endurance, speed, flexibility, and agility were assessed in this national programme. Percentile values were estimated as a function of age stratified by sex using a parametric method providing smooth centile curves and explicit formulae for the centile estimates. Values from the 10th to the 90th percentile are reported. The influence of body weight according to sex on the physical fitness level was also examined using an analysis of covariance adjusted for age. Physical fitness levels were slightly better in boys, except for agility and flexibility, in which girls performed better (Cohen's coefficient, 0.20-0.45; P

BACKGROUND AND PURPOSE: Objective and quantitative data to define cerebellar vermis and/or brain stem hypoplasia in children are lacking. Our aim was to provide MR imaging biometric references for the cerebellar vermis and brain stem from a large cohort of children with normal cerebellums. MATERIALS AND METHODS: The MR imaging data were retrospectively selected from our hospital data base from January 1, 2014, to December 31, 2017. All MR imaging examinations of children between 1 day and 15 years of age, including midline sagittal sections, were included. Children with a clinical history or MR imaging abnormalities that may affect the posterior fossa were excluded. We manually measured four 2D parameters: vermian height, anterior-posterior diameter of the vermis, anterior-posterior diameter of the midbrain-pons junction, and anterior-posterior midpons diameter. The inter- and intraobserver agreement was evaluated. RESULTS: Seven hundred eighteen children were included (372 boys and 346 girls), from 1 day to 15 years of age. Normal values (third to 97th percentiles) were provided for each parameter. The vermis parameters showed a rapid growth phase during the first year, a slower growth until the fifth year, and finally a near-plateau phase. The brain stem parameters showed more progressive growth. The intra- and interobserver agreement was excellent for all parameters. CONCLUSIONS: We provide reference biometric data of the vermis and the brain stem using simple and reproducible measurements that are easy to use in daily practice. The relevance of these 2D measurements should be further validated in diseases associated with cerebellar abnormalities.

Introduction Reports of elevated bone mass (EBM) on routine DXA scanning are not infrequent. However, epidemiological studies of EBM are few in number and definition thresholds variable. The purpose of this study was to assess the prevalence and causes of EBM in the general population referred to a single university hospital - catering for a population of 4 million inhabitants - for DXA scanning. Material and methods DXA databases were initially searched for individuals with a bone mineral density (BMD) Z-score ≥+4 at any site in the lumbar spine or hip from April 1st, 2008 to April 30st, 2018. Two Hologic scanners were available at the Lille University Hospital (France). Prevalence of EBM was evaluated, as were causes associated with EBM. Results At the lumbar spine, 18,229 bone density tests were performed in women and 10,209 in men. At the hip, 17,390 tests were performed in women and 9857 in men. The total number of patients who had at least one bone density test was 14,745, of which 64.2% were female. Of these 14,745 patients, 211 had a Z-score ≥+4 at any site, i.e. a prevalence of 1.43% [1.25%-1.64%]. The DXA scans and medical records of 92 men and 119 women with elevated BMD were reviewed to assess causes. An artefactual cause was found in 164 patients (75%) with EBM (mostly degenerative disease of the spine), and an acquired cause of focal EBM was found in only 2 patients, both of whom had sclerotic bone metastases from prostate cancer. An acquired cause of generalized EBM was found in 32 patients (15%), the vast majority of whom had renal osteodystrophy (n = 11), followed by hematological disorders (n = 9; e.g. myeloproliferative syndromes and mastocytosis) and diffuse bone metastases from solid cancer (n = 5). Of the remaining causes, rare hereditary diseases (e.g. osteopetrosis…) and unexplained EBM were found in 10 and 6 cases respectively. Conclusion The prevalence of EBM (Z-score ≥+4 at any site) was 1.43% [1.25%-1.64%]. In nearly all instances (97.1%) the explanation for EBM could be found in the medical record and through conventional investigations. This study suggests that the main cause of EBM is degenerative disease of the spine. Further studies are needed to differentiate artefactual EBM from hereditary or acquired EBM, and to investigate unexplained EBM. Genetic testing may prove useful in elucidating rare unknown causes.

Objectives:To investigate alterations in the serum proteome of patients with systemic sclerosis (SSc)-associated pulmonary hypertension (PAH), to identify proteins that correlated with hemodynamic severity and to determine their possible pathogenic role.Methods:Patients were included if they fulfilled the following criteria: diagnosis of limited cutaneous SSc, no extensive interstitial lung disease (ILD), and no treatment with PAH-specific therapy. Patients were classified as cases if they had a definitive diagnosis of PAH confirmed by right heart catheterization (RHC) and a serum sample collected on the same day as RHC. They were classified as controls if they had no sign suggestive of PAH on echocardiography.Results:In a first exploratory step, serum expression of 1129 proteins was assessed in 15 cases and 16 controls by a high-throughput proteomic assay (SOMAscan). We identified 53 proteins differentially expressed between the 2 groups. Among these 53 candidates, only 2 correlated significantly with pulmonary vascular resistance (PVR): chemerin (p=0.01,ρ=0.62) and SET nuclear proto-oncogen (SET) (p=0.01,ρ=0.62).To validate these results, serum levels of chemerin and SET were measured by ELISA assay in 25 additional cases and 19 additional controls. Chemerin levels were confirmed to be significantly higher in cases (p=0.01) and correlated with PVR (p=0.01,ρ=0.46).In a second step, to study the potential pathophysiological role of chemerin, we performed confocal immunofluorescence analyses on explanted lungs of healthy controls, SSc-ILD without PAH and SSc-PAH patients. Chemerin receptor, CMKLR1, was significantly increased on SSc-ILD and SSc-PAH pulmonary artery smooth muscle cells (PA-SMC).We then tested the effect of chemerin on PA-SMC proliferation by stimulating PA-SMCs from idiopathic pulmonary arterial hypertension (iPAH) patients with serum from SSc patients with and without PH, in the presence or absence of a CMKLR1 inhibitor. PA-SMCs from iPAH were confirmed to have higher mRNA expression of CMKLR1 than controls (p=0.03). Serum from SSc-PH patients induced a significantly higher PA-SMC proliferation (p=0.005) than serum from controls. This difference was no longer significant (p=0.69) when adding the CMKLR1 inhibitor α–NETA.Conclusion:Chemerin is a surrogate biomarker for PVR in SSc-PAH. Increased chemerin and its receptor, CMKLR1, contribute to the SSc-PAH pathogenesis by inducing PA-SMC proliferation.Acknowledgments:NoneDisclosure of Interests:Sebastien SANGES: None declared, Lisa Rice: None declared, Ly Tu: None declared, Jean-Luc Cracowski Grant/research support from: JL Cracowski received grants from United Therapeutic, Bioprojet and Topadur, David Montani Grant/research support from: Dr. MONTANI reports grants and personal fees from Actelion, grants and personal fees from Bayer, personal fees from GSK, personal fees from Pfizer, personal fees from MSD, personal fees from Chiesi, outside the submitted work, Julio Mantero: None declared, Camille Ternynck: None declared, Guillemette Marot: None declared, Eric Hachlla: None declared, David Launay Grant/research support from: Dr. Launay reports personal fees from Actelion, grants and personal fees from Takeda, grants and personal fees from CSL Behring, outside the submitted work., Marc Humbert Grant/research support from: Dr. Humbert reports personal fees from Actelion, grants and personal fees from Bayer, grants and personal fees from GSK, personal fees from Merck, from United Therapeutics, personal fees from Acceleron, outside the submitted work., Christophe Guignabert: None declared, Robert Lafyatis Grant/research support from: RL holds research grants from Formation, Elpidera and Kiniksa., Consultant of: R.L. has served as a consultant for Bristol Myers Squibb, Boehringer-Mannheim, Merck, Magenta and Genentech/Roche

Objective To identify clinical parameters and intrapartum fetal heart rate parameters associated with a risk of umbilical cord acidosis at birth, using an automated analysis method based on empirical mode decomposition. Methods Our single-center study included 381 cases (arterial cord blood pH at birth pHa ≤7.15) and 1860 controls (pHa ≥7.25) extracted from a database comprising 8,383 full datasets for over-18 mothers after vaginal or caesarean non-twin, non-breech deliveries at term (>37 weeks of amenorrhea). The analysis of a 120-min period of the FHR recording (before maternal pushing or the decision to perform a caesarean section during labor) led to the extraction of morphological, frequency-related, and long- and short-term heart rate variability variables. After univariate analyses, sparse partial least square selection and logistic regression were applied. Results Several clinical factors were predictive of fetal acidosis in a multivariate analysis: nulliparity (odds ratio (OR) 95% confidence interval (CI)]: 1.769 [1.362–2.300]), a male fetus (1.408 [1.097–1.811]), and the term of the pregnancy (1.333 [1.189–1.497]). The risk of acidosis increased with the time interval between the end of the FHR recording and the delivery (OR [95%CI] for a 1-min increment: 1.022 [1.012–1.031]). The risk factors related to the FHR signal were mainly the difference between the mean baseline and the mean FHR (OR [95%CI]: 1.292 [1.174–1.424]), the baseline range (1.027 [1.014–1.040]), fetal bradycardia (1.038 [1.003–1.075]) and the late deceleration area (1.002 [1.000–1.005]). The area under the curve for the multivariate model was 0.79 [0.76; 0.81]. Conclusion In addition to clinical predictors, the automated FHR analysis highlighted other significant predictors, such as the baseline range, the instability of the FHR signal and the late deceleration area. This study further extends the routine application of automated FHR analysis during labor and, ultimately, contributes to the development of predictive scores for fetal acidosis.